SYSTEMATIC SYNTHESIS AND CHARACTERIZATION OF THE 2-λ5- PHOSPHAQUINOLIN-2-ONE SCAFFOLD TOWARDS THEIR OPTIMIZATION AND APPLICATION by JEREMY PATRICK BARD A DISSERTATION Presented to the Department of Chemistry and Biochemistry and the Division of Graduate Studies at the University of Oregon in partial fulfillment of the requirements for the degree of Doctor of Philosophy September 2021 DISSERTATION APPROVAL PAGE Student: Jeremy Patrick Bard Title: Systematic Synthesis and Characterization of the 2-λ5-Phosphaquinolin-2-one Scaffold Towards Their Optimization and Application This dissertation has been accepted and approved in partial fulfillment of the requirements for the Doctor of Philosophy degree in the Department of Chemistry and Biochemistry by: Dr. Ramesh Jasti Chairperson Dr. Michael Haley Co-Advisor Dr. Darren Johnson Co-Advisor Dr. Michael Pluth Core Member Dr. John Halliwill Institutional Representative and Andy Karduna Interim Vice Provost for Graduate Studies Original approval signatures are on file with the University of Oregon Division of Graduate Studies. Degree awarded September 2021 ii © 2021 Jeremy Patrick Bard iii DISSERTATION ABSTRACT Jeremy Patrick Bard Doctor of Philosophy Department of Chemistry and Biochemistry June 2021 Title: Systematic Synthesis and Characterization of the 2-λ5-Phosphaquinolin-2-one Scaffold Towards Their Optimization and Application The recently discovered phosphaquinolinone scaffold combines photophysical activity and supramolecular functionality to serve as a promising new class of compounds for a variety of different applications. The first part of this dissertation focuses on our work in developing a deep, fundamental understanding of many different aspects of the structure, including the photophysical properties, the solution-state dimerization, and the solid-state crystal packing structures. This was performed through a series of systematic syntheses focuses on backbone composition, substituent group placement, and phosphorus center modification. Through a combination of experimental and computational approaches, a series of relationships and trends have been drawn to allow for prediction of both emission energy and dimerization strength of previously not prepared heterocycles based solely upon computed values. These trends open the door for guided design of future heterocycles. The second part of this dissertation focuses on building off of the fundamental knowledge gained in the initial structure-property relationship studies and applying those findings to application-driven projects. The first of these involves preparing a series of conjugated host molecules that contain the phosphaquinolinone moiety. These hosts are capable of binding HSO -4 both strongly and selectively and are able to extract it from iv aqueous solutions. These hosts can potentially be utilized in high-level nuclear waste remediation processes, as the removal of HSO -4 is crucial to improving the currently used vitrification methods. The second of these studies involves the development of the PN scaffold as a live cell imaging reagent. Initial results indicate that this scaffold indeed holds promise as a useful cell imaging reagent as it is non-cytotoxic, relatively pH- insensitive, and cell-permeable. This dissertation contains both previously published and unpublished co-authored materials. v CURRICULUM VITAE NAME OF AUTHOR: Jeremy Patrick Bard GRADUATE AND UNDERGRADUATE SCHOOLS ATTENDED: University of Oregon, Eugene Eastern Oregon University, La Grande DEGREES AWARDED: Doctor of Philosophy, Chemistry, 2021, University of Oregon Bachelor of Science, Chemistry, 2016, Eastern Oregon University AREAS OF SPECIAL INTEREST: Organic Chemistry Physical Organic Chemistry PROFESSIONAL EXPERIENCE: Graduate Teaching Fellow, University of Oregon, 2016-2021 Instructor of Record, University of Oregon, 2020 GRANTS, AWARDS, AND HONORS: Graduate Student Award for Excellence in the Teaching of Chemistry, University of Oregon, 2021 UO Doctoral Dissertation Research Fellowship, University of Oregon, 2020 Graduate Student Award for Excellence in the Teaching of Chemistry, University of Oregon, 2017 Dean’s First Year Merit Award, University of Oregon, 2016 Student Leader of the Year, Eastern Oregon University, 2016 Outstanding Student of Chemistry, Eastern Oregon University, 2016 National SCI Scholar, Society of Chemical Industry, 2015 vi Sharing the Learning Funding Recipient, Eastern Oregon University, 2015 Outstanding Freshman Chemist, Eastern Oregon University, 2013 PUBLICATIONS: Bard, J.P., McNeill, J.N., Zakharov, L.N., Johnson, D.W., Haley, M.M. Isr. J. Chem. 2021, 61, 217–221. Bard, J.P., Johnson, D.W., Haley, M.M. Synlett 2020, 31, 1862–1877. Bard, J.P., Mancuso, J.L., Deng, C.-L., Zakharov, L.N., Johnson, D.W., Haley, M.M. Supramol. Chem. 2020, 32, 49–55. Bard, J.P., Bates, H.J., Deng, C.-L., Zakharov, L.N., Johnson, D.W., Haley, M.M. J. Org. Chem. 2020, 85, 85–91. Deng, C.-L., Bard, J.P., Zakharov, L.N., Johnson, D.W., Haley, M.M. Org. Lett. 2019, 21, 6427–6431. Nojo, W., Reingold, I.D., Bard, J.P., Chase, D.T., Deng, C.-L., Haley, M.M. ChemPlusChem 2019, 84, 1391–1395. Deng, C.-L., Bard, J.P., Zakharov, L.N., Johnson, D.W., Haley, M.M. J. Org. Chem. 2019, 84, 8131–8139. Bard, J.P., Deng, C.-L., Richardson, H.C., Odulio, J.M., Barker, J.E., Zakharov, L.N., Cheong, P.H.-Y., Johnson, D.W., Haley, M.M. Org. Chem. Front. 2019, 6, 1257– 1265. Deng, C.-L., Bard, J.P., Lohrman, J.A., Barker, J.E., Zakharov, L.N., Johnson, D.W., Haley, M.M. Angew. Chem. Int. Ed. 2019, 58, 3934–3938. Frederickson, C.K., Barker, J.E., Dressler, J.J., Zhou, Z., Hanks, E.R., Bard, J.P., Zakharov, L.N., Petrukhina, M.A., Haley, M.M Synlett 2018, 29, 2562–2566 (highlighted by Swager, T.M. & Yoshinaga, K. Synfacts 2018, 14, 1243). vii Bard, J.P., Deenik, P.R., Hamann, K.R., Morales, D.A., Cavinato, A.G (2016). In M.J. Mio & M.A. Benvenuto (eds.), Building and Maintaining Award-Winning ACS Student Member Chapters, Volume 2: Specific Program Areas (pp. 73–94). DOI: 10.1021/bk-2016-1230.ch008. viii ACKNOWLEDGMENTS There are countless people that I would like to thank, both personally and professionally. To my parents, Angie and Rob Bard, thank you for all of your love and support throughout my entire life. You have always been encouraging and supportive of my choices in schooling/jobs/life and without the two of you, I would certainly not have pushed myself to get a PhD. To the rest of my family in Eastern Oregon (La Grande) – the Irelands, the Bards, the Sams, the Vencills, Greg and Katie Mills – thank you all for making my visits back home overflow with love, family, and good times. To Ron Kelley, Anna Cavinato, Colby Heideman, and Colin Andrew at EOU, thank you for inspiring me to pursue chemistry, both in the lab and in the classroom. To my church family at the First Christian Church in La Grande, that you all for the kind words, letters of encouragement, and constant support for me throughout my entire life. In Eugene, I first want to thank everyone in my cohort, especially Hazel Fargher, Josh Barker, Jordan Levine, Tawney Knecht, Amber Rolland, and Ruth Maust, for going through this adventure of graduate school with me. Without the study sessions, coffee breaks, bar visits, daily banter, and inside jokes, grad school would have been much less entertaining, and the friendships formed will be something I will value forever, and I look forward to where the winds take us all. To my mentors and friends, Jeff Van Raden, Erik Leonhardt, Dr. Matt Cerda, Dan Seidenkranz, Brittany White-Mathieu, and Justin Dressler for always helping me with research, writing, and presentations. To past and present Haley lab members, Conerd, Justin, Josh, Gabby, Nolan, Bella, Efrain, and all of the undergraduates and rotation students that have come and gone from the lab, thank you all for making lab a very positive environment to work in. Even during tough times, I always ix was able to look forward to fun conversations, random thoughts, endless jokes, and comradery. To Past and Present DWJ lab members, especially Ngoc-Minh, Jess, Toby, Jordan, Trevor, Hazel, Thais, Hannah, and Grace, thank you all for always being there to discuss topics of mental health, equity, and anything else I wandered over to your office to talk about. Both labs have really shaped how I think about both research and many other things outside of work. To the Students that I have mentored while here, Jenna Mancuso, Turner Newton, Jacob Odulio, Hannah Bates, Nolan McNeill, Isabel Lopez, Janiel Elizarraga-Oregel, Holden Howard, Arman Garcia, and Jacob Mayhugh, thank you all for working with me and helping me develop as a teacher and a mentor. To my partner Hazel, thank you for being so loving and supportive throughout our time here. Without your love and support, I likely would not have made it through the challenges of grad school Our many trips and movie nights are things I will always think about during hard times. To Chunlin, my main mentor and great friend, thank you for helping me settle in lab after a rough first year and teaching me all I know. Without you being there, I would not have been able to keep PN afloat like we did, and I will be forever grateful of the lessons you taught in tenacity, perseverance, confidence, and creativity. To my thesis committee members, Dr. Ramesh Jasti, Dr. Michael Pluth, Dr. John Halliwill, thank you for your insight and guidance throughout grad school. To my advisors, Mike and Darren, words cannot express how grateful I am that you both were willing to have me join the lab despite my less than amazing performance during first year. You have both taught me how to wear the various hats needed in academia and you have both been supportive at every step. Lastly, I would like to thank the NSF (CHE-1607214) and the University of Oregon Graduate School (UO Doctoral Dissertation Fellowship) for funding. x This thesis is dedicated to David Lofdahl, who made undergraduate studies much more fun by being brilliant, creative, kind, ambitious, and an all-around amazing person and friend. While he wasn’t able to go on to graduate school and further his studies, he’s been with me in thoughts and memories of happy times throughout my PhD. xi TABLE OF CONTENTS Chapter Page I. BUMPY ROADS LEAD TO BEAUTIFUL PLACES: THE TWISTS AND TURNS IN DEVELOPING A NEW CLASS OF PN- HETEROCYCLES ...................................................................................................... 1 1.1 Introduction ...................................................................................................... 1 1.2 Initial Discovery............................................................................................... 4 1.3 Setbacks Breathe New Life .............................................................................. 8 1.4 A New Dynamic Duo Develops Dozens of Derivatives .................................. 10 1.5 Physicochemical Properties ............................................................................. 14 1.5.1 Fluorescence ........................................................................................... 14 1.5.2 Molecular Structures ............................................................................... 21 1.5.3 Solution Dimerization Studies ................................................................ 22 1.6 Applying What we have Learned .................................................................... 26 1.6.1 Development of Supramolecular Host .................................................... 26 1.6.2 Use of PN Moiety as an Impressive Fluorophore ................................... 30 1.7 Conclusions and Outlook ................................................................................. 31 II. SYNTHESIS, PHOTOPHYSICAL PROPERTIES, AND SELF- DIMERIZATION STUDIES OF 2-λ5-PHOSPHAQUINOLIN-2-ONES ................... 33 2.1 Introduction ...................................................................................................... 33 2.2 Results and Discussion .................................................................................... 36 2.2.1 Synthesis ................................................................................................. 36 2.2.2 Photophysical Properties ......................................................................... 38 2.2.3 Dimer Formation in Solution .................................................................. 44 xii Chapter Page 2.2.4 Dimer Formation in Solid State .............................................................. 49 2.3 Conclusions ...................................................................................................... 51 2.4 Experimental Section ....................................................................................... 52 III. EXPLOITING THE HYDROGEN BOND DONOR/ACCEPTOR PROPERTIES OF PN-HETEROCYCLES: SELECTIVE ANION RECEPTORS FOR HYDROGEN SULFATE ............................................................ 68 3.1 Introduction ...................................................................................................... 68 3.2 Results and Discussion .................................................................................... 71 3.3 Conclusions ..................................................................................................... 79 3.4 Experimental Section ...................................................................................... 80 IV. AMPLIFICATION OF THE QUANTUM YIELDS OF 2‑λ5‑PHOSPHAQUINOLIN-2-ONES THROUGH PHOSPHORUS CENTER MODIFICATION ........................................................................................ 87 4.1 Introduction ...................................................................................................... 87 4.2 Results and Discussion .................................................................................... 89 4.3 Conclusions ..................................................................................................... 95 4.4 Experimental Section ...................................................................................... 96 V. A HIGHLY FLUORESCENT PN-HETEROCYCLE-FUSED PYRENE DERIVATIVE WITH STRONG SELF-DIMERISATION THROUGH HYDROGEN BONDING ............................................................................................ 101 5.1 Introduction ...................................................................................................... 101 5.2 Results and Discussion .................................................................................... 103 5.3 Conclusions ..................................................................................................... 107 5.4 Experimental Section ...................................................................................... 108 xiii Chapter Page VI. THIONATION OF THE 2‐λ5‐PHOSPHAQUINOLIN‐2‐ONE SCAFFOLD WITH LAWESSON'S REAGENT ........................................................ 112 6.1 Introduction ...................................................................................................... 112 6.2 Results and Discussion .................................................................................... 113 6.3 Conclusions ..................................................................................................... 120 6.4 Experimental Section ...................................................................................... 120 VII. UTILIZATION OF THE 2‐λ5‐PHOSPHAQUINOLIN‐2‐ONE SCAFFOLD AS A NON-CYTOTOXIC, pH-INSENSITIVE, AND LIVE CELL-PERMEABLE IMAGING REAGENT ............................................................ 126 7.1 Introduction ...................................................................................................... 126 7.2 Results and Discussion .................................................................................... 128 7.3 Conclusions and Future Works ....................................................................... 136 7.4 Experimental Section ...................................................................................... 137 VIII. DEVELOPMENT OF A TRIPODAL SWITCHABLE, SELECTIVE, AND SENSITIVE HOST MOLECULE CAPABLE OF HSO –4 EXTRACTION TOWARDS NUCLEAR WASTE REMEDIATION .......................................................................................................... 145 8.1 Introduction ...................................................................................................... 145 8.2 Results and Discussion .................................................................................... 149 8.3 Conclusions and Future Works ........................................................................ 153 8.4 Experimental Section ...................................................................................... 155 IX. CONCLUDING REMARKS................................................................................. 160 APPENDICES ............................................................................................................. 161 A. Supplementary Information for Chapter II ....................................................... 161 B. Supplementary Information for Chapter III ..................................................... 298 xiv Chapter Page C. Supplementary Information for Chapter IV ..................................................... 359 D. Supplementary Information for Chapter V ....................................................... 404 E. Supplementary Information for Chapter VI ..................................................... 410 F. Supplementary Information for Chapter VII .................................................... 431 G. Supplementary Information for Chapter VIII ................................................... 448 H. Naphtho[2,1‑e]‑1,2-azaphosphorine 2‑Oxide Derivatives: Synthesis, Optoelectronic Properties, and Self-Dimerization Phenomena (with Supplementary Information) ........................................................................................ 454 I. PN-Containing Pyrene Derivatives: Synthesis, Structure, and Photophysical Properties (with Supplementary Information) ...................................... 554 REFERENCES CITED ................................................................................................ 622 xv LIST OF FIGURES Figure Page 1. Figure 1.1 Hydrogen- and halogen-bonding supramolecular hosts prepared and studied in the Haley/Johnson collaboration. Atoms involved in anion binding are bolded..................................................................... 3 2. Figure 1.2 Structure of the phosphaquinolinone compared to analogous coumarin and carbostyril moieties. ....................................................................... 10 3. Figure 1.3 (a) HOMO (gray) and LUMO (purple) occupancy levels on the carbons in the 3 and 6 positions of the phosphaquinolinone backbone as determined at the B3LYP/6-31g(d) level of theory. (b) Structure of disubstituted PN-naphthalene heterocycles 11 and (bottom) specific substituent groups and yields of each derivative for two-step cyclization/hydrolysis. ........................................................................................... 11 4. Figure 1.4 Relationship between the HOMO-LUMO gaps and the experimental emission energies of (blue) heterocycles 10b, 11a-11d and (red) heterocycles 10b, 11a-11d, and 11m ............................................................ 15 5. Figure 1.5 Representative phosphaquinolinone scaffolds colored by their respective experimental emission colors ....................................................... 20 6. Figure 1.6 Comparison of all measured Stokes shifts and brightnesses ............... 20 7. Figure 1.7 Single crystal structures of (a) 9j, (b) 10j monomer, and (c) 10j-10j dimer as representative structures for typical 9 and 10/11 structures. Ellipsoids drawn at 30% probability. Non-hydrogen bonding hydrogen atoms omitted for clarity ........................................................................ 21 8. Figure 1.8 Representative LFER plots for dimerization strengths of heterocycles (a) 11d-11g and (b) 10b, 11b, 11d, and 11m ................................... 23 9. Figure 1.9 Comparison of all collected phosphaquinolinone dimerization strengths ........................................................................................... 26 10. Figure 1.10 Partial 1H NMR spectra of a 1.13 mM solution of 28b in 10% DMSO-d6 in CDCl3 by itself and in the presence of 10 equiv. of each guest ............................................................................................................... 28 xvi Figure Page 11. Figure 1.11 Coordination environment of HSO –4 in the binding pocket of 28b in the solid state. Ellipsoids drawn at 30% probability. Non- hydrogen bonding hydrogens omitted for clarity................................................... 29 12. Figure 1.12 Emission color coordinates in the CIE 1931 chromaticity diagram of a 2:1:10 v:v:v mixture of 33a:33c:33d excited at 430 nm .................. 30 13. Figure 2.1 Coumarin and two congeners, carbostyril and phosphaquinolinone, along with known phosphaquinolinones A–F ..................... 34 14. Figure 2.2 Atomic contributions (calculated at B3LYP/6-31g(d) level of theory) to the HOMO (left) and LUMO (right) electron densities of the unsubstituted PN-heterocycle core and numbering order for core carbons (middle). Atomic contributions are shown only for the readily functionalizable positions ...................................................................................... 37 15. Figure 2.3 Emission spectra of (a) heterocycles 1b, 1d–1g and (b) heterocycles 1g–1l as well as (c) plot of trend between substituent electronic properties and emission energies of 1. The σ value of 1k was approximated by addition of the σmeta and σpara values of the two nitrile groups. All experimental values collected in CHCl3. ............................................ 40 16. Figure 2.4 (a) Calculated LUMO levels vs. Hammett parameter of R1 substituents of R2 = t-Bu heterocycles 1 and (b) calculated HOMO levels vs. Hammett parameter of R2 substituents of R1 = CN heterocycles 1. Orbital energy levels calculated at the PBE0/6-311G(d,p) level of theory. The σ value of 1k was approximated by addition of the σmeta and σpara values of the two nitrile groups ...................................................................... 42 17. Figure 2.5 Orientation of most dominant electronic transitions and the corresponding orbitals for heterocycles 1b, 1d–1g, and 1p; orbital energies in eV ........................................................................................................ 42 18. Figure 2.6 Correlation between calculated HOMO–LUMO energy gap levels versus experimental emission energies of (a) heterocycles 1b, 1d– 1g, and (b) heterocycles 1b, 1d–1g, and 1p ........................................................... 44 19. Figure 2.7 Positive trends between EWG on (a) R1 and (b) R2 with dimerization constants of 1 .................................................................................... 46 xvii Figure Page 20. Figure 2.8 Schematic examples of (a) orbital overlap within monomer units in the R–S heterodimer structure and (b) poor alignment between orbitals within each monomer in the S–S homodimer structure, where the phenoxy oxygen lone pairs are represented in red and align with the P–O σ* and P–N σ* orbitals and the P–O σ* and P–C σ* orbitals, respectively ............................................................................................................ 48 21. Figure 2.9 ΔGexp values versus ΔGpred. Blue data points were omitted from the initial model, and tested as a validation set of data, showing a good correlation to the model ................................................................................ 49 22. Figure 2.10 Solid state structures of (a) the monomer and dimer of 1m and (b) the monomer and staggered hydrogen bonding network of 1e ................. 50 23. Figure 2.11 Solid state N⋯O distances plotted against solution state Kdim values measured in CDCl3 ............................................................................. 51 24. Figure 3.1 a) Structure of the PN‐heterocycle homodimer linked by self‐ complementary hydrogen bonds. b) Structure of receptors 1 studied in this work. The relevant protons are marked to assign NMR peaks ....................... 70 25. Figure 3.2 Partial 1H NMR spectra of 1b (1.13 mm) in 10 vol% [D6]DMSO/CDCl3 in a) the absence and b) the presence of 10 equiv. hydrogen sulfate, c) nitrate, d) chloride, e) bromide, and f) iodide. All anions were used as their respective TBA salts. The two meta‐protons with respect to Hb on the central nitrophenyl core are marked with (*) .............. 73 26. Figure 3.3 a) X‐ray structure of 1b⋅HSO −4 complex; thermal ellipsoids are drawn at the 25% probability level. The TBA cation is omitted for clarity. b) The coordination environment of HSO −4 showing seven hydrogen bonds (indicated by black dotted lines) ................................................. 76 27. Figure 3.4 a) Snapshot showing the bond paths and BCPs for 1 b⋅HSO −4 complex based on AIM analysis. Red dots indicate BCPs, and blue dotted lines denote bond paths. Values of electron density ρ(r) are given for the relevant BCPs (in a.u.). b) Snapshot showing the NCI plot for 1 b⋅HSO −4 complex. NCI regions are represented as solid surfaces and blue‐green‐red scaling from −0.02 < sign(λ2)ρ(r) < 0.02 (in a.u.), where red surface indicates strong repulsion, blue surface strong attraction and green surface relatively weak interactions. Isosurface cutoff for NCI=0.5. The arrows in the Figure indicate the green isosurfaces existed between anion and alkyne moieties. ..................................................................... 77 xviii Figure Page 28. Figure 4.1 Well-studied coumarin and carbostyril scaffolds (top) compared to phosphaquinolinone analogues (bottom). ........................................ 88 29. Figure 4.2 Absorption (solid lines) and fluorescence (dotted lines) spectra of 2 in CHCl3 at 298 K. ............................................................................ 91 30. Figure 4.3 Selected bond length and dihedral angle in the optimized S0 and S1 structures of 2f calculated by DFT and TD-DFT methods at the PCM(CHCl3)-PBE0/TZVP level of theory, respectively. .................................... 93 31. Figure 4.4 (a) Characteristic PN-heterocycle dimer for 2f with the O···N distance (Å) shown as well as (b) bond angles and (c) torsional angles formed within monomers upon dimerization. Ellipsoids drawn at 30% probability. ............................................................................................................ 95 32. Figure 5.1 Previously reported phosphaquinolinone scaffolds as well as new PN-fused pyrene 2. ........................................................................................ 102 33. Figure 5.2 X-ray crystal structure of 2 showing both pyrene π–π stacking and phosphonamidate dimer distances; ellipsoids drawn at 30% probability. ............................................................................................................ 104 34. Figure 5.3 31P NMR spectra of 2 from VC NMR experiment as well as generated fit and residuals (inset). ......................................................................... 105 35. Figure 5.4 (a) Absorption and emission spectra of a 1 μM solution of 2 and (b) emission spectra of 2 at varying concentrations, showing excimer emission at higher concentrations in CHCl3, where λex = 365 nm. ........................................................................................................................ 106 36. Figure 6.1 Lawesson’s Reagent and a sampling of commonly prepared thiocarbonyl compounds. ...................................................................................... 112 37. Figure 6.2 ORTEP drawing of the thioheterocycle 2e meso-dimer; thermal ellipsoids drawn at 30 % probability level. .............................................. 116 38. Figure 6.3 Stacked absorption and emission spectra of heterocycles 2. .............. 117 39. Figure 7.1 examples of core fluorophore scaffolds and the phosphaquinolinone scaffold ................................................................................ 127 xix Figure Page 40. Figure 7.2 Initial images of HeLa cells upon treatment with a 25 μM solution of 1 and incubation for 30 minutes. ........................................................ 131 41. Figure 7.3 Initial images of HeLa cells upon treatment with a 25 μM solution of 3 and incubation for 30 minutes and b) cytotoxicity data. ................. 133 42. Figure 7.4 Cytotoxicity studies on heterocycle 3 showing no significant cytotoxicity up to 150 μM. .................................................................................... 134 43. Figure 7.5 Colocalization with 8 and Lysotracker Deep Red. ............................. 136 44. Figure 8.1 Structures of the studied bisurea host 1 and hybrid PN-urea host 2 as well as the structure of proposed 3-armed host 3. ................................. 147 45. Figure 8.2 The two conformations that 3 can take when in the presence of HSO -4 (conformation A, left), or Cl - (conformation B, right) ........................... 148 46. Figure 8.3 1H NMR titration experiment of 3 with additions of Cl-. Free host is shown on top. ............................................................................................. 151 47. Figure 8.4 31P NMR titration experiment of 3 with additions of Cl-. Free host is shown on top. ............................................................................................. 151 48. Figure 8.5 1H NMR titration experiment of 3 with additions of HSO -4 . Free host is shown on top and the 1:1 3:HSO -4 point is shown in the dark blue spectrum. ....................................................................................................... 152 49. Figure 8.6 31P NMR titration experiment of 3 with additions of HSO -4 . Free host is shown on top and the 1:1 3:HSO -4 point is shown in the dark blue spectrum. ....................................................................................................... 153 xx LIST OF TABLES Table Page 1. Table 1.1 Photophysical properties for heterocycles 10. ..................................... 7 2. Table 1.2 Synthetic yields for heterocycles 14, 17, 20, and 27. ........................... 12 3. Table 1.3 Photophysical properties of disubstituted PN-naphthalenes 11. ........... 16 4. Table 1.4 Photophysical properties of PN-anthracenes 14, PN- phenanthrenes 17 and 20, PN-pyrene 21, and P-phenyl heterocycles 27. ............ 18 5. Table 1.5 Dimerization strengths of select examples of heterocycles 10, 11, 17, 20, 21, and 27. ........................................................................................... 24 6. Table 1.6 Photophysical properties of 3-ring PN pyrene derivatives 33. ............ 31 7. Table 2.1 Photophysical properties for PN-heterocycles 1. ................................. 39 8. Table 2.2 Orbital energy levels for 1a–1p calculated at the PBE0/6- 311G(d,p) level of theory. ..................................................................................... 41 9. Table 2.3 Dimerization constants (M−1) of heterocycles 1 in H2O- saturated CDCl3. ................................................................................................... 45 10. Table 2.4 ΔGcalc and ΔGexp values of heterocycles 1. .......................................... 47 11. Table 2.5 Solid state N⋯O distances of selected heterocycles 1. . ....................... 51 12. Table 3.1 Association constants (Ka, m −1) of receptors 1 with various anions in 10 vol% [D6]DMSO/CDCl3 at 298 K. ................................................... 72 13. Table 4.1 Photophysical Properties and HOMO–LUMO Energy Gaps of Heterocycles 2a. .................................................................................................... 91 14. Table 4.2 Dimerization Constants and Energies for 2. ......................................... 94 15. Table 6.1 Photophysical properties of heterocycles 2. ......................................... 118 16. Table 7.1 Photophysical properties of new heterocycles in CHCl3 at 298 K. ........................................................................................................................... 129 xxi Table Page 17. Table 7.2 Photophysical properties of new heterocycles in ca. 5% DMSO in pH 7.4 PBS Buffer at 298 K. ................................................................ 130 xxii LIST OF SCHEMES Scheme Page 1. Scheme 1.1 Proposed synthesis of dithiol 5 and macrocyclic disulfide 6 redox pair along with the actual PN-heterocyclic product 7 formed from the reaction, which was confirmed by x-ray crystallography. ORTEP ellipsoids drawn at 50% probability. CCDC 1976534. ......................................... 5 2. Scheme 1.2 Synthetic pathway for the various PN frameworks. ......................... 7 3. Scheme 1.3 Proposed mechanism of phosphonimidate 9 cyclization. .................. 8 4. Scheme 1.4 Synthesis of PN-pyrene 21. .............................................................. 13 5. Scheme 1.5 Synthesis of heterocycles 27. ............................................................ 14 6. Scheme 1.6 Synthesis of hybrid hosts 28. Relevant protons on 28 labeled for identification purposes for Figure 1.10. .............................................. 28 7. Scheme 1.7 Synthesis of 3-ring PN pyrenes 33. .................................................. 31 8. Scheme 2.1 General synthetic pathway for disubstituted PN heterocycles. .......................................................................................................... 37 9. Scheme 3.1 Synthesis of Iodoheterocycle Coupling Piece 5. .............................. 81 10. Scheme 3.2 Synthesis of Ethynylaniline Coupling Piece 8 and Receptors 1a/1b. .................................................................................................................... 83 11. Scheme 4.1 Synthesis of Phosphaquinolinones 2.................................................. 90 12. Scheme 5.1 Synthesis of PN-pyrene 2. ................................................................ 103 13. Scheme 6.1 Conversion of oxo-heterocycles 1 to thio-heterocycles 2 with Lawesson’s Reagent (LR). ............................................................................ 114 14. Scheme 7.1 Synthesis of Heterocycle 1. .............................................................. 129 15. Scheme 7.2 synthesis of methylated PN 3............................................................. 131 16. Scheme 7.3 synthesis of heterocycle 8. ................................................................ 134 17. Scheme 8.1 Synthesis of 3-armed hybrid host 3 .................................................. 150 xxiii CHAPTER I BUMPY ROADS LEAD TO BEAUTIFUL PLACES: THE TWISTS AND TURNS IN DEVELOPING A NEW CLASS OF PN-HETEROCYCLES This chapter includes previously published and co-authored material from Bard, J.P., Johnson, D.W., Haley, M.M. “Bumpy Roads Lead to Beautiful Places: The Twists and Turns in Developing a New Class of PN-Heterocycles.” Synlett 2020, 31, 1862–1877. This review article was written by Jeremy P Bard and editorial support was given by Michael. M. Haley and Darren W. Johnson. This accounts article overviews the story and science behind the initial discovery and fundamental studies on the phosphaquinolinone scaffold. It summarizes and compares the findings from the first set of papers on the project and hints at where future studies on the project may be heading. 1.1 Introduction The field of supramolecular chemistry continues to grow and diversify, especially as more creative, functional, and predictably dynamic systems are developed. From drug molecule encapsulation within supramolecular cavitands1 to molecular machines,2 supramolecular chemistry has applications in several different areas based on the variety of molecular interactions it entails. One application that has long been a hallmark of supramolecular chemistry is host–guest chemistry. Many disparate fields such as medical,1,3,4 agricultural,5 and environmental6–12 have benefited from host–guest chemistry 1 in recent years with the development of drug-containing capsules, nutrient sensors, and noncovalent waste remediation systems, respectively. Because of this broad yet varied applicability, host–guest ‘chemistry’ spans chemical biology, materials sciences, agricultural and food/fragrance research, biology, and biomedical engineering, among other fields. Of the variety of potential guests, anionic species represent a specifically challenging target in this area due to their high solvation energies, diffuse charges, and lack of strong attractions between anions and most hosts.13 Anions are bound through hydrogen bonding or other similar reversible electrostatic interactions. Upon the binding of these guests, many hosts are monitored through chemical, photophysical, or physical methods, and the reversible response can then dynamically report anion concentration in the medium tested. In the lab, this typically is observed via NMR, UV/Vis, and/or fluorescence spectroscopies, while in real-world applications reporter devices such as electrochemical sensors, chemically sensitive field-effect transistors (ChemFETs), or fluorescence microscopy are preferred. There exist innumerable hosts capable of providing signal transduction or reporting guest binding, yet as more and more new and interesting analytes, cellular pathways, problematic contaminants, and chemical markers are discovered, the demand for new responsive hosts will continue to rise as well. Towards this aim, our lab has developed several arylethynyl frameworks (Figure 1.1) capable of binding a variety of anionic guest molecules, including halides,14–18 oxoanions,19–21 and hydrochalcogenides.22–24 These hosts take advantage of both their multidentate binding pockets formed from the meta-substitution of the phenyl or pyridyl 2 cores with two arylethynyl arms as well as the fluorescent nature of the π-conjugated backbone. N C t-Bu H t-Bu t-Bu H t-Bu NH HN NH HN O NH HN O O NH HN O OMe OMe OMe OMe 1 2 Me N N t-Bu t-Bu MeO2S SO2Me NH HN S S I I O O n n 3 4 (n = 1, 2, 3) Figure 1.1 Hydrogen- and halogen-bonding supramolecular hosts prepared and studied in the Haley/Johnson collaboration. Atoms involved in anion binding are bolded. The original hosts in this series were designed in 2006 by Orion Berryman in the Johnson lab and Charles Johnson in the Haley lab and were based on bis-sulfonamide binding units.25 Our first graduate student to be formally co-advised on this project, Calden Carroll, quickly discovered that bisureas such as 1 were superior as these could offer four or five hydrogen bonds to the anionic guest in reproducible 1:1 host–guest binding stoichiometries, depending on the protonation state of the pyridine.14 This opened a floodgate of 13 eventual co-advised students and postdocs over the next 14 years who explored anion–π-interactions, the effect of increasing or reducing the number of urea binding units, the effects of different heterocyclic cores, and the physical organic chemistry of these receptors and their guests.16,19–24 Along the way, graduate student Blake Tresca further improved upon the early designs by replacing the pH-sensitive pyridine core with 3 a benzene as in 2 and showed that the C–H···anion interaction could be tuned by installing electron-donating/electron-withdrawing groups para to the CH unit.26 Very recently, postdoctoral researcher Jessica Lohrman extended this receptor class to include halogen- bonding recognition units by showing that we could switch out the urea groups with polarized iodine atoms (e.g., 3).18 One less explored binding motif in our studies is that of bisamides, such as shown in 4. One of our first examples of anion binding in the arylethynyl scaffolds was a derivative of 4 (n = 1) where Orion and Charles reduced the disulfide motif and protected it as the thioacetate; nonetheless, the receptor bound chloride weakly.27 Several years later graduate student Chris Vonnegut and undergraduate Airlia Shonkwiler prepared a series of disulfide macrocycles based on 4 (n = 1–3).18,28 Of the molecules, thin films of 4 (n = 3) showed a turn-on fluorescence response in the presence of HCl, accompanied with a red shift in emission. X-ray crystallography revealed that the chloride anion sat nicely within the binding pocket of protonated 4 (n = 3). In contrast, when the film was treated with trifluoroacetic acid (TFA), it showed a different emission response than with HCl, suggesting a potential for discrimination between different anionic guests with host 4 (n = 3). We never guessed at the time that this simple modification would ultimately result in the surprising discovery of new PN-heterocycles. 1.2 Initial Discovery The original purpose of the disulfide macrocycles was to function as cellular, redox- active probes between the fluorescent, reduced dithiol form and the nonfluorescent, oxidized disulfide state. Despite the best efforts of Calden and Chris,28,29 along with those of visiting Japanese graduate student Daisuke Inokuchi, we could never get this project 4 over the proverbial goal line: one methylene (4, n = 1) was incredibly reactive and oxidized to the 13-membered disulfide ring in a matter of minutes, whereas formation of the larger macrocycles (4, n = 2–3) required a strong chemical oxidant (iodine). As a final effort, Chris and Airlia decided to target dithiol 5/disulfide 6 (Scheme 1.1) with the belief that it would be easier to reduce/oxidize. Attempts to condense the starting bisaniline with thiosalicylic acid using a variety of peptide-coupling conditions only gave polymeric products. In one last-ditch attempt they investigated a procedure for aromatic polypeptide synthesis that uses triphenylphosphite (P(OPh)3) in the presence of pyridine at high temperature;30 however, as if Monty Python themselves dictated the formed product, it was now time for something completely different. CO2H SH HS P(OPh)3 HN O N pyr, 100 °C N t-Bu t-Bu t-Bu NH2 H2N NH SH t-Bu PhO OPh O t-Bu P N N P OPh 5 N OPh 7 t-Bu N t-Bu t-Bu NH HN S S O O 6 Scheme 1.1 Proposed synthesis of dithiol 5 and macrocyclic disulfide 6 redox pair along with the actual PN-heterocyclic product 7 formed from the reaction, which was confirmed by x-ray crystallography. ORTEP ellipsoids drawn at 50% probability. CCDC 1976534. 5 Ox. Red. Analysis of the reaction mixture by TLC revealed the presence of a polar, highly fluorescent material as the main product. The 1H NMR spectrum of the yellow solution showed that there were clearly too many aromatic signals, meaning the material almost certainly was not 5 or 6. After sitting on the benchtop for a few days, yellow crystals suitable for X-ray diffraction had formed inside the NMR tube. Much to our surprise, the crystal structure revealed formation of the meta-terphenyl-like structure 7 where a 2,6- disubstituted pyridine ring linked two independent ‘phosphaquinoline’ moieties (Scheme 1.1).28 This molecule had little to no precedent in the literature yet was clearly the main product of the reaction. A quick literature search into similar systems dating back to the 1950s showed that while there are many known phosphorus heterocycles,31–39 along with reviews on similar conjugated organophosphorus materials,40,41 ‘PN-heterocycles’ (phosphorus- and nitrogen- containing) are rather rare as their synthesis and isolation are often plagued with difficulties.42–52 Realizing we had potentially uncovered an efficient route to PN-heterocycles, we went back to the drawing board and simplified the synthetic sequence to start from ortho- ethynylanilines, which in turn are easily prepared from commercially available or previously published ortho-haloanilines. As shown in Scheme 1.2, treatment of ethynylaniline 8 with only P(OPh)3 at 100 °C (i.e., omitting the thiosalicylic acid) afforded phosphonimidate 9, which we soon discovered could be hydrolyzed in wet THF to furnish phosphonamidate 10. Both structures were confirmed by X-ray crystallography (vide infra). With this simplified synthesis, Vonnegut and Shonkwiler prepared a series of 6 congeners with aryl groups ranging from electron-rich to electron-poor (Scheme 1.2 and Table 1.1). R a P(OPh)3 a pyr R b b 100-110 °C P OPh NH2 N c c OPh 8, no fusion 9, no fusion 12, b-benzo fusion 13, b-benzo fusion 15, a-benzo fusion 16, a-benzo fusion 18, c-benzo fusion 19, c-benzo fusion H2O a THF R b 60 °C P OPh N c H O 10, no fusion 14, b-benzo fusion 17, a-benzo fusion 20, c-benzo fusion Scheme 1.2 Synthetic pathway for the various PN frameworks. Table 1.1 Photophysical properties for heterocycles 10 Stokes shift Entry Yield (%)a R λ b babs (nm) λem (nm) (nm/cm-1)b 10a 39 3,5-(CF3)2C6H3 349 434 85/5600 10b 43 4-CNC6H4 349 430 81/5400 10c 40 4-(CO2Et)C6H4 351 432 81/5300 10d 80 4-ClC6H4 359 422 63/4200 10e 32 Ph 342 418 76/5300 10f 52 4-MeC6H4 341 413 72/5100 10g 37 4-MeOC6H4 339 410 71/5100 10h –c 4-Me NC H –c –c –c2 6 4 10i 73 n-pen 318 383 65/5300 10j 22 2-pyridyl 363 442 79/4900 a Yields reported over two-step cyclization/hydrolysis. b Values collected in CHCl3 at room temperature. cNot determined as the imidate did not hydrolyze to the amidate form. 7 Focusing on heterocycles 10, nearly every derivative shared a common absorbance peak around 350 nm, yet emission wavelengths ranged from 383–442 nm and Stokes shifts ranged from 63–85 nm/4200–5600 cm-1 (Table 1.1). Our initial communication on this class of compounds also reported details of the emission spectra, showing a correlation between more withdrawing substituent groups and more redshifted emissions.53 Chris then performed preliminary mechanistic studies to determine a rough reaction pathway for the cyclization (Scheme 1.3).28 He found that the reaction does not proceed using a non-nucleophilic base such as diisopropylethylamine, suggesting that the relatively nucleophilic pyridine first adds to the P(OPh)3. The aniline nitrogen then can add to the activated phosphorus center to afford the respective phosphoramidite upon deprotonation. The alkyne is next likely attacked by the phosphorus center before a series of proton transfers to produce the heterocyclic imidate 9. Scheme 1.3 Proposed mechanism of phosphonimidate 9 cyclization. 1.3 Setbacks Breathe New Life The initial excitement and momentum generated by our PN-heterocycle discovery was tempered by the fact both Vonnegut and Shonkwiler graduated in early 2016. 8 Nonetheless, the project would be given continuity and new life – or so that was the plan – by two new junior research team members and an undergraduate researcher in the group, Noah Takaesu, who Chris and Airlia had trained. Unfortunately, unforeseen personnel issues and re-evaluation of career goals by the junior members left only Noah to push the project forward by the end of winter 2017. At the same time, the project had been injected with its first generous funding through the US NSF ‘INFEWS’ program in the summer of 2016. As a result, a serious reassessment of the project direction, research personnel, and continuity was needed. While ‘hope springs eternal’ serves as far more powerful guidance in the context of the current global pandemic, the metaphor fit the timing of Spring 2017 for this project – we were fortunate to breathe new life into the project by hiring postdoctoral researcher Chun-Lin Deng and (somehow, miraculously) convincing first-year graduate student Jeremy Bard to join the project. Though there was some overlap with Noah, he too soon graduated and left that summer for graduate school. Unfortunately, there was minimal knowledge transfer, something that everyone who has worked in a research lab knows is critical. Chun-Lin and Jeremy essentially had to start from scratch and figure out what to do with the project, and because of this, the rate of progress diminished greatly. Every research talk given on the project over the following year had a different introduction and scope, as we were trying to find the most compelling story we could tell and find how our work fit into the bigger picture of the grant and the over-arching project. Though a large amount of effort was being exerted, the barrier of no knowledge transfer with two new researchers to the project was almost too much to surmount. Some interesting results were generated over the next year, yet very few significant discoveries were made, resulting in 9 no papers for close to 18 months. After an arduous group meeting at the end of spring 2018, we elected to pull the plug on the PN-heterocycle studies and allow the project to sunset. This is probably one of the last things that a graduate student wants to hear right after they have advanced to candidacy (i.e., Bard), having just put so much thought and effort into the future of the project. Admittedly that meeting was a letdown, although we left with enough inspiration for the rest of the year to wrap things up and try to be creative, as sunsetting a project can provide a certain sense of freedom perhaps to try new ideas. And as many theologians, musicians, and even a butler once said, ‘the darkest hour is before the dawn’. 1.4 A New Dynamic Duo Develops Dozens of Derivatives As Jeremy and Chun-Lin worked to tie up loose ends and finish their ongoing projects, Bard went back to the beginning to build off the initial results from Vonnegut on the PN-naphthalene system analogous to 10. That initial report hinted that there was a lot that could be learned about this new moiety and begged the question as to whether phosphaquinolinone optoelectronic properties could be modified in a similar fashion as coumarin and carbostyril, two well-known, well-studied chromophores (Figure 1.2).54–72 There is an obvious structural relationship between the latter two structures in Figure 1.2, where the carbonyl in carbostyril is replaced with an isolobal P(OR)=O group to afford the phosphaquinolinone scaffold. P OPh O O N O NH H O Coumarin Carbostyril Phosphaquinolinone Figure 1.2 Structure of the phosphaquinolinone compared to analogous coumarin and carbostyril moieties. 10 Taking inspiration from the structure–property relationships drawn for the coumarin and carbostyril family of fluorophores, Jeremy set out to perform structure– property relationship studies with substituent groups at two different sites upon the backbone. Frontier orbital occupancy calculations by Chun-Lin suggested that studying substituent effects of groups located at carbons 3 and 6 on the backbone (Figure 1.3, a) would be the most fruitful.73–77 Use of the same synthetic steps given in Scheme 1.2 furnished a large family of disubstituted heterocycles 11 (Figure 1.3, b), the properties of which are discussed in the next section. Figure 1.3 a) HOMO (gray) and LUMO (purple) occupancy levels on the carbons in the 3 and 6 positions of the phosphaquinolinone backbone as determined at the B3LYP/6-31g(d) level of theory. b) Structure of disubstituted PN-naphthalene heterocycles 11 and (bottom) specific substituent groups and yields of each derivative for two-step cyclization/hydrolysis. We were also curious about how extension of the arene π-electron backbone could affect the photophysical properties of the phosphaquinolinone moiety. Noah had originally started examining this idea by using the synthetic steps outlined in Scheme 1.2, though starting on naphthalene derivative 12 rather than phenyl derivative 8, to first give the PN- anthracene imidates 13 and subsequently amidates 14 in moderate to good yields (Table 1.2).78 11 Building upon this linear extension of the aromatic backbone (b ring in Scheme 1.2), Chun-Lin’s first study focused on the effect of its nonlinear extension (a and c rings).79 Two families of PN-phenanthrene derivatives were prepared, where the first started with aminonaphthalenes 15 that were cyclized to ‘bent-up’ PN-phenanthrene imidates 16 and subsequently hydrolyzed to ‘bent-up’ amidates 17. The second was made starting from cyclization of aminonaphthalenes 18 to ‘bent-down’ PN-phenanthrene imidates 19 and hydrolysis to amidates 20 (Scheme 1.2 and Table 1.2). Table 1.2 Synthetic yields for heterocycles 14, 17, 20, and 27 Entry R Yield (%)a Entry R Yield (%)a 14a 4-MeOC6H4 47 20c 4-CNC6H4 16 14b 4-MeC6H4 70 20d 4-CH3SO2C6H4 39 14c 4-CF3C6H4 33 20e 4-CF3C6H4 18 14d 4-CNC6H4 51 20f 4-MeOC6H4 16 17a 4-CNC6H4 34 27a CN 21 17b 4-CF3C6H4 31 27b CF3 58 17c 4-MeOC6H4 33 27c Cl 31 17d 4-MeC6H4 27 27d H 61 20a 3,4-(CN)2C6H3 32 27e t-Bu 65 20b 4-CF3SO2C6H4 30 27f OEt 31 aYields reported for two-step cyclization/hydrolysis. To further expand the arene backbone, we next prepared PN-pyrene 21 following the steps outlined in Scheme 1.4. Reaction of known nitropyrenol 22 with triflic anhydride furnished nitrotriflate 23. Sonogashira cross-coupling of 23 with 4-tolylacetylene furnished nitropyrene 24, which was then reduced using Zn in AcOH to yield aminopyrene 25. Lastly, cyclization of 25 with P(OPh)3 and then hydrolysis gave PN-pyrene 21. 80 12 Tf2O Et3N, CH2Cl2 NO2 NO2 0 °C to r.t. OH 97% OTf 22 23 Me NO2 Zn Pd(PPh3)2Cl2, CuI AcOH Et3N, THF EtOAc 77% 55% 24 Me NH2 1. P(OPh) NH3 O pyr, 110 °C P OPh 2. THF, H2O 60 °C 28% Me 25 Me 21 Scheme 1.4 Synthesis of PN-pyrene 21. Having studied both substituent effects upon the backbone as well as effects of arene core modification, we then probed potential substituent effects directly upon the phosphorus center. For this, Jeremy, Chun-Lin, and rotation student Hannah Bates performed the cyclization reaction on a smaller set of substituted ethynylanilines 26, except this time using PhP(OPh)2 to afford the P-phenyl heterocycles 27 (Scheme 1.5). 81 There were two reasons that we were interested in examining this P-substitution: (a) derivatives 27 have one less degree of freedom than their heterocycle 11 analogues, suggesting a potentially higher quantum yield, and (b) the change in both the steric and electronic nature of the phenyl group in 27 might have substantial effects upon the solid-state properties. 13 CN CN 1. PhP(OPh)2 pyr, 100 °C R R 2. THF, H2O P Ph 60 °C N O NH H2 26 27 Scheme 1.5 Synthesis of heterocycles 27. 1.5 Physicochemical Properties 1.5.1 Fluorescence The photophysical properties of the original PN-heterocycles 10 (Table 1.1) achieved decent Stokes shifts and elucidated the relationship between emission energy and the electronic nature of the substituent groups. However, these initial results did not offer a thorough understanding as to why these properties were changing and/or why the general trends were present. In addition, neither complete characterization of the photophysical properties (i.e., absorption coefficients, quantum yields, fluorescence lifetimes) nor a comprehensive rationalization of the trends observed were performed at the time of the discovery. Understanding these initial trends, building upon the initial family of molecules, and developing more complete sets of optoelectronic properties were the primary objectives Jeremy and his coworkers wanted to address with disubstituted heterocycles 11. Upon successful synthesis, their photophysical properties were measured and are listed in Table 1.3. With this family, two trends for the effect of various substituent groups can be seen, where both more donating C6-substituent groups and more withdrawing C3- substituent groups led to redshifting in the emission. This correlates nicely with the frontier orbital occupancy calculations, which showed a predominance of the LUMO on C3 and a predominance of the HOMO on C6. These substituent effect trends support the hypothesis 14 that the emission is redshifting due to a lowering of the LUMO or a raising of the HOMO, respectively. To further support this idea, Chun-Lin calculated the geometries and energy levels of the HOMOs and LUMOs for each derivative, uncovering an interesting predictive tool. Not only did we see the expected trends within the HOMOs and LUMOs of analogous derivatives 11a–m, but we also found a very nice correlation between the computationally predicted HOMO–LUMO energy gap and the experimental emission energies (Figure 1.4, blue). With this relationship, we realized that we potentially had an excellent way to predict the emission energies of future heterocycles based solely on their computationally derived HOMO–LUMO energy gaps. Figure 1.4 Relationship between the HOMO-LUMO gaps and the experimental emission energies of (blue) heterocycles 10b, 11a-11d and (red) heterocycles 10b, 11a-11d, and 11m. 15 Table 1.3 Photophysical properties of disubstituted PN-naphthalenes 11a λabs (nm), λem (nm), Stokes shift Brightness cmpd R1 R2 ε (M–1cm–1) ϕ (%)b (nm/cm–1) (ε x ϕ) 11a 4-CN CN 346, 12000 430, 18 84/5646 2160 11b 4-CN CF3 341, 20000 429, 11 88/6015 2200 11c 4-CN Cl 358, 23000 450, 11 92/5710 2530 11d 4-CN t-Bu 358, 22000 453, 11 95/5858 2420 11e 4-OMe t-Bu 344, 16000 421, 6 77/5316 960 11f 4-Me t-Bu 343, 14000 424, 8 81/5569 1120 11g H t-Bu 343, 17000 430, 8 87/5899 1360 11h 3,4-(CN)2 t-Bu 371, 19000 477, 41 106/5989 7790 11i 4-Cl t-Bu 345, 19000 431, 8 86/5784 1520 11j H CN 337, 12000 410, 13 73/5283 1560 11k 4-OMe CN 345, 15000 471, 28 126/7754 4200 11l H CO2Et 335, 12000 411, 10 76/5519 1200 11m 4-CN OEt 379, 25000 490, 24 111/5977 6000 a Values collected in CHCl3 at room temperature. b Excited at 365 nm and collected using a quinine sulfate (in 0.1 M H2SO4) standard. Based on this equation, we ‘screened’ many different theoretical congeners to see if we could achieve even more redshifted emission. Calculations suggested that an ethoxy group on the C6-position would have an immense effect on the emission energy, predicted to be 2.50 eV (496 nm). This was somewhat surprising, as the σpara value of the –OEt substituent was not that much more donating than the previously most donating tert-butyl substituent of 11d. Upon the synthesis of ethoxy-substituted 11m, the emission was determined to be at 490 nm (2.53 eV), giving a nearly perfect match (Table 1.3). This demonstrated that we were able to reliably predict the emission energy of future congeners, as well as gave us a new predictive relationship between HOMO–LUMO energy gaps (Figure 1.4, red). 16 In addition to these two relationships, we also determined the complete set of photophysical properties (Table 1.3). These values were all suboptimal for their potential use as fluorescent dyes in most cases and begged the question of how could they be improved. This question served as a foundation for many aims of the project mentioned below. As shown by the diversity of syntheses in Schemes 1.2, 1.4, and 1.5, we spent a large amount of time and effort examining the variety of effects that different backbone modifications have on the fluorescence of these heterocycles. From Noah’s work with the PN-anthracenes, he found that 14 exhibited much more redshifted emissions and significantly larger Stokes shifts likely due to the increased conjugation of the backbone (Table 1.4). While 14 possessed significantly larger absorption coefficients, the molecules still retained low quantum yields, leading to low brightness values. Following this study, Chun-Lin examined both ‘bent-up’ PN-phenanthrenes 17 and ‘bent-down’ PN-phenanthrenes 20, the photophysical properties of which are also given in Table 1.4. With both families, we again noticed much more modest absorption coefficients and emission wavelengths yet found that quantum yields of up to 93% with heterocycles 20; however, the absorption coefficients kept brightness values low. To overcome this issue, Jeremy, with the help of rotation student Jenna Mancuso, prepared PN-pyrene 21. Its emission maximum was 465 nm, affording a Stokes shift of 3800 cm–1. Gratifyingly, we found that we not only achieved a quantum yield of 70% but also attained an absorption coefficient of 26000 M–1cm–1, giving 21 a brightness value of 18000 M–1cm–1 (Table 1.4). Further, fluorescence experiments at higher concentration suggested that above 2 mM in CHCl3, excimer formation could still be observed, illustrated 17 by the growth of a very redshifted peak in the emission spectrum at 582 nm.82–87 With some modification, this motif could have potential for integration into Table 1.4 Photophysical properties of PN-anthracenes 14, PN-phenanthrenes 17 and 20, PN-pyrene 21, and P-phenyl heterocycles 27a λabs (nm), λem (nm), ϕ Stokes shift Brightness Entry ε (M–1cm–1) (%)b (nm / cm–1) (ε x ϕ) 14a 339, 27000 464, 7 125 / 7900 1900 14b 331, 27000 469, 9 138 / 8900 2400 14c 327, 21000 492, 2 165 / 10000 420 14d 336, 31000 506, 4 170 / 10000 1200 17a 384, 13000 461, 12 77 / 4300 1600 17b 375, 9800 450, 10 75 / 4400 980 17c 374, 25000 442, 16 68 / 4100 4000 17d 371, 15000 440, 9 69 / 4200 1400 20a 404, 12000 493, 93 89 / 4500 11000 20b 397, 5200 490, 80 93 / 4800 4100 20c 389, 10000 469, 36 80 / 4400 3600 20d 388, 7400 470, 66 82 / 4500 4900 20e 380, 6900 457, 29 77 / 4400 2000 20f 372, 6800 441, 19 69 / 4200 1300 21 395, 26000 465, 70 70 / 3800 18000 27a 348, 15000 447, 76 99 / 6400 11400 27b 343, 18000 449, 38 106 / 6900 6840 27c 360, 19000 474, 43 114 / 6700 8170 27d 352, 18000 467, 50 115 / 7000 9000 27e 360, 22000 475, 51 115 / 6700 11220 27f 381, 22000 515, 35 134 / 6800 7700 a Values collected in CHCl3 at room temperature. b Excited at 365 nm and collected using a quinine sulfate (in 0.1 M H2SO4) standard. larger systems that could take advantage of both its photophysical and supramolecular properties. 18 Another factor that can be controlled with the PN-heterocycles that cannot be altered in either coumarin or carbostyril is substitution at the phosphorus center. In the examples above, all contain a phenoxy group attached to the phosphorus center. To explore any potential substituent effects on this position as well, we prepared the P-phenyl family 27. The photophysical properties of 27 were very exciting, as we saw an almost universal improvement compared to heterocycles 11 (Tables 1.3 and 1.4), specifically a dramatic increase in the quantum yields and a slight redshifting in the emissions as well as improvement of the Stokes shifts in most cases. We attributed this to both a slight rigidification of the scaffold as well as an increase in planarity between the aromatic core and the pendent aryl group in the excited state of 27 (based upon TD-DFT calculated geometries). This family is also favorable, as the synthesis, isolation, and solubility all allow for its easier production and use, suggesting that any future fluorophore applications should include this modification. Several different families of phosphaquinolinones have been built based off the simple cyclization found by Vonnegut and Shonkwiler, all of which having their own pros and cons. From these studies, we have accessed a wide range of emission wavelengths (383–515 nm), Stokes shifts (3800–10000 cm–1), and brightness levels (420–18000 M– 1cm–1, Figure 1.5 and Figure 1.6). In each family, we found that withdrawing substituents upon the pendent aryl groups lead to both redshifted emissions and subsequently larger Stokes shifts. We also determined that increasing the conjugation of the backbone leads to redshifting in the emission as well and can lead to increased brightness. Lastly, we found that the replacement of the P-phenoxy group with a P-phenyl group leads to even greater increases in brightness, redshifted emission colors, and larger Stokes shifts (Figure 1.6). 19 Figure 1.5 Representative phosphaquinolinone scaffolds colored by their respective experimental emission colors. Figure 1.6 Comparison of all measured Stokes shifts and brightnesses. 20 1.5.2 Molecular Structures An advantage of the PN-heterocycles is their high crystallinity, thus making it relatively easy to obtain molecular structures via single-crystal X-ray diffraction. Figure 1.7 shows archetypical structures for the imidate (e.g., 9) and amidate (e.g., 10) forms. Based on the bond lengths of the 17 structures obtained to date, the aromatic rings in the backbone as well as the pendent aryl rings on the heterocycles behave as true aromatics with bond lengths ranging from 1.38–1.40 Å. Within the PN-heterocyclic rings, the C=C double bonds are best described as isolated double bonds with bond lengths around 1.34– 1.36 Å. The P–C and N–C bond lengths are also tightly clustered in the range of 1.76–1.79 Å and 1.38–1.40 Å, respectively. The greatest difference is the P–N bond length, which changes from 1.55–1.56 Å in 7 and 9j (the only two imidate structures we have secured) to a range of 1.63–1.65 Å in the amidate form (where we have data for over a dozen structures). All of the structures show that the PN-heterocyclic rings have only small deviations from planarity. The dihedral angles between the heterocyclic cores and the pendent aryl rings varying from as little as 2° up to ca. 45°, which indicates very good to excellent communication between the two π-systems. Figure 1.7 Single crystal structures of (a) 9j, (b) 10j monomer, and (c) 10j-10j dimer as representative structures for typical 9 and 10/11 structures. Ellipsoids drawn at 30% probability. Non-hydrogen bonding hydrogen atoms omitted for clarity. 21 A hallmark characteristic of the amidate structures is dimerization in the solid state due to the adjacency of the P=O hydrogen-bond acceptor and the N–H hydrogen-bond donor. This permits nearly all of the amidates to form strong centrosymmetric, head-to-tail meso-dimers between one R and one S enantiomer with N–H···O bond lengths ranging from 2.77–2.82 Å (Figure 1.7, c). The tetrahedral phosphorus centers give the dimer a pseudo-eight membered chair arrangement connected by the two head to-tail N–H···(O)P hydrogen bonds. Interestingly, a decrease in the N–H···O bond lengths is observed when more withdrawing substituents are appended to the scaffold. These two factors hinted that there may be substituent effects in the solution-state dimer strengths as well (vide infra). The two exceptions to this common dimeric orientation involve sterically congested derivatives such as 11f, where a staggered, ‘polymeric’ supramolecular system forms in which a single monomer hydrogen bonds to two separate monomers rather than forming the normal head-to-tail dimer. 1.5.3 Solution Dimerization Studies Another series of studies performed on these scaffolds has been examination of substituent effects in the solution dimerization affinities of these compounds. To measure these dimerization strengths, we used variable-concentration (VC) 1H NMR spectroscopy experiments followed by subsequent data fitting using nonlinear regression analysis to measure the dimerization strengths of each heterocycle.88 Though more polar solvents, including DMSO and CH3CN, destroy the dimer and/or permit limited solubility, H2O– saturated CHCl3 allowed us to collect consistent measurements across a range of similar compounds. 22 First, we performed these measurements upon heterocycles 11 as well as heterocycles 10b, 10e, and 10g (Table 1.5). With these values, alongside the previously reported value of 130 M–1 for 10b, we determined linear free energy relationships (LFERs) for substituent effects at both C3 and C6. In these, we found that withdrawing groups at either end of the backbone led to an increase in dimer strength, as shown by the two representative linear free energy relationship plots (Figure 1.8). Figure 1.8 Representative LFER plots for dimerization strengths of heterocycles (a) 11d- 11g and (b) 10b, 11b, 11d, and 11m. 23 Table 1.5 Dimerization strengths of select examples of heterocycles 10, 11, 17, 20, 21, and 27 Entry K –1 adim (M ) Entry Kdim (M –1)a Entry K –1 adim (M ) 10b 130 11l 200 20e 84 10e 62 11m 87 20f 77 10g 56 17a 206 21 179 11b 293 17b 150 27b 82 11d 70 17c 146 27c 54 11e 36 17d 121 27d 24 11f 38 20b 306 27e 22 aValues collected in H2O-saturated CDCl3 at room temperature. Values reported with errors less than 15%. Additionally, we determined that the R2 substituents had a larger effect upon the dimer strength than analogous R1 substituents, likely due to their proximity to the phosphaquinolinone hydrogen. Within this series of derivatives, we determined a dimerization constant of 525 M–1 for heterocycle 11j, which is among the highest reported value for similar head-to-tail hydrogen-bonding dimers.89 These findings prompted more questions. Why are these dimers so strong? Why do they prefer to dimerize as meso-dimers between R and S enantiomers? Are there any predictive trends similar to those observed for the emission energy? For answers, we turned to our collaborators 50 miles up the road from us at Oregon State University, the P. H.-Y. Cheong group. In Cheong’s group, graduate student Camille Richardson performed an extensive amount of modeling of our systems and came to a few important conclusions. First, she found that there is likely a stereoelectronic effect aiding both the strength of our dimers as well as directing them to form dimers in the meso-dimer orientation. She also determined that there was indeed a linear relationship that could be used to predict the 24 strengths of each derivative based on the Hammett parameters of the two substituent groups. Though solubility limited our ability to measure dimerization values for PN- anthracenes 14, we determined dimerization strengths for nearly all other π-extended PN derivatives (Table 1.5), obtaining dimerization values from 121–206 M–1 for 17, 77–306 M–1 for 20, and 179 M–1 for 21. For PN-phenanthrenes 20, Chun-Lin performed electrostatic potential (ESP) mapping, dipole calculations, and noncovalent interaction (NCI) plots to help explain the strengths and orientations of the dimers. The ESP maps showed that the N–H and P=O were the most electron-poor and electron-rich sites upon the scaffold, respectively. When dimerized, these two sites interact, which leads to a cancelling of the net dipole of the two monomers while in the R-S meso-dimer form. When looking at the analogous S-S dimer, less cancelling of the net dipole exists, and hugely repulsive domains are seen between the two adjacent –OPh groups of each monomer. The dimerization constants of the P-phenyl heterocycles 27 (Table 1.5) range from 22–82 M–1, which are roughly three times weaker than the analogous P-phenoxy heterocycles 10 or 11. To explain this, we again turned to NCI analysis, as well as natural bonding orbital (NBO) analysis. When comparing the NCI plots of analogous 11 and 27 derivatives, a larger repulsive interaction between the phenyl ring of one monomer and the backbone of the other monomer is seen in 27 compared to the phenoxy in 11. Additionally, a stronger interaction is observed within the NBO plot between the no of the P=O moiety of one monomer and the π*N–H of the other in 11 when compared to 27. 25 Figure 1.9 Comparison of all collected phosphaquinolinone dimerization strengths. With all these derivatives, we can achieve very strong and self-specific dimer formation with the phosphaquinolinone moiety. A subtle interplay between sterics and electronics gives us many potential pathways to improve, modify, and tune the strengths of our dimers. The P-phenoxy families serve as more stable hydrogen bond dimers than the P-phenyl family, and we discovered that even the bulkier PN-phenanthrenes 17 and 20 can rival some of the strongest PN-naphthalene 11 dimer strengths (Figure 1.9). 1.6 Applying What We Have Learned 1.6.1 Development of Supramolecular Host With the breadth of fundamental studies now in hand, we were finally ready to apply what we had learned. Through some careful design, thoughtful choice of substituent groups for the PN moiety guided by Jeremy’s results, and many, many chromatography columns, Chun-Lin developed a two-armed host framework containing both PN- heterocycle and urea arms (28 in Scheme 1.6).90 The design of this unsymmetrical host featuring one urea ‘arm’ was critical: preliminary studies of bifunctional PN-compounds 26 showed that the molecules had too strong a tendency to form hydrogen-bonded polymers rather than serve as monomeric hosts for other molecular guests (a tendency that might be attractive in its own right to researchers in supramolecular polymers). The synthetic design for these ‘hybrid hosts’ started with iodination of 11d with ICl to afford iodinated PN coupling partner 29 (Scheme 1.6). The other coupling partner was built via sequential Sonogashira cross-coupling reactions starting with terminal acetylene 30 and the respective dihalobenzene to give asymmetric intermediates 31. Anilines 31 were then coupled with trimethylsilylacetylene (TMSA) to afford 32. Finally, desilylation in basic MeOH, cross- coupling with 29, and condensation with an isocyanate furnished hybrid hosts 28. Based on some simple geometric models, we believed that 28 would possess an excellent binding pocket for HSO –4 due to the tetrahedral phosphorus center allowing for complementary numbers of hydrogen-bond donors and acceptors as well as a nonplanar binding pocket. Upon initial tests, we were excited to see significant peak shifts in the 1H NMR and 31P NMR spectra of the host upon treatment with TBAHSO4 (Figure 1.10, bottom), from which we calculated a moderately strong association constant of 9600 M–1 in 10% DMSO-d6 in CDCl3. This result became even more exciting when we ran similar experiments with several other similar anionic guests, and none showed significant shifting of the phosphaquinolinone N–H signal (Ha) (Figure 1.10). Chun-Lin quickly assembled a manuscript with these results yet missing was one essential piece of data – an Xray structure of the host–guest complex. After hundreds of attempts and ‘one more try’ being said to the bosses countless times, Chun-Lin finally succeeded in growing single crystals suitable for X-ray crystallography, which clearly confirmed our design hypothesis. 27 CN CN ICl t-Bu 1% TFA t-Bu P OPh AcOH P OPh N N O 54% H OH I 11d 29 R 1,3-diiodobenzene t-Bu OR 1,3-dibromo-5-nitrobenzene X Pd(PPh3)2Cl2, CuI t-Bu Et N, THF NH 32 NH2 30 31a, R = H, X = I 31b, R = NO2, X = Br R TMSA Pd(PPh3)2Cl2, CuI t-Bu Et3N, THF TMS NH2 32a, R = H 32b, R = NO2 R 1. K2CO3, MeOH t-Bu b t-Bu 2. 29, Pd(PPh3)4 H CuI, Et3N, THF c a NH HN d O P 3. O2N NCO O NH PhO toluene NO2 CN 28a, R = H 28b, R = NO2 Scheme 1.6 Synthesis of hybrid hosts 28. Relevant protons on 28 labeled for identification purposes for Figure 1.10. Figure 1.10 Partial 1H NMR spectra of a 1.13 mM solution of 28b in 10% DMSO-d6 in CDCl3 by itself and in the presence of 10 equiv. of each guest. 28 The structure showed seven hydrogen-bonding interactions between the host and the guest (Figure 1.11) and provided an ideal binding pocket for this highly acidic protic oxoanion. Figure 1.11 Coordination environment of HSO –4 in the binding pocket of 28b in the solid state. Ellipsoids drawn at 30% probability. Non-hydrogen bonding hydrogens omitted for clarity. In addition to this nearly ideal geometric complementarity, the host exhibited reversible binding of HSO –4 as well. Upon simple liquid–liquid extraction conditions with sulfuric acid solutions, we observed that our host both survived and bound a significant amount of HSO –4 . After extraction, water washing of the organic layer of the host–guest complex showed a complete reversal of binding of the HSO –4 guest and complete recovery of the host. This also highlights one unusual feature of this class of compounds for molecule and ion recognition: the PN unit, while slightly acidic itself, is quite robust in acid and can enable binding of highly acidic guests. The P=O hydrogen-bond acceptor motif is particularly privileged for this attribute, as it is an excellent hydrogen-bond acceptor while paradoxically being a poor base (pKaH+ << 0). 29 1.6.2 Use of PN Moiety as an Impressive Fluorophore Taking advantage of all we had learned about the fluorescence of these heterocycles, Chun-Lin developed the π-extended tricyclic PN-pyrenes 33 (Scheme 1.7).91 Starting from aminopyrenes 34, cyclization with PhP(OPh)2 and subsequent iodination furnished intermediates 35. Lastly, Sonogashira cross-coupling accompanied by Pd- mediated indole formation gave 33a–d. As this system includes the P-phenyl modification seen in 27, the increased π-system of 21, and the appropriate placement of substituent groups guided by our previous studies, we were able to access improved photophysical properties (large Stokes shifts, high brightness, and redshifted emission; Table 1.6) With these compounds we achieved both emission wavelengths up to 622 nm as well as the highest brightness values we have measured for the phosphaquinolinone moiety (9700– 22000 cm–1M–1). Through a series of computations that modeled the geometries and interactions in the excited state and spectroscopic experiments, we deduced that this was due to an increase in planarity upon excitation, as well as a suppression of any excimer formation. Additionally, we found that using a mixture of 33a, 33c, and 33d we were able to produce nearly perfect white light emission in solution (Figure 1.12). Figure 1.12 Emission color coordinates in the CIE 1931 chromaticity diagram of a 2:1:10 v:v:v mixture of 33a:33c:33d excited at 430 nm. 30 I 1. PhP(OPh)2 NH2 pyr, 110 °C NH O P 2. NIS, TFA Ph AcOH, r.t. R R 34a, R = Bu (83%) 35a, R = Bu (62%) 34b, R = 3,5-(CF3)2C6H3 (72%) 35b, R = 3,5-(CF3)2C6H3 (81%) Ar Ar Pd(PPh3)2Cl2, CuI N O P Et3N, THF, 80 °C Ph R 33a, R = Bu, Ar = Ph (87%) 33b, R = Bu, Ar = 4-(Ph2N)C6H4 (63%) 33c, R = 3,5-(CF3)2C6H3, Ar = Ph (81%) 33d, R = 3,5-(CF 3)2C6H3, Ar=4-(Ph2N)C6H4 (67%) Scheme 1.7 Synthesis of 3-ring PN pyrenes 33. Table 1.6 Photophysical properties of 3-ring PN pyrene derivatives 33a λabs (nm), λem (nm), Stokes shift Brightness Entry ε (M–1cm–1) ϕ (%)b (nm/cm–1) (ε x ϕ) 33a 430, 38000 459, 57 29/1500 22000 33b 431, 32000 551, 62 120/5100 20000 33c 450, 32000 521, 61 71/3000 19000 33d 437, 42000 622, 23 185/6800 9700 aValues collected in CHCl3 at room temperature. bExcited at 365 nm and collected using a quinine sulfate (in 0.1 M H2SO4) standard. 7 Conclusions and Outlook In the first three years of this new project, it went through quite a rollercoaster ride – as many projects do –that might have derailed it had it not been for the tenacity of Jeremy and Chun-Lin. The project went from an exciting accidental discovery, to something that had great potential during a period of research staff turnover, to a project which was slated for termination. However, over the last 18 months, a new light has shined on this 31 fluorophore class (or was it emitted?) through both fundamental studies and initial application-based projects. After a middle of the night stay of execution, what does this new metaphorical morning hold for this project? With all we have learned from our original studies, and the variety of skills, instruments, and connections under the project’s toolbelt, new directions are not lacking. We think some of the unusual properties of this receptor will enable new applications: the receptor is a fluorophore highly stable in acidic media, it has a strong hydrogen-bond donor adjacent to a powerful yet non basic hydrogen-bond acceptor, and the composition of matter is new while maintaining similarities to venerable compound classes of use in chemical biology, medicine, and supramolecular polymers among others. Work is currently underway looking for how this new recognition motif might target other oxoanionic guests, including phosphates due to their relevance in many areas. Additionally, perhaps following inspiration from D.W.J.’s academic family, work into utilization of this unusually strong dimer-forming moiety in a supramolecular capsule system is under consideration. Finally, with what we know about functionalizing this fluorophore, either through post synthetic modification or careful derivatization from the beginning, integration into both biological and other imaging applications might be around the corner. 32 CHAPTER II SYNTHESIS, PHOTOPHYSICAL PROPERTIES, AND SELF-DIMERIZATION STUDIES OF 2-λ5-PHOSPHAQUINOLIN-2-ONES This chapter includes previously published and co-authored material from Bard, J.P., Deng, C.-L., Richardson, H.C., Odulio, J.M., Barker, J.E., Zakharov, L.N., Cheong, P.H.-Y., Johnson, D.W., Haley, M.M. “Synthesis, Photophysical, and Dimerization Properties of 2- λ5-Phosphaquinolin-2-ones.” Org. Chem. Front. 2019, 6, 1257–1265. This a was written by Jeremy P Bard with editorial support was given by Michael. M. Haley and Darren W. Johnson. Experimental support was given by Chun-Lin Deng, Jacob M. Odulio, and Joshua E. Barker and computational support was supplied by H. Camille Richardson and Paul. H.- Y. Cheong. This chapter highlights one of the earliest structure-property relationship studies upon the phosphaquinolinone scaffold. 2.1 Introduction The coumarin (2H-1-benzopyran-2-one) scaffold1–7 along with its aza-analogue carbostyril (2(1H)-quinolinone)8–13 comprise a fascinating class of compounds. In addition to marked physiological activity,14,15 the coumarin/carbosytril framework has been widely established as one of the most useful small molecule fluorophores (Figure 2.1). With respectable Stokes shifts and quantum yields as well as good chemical stability, this scaffold and its derivatives have been the subject of a plethora of studies and applications.16–18 The variety of derivatization for both molecules is impressive, as a 33 multitude of substituents can be installed on the frameworks. Nonetheless, there are very few examples of modification of the base heterocyclic skeletons themselves, limiting the applications and functionalities to the lactone/lactam cores. Judicious modification of the backbone could afford a wealth of new derivatives whose improved and modified properties would allow for further applicability of these molecules. P OPh O O N O NH H O Coumarin Carbostyril Phosphaquinolinone Ph R' NBn R NH P N P P R'' EtO O R O Ar O A, R = Ph C D B, R = OPh R1 R R2 P OPh N H O P OPhN O E, no fusion H F, benzo fusion 1 Figure 2.1 Coumarin and two congeners, carbostyril and phosphaquinolinone, along with known phosphaquinolinones A–F. One such modification could be replacement of the carbonyl moiety (C=O) with an isolobal P(OR)=O group to yield a “phosphaquinolinone”. While such six-membered heterocycles containing adjacent phosphorus and nitrogen (PN) atoms have been known since 1960 (phosphinamidate A, phosphonamidate B),19,20 their syntheses and isolation were often plagued by various challenges. More recent work has examined metal-mediated routes to phosphonamidates such as C.21–25 A family of structurally related phosphinamides (e.g., D) has also been investigated as a route to chiral phosphines.26–29 Further, a similar five-membered phosphinamide system has recently been reported showing uniquely 34 flexible dimerization properties favourable for self-assembled soft materials.30 Despite the recent revival in interest, structures that encompass such six-membered PN-heterocyclic motifs are rather uncommon. To help address this issue, we recently reported a series of water- and air-stable phosphonamidates based on scaffold E.31 Along with the benzo-fused analogues F,32 this class of heterocycles is fluorescent, with electron withdrawing groups (EWG) at R leading to a red-shifted emission and electron donating groups (EDG) furnishing a blue-shifted emission. Additionally, the strong polarization of the oxygen in the hydrogen bond accepting P=O unit and the adjacent acidic N–H hydrogen bond donor lead to surprisingly strong dimerization between the R and S enantiomers (meso-dimer), potentially due to a minimization of repulsive secondary interactions. Though these properties are both intriguing and give promise for unique applications of this PN scaffold, a more detailed, systematic understanding of their fundamental structure-property relationships must be acquired first before any applications can be pursued. Herein we present the synthesis, optoelectronic properties, computational examination, and dimerization studies both in solution and in the solid state of a series of phosphaquinolinones based on phosphonamidate 1. We have dedicated this manuscript to Prof Julius Rebek, Jr. for his mentorship, friendship, and tremendous achievements in molecular recognition, self-replicating systems, tests for reactive intermediates, self-assembly, and hydrogen bonding, among many other areas. Therefore, we would be remiss not to point out that one of us (DWJ) learned of the strength of simple homo- and hetero-dimers of cyclic ureas, lactams, and cyclic sulfamides from, first, Rebek’s report of a tetrameric hydrogen bonded capsule 35 assembled through strong, complementary hydrogen bonds between cyclic ureas and sulfamides;33 and, second, from Prof. Rebek’s class on molecular recognition at The Scripps Research Institute. In these studies, Rebek and coworkers discovered that heterodimers between simple model cyclic ureas and sulfamides were stronger than their homodimers.33 Subsequent studies by Fraser Hof in the lab revealed the homodimer association constants ranged from 0.7 – 1.1 M–1 and the heterodimer was almost two orders of magnitude more stable (Ka of 50 M –1) in CD2Cl 34 2 Zimmerman and coworkers later performed an incredible service to this field by providing a survey of hundreds of such simple hydrogen bonded dimers.35 These studies revealed a similar range for association constants in simple DA-AD hydrogen bonded systems in nonpolar solvents, underscoring the magnitude of association constants of upwards of 500 M–1 in the compounds of class 1 (c.f. Table 2.3). 2.2 Results and Discussion 2.2.1 Synthesis To modify the electron distribution on the six-membered PN heterocyclic core effectively, atomic coefficients analysis of the frontier molecular orbitals (FMOs) was performed on the unsubstituted PN-skeleton (Figure 2.2). The results show that carbon 3, on which the R1-substituted aryl ring resides, has a higher contribution to the LUMO. In contrast, carbon 6 shows a higher contribution to the HOMO occupancy levels. These results suggest that an EDG on C6 would efficiently raise the energy level of the HOMO, while an EWG on C3 would readily lower the energy level of the LUMO.36–38 This should lead to a typical donor–acceptor (D-A) system and thus will likely push emission to longer wavelengths, in analogy to the well-established design principles for carbostyril 36 fluorophore development to further red-shift emission and increase the quantum yield.10,13 5 4 6 3 7 P OPhN 8 H O 15% 19% 7% 3% P OPh P OPh N N H O H O HOMO LUMO Figure 2.2 Atomic contributions (calculated at B3LYP/6-31g(d) level of theory) to the HOMO (left) and LUMO (right) electron densities of the unsubstituted PN-heterocycle core and numbering order for core carbons (middle). Atomic contributions are shown only for the readily functionalizable positions. 3a, R1 = CN 1 1 R2 R R R1 3b, R1 = OMe 1. P(OPh)3, pyr 3c, R1 = H 100 °C, 12 h R2 R2Pd(PPh3)2ClI 2 2. THF,H2O CuI, THF 60 °C, 1 h P OPh NH N2 DIPA or TEA ONH H2 2a, R2 = CN 4a-p 1a-p 2b, R2 = CF3 TMS (28-82%) (26-61%) 2c, R2 = Cl 1. NaHCO3 a, R1 = H, R2 = H i, R1 = 4-Me, R2 = t-Bu 2d, R2 = t-Bu TMSA MeOH, CHCl3 b, R1 = 4-CN, R2 = H j, R1 = H, R2 = t-Bu 2e, R2 = CO2Et NH 1 2 Pd(PPh ) Cl 2 2. ArX, CuI, THF c, R = 4-OMe, R = H k, R 1 = 3,4-(CN) , R2 2 = t-Bu3 2 2 2f, R2 = OEt CuI, THF Pd(PPh ) Cl d, R1 = 4-CN, R2 3 2 2 = CN l, R 1 = 4-Cl, R2 = t-Bu DIPA or TEA t-Bu DIPA or TEA e, R 1 = 4-CN, R2 = CF3 m, R 1 = H, R2 = CN f, R1 = 4-CN, R2 = Cl n, R1 = 4-OMe, R2 = CN 5 g, R1 = 4-CN, R2 = t-Bu o, R1 = H, R2 = CO2Et h, R1 = 4-OMe, R2 = t-Bu p, R1 = 4-CN, R2 = OEt Scheme 2.1 General synthetic pathway for disubstituted PN heterocycles. To test this hypothesis, a family of PN-heterocycles containing a variety of EWGs and EDGs on carbons 3 and 6 (1a-1p) were synthesized according to Scheme 2.1. Typically, readily accessible 2-iodoaniline derivatives 239 were alkynylated with terminal arylacetylenes 3 via Sonogashira cross-coupling to form the requisite arylethynylaniline precursors 4. Because of purification difficulties, compounds 4i-4l were prepared by an alternate route. Starting from known aniline 5,40 desilylation and Sonogashira cross- coupling of the crude product with the respective aryl halide afforded the remaining arylethynylanilines 4i-4l. Finally, precursors 4 were treated with P(OPh)3 in pyridine for 37 12-48 h at 110 °C and subsequently hydrolyzed to furnish PN-heterocycles 1. Yields of 1 range from 26-61%, and recrystallization from CHCl3 and hexanes gave analytically pure product. Examination of the 1H and 31P NMR spectra of 1 in CDCl3 revealed a few interesting characteristics of this class of heterocycles. Specifically, the proton signal for the hydrogen attached to C4 shows up as a doublet with a relatively large coupling constant of ca. 40 Hz due to splitting by the phosphonamidate P. Additionally, the N–H proton shifts appear as a broad singlet within the 7-10 ppm range and the 31P shifts show up as a doublet (J = ca. 40 Hz) around 9-12 ppm; however, both signals shift somewhat as a function of concentration because of dimer formation in solution (vide infra; see Appendix A). 2.2.2 Photophysical Properties. With compounds 1a-1o in hand, their photophysical properties were measured and the results are summarized in Table 2.1. Based on the theoretical results above, one could expect that either withdrawing R1 substituents or donating R2 substituents would induce a red shift in the emission. In general, this hypothesis is corroborated by the absorption and emission properties of the designed families, where one group contains a withdrawing cyano group for R1 and a variety of EDG and EWG for R2 (Figures 2.3a and A.4, a), and the other contains a donating tert-butyl group for R2 with a range of EDG and EWG for R1 (Figures 2.3b and A.4, b). It is worth noting that the fluorescence behavior of the phosphaquinolinones is similar to that of analogously substituted carbostyrils, though somewhat red-shifted. For example, 3-phenylcarbostyril absorbs at 345 nm, and emits at 410 nm, whereas 1a absorbs at 354 nm and emits at 427 nm.13 38 Table 2.1 Photophysical properties for PN-heterocycles 1a Stokes λabs λem cmpd R1 R2 Shift ε (cm–1M–1) ɸ (%)b τ (ns)c (nm) (nm) (nm/cm–1) 1a H H 335 417 82/5869 13000 8 0.2 1b 4-CN H 348 442 94/6112 22000 11 0.3 1c 4-OMe H 340 411 71/5080 17000 7 0.2 1d 4-CN CN 346 430 84/5646 12000 18 0.5 1e 4-CN CF3 341 429 88/6015 20000 11 0.3 1f 4-CN Cl 358 450 92/5710 23000 11 0.7 1g 4-CN t-Bu 358 453 95/5858 22000 11 0.5 1h 4-OMe t-Bu 344 421 77/5316 16000 6 0.3 1i 4-Me t-Bu 343 424 81/5569 14000 8 0.3 1j H t-Bu 343 430 87/5899 17000 8 0.3 3,4- 1k t-Bu 371 477 106/5989 19000 41 1.9 (CN)2 1l 4-Cl t-Bu 345 431 86/5784 19000 8 0.4 1m H CN 337 410 73/5283 12000 13 0.3 1n 4-OMe CN 345 471 126/7754 15000 28 0.7 1o H CO2Et 335 411 76/5519 12000 10 0.2 1p 4-CN OEt 379 490 111/5977 25000 24 2.4 a All measurements obtained at room temperature in CHCl3. b Quantum yield measurements obtained with ca. 10–5 M solutions. c λex = 344 nm; decay curves fitted to a monoexponential model. In these two families, clear trends can be drawn between substituent group electronic character and the emission energy (Figure 2.3c), which are supported by further functional group orientations studied on both positions (Figure A.4). 39 Figure 2.3 Emission spectra of a) heterocycles 1b, 1d–1g and b) heterocycles 1g–1l as well as c) plot of trend between substituent electronic properties and emission energies of 1. The σ value of 1k was approximated by addition of the σmeta and σpara values of the two nitrile groups. All experimental values collected in CHCl3. Though there is a linear trend between emission energies and the Hammett para parameter41 on R1 (red line in Figure 2.3c, R2 = 0.975), the trend between emission energy and Hammett parameter on R2, though present, is not as clear (blue line in Figure 2.3c, R2 = 0.674). These trends are exemplified when comparing emission wavelengths of 1k (477 nm) and 1h (421 nm) (Table 2.1), which contain a withdrawing 3,4-(CN)2 moiety and a donating 4-OMe group, respectively. To gain insight into these trends and correlate them to substituent effects on the electronic structures, density functional theory (DFT) calculations were performed on 1a-1p (Table 2.2). Based on this data, there is indeed a substituent effect from groups on R1. The HOMO levels trend upwards with more donating groups, going from −6.89 (1d) to −6.43 eV (1g) (Table 2.2, Figure 2.4a), and the LUMO goes from −2.62 (1k) to −1.70 eV (1h) (Table 2.2, Figure 2.4b) with more withdrawing groups on R1. As shown in Figure 2.5, the FMOs of 1e-g encompass the entire molecular systems, so the predominant transitions are π → π* in nature. 40 Table 2.2 Orbital energy levels for 1a–1p calculated at the PBE0/6-311G(d,p) level of theory HOMO LUMO HOMO-LUMO Cmpd (eV) (eV) Gap (eV) 1a −6.40 −1.84 4.56 1b −6.59 −2.28 4.31 1c −6.08 −1.74 4.34 1d −6.89 −2.50 4.39 1e −6.83 −2.43 4.40 1f −6.63 −2.41 4.22 1g −6.43 −2.24 4.19 1h −6.04 −1.70 4.34 1i −6.22 −1.76 4.46 1j −6.29 −1.81 4.48 1k −6.58 −2.62 3.96 1l −6.34 −1.91 4.43 1m −6.69 −2.13 4.56 1n −6.29 −2.03 4.26 1o −6.55 −1.96 4.59 1p −6.16 −2.27 3.89 TD-DFT was also performed to give a theoretical representation of the electronic transitions taking place (Figure 2.5). For each heterocycle, the S0S1 transition is dominated by the HOMOLUMO transition, which is in good agreement with experimental absorption values (Table 2.1). 41 Figure 2.4 a) Calculated LUMO levels vs. Hammett parameter of R1 substituents of R2 = t-Bu heterocycles 1 and b) calculated HOMO levels vs. Hammett parameter of R2 substituents of R1 = CN heterocycles 1. Orbital energy levels calculated at the PBE0/6- 311G(d,p) level of theory. The σ value of 1k was approximated by addition of the σmeta and σpara values of the two nitrile groups. Figure 2.5 Orientation of most dominant electronic transitions and the corresponding orbitals for heterocycles 1b, 1d–1g, and 1p; orbital energies in eV. 42 The second longest wavelength absorption (ca. 300 nm) is predominantly composed of the HOMO-1LUMO transition and matches the experimental data for each heterocycle as well (Figure A.4). In an attempt to better understand the electrochemical nature of these orbitals cyclic voltammetry (CV) measurements were collected for a subset of heterocycles 1 (Figure A.22). While electrochemical gap values of ca. 4.0 eV could be determined, the poor behavior of the compounds upon measurement prevented accurate experimental determination of the HOMO and LUMO energy levels. Comparison of the computed HOMO–LUMO energy gaps of 1 with the experimental emission energies (Figure 2.6a) showed that values are in very good agreement, such that the model should be able to predict emission energies accurately. To demonstrate this, we designed “optimized” heterocycle 1p (R1 = 4-CN and R2 = OEt), as the –OEt group can donate relatively strongly with a Hammett para parameter of −0.24 and thus should afford a dramatically red-shifted emission. The HOMO (−6.16 eV) and LUMO (−2.27 eV) levels were calculated, yielding a HOMO–LUMO gap of 3.89 eV. Based on this value, and the trend given by the related heterocycles in Figure 2.6a, the predicted emission energy value for 1p is 2.50 eV (496 nm). To validate this prediction, 1p was prepared in a similar fashion shown in Scheme 2.1 starting from iodoaniline 2f. Subsequent photophysical characterization showed λem = 490 nm (λabs = 379 nm, ε = 25000 M –1cm–1, ϕ = 24%, and τ = 2.4 ns). This is in excellent agreement with the predicted value (Figure 2.6b), showing that the trend seen between emission and HOMO–LUMO energy gaps can be empirically used to predict the emission of this PN scaffold. 43 Figure 2.6 Correlation between calculated HOMO–LUMO energy gap levels versus experimental emission energies of (a) heterocycles 1b, 1d–1g, and (b) heterocycles 1b, 1d– 1g, and 1p. 2.2.3 Dimer Formation in Solution In addition to studying the structure-property relationships between substituents and the photophysical aspects of heterocycles 1, we have also investigated the effects that these substitutions have on the dimerization strengths. Based on the previously reported value of 130 M–1 for 1b,31 and the role of the N-H hydrogen acting as the dominant hydrogen bonding unit, further polarization of the N-H bond should lead to even higher dimer strengths. Logic would follow that including various withdrawing groups upon the 44 scaffold should lead to this enhanced polarization. With these principles in mind, the dimer strengths of heterocycles 1 with a variety of EWG and EDG appended were studied using variable concentration (VC) NMR experiments in H2O-saturated CDCl3, with the results listed in Table 2.3 (see experimental section for measurement details). Table 2.3 Dimerization constants (M−1) of heterocycles 1 in H2O-saturated CDCl a 3 Entry Kdim Entry Kdim 1a 62b 1i 38b 1b 130c 1j 44 1c 56 1k –d 1d –d 1l –d 1e 293 1m 525 1f –d 1n –d 1g 70 1o 200 1h 36 1p 87 a All values ±10%. b 31P NMR signal tracked concomitantly to give 65 M−1 for 1a and 41 M−1 for 1i, which agree well with the respective 1H NMR values. c Previously reported in ref. 31. d Not measurable due to low solubility. Once the data is organized into families sharing either a similar R1 or R2 group, the resultant two LFERs (Figures 2.7a and 2.7b) show that more withdrawing groups upon either R1 or R2 lead to stronger dimer formation. Notably, the strength changes over 2.5 times as much with varying σpara of the substituents on R 2 than it does for R1 based on the slope of the trends, showing the R2 position is more sensitive to influencing dimerization strength. This is best illustrated when comparing heterocycles 1b and 1m, which have a nitrile group in place of R1 and R2, respectively. Installing the cyano unit on the para position with respect to the N–H in 1m likely causes a much greater polarization, leading to a vastly increased dimer strength of 525 M–1. To our knowledge, this value exceeds any previously reported for similar D-A dimer systems.35 45 Figure 2.7 Positive trends between EWG on a) R1 and b) R2 with dimerization constants of 1. To better understand the nature of this dimerization, ΔG values (ΔGcalc) were calculated and compared to experimental values (ΔGexp) (Table 2.4). While the computed ΔGcalc values are very similar to the ΔGexp values, the trends do not track in all cases. The ΔGexp values are incredibly close to each other, making it difficult to precisely match computationally. Interestingly, the gas phase free energies matched experimental trends more closely (Table A.17), with several additional computational methods explored (see Appendix A). 46 Table 2.4 ΔGcalc and ΔGexp values of heterocycles 1 a Entry ΔGcalc ΔGexp 1g −3.1 −2.5 1b −2.1 −2.9 1e −2.4 −3.4 1p −1.6 −2.6 1j −2.2 −2.2 1m −2.7 −3.7 1a −3.3 −2.4 1ob −2.6 −3.1 1h −2.5 −2.1 1c –2.5 –2.4 a Optimization performed with PBE/6-31G(d); single points done at WB97X/6- 311++G(2df,p). Solvation corrections done in CHCl3 at PBE/6-31+G(d,p)/SMD. b CO2Me ester substituent was used in place of the CO2Et ester, which share very similar Hammett parameters, to lessen the computational load. The models also show that the most stable dimer is always formed between one R and one S enantiomer because of stereoelectronic effects between phenoxy groups on each phosphorus center, corroborating the crystal packing structures reported in this paper (Figures 2.8, A.1-A.3 and A.6) as well as those of previous studies.31,32 In the heterodimer, the phenoxy oxygen lone pairs can donate into the P–O σ* and P–N σ* orbitals, which are stabilizing interactions (Figure 2.8a). In the homodimer only one phenoxy oxygen can be in the correct orientation to donate into the P–O σ* and P–N σ* orbitals; the other one is rotated to avoid steric collision between the phenoxy groups (Figure 2.8b). The rotated phenoxy group donates into the P–O σ* and P–C σ* orbitals, which are still stabilizing interactions, but less stabilizing than the lone pairs donating into the P–O σ* and P–N σ* orbitals. When the phenoxy groups are replaced with methoxy groups, there is no appreciable energy difference between the homodimer and heterodimer. 47 Figure 2.8 Schematic examples of (a) orbital overlap within monomer units in the R–S heterodimer structure and (b) poor alignment between orbitals within each monomer in the S–S homodimer structure, where the phenoxy oxygen lone pairs are represented in red and align with the P–O σ* and P–N σ* orbitals and the P–O σ* and P–C σ* orbitals, respectively. Using a multiple linear regression model in R,42–44 the ΔGexp values were plotted as a function of the σpara values of both the R 1 and R2 groups, giving a method for the prediction of the strength of a dimer with any combination of R1 and R2 substituent groups on any similar phosphaquinolinone molecule (Equation 2.1). Two values were excluded from the initial model and used as a validation set to verify the predictive ability of the model (Figure 2.9, Table A.18). 48 Equation 2.1 Relationship between substituent group Hammett parameters and predicted strength of dimerization for heterocycles 1. Figure 2.9 ΔGexp values versus ΔGpred. Blue data points were omitted from the initial model, and tested as a validation set of data, showing a good correlation to the model. 2.2.4 Dimer Formation in solid state In an attempt to corroborate solution-state data for the strength of the hydrogen bonding interactions between 1 monomers with hydrogen bonding in the solid state, single crystals were grown by vapor diffusion of pentane into concentrated CHCl3 solutions of 1b, 1c, 1e, 1g, and 1m (Figures 2.10 and A.1-A.3). In the solid-state structures, heterocycles 1b, 1c, and 1m crystalize as the previously observed31,32 meso-dimers discussed above (Figure 2.10a). Interestingly, both 1e and 1g instead form a staggered, repeating hydrogen bonding system, where the N–H and P=O moiety of each monomer coordinates with a different heterocycle, forming a continuous zigzag chain (Figure 2.10b). This alternative packing mode is likely due to steric interactions caused by the t-Bu and 49 the trifluoromethyl groups on 1e and 1g, respectively, thus likely inhibiting formation of the usual dimer structure in the solid state. Figure 2.10 Solid-state structures of a) the monomer and dimer of 1m and b) the monomer and staggered hydrogen bonding network of 1e. Regardless of the molecular packing, which can be influenced by various factors that do not affect the solution state, each structure shows the characteristic N–H•••O interactions of the phosphonamidate scaffold, distances that are summarized in Table 2.5. Compared to the respective solution state dimerization strength (Figure 2.11), the data is suggestive of a close relationship between the two, where the congeners with the higher 50 Kdim values indeed have shortened N–H•••O distances. Though there exist a multitude of factors that influence the solid state and the solution state separately, this relationship may hint toward potential guided design of these molecules as subunits in larger hydrogen- bonded systems. Table 2.5 Solid state N•••O distances of selected heterocycles 1 N•••O Entry distance (Å) 1b 2.809(2) 1c 2.821(11) 1e 2.807(4) 1g 2.815(2) 1m 2.768(2) Figure 2.11 Solid-state N•••O distances plotted against solution state Kdim values measured in CDCl3. 2.3 Conclusions In summary, we report an expedited synthesis of a unique PN heterocyclic scaffold, as well as studied the effects of substitution upon two sites. Specifically, the relationships between 51 calculated HOMO and LUMO levels of each derivative and the experimental emission characteristics were developed. The design principles learned from this correlation were then employed to synthesize another derivative with further red-shifted emission. In addition, we elucidated the nature of the very strong meso-dimers observed for these heterocycles by characterizing their solution state strengths as a function of substituent groups, comparing them with computed values, and correlating their solid-state N⋯O distances. The work described above addresses deficiencies in the knowledge about this new scaffold and provides both experimental and computational evidence towards current hypotheses surrounding them. This work will assist future guided design of this unique heterocycle for applications in chemosensing, anion sensing, and supramolecular materials, which we believe are worth additional exploration by us and hopefully others given the strong, complementary hydrogen bonding and emerging anion binding selectivity.45 2.4 Experimental Section General. All reactions requiring the lack of O2 and H2O were performed under an N2 atmosphere using Schlenk technique. Colum chromatography was performed using silica gel (240–300 mesh), with solvent systems being referenced to the most abundant solvent. NMR spectra were acquired at room temperature on a Varian Inova 500 (1H: 500 MHz, 13C: 126 MHz, 19F: 471 MHz, 31P: 202 MHz) or a Bruker Avance III HD 500 equipped with a Prodigy multinuclear cryoprobe (1H: 500 MHz, 13C: 126 MHz). 1H and 13C chemical shifts (δ) are expressed in parts per million (ppm) relative to residual CHCl3 shifts ( 1H: 7.26 ppm, 13C: 77.16 ppm) or residual DMSO shifts (1H: 2.50 ppm, 13C: 39.52 ppm). 31P NMR are referenced to 85% H3PO4 (δ 0 ppm) as an external reference, and 19F NMR are referenced to CFCl3 (δ 0 ppm) as an external standard. UV-vis spectra were recorded using 52 an Agilent Technologies Cary 60 UV-vis spectrophotometer in HPLC grade CHCl3. Fluorescence emission spectra were recorded using a Horiba Jobin Yvon FluoroMax-4 fluorimeter exciting at 365 nm. Quantum yields (ϕ) were determined through comparison of the emission and absorption intensities of the analyte to those of a 0.1M H2SO4 quinine sulfate.46 Fluorescence lifetime measurements were recorded using a Horiba FluoroHub Single Photon Counting Controller with a TemPro Fluorescence Lifetime System attachment. High-resolution mass spectra (HRMS) were recorded on a Waters XEVO G2- XS mass spectrometer. CV measurements were collected using a Bio-Logic SP-50 potentiostat. Compounds 2a-2e,394a-4c,31 1a-1c,31 and 540 were prepared as previously described. General procedure for determination of solution-state dimerization strengths. CDCl3 was mixed in a 1:1 ratio with H2O, shaken vigorously, then allowed to separate. The organic phase was then separated and used to prepare ca. 20 μM solutions of heterocycle 1. These solutions were then diluted through addition of known amounts of the CDCl3 solvent, with NMR spectra being collected after each addition. The chemical shift of the N-H signal was tracked and fitted to generate the dimerization values.47 General procedure for terminal acetylenes 3 or 5’. The TMS-protected variant of arylacetylene 3a-3b (1.0 equiv.), or TMS-protected arylethynylaniline 5 (1.0 equiv.) when applicable, and NaCO3 (3 equiv.) were dissolved in a 3:2 mixture of CHCl3:MeOH (0.06 M solution) and stirred for 3 hours. The solution was concentrated in vacuo, and the mixture was dissolved in CH2Cl2 before being added to a separatory funnel. The mixture was washed with deionized water (3x), dried (Na2SO4), filtered, and concentrated in vacuo 53 to yield the respective terminal acetylene 3 or 5’. The crude material was immediately carried forward for the subsequent cross-coupling reaction. General procedure for Sonogashira cross-coupling. Terminal arylacetylene 3 (1 equiv.), substituted iodoaniline 2 (1 equiv.), Pd(PPh3)2Cl2 (0.1 equiv.), and CuI (0.1 equiv.) were added to THF (~0.14 M solution). For 4i-4l, 3 and 2 were replaced by crude terminal arylethynylaniline 5’ (1 equiv.) and the appropriate haloarene (1 equiv.), respectively. The mixture was place under an N2 atmosphere and stirred for 10 min. DIPA or TEA was then added to achieve a 3:2 solvent to base ratio. The solution was stirred for 24-48 h before being filtered through silica gel and concentrated in vacuo. The crude material was then purified using column chromatography to give product 4. Yields reported are the combined yields for respective deprotections of the arylacetylenes and the subsequent cross-coupling reactions. General procedure for cyclizations. To a scintillation vial arylethynylaniline 4 (1 equiv.) and P(OPh)3 (1.1–2.0 equiv.) were added and dissolved in pyridine (0.35 M). The vial was sealed and heated to 110 °C for 24-48 h. The mixture was then diluted with toluene, and the solvent was removed in vacuo. The crude material was redissolved in THF, and 5-10 drops of water were added. The solution was then heated at 60 °C for 1 h, before being dried (NaSO4), filtered, and concentrated in vacuo. The crude mixture was then purified by column chromatography. Reported yields are listed for >95% pure product off the column, though all analyses were performed using solid that had been recrystallized from hexanes and CHCl3 to a purity of at least 99% by NMR spectroscopy. Iodoaniline 2f. In a round bottom flask, 4-amino-3-iodophenol48 (782 mg, 3.3 mmol, 1.0 equiv.) and CsCO3 (2.72 g, 8.3 mmol, 2.5 equiv.) were dissolved in DMF (18.5 mL) and 54 stirred at room temperature for 10 min. Using a syringe pump, EtI (468 mg, 3.0 mmol, 0.9 equiv.) in DMF (1.5 mL) was added to the solution over 6 h. After stirring an additional 48 h, the mixture was diluted with excess H2O. The product was extracted using EtOAc and the organic layer was dried (Na2SO4), filtered, and concentrated in vacuo to obtain 2f (443 mg, 51%) as a red-brown oil whose spectroscopic data matched those previously reported.49 Arylethynylaniline 4d. Following the general Sonogashira procedure, iodoaniline 2a (367 mg, 1.5 mmol, 1 equiv.), crude 4-ethynylbenzonitrile 3a (191 mg, 1.5 mmol, 1 equiv.), Pd(PPh3)2Cl2 (106 mg, 0.15 mmol, 0.1 equiv.), and CuI (29 mg, 0.15mmol, 0.1 equiv.) were reacted for 48 h using DIPA as the base. Column chromatography (3:2 hexanes:EtOAc) afforded 4d (201 mg, 55%) as a pale brown solid. 1H NMR (500 MHz, CDCl3) δ 7.70–7.59 (m, 5H), 7.41 (dd, J = 8.5, 2.0 Hz, 1H), 6.74 (d, J = 8.5 Hz, 1H), 4.79 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 151.22, 136.87, 134.09, 132.35, 132.16, 127.33, 119.16, 118.40, 114.45, 112.32, 107.16, 100.72, 94.46, 87.83. HRMS (ASAP) [M+H]+ calcd for C16H9N3 244.0875, found 244.0902. Arylethynylaniline 4e. Following the general Sonogashira procedure, iodoaniline 2b (1.01 g, 3.5 mmol, 1 equiv.), crude 4-ethynylbenzonitrile 3a (445 mg, 3.5 mmol, 1 equiv.), Pd(PPh3)2Cl2 (244 mg, 0.348 mmol, 0.1 equiv.), and CuI (66 mg, 0.348 mmol, 0.1 equiv.) were reacted for 48 h using DIPA as the base. Column chromatography (5:1 hexanes:EtOAc) afforded 4e (282 mg, 28%) as a brick red solid. 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 2H), 7.63 (s, 1H), 7.61 (d, J = 8.3 Hz, 2H) 7.40 (dd, J = 8.5, 1.4 Hz, 1H), 6.77 (d, J = 8.6 Hz, 1H), 4.59 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 150.51, 132.32, 132.10, 130.02 (q, J = 4.0 Hz), 127.71, 127.57 (q, J = 3.6 Hz), 124.26 (q, J = 271 55 Hz), 120.25 (q, J = 33.2 Hz), 118.51, 114.15, 112.04, 106.43, 93.96, 88.98. 19F NMR (471 MHz, CDCl3) δ –61.60. HRMS (ASAP) [M+H] + calcd for C16H9F3N2 287.0796, found 287.0829. Arylethynylaniline 4f. Following the general Sonogashira procedure, iodoaniline 2c (543 mg, 2.14 mmol, 1.0 equiv.), crude 4-ethynylbenzonitrile 3a (272 mg, 2.14 mmol, 1 equiv.), Pd(PPh3)2Cl2 (147 mg, 0.214 mmol, 0.10 equiv.), and CuI (40 mg, 0.214 mmol, 0.1 equiv.) were reacted for 24 h using TEA as the base. Column chromatography (5:1:1 hexanes:EtOAc:CH2Cl2) gave 4f (329 mg, 61%) a dark orange solid. 1H NMR (500 MHz, CDCl3) δ 7.64 (dd, J = 8.4, 2.1 Hz, 2H), 7.59 (dd, J = 8.4, 2.0 Hz, 2H), 7.33 (s, 1H), 7.13 (d, J = 8.7 Hz, 1H), 6.67 (dd, J = 8.8, 2.0 Hz, 1H), 4.28 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 146.79, 132.27, 132.05, 131.68, 130.76, 127.85, 122.57, 118.54, 115.83, 111.88, 108.16, 93.97, 89.28. HRMS (ASAP) [M+H]+ calcd for C15H9ClN2 253.0533, found 253.0560. Arylethynylaniline 4g. Following the general Sonogashira procedure, iodoaniline 2d (414 mg, 1.5 mmol, 1 equiv.), crude 4-ethynylbenzonitrile 3a (190 mg, 1.5 mmol, 1 equiv.), Pd(PPh3)2Cl2 (105 mg, 0.15 mmol, 0.1 equiv.), and CuI (28.7 mg, 0.15 mmol, 0.1 equiv.) were reacted for 24 h using DIPA as the base. Column chromatography (4:1 hexanes:EtOAc) gave 4g (201 mg, 49%) as a pale brown solid. 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 2.3 Hz, 1H), 7.23 (dd, J = 9.1, 2.7 Hz, 1H), 6.70 (d, J = 8.5 Hz, 1H), 4.19 (s, 2H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 145.87, 141.12, 132.14, 131.89, 128.93, 128.48, 128.22, 118.67, 114.64, 111.25, 106.34, 92.75, 91.40, 34.02, 31.45. HRMS (ASAP) [M+H]+ calcd for C19H18N2 275.1548, found 275.1570. 56 Arylethynylaniline 4h. Following the general Sonogashira procedure, iodoaniline 2d (410 mg, 1.5 mmol, 1 equiv.), crude 4-ethynylanisole 3b (204 mg, 1.5 mmol, 1 equiv.), Pd(PPh3)2Cl2 (103 mg, 0.15 mmol, 0.1 equiv.), and CuI (27 mg, 0.15 mmol, 0.1 equiv.) were reacted for 24 h using DIPA as the base. Column chromatography (15:1:1 hexanes:EtOAc:CH2Cl2) afforded 4h (180 mg, 43%) as a red oil. 1H NMR (500 MHz, CDCl3) δ 7.48 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 2.4 Hz, 1H), 7.17 (dd, J = 8.5, 2.4 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.4 Hz, 1H), 4.15 (s, 2H), 3.83 (s, 3H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 159.66, 145.37, 141.01, 133.05, 128.73, 126.88, 115.68, 114.39, 114.14, 108.03, 94.21, 85.14, 55.45, 34.05, 31.55. HRMS (ASAP) [M+H]+ calcd for C19H21NO 280.1701, found 280.1730. Arylethynylaniline 4i. TMS-ethynylaniline 5 (599 mg, 2.44 mmol, 1 equiv.) was desilated using the general method, then the crude product was mixed with 4-iodotoluene (638 mg, 2.93 mmol, 1.2 equiv.), Pd(PPh3)2Cl2 (171 mg, 0.244 mmol, 0.10 equiv.), and CuI (45 mg, 0.244 mmol, 0.1 equiv.) and reacted for 24 h using TEA as the base following the general Sonogashira procedure. Column chromatography (15:1:1 hexanes:EtOAc:CH2Cl2) afforded 4i (508 mg, 79%) as an orange solid. 1H NMR (500 MHz, CDCl3) δ 7.43 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 2.4 Hz, 1H), 7.21–7.12 (m, 3H), 6.69 (d, J = 8.3 Hz, 1H), 4.16 (s, 2H), 2.38 (s, 3H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 145.46, 141.01, 138.38, 131.50, 129.26, 128.79, 127.04, 120.48, 114.39, 107.88, 94.45, 85.86, 34.06, 31.56, 21.65. HRMS (ASAP) [M+H]+ calcd for C19H21N 264.1752, found 264.1754. Arylethynylaniline 4j. TMS-ethynylaniline 5 (600 mg, 2.44 mmol, 1 equiv.) was desilated using the general method, then the crude product was mixed with iodobenzene (598 mg, 2.92 mmol, 1.2 equiv.), Pd(PPh3)2Cl2 (172 mg, 0.244 mmol, 0.10 equiv.), and CuI (43 mg, 57 0.243 mmol, 0.1 equiv.) and reacted for 24 h using TEA as the base following the general Sonogashira procedure. Column chromatography (15:1:1 hexanes:EtOAc:CH2Cl2) gave 4j (499 mg, 82%) as a brown oil. 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 7.2 Hz, 2H), 7.46–7.31 (m, 4H), 7.19 (dd, J = 8.4, 2.5 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 4.16 (s, 2H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 145.54, 141.04, 131.62, 128.85, 128.50, 128.26, 127.24, 123.57, 114.44, 107.64, 94.30, 86.59, 34.07, 31.56. HRMS (ASAP) [M+H]+ calcd for C18H19N 250.1596, found 250.1606. Arylethynylaniline 4k. TMS-ethynylaniline 5 (224 mg, 0.911 mmol, 1 equiv.) was desilated using the general method, then the crude product was mixed with 4-iodo-1,2- benzenedicarbonitrile (232 mg, 0.911 mmol, 1.0 equiv.), Pd(PPh3)2Cl2 (64 mg, 0.091 mmol, 0.10 equiv.), and CuI (17 mg, 0.091 mmol, 0.1 equiv.) and reacted for 24 h using TEA as the base following the general Sonogashira procedure. Column chromatography (5:1:1 hexanes:EtOAc:CH2Cl2) afforded 4k (199 mg, 73%) as a light orange solid. 1H NMR (500 MHz, CDCl3) δ 7.90 (s, 1H), 7.85–7.69 (m, 1H), 7.36 (s, 1H), 7.30–7.24 (m, 2H), 6.71 (dd, J = 8.7, 2.0 Hz, 1H), 4.18 (s, 2H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 146.26, 141.39, 135.79, 135.29, 133.62, 129.70, 129.18 (2C), 116.47, 115.39, 114.93, 114.89, 113.97, 105.37, 94.78, 91.00, 34.11, 31.46. HRMS (ASAP) [M+H]+ calcd for C20H17N3 300.1501, found 300.1511. Arylethynylaniline 4l. TMS-ethynylaniline 5 (599 mg, 2.44 mmol, 1 equiv.) was desilated using the general method, then the crude product was mixed with 1-bromo-4- chlorobenzene (471 mg, 2.44 mmol, 1.0 equiv.), Pd(PPh3)2Cl2 (172 mg, 0.244 mmol, 0.10 equiv.), and CuI (47 mg, 0.244 mmol, 0.1 equiv.) and reacted for 24 h using TEA as the base following the general Sonogashira procedure. Column chromatography (10:1:1 58 hexanes:EtOAc:CH2Cl2) gave 4l (319 mg, 46%) as a brown oil. 1H NMR (500 MHz, CDCl3) δ 7.46 (d, J = 7.1 Hz, 2H), 7.37 (s, 1H), 7.33 (d, J = 7.4 Hz, 2H), 7.20 (d, J = 8.5 Hz, 1H), 6.69 (d, J = 8.5 Hz, 1H), 4.15 (s, 2H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 145.58, 141.12, 134.22, 132.78, 128.85, 128.84, 127.50, 122.09, 114.53, 107.27, 93.16, 87.64, 34.07, 31.53. HRMS (ASAP) [M+H]+ calcd for C18H18ClN 284.1206, found 284.1226. Arylethynylaniline 4m. Following the general Sonogashira procedure, iodoaniline 2a (1 g, 4.1 mmol, 1 equiv.), phenylacetylene (530 mg, 5.19 mmol, 1.25 equiv.), Pd(PPh3)2Cl2 (287 mg, 0.41 mmol, 0.1 equiv.), and CuI (78 mg, 0.41 mmol, 0.1 equiv.) were reacted for 24 h using DIPA as the base. Column chromatography (8:1:1 then 6:1:1 hexanes:EtOAc:CH2Cl2) furnished 4m (599 mg, 67%) as a dark brown oil. 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 1.9 Hz, 1H), 7.58–7.46 (m, 2H), 7.44–7.28 (m, 4H), 6.71 (d, J = 8.5 Hz, 1H), 4.81 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 151.15, 136.44, 133.31, 131.68, 129.01, 128.63, 122.42, 119.50, 114.09, 108.28, 100.20, 96.32, 83.48. HRMS (ASAP) [M+H]+ calcd for C15H10N2 219.0922, found 219.0950. Arylethynylaniline 4n. Following the general Sonogashira procedure, iodoaniline 2a (358 mg, 1.5 mmol, 1 equiv.), crude 4-ethynylanisole 3b (206 mg, 1.5 mmol, 1 equiv.), Pd(PPh3)2Cl2 (103 mg, 0.15 mmol, 0.1 equiv.), and CuI (28 mg, 0.15 mmol, 0.1 equiv.) were reacted for 24 h using DIPA as the base. Column chromatography (8:1:1 then 2:1:1 hexanes:EtOAc:CH2Cl2) furnished 4n (197 mg, 53%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 1.9 Hz, 1H), 7.46 (d, J = 8.9 Hz, 2H), 7.35 (dd, J = 8.5, 2.0 Hz, 1H), 6.90 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.5 Hz, 1H), 4.74 (s, 2H), 3.84 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 160.26, 150.98, 136.31, 133.25, 133.09, 119.56, 114.50, 59 114.32, 114.02, 108.81, 100.37, 96.47, 82.22, 55.51. HRMS (ASAP) [M+H]+ calcd for C16H12N2O 249.1028, found 249.1028. Arylethynylaniline 4o. Following the general Sonogashira procedure, iodoaniline 2e (2.74 g, 9.4 mmol, 1 equiv.), phenylacetylene 3c (1.09 g, 9.4 mmol, 1 equiv.), Pd(PPh3)2Cl2 (200 mg, 0.285 mmol, 0.03 equiv.), and CuI (50 mg, 0.28 mmol, 0.03 equiv.) were reacted for 24 h using TEA as the base. Column chromatography (10:1:1 then 7:1:1 hexanes:EtOAc:CH2Cl2) gave 4o (1.99 g, 80%) a light orange solid. 1H NMR (500 MHz, CDCl3) δ 8.10 (d, J = 2.1 Hz, 1H), 7.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.56–7.50 (m, 2H), 7.42– 7.30 (m, 3H), 6.70 (d, J = 8.5 Hz, 1H), 4.76 (s, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 166.23, 151.55, 140.97, 134.38, 131.55, 131.17, 128.49, 122.93, 119.72, 113.34, 107.09, 95.12, 84.91, 60.58, 14.48. HRMS (ASAP) [M+H]+ calcd for C17H15NO2 266.1181 found 266.1215. Arylethynylaniline 4p. Following the general Sonogashira procedure, crude ethynylbenzonitrile 3a (477 mg, 3.75 mmol, 1.5 equiv.), 4-ethoxy-2-iodoaniline 2f (655 mg, 2.49 mmol, 1.0 equiv.), Pd(PPh3)2Cl2 (110 mg, 0.16 mmol, 0.063 equiv.), and CuI (29 mg, 0.15 mmol, 0.061 equiv.) were reacted for 24 h using TEA as the base. Column chromatography (5:1:1 hexanes:EtOAc:CH2Cl2) gave 4p (551 mg, 56%) as a dark orange solid. 1H NMR (500 MHz, CDCl3) δ 7.72–7.51 (m, 4H), 6.90 (d, J = 2.9 Hz, 1H), 6.82 (dd, J = 8.8, 2.9 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 4.00 (s, 2H), 3.97 (q, J = 7.0 Hz, 2H), 1.38 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 151.42, 142.48, 132.24, 132.00, 128.33, 119.42, 118.66, 116.98, 116.32, 111.54, 107.49, 93.09, 90.86, 64.38, 15.06. HRMS (ASAP) [M+H]+ calcd for C17H14N2O 263.1184, found 263.1221 60 Phosphaquinolinone 1d. Following the general cyclization procedure, arylethynylaniline 4d (200 mg, 0.82 mmol, 1 equiv.) and P(OPh)3 (310 mg, 0.984 mmol, 1.2 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.10) gave 1d (109 mg, 26%) as a pale yellow solid; mp >250 °C. 1H NMR (500 MHz, CDCl3) δ 9.85 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 7.9 Hz, 2H), 7.65 (s, 1H), 7.62 (d, J = 39.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.5 Hz, 1H), 7.07 (t, J = 7.7 Hz, 2H), 6.99 (t, J = 7.4 Hz, 1H), 6.83 (d, J = 7.9 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 149.85 (d, J = 9.1 Hz), 143.52, 141.70 (d, J = 5.1 Hz), 139.29 (d, J = 8.8 Hz), 135.30, 134.05, 133.03, 129.80, 128.57 (d, J = 6.3 Hz), 125.78, 124.90 (d, J = 159 Hz), 121.03 (d, J = 4.1 Hz), 119.48 (d, J = 15.2 Hz), 118.56 (d, J = 10.0 Hz), 118.47, 118.41, 112.93, 104.99. 31P NMR (202 MHz, CDCl3) δ 9.53 (d, J = 39.1 Hz). HRMS (ASAP) [M+H] + calcd for C22H14N3O2P 384.0902, found 384.0903. Phosphaquinolinone 1e. Following the general cyclization procedure, arylethynylaniline 4e (260 mg, 0.917 mmol, 1 equiv.) and P(OPh)3 (340 mg, 1.10 mmol, 1.2 equiv.) in pyridine were reacted for 48 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.23) gave 1e (286 mg, 61%) as a pale yellow solid; mp 227-229 °C. 1H NMR (500 MHz, CDCl3) δ 9.67 (s, 1H), 7.96 (d, J = 7.9 Hz, 2H), 7.78 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 39.2 Hz, 1H), 7.59 (s, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.14 (d, J = 8.6 Hz, 1H), 7.07 (t, J = 7.7 Hz, 2H), 6.98 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 7.8 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 150.02 (d, J = 9.1 Hz), 142.71, 142.50 (d, J = 5.2 Hz), 139.70 (d, J = 9.0 Hz), 132.95, 129.73, 128.50 (d, J = 6.5 Hz), 127.22 125.58 (d, J = 1.7 Hz), 125.07, 124.25 (q, J = 160 Hz), 123.78 (q, J = 33.2 Hz), 122.91, 121.06 (d, J = 4.1 Hz), 118.88 (d, J = 15.0 Hz), 118.60, 118.10 (d, J = 9.8 Hz), 112.61. 31P NMR (202 MHz, CDCl3) δ 10.09 (d, J = 39.2 61 Hz). 19F NMR (471 MHz, CDCl3) δ –61.91. HRMS (ASAP) [M+H] + calcd for C22H14F3N2O2P 427.0823, found 427.0808. Phosphaquinolinone 1f. Following the general cyclization procedure, arylethynylaniline 4f (285 mg, 1.13 mmol, 1 equiv.) and P(OPh)3 (699 mg, 2.25 mmol, 2 equiv.) in pyridine were reacted for 24 h. The crude mixture was recrystallized from hot CH2Cl2 and hexanes. The solid was isolated and washed with hexanes to afford 1f (389 mg, 44%; Rf = 0.22 in 2:1:1 hexanes:EtOAc:CH2Cl2) as a yellow solid; mp >250 °C. 1H NMR (500 MHz, DMSO- d6) δ 10.30 (s, 1H), 8.07 (d, J = 38.5 Hz, 1H), 8.04 (d, J = 7.6 Hz, 2H), 7.96 (d, J = 8.1 Hz, 2H), 7.62 (s, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.23 (t, J = 8.1 Hz, 2H), 7.08 (d, J = 7.4 Hz, 2H), 6.87 (d, J = 7.9 Hz, 2H). 13C NMR (126 MHz, DMSO-d6) δ 149.97 (d, J = 9.0 Hz), 141.82 (d, J = 4.0 Hz), 139.83 (d, J = 9.6 Hz), 139.27, 132.78, 130.41 (d, J = 107 Hz), 129.65, 128.02 (d, J = 6.5 Hz), 125.01, 124.17, 124.11, 122.92, 120.80 (d, J = 4.0 Hz), 120.38 (d, J = 15.1 Hz), 118.64, 118.30 (d, J = 9.8 Hz), 110.77. 31P NMR (202 MHz, DMSO-d6) δ 8.36 (d, J = 38.3 Hz). HRMS (ASAP) [M+H] + calcd for C21H14ClN2O2P 393.0560, found 393.0576. Phosphaquinolinone 1g. Following the general cyclization procedure, arylethynylaniline 4g (200 mg, 0.729 mmol, 1 equiv.) and P(OPh)3 (0.271 g, 0.874 mmol, 1.2 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.30) afforded 1g (108 mg, 36%) as a pale yellow solid; mp >250 °C. 1H NMR (500 MHz, CDCl3) δ 8.39 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 7.5 Hz, 2H), 7.68 (d, J = 38.7 Hz, 1H), 7.42–7.35 (m, 1H), 7.32 (s, 1H), 7.09 (t, J = 7.7 Hz, 2H), 6.98 (t, J = 7.5 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 1.31 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 150.34 (d, J = 9.0 Hz), 144.49, 143.88 (d, J = 5.1 Hz), 140.64 (d, J = 9.4 Hz), 137.71 (d, J = 2.0 Hz), 62 132.73, 129.58, 129.26, 128.36 (d, J = 6.4 Hz), 127.46, 125.09, 122.76 (d, J = 161 Hz), 121.17 (d, J = 4.1 Hz), 119.21 (d, J = 14.1 Hz), 118.91, 117.34 (d, J = 9.3 Hz), 111.75, 34.34, 31.46. 31P NMR (202 MHz, CDCl3) δ 10.84 (d, J = 39.6 Hz). HRMS (ASAP) [M+H]+ calcd for C25H23N2O2P 415.1575, found 415.1588. Phosphaquinolinone 1h. Following the general cyclization procedure, arylethynylaniline 4h (174 mg, 0.623 mmol, 1 equiv.) and P(OPh)3 (231 mg, 0.747 mmol, 1.2 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.25) afforded 1h (115 mg, 44%) as a pale yellow solid; mp 98-101 °C. 1H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 40.6 Hz, 1H), 7.35–7.29 (m, 2H), 7.13 (t, J = 7.7 Hz, 2H), 7.05–6.91 (m, 6H), 6.88 (d, J = 8.8 Hz, 1H), 3.86 (s, 3H), 1.32 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 159.99, 150.66 (d, J = 8.9 Hz), 144.28, 140.27 (d, J = 6.3 Hz), 136.76 (d, J = 2.3 Hz), 129.49, 129.18 (d, J = 6.8 Hz), 128.19 (d, J = 9.4 Hz), 127.74, 127.03, 124.88, 124.85 (d, J = 159.4 Hz), 121.34 (d, J = 4.2 Hz), 119.98 (d, J = 14.2 Hz), 116.77 (d, J = 9.1 Hz), 114.49, 55.53, 34.32, 31.52. 31P NMR (202 MHz, CDCl3) δ 10.99 (d, J = 40.6 Hz). HRMS (ASAP) [M + H]+ calcd for C25H26NO3P 420.1729, found 420.1733. Phosphaquinolinone 1i. Following the general cyclization procedure, arylethynylaniline 4i (251 mg, 1.93 mmol, 1 equiv.) and P(OPh)3 (718 mg, 2.314 mmol, 1.2 equiv.) in pyridine were reacted for 48 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.50) afforded 1i (389 mg, 50%) as a yellow solid; mp 95-96 °C. 1H NMR (500 MHz, CDCl3) δ 7.78 (s, 1H), 7.73 (d, J = 7.8 Hz, 2H), 7.58 (d, J = 40.4 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 6.4 Hz, 2H), 7.09 (t, J = 7.3 Hz, 2H), 7.01–6.90 (m, 4H), 2.41 (s, 3H), 1.30 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 150.73 (d, J = 9.3 Hz), 144.01, 141.22 (d, J = 5.9 Hz), 63 138.35, 137.20, 132.94 (d, J = 9.1 Hz), 129.74, 129.43, 127.92, 127.77 (d, J = 6.7 Hz), 126.96, 124.78 (d, J = 159 Hz), 124.73, 121.38 (d, J = 4.1 Hz), 119.72 (d, J = 14.3 Hz), 116.99 (d, J = 9.2 Hz), 34.28, 31.51, 21.43. 31P NMR (202 MHz, CDCl3) δ 11.79 (d, J = 40.3 Hz). HRMS (ASAP) [M + H]+ calcd for C25H26NO2P 404.1779, found 404.1787. Phosphaquinolinone 1j. Following the general cyclization procedure, arylethynylaniline 4j (500 mg, 2.00 mmol, 1 equiv.) and P(OPh)3 (744 mg, 2.40 mmol, 1.2 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.66) gave 1j (436 mg, 56%) as a yellow solid; mp 153-154 °C. 1H NMR (500 MHz, CDCl3) δ 7.78 (s, 1H), 7.73 (d, J = 7.8 Hz, 2H), 7.58 (d, J = 40.4 Hz, 1H), 7.32–7.23 (m, 4H), 7.09 (t, J = 7.3 Hz, 2H), 7.01–6.90 (m, 4H), 2.41 (s, 3H), 1.30 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 150.68 (d, J = 9.2 Hz), 144.07, 142.03 (d, J = 5.8 Hz), 137.29 (d, J = 2.0 Hz), 135.88 (d, J = 9.1 Hz), 129.44, 129.01, 128.39, 128.15, 127.96 (d, J = 6.6 Hz), 127.06, 124.84 (d, J = 160 Hz), 124.77, 121.36 (d, J = 4.2 Hz), 119.61 (d, J = 14.3 Hz), 117.06 (d, J = 9.2 Hz), 34.29, 31.51. 31P NMR (202 MHz, CDCl3) δ 11.38 (d, J = 40.1 Hz). HRMS (ASAP) [M+H]+ calcd for C24H24NO2P 390.1623, found 390.1621. Phosphaquinolinone 1k. Following the general cyclization procedure, arylethynylaniline 4k (218 mg, 0.729 mmol, 1 equiv.) and P(OPh)3 (452 mg, 1.46 mmol, 2 equiv.) in pyridine were reacted for 48 h. The crude mixture was triturated with hot EtOAc. The resulting yellow solid was isolated and washed with hexanes to afford 1k (109 mg, 34%; Rf = 0.24 in 2:1:1 hexanes:EtOAc:CH2Cl2) as a light yellow solid; mp >250 °C. 1H NMR (500 MHz, DMSO-d6) δ 10.14 (s, 1H), 8.54 (s, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.32 (d, J = 37.8 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.55 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.24 (t, J = 7.7 Hz, 2H), 7.09 (t, J = 7.5 Hz, 1H), 7.04 (d, J = 8.5 Hz, 1H), 6.90 (d, J = 7.9 Hz, 2H), 1.27 (s, 64 6H). 13C NMR (126 MHz, DMSO-d6) δ 150.06 (d, J = 8.8 Hz), 145.14, 145.12, 143.08, 141.17 (d, J = 10.6 Hz), 138.45 (d, J = 2.3 Hz), 134.43, 131.76 (d, J = 5.5 Hz), 131.52 (d, J = 7.9 Hz), 129.67, 129.61, 127.76, 124.94, 120.93 (d, J = 4.1 Hz), 119.72 (d, J = 159 Hz), 118.51 (d, J = 14.8 Hz), 116.46 (d, J = 9.5 Hz), 115.90 (d, J = 17.6 Hz), 115.30, 112.86, 33.89, 31.05. 31P NMR (202 MHz, DMSO-d6) δ 9.15 (d, J = 37.7 Hz). HRMS (ASAP) [M+H]+ calcd for C26H22N3O2P 440.1528, found 440.1542. Phosphaquinolinone 1l. Following the general cyclization procedure, arylethynylaniline 4l (287 mg, 1.01 mmol, 1 equiv.) and P(OPh)3 (627 mg, 2.02 mmol, 2.0 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2; Rf = 0.36) furnished 1l (256 mg, 60%) as a yellow solid; mp 192-194 °C. 1H NMR (500 MHz, CDCl3) δ 7.85 (s, 1H), 7.76 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 39.8 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.5 Hz, 1H), 7.31 (s, 1H), 7.10 (t, J = 7.7 Hz, 2H), 6.99 (t, J = 7.4 Hz, 1H), 6.96–6.86 (m, 3H), 1.31 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 150.55 (d, J = 9.2 Hz), 144.29, 142.17 (d, J = 5.8 Hz), 137.28 (d, J = 2.1 Hz), 134.47, 134.38 (d, J = 9.5 Hz), 129.53, 129.21, 129.16, 128.44, 127.17 (d, J = 1.8 Hz), 124.92 (d, J = 1.7 Hz), 123.65 (d, J = 160 Hz), 121.27 (d, J = 4.1 Hz), 119.51 (d, J = 14.2 Hz), 117.11 (d, J = 9.3 Hz), 34.32, 31.49. 31P NMR (202 MHz, CDCl3) δ 11.02 (d, J = 39.9 Hz). HRMS (ASAP) [M+H] + calcd for C24H23ClNO2P 424.1233, found 424.1256. Phosphaquinolinone 1m. Following the general cyclization procedure, arylethynylaniline 4m (587 mg, 2.69 mmol, 1 equiv.) and P(OPh)3 (1.084 g, 3.50 mmol, 1.3 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2; Rf = 0.20) gave 1m (405 mg, 42%) as a yellow solid; mp 249-251 °C. 1H NMR (500 MHz, CDCl3) δ 9.62 (s, 1H), 7.84 (d, J = 7.5 Hz, 2H), 7.61–7.39 (m, 6H), 7.13–7.03 (m, 3H), 6.96 (t, J = 65 7.4 Hz, 1H), 6.90–6.83 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 150.21 (d, J = 9.2 Hz), 143.46 (d, J = 1.8 Hz), 139.91 (d, J = 5.9 Hz), 134.78, 133.20, 129.60 (d, J = 1.6 Hz), 129.36, 128.05 (d, J = 6.5 Hz), 126.69 (d, J = 158 Hz), 125.41 (d, J = 1.8 Hz), 121.27 (d, J = 4.1 Hz), 119.87 (d, J = 15.3 Hz), 118.82, 118.39 (d, J = 9.6 Hz), 104.34. 31P NMR (202 MHz, CDCl3) δ 10.31 (d, J = 40.2 Hz). HRMS (ASAP) [M+H] + calcd for C21H15N2O2P 359.0949, found 359.0995. Phosphaquinolinone 1n. Following the general cyclization procedure, arylethynylaniline 4n (190 mg, 0.76 mmol, 1 equiv.) and P(OPh)3 (285 mg, 0.92 mmol, 1.2 equiv.) in pyridine were reacted for 36 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2 (Rf = 0.10) then 20:1 CH2Cl2:MeOH) furnished 1n (88 mg, 30%) as a yellow solid; mp 238-239 °C. 1H NMR (500 MHz, CDCl3) δ 9.75 (s, 1H), 7.80 (d, J = 8.7 Hz, 2H), 7.56 (s, 1H), 7.47 (d, J = 40.4 Hz, 1H), 7.42 (d, J = 7.2 Hz, 1H), 7.15–7.01 (m, 5H), 6.99–6.92 (m, 1H), 6.88 (d, J = 8.4 Hz, 2H), 3.90 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 160.65, 150.25 (d, J = 9.1 Hz), 143.19 (d, J = 1.8 Hz), 138.16 (d, J = 6.2 Hz), 134.52, 132.84, 129.59, 129.31 (d, J = 6.7 Hz), 127.05 (d, J = 8.8 Hz), 126.23 (d, J = 156 Hz), 125.38 (d, J = 1.8 Hz), 121.29 (d, J = 4.0 Hz), 120.11 (d, J = 15.3 Hz), 118.90, 118.26 (d, J = 9.7 Hz), 114.82, 104.29, 55.60. 31P NMR (202 MHz, CDCl3) δ 10.64 (d, J = 40.4 Hz). HRMS (ASAP) [M+H] + calcd for C22H17N2O3P 389.1055, found 389.1078. Phosphaquinolinone 1o. Following the general cyclization procedure, arylethynylaniline 4o (1.69 g, 6.37 mmol, 1 equiv.) and P(OPh)3 (2.37 g, 7.65 mmol, 1.2 equiv.) in pyridine were reacted for 24 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2; Rf = 0.20) afforded 1o (1.42 g, 55%) as a yellow solid; mp 176-178 °C. 1H NMR (500 MHz, CDCl3) δ 9.60 (s, 1H), 8.02 (s, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 7.7 Hz, 2H), 7.65 (d, J = 66 40.6 Hz, 1H), 7.51 (t, J = 7.5 Hz, 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.08 (d, J = 8.5 Hz, 1H), 7.03 (t, J = 7.6 Hz, 2H), 6.93 (d, J = 7.4 Hz, 1H), 6.90 (d, J = 8.3 Hz, 2H), 4.36 (q, J = 6.9 Hz, 3H), 1.39 (t, J = 7.1 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 166.10, 150.43 (d, J = 9.1 Hz), 143.76 (d, J = 1.8 Hz), 141.43 (d, J = 6.0 Hz), 135.31 (d, J = 8.8 Hz), 132.66, 131.52, 129.50 (d, J = 1.6 Hz), 129.22, 128.88, 128.02 (d, J = 6.6 Hz), 125.18 (d, J = 158 Hz), 125.14 (d, J = 1.7 Hz), 123.26, 121.34 (d, J = 4.0 Hz), 119.16 (d, J = 15.0 Hz), 117.41 (d, J = 9.6 Hz), 61.05, 14.52. 31P NMR (202 MHz, CDCl3) δ 11.25 (d, J = 40.5 Hz). HRMS (ASAP) [M+H]+ calcd for C23H20NO4P 406.1208, found 406.1229. Phosphaquinolinone 1p. Following the general cyclization procedure, arylethynylaniline 4p (369 mg, 1.41 mmol, 1 equiv.) and P(OPh)3 (872 mg, 2.81 mmol, 2 equiv.) in pyridine were reacted for 48 h. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2; Rf = 0.12) afforded 1p (306 mg, 54%) as a yellow solid; mp 247-250 °C. 1H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 7.2 Hz, 2H), 7.76–7.69 (m, 3H), 7.59 (d, J = 38.8 Hz, 1H), 7.11 (t, J = 8.2 Hz, 2H), 7.01 (t, J = 7.6 Hz, 1H), 6.98–6.87 (m, 4H), 6.85 (d, J = 2.6 Hz, 1H), 4.01 (q, J = 7.0 Hz, 2H), 1.41 (t, J = 6.9 Hz, 3H).13C NMR (126 MHz, CDCl3) δ 153.71, 150.23 (d, J = 9.0 Hz), 143.00, 140.42 (d, J = 9.2 Hz), 133.75 (d, J = 2.2 Hz), 132.76, 129.63, 128.43 (d, J = 6.6 Hz), 125.23, 123.95 (d, J = 161 Hz), 121.17 (d, J = 4.3 Hz), 120.31 (d, J = 14.1 Hz), 119.87, 118.84, 118.57 (d, J = 9.3 Hz), 114.79, 111.95, 64.25, 14.99. 31P NMR (202 MHz, CDCl3) δ 10.29 (d, J = 38.9 Hz). HRMS (ASAP) [M+H] + calcd for C23H19N2O3P 403.1212, found 403.1220. 67 CHAPTER III EXPLOITING THE HYDROGEN BOND DONOR/ACCEPTOR PROPERTIES OF PN HETEROCYCLES: SELECTIVE ANION RECEPTORS FOR HYDROGEN SULFATE This chapter includes previously published and co-authored material from Deng, C.-L., Bard, J.P., Lohrman, J.A., Barker, J.E., Zakharov, L.N., Johnson, D.W., Haley, M.M. “Exploiting the Hydrogen Bond Donor/Acceptor Properties of PN-Heterocycles: Selective Anion Receptors for Hydrogen Sulfate.” Angew. Chem. Int. Ed. 2019, 58, 3934–3938. This story highlights our work on developing a hybrid urea- and phosphaquinoline-containing host for the binding of HSO –4 in both aqueous and organic solutions. 3.1 Introduction Selective detection and recognition of various anions have attracted substantial attention.1 Hydrogen sulfate (bisulfate, HSO –4 ) is of considerable interest owing to its concern as a contaminant in agricultural and industrial fields.2 This hydroxyanion is a moderate acid (pKa≈2.0)3 and is abundant in aqueous sulfuric acid and salt solutions. Meanwhile, the important sulfate (SO 2–4 ) anion will equilibrate with bisulfate ions in low pH environment. Hydrogen sulfate is the most prevalent inorganic component in lower and upper atmospheric aerosols and plays a role in aerosol homogeneous nucleation.4 Additionally, the HSO –4 anion can also act as an important and effective catalyst for various chemical transformations.5 As a result, the design and development of various artificial 68 host molecules for HSO –4 anion binding has become a highly desirable target in supramolecular chemistry. Unfortunately, development of synthetic receptors that are capable of selective recognition and binding toward HSO –4 has proven challenging because of its H-bonding donor/acceptor nature as well as its unique tetrahedral geometry.6 Over the past few decades, only a handful of selective receptors for HSO –4 have been documented. 7,8 These molecular systems are mainly composed of the well-known acidic (N–H, O–H) and/or neutral (C–H) hydrogen bond (HB) donors and basic nitrogen atoms (such as amine, imine, imidazole, or pyridine motifs)7 or carbonyl8 motifs as the perceived HB accepting sites. The resulting multidentate and/or macrocyclic architectures with convergent and complementary HB contacts typically give rise to strong anion binding affinities in solution phase, although selectivity is often far from optimum. Furthermore, stabilization of HSO – 4 by complexation with receptors bearing basic moieties in the solid state has always been challenging since the protic oxyanion is susceptible to proton transfer to the hostmolecules.7b,7d Hydroxyanions including HSO –4 are well-known to dimerize by forming anti-electrostatic, self-complementary (O–H)anion•••Oanion hydrogen bonds in crystal structures,9,10 or are prone to undergo proton transfer to generate SO 2– ion,114 both of which would facilitate the electrostatic contacts with the HB donors due to the pronounced and unitary negative charge density. As a consequence, these competitive processes make co-crystallization of host-guest complexes involving HSO –4 a significant challenge. A search for structures involving monomeric, pristine HSO –4 anion in the Cambridge Structural Database (CSD) reveals that numerous HSO –4 co-crystals have been engineered/reported. Most of these examples are single component systems with undefined 69 or ill-defined binding cavities, in which HSO –4 ions act as solvates to bridge the host molecules; thus, the limited coordinations to the anion found in these complexes likely result from crystal packing (Table B.1). Our studies have demonstrated that arylethynyl-based bis-urea derivatives provide a preorganized, attractive binding pocket for spherical halide anions.12 By modifying the number of urea donors and incorporating different aryl cores, the obtained tripodal13 and bipodal14 receptors effectively increase their selectivity for nitrate and dihydrogen phosphate binding, respectively. In our recent effort in developing novel fluorescent phosphorus- and nitrogen-containing (PN) heterocycles,15 we found that the cis-configured phosphonamidate motif exhibits extremely strong self-dimerization through self- complementary N–H and P=O HB donor/acceptor interactions (Figure 3.1a).16 Notably, the chiral phosphonyl group in this molecular system not only increases the HB acidity of the N@H but also functions as a strong hydrogen-bond-accepting17,18 subunit. This in turn confers higher affinities for anion recognition, especially for acidic anions like HSO –4 , than the commonly-used amide functionality. Figure 3.1 a) Structure of the PN‐heterocycle homodimer linked by self‐complementary hydrogen bonds. b) Structure of receptors 1 studied in this work. The relevant protons are marked to assign NMR peaks. 70 More importantly, the electrostatic and geometric complementarity between the non- planar alignment of the highly polarized P=O and acidic N–H moieties and HSO –4 anion suggest this unusual phosphonamidate could be a selective scaffold for HSO –4 anion- binding. Herein, we report the design and synthesis of two hybrid receptors 1 (Figure 3.1b) combining PN-heterocycle and urea units within an acyclic arylethynyl framework. Based on solution phase and solid-state analysis, in combination with DFT calculations, the precise spatial arrangement of HB binding sites (C–H, N–H, and P=O) in the structures are responsible for the observed high selectivity and affinity towards HSO –4 anion over halides and other oxyanions. 3.2 Results and Discussion Receptors 1 were readily prepared based on the strategies utilized for related aryl- acetylene hosts in a stepwise manner (see Experimental Section) and their structures were confirmed by NMR and high-resolution mass spectra. The assignments for relevant protons (see Figure 3.1b) were inferred based on the corresponding 1H-13C HSQC and 1H-1H NOESY experiments (Figures B.5–B.10). Single crystals of 1a and 1b were grown by slow evaporation of CH2Cl2/MeOH and CHCl3/DMSO solutions, respectively, which unambiguously confirmed the structures of the anticipated host systems (Figures B.1 and B.2).19 The solid-state structures provide insight into the HB-accepting and -donating capabilities of the PN heterocycle and suggest the aromatic C–H bonds in the phenyl core could contribute HB interactions as well. To probe the anion-binding properties of the receptors, 1H NMR spectroscopic studies were initially performed in 9:1 [D6]DMSO/CDCl 203. Upon addition of 10 equiv. of the tetrabutylammonium (TBA) salts of HSO –4 , Cl –, Br–, I–, NO –3 , as well as ClO – 4 anion (which are common interfering ions in 71 acidic media) to receptor 1a, significant downfield shifts were observed for the proton signals of the urea N-Hd resonances in the cases of HSO –4 and halides (Figure B.11). In contrast, subtle and negligible changes in the NMR spectra were found for I– and ClO –4 , suggesting weak and no interactions, respectively. Quantitative NMR titration studies were then performed and the resulting binding isotherms were fit to a 1:1 binding model using a global fitting method to provide the binding constants (Ka) in Table 3.1. Comparison of the anion binding affinities in Table 3.1 revealed that both 1a and 1b show impressive HSO –4 selectivity over halides and other oxoanions. The NO2-substituted variant 1b, compared to 1a, exhibited nearly seven-fold higher binding strength with enhanced HSO –4 selectivity. Binding of the halides to both receptors appears to be driven largely by the size/negative charge densities of the anions with Ka values decreasing in accord with the Hofmeister order of Cl– >Br– > I–. Notably, the trigonal-planar anion NO –3 is bound weakly by both receptors. Table 3.1 Association constantsa (Ka, M −1) of receptors 1 with various anions in 10 vol% [D6]DMSO/CDCl3 at 298 K 1a RAb 1b RAc HSO −4 1420 (1480) 1 9600 1 (10 500) NO −3 40 (30) 0.028 105 0.011 (100) Cl− 200 0.14 260 0.027 Br− 30 0.021 75 0.008 I− –d 0 20 0.002 ClO −4 – d 0 –d 0 a 1:1 binding fit. All reported association constants represent the average value from triplicate titrations. The values derived from 31P NMR titrations are given in parentheses. Uncertainties are less than 15 %. All anions were used as TBA salts. b RA=relative affinity. Relative to the 1H NMR titration derived Ka for 1a⋅HSO −4 . c Relative to the 1H NMR titration derived K − da for 1b⋅HSO4 . No binding or too weak to be quantified. 72 Inspection of the 1H NMR spectra of the complexes provides useful information indicative of the coordination modes of 1b with the different anions. As expected, all urea protons Hc and Hd showed anion-binding induced downfield shifts in varying degrees during titrations (Figure 3.2). The 1H NMR spectrum of 1b with HSO –4 displayed a significant downfield shift of the phosphonamidate Ha resonance (Δδ = +1.72 ppm). In addition, the signal attributed to the inner aromatic proton (Hb) moved considerably to the downfield region as well (Δδ = +0.96ppm), together with another C–H proton (He) of the nitrophenyl of the urea “arm” (Δδ = ca.+0.28ppm). It is worth noting that the other two magnetically non-equivalent proton signals belonging to the central nitrophenyl core were upfield shifted and eventually merged, which might be related to a dramatic conformational rearrangement to reorganize the two “arms” of 1b upon the encapsulation of HSO –4 . These observations suggested that HSO –4 anion was directly included within the proposed cavity of hybrid receptor 1b via the complementary HB interactions. Figure 3.2 Partial 1H NMR spectra of 1b (1.13 mm) in 10 vol% [D6]DMSO/CDCl3 in a) the absence and b) the presence of 10 equiv. hydrogen sulfate, c) nitrate, d) chloride, e) bromide, and f) iodide. All anions were used as their respective TBA salts. The two meta‐ protons with respect to Hb on the central nitrophenyl core are marked with (*). 73 In contrast, a much smaller shift for Ha (Δδ = +0.35 ppm) was detected in the case of NO –3 , indicating the phosphonamidate N–H proton also contributes to the guest complexation but to a lesser extent compared to HSO –4 . In addition, the small downfield shift for Hb suggested the aryl C–H hydrogen bond unit might not actively participate in complexation. Presumably, the trigonal-planar NO –3 anion loosely bridges the two arms of the receptor via favorable HB interactions among the phosphonamidate and urea N–H subunits to form a two-site binding mode due to the constrained binding cavity, as indicated by the DFT modeling (see Appendix B). The Cl–/Br– additions elicited little to no shifting of Ha, while considerable Δδ of 0.77 and 0.25 ppm occurred for the proton Hb, respectively. This implies that the smaller spherical halides are binding primarily in the vicinity of the urea cleft containing additional aromatic C–H hydrogen bond donor flanked by the central nitrophenyl core; thus, the low affinities observed for nitrate and the halides can be explained in terms of less hydrogen bonding complementarity and spatial fit toward the receptor, since all binding sites of 1b are not fully utilized and the electronegative P=O binding unit may preclude the effective coordination for non-protic anions. Additionally, 1H NMR competition experiments of receptor 1b and HSO –4 with NO3 – or Cl– anions were also performed (Figure B.43). The observed guest displacements between HSO4– and the competing anions demonstrate that receptor 1b has a definitive binding preference for HSO –4 . With regard to host 1a, similar magnitudes of downfield shifts were also observed for the urea protons for nitrate and halide anions, whereas only very small downfield perturbations were observed for the protons Hb with the exception of HSO –4 anion. Although the entropic contribution to binding cannot be neglected, the deletion or 74 deactivation of the C–H HB element seems to cause a large loss of all investigated anion affinities, and this effect is even more pronounced in the case of HSO4–, as shown by the association constants for 1 given in Table 3.1. Gratifyingly, single crystals of the 1b•HSO –4 complex were obtained by diffusing n- pentane into a DMSO/CHCl3 solution of receptor 1b containing an excess of TBAHSO . 19 4 The resulting structure shows that the receptor adopts a twisted “U” shape conformation in which one HSO – 4 anion is nicely trapped inside the binding pocket of 1b (Figure 3.3a). Within this solid-state structure, the distance between the oxygen atom in the P=O moiety and the oxygen atom in the HSO –4 anion is 2.569 Å, and the N(H a)•••O distance is 2.779 Å. These extremely short atomic distances engaged in HBs11 indicate that the polarized P=O and acidic N–Ha units strongly attract the anion. Apparent triple N–H•••O hydrogen bonds between the urea motif and guest and two cooperative C(Hb)•••O and C(He)•••O interactions (3.177 and 3.096 Å, respectively) are also observed; thus, this overall structure is stabilized by seven intramolecular hydrogen bonds within the HSO –4 anion (as well as the electrostatic interaction with a single TBA+ countercation), corroborating the results observed in solution and fulfilling our expectation that the phosphonamidate domain is involved in the binding via the formation of hetero-complementary hydrogen bonds. To the best of our knowledge, host 1b is the only organic molecule reported to date that shows heptacoordination of a prototypic hydrogen sulfate ion by a single anion receptor, which can apparently be ascribed to the tight binding and ideal topological complementarity between the hybrid arylethynyl host and HSO –4 . Additionally, the anion interacts with an adjacent receptor via two very weak intermolecular C–H•••O contacts to provide a weak 75 dimeric complex with pseudo-2:2 stoichiometry, which likely results from crystal packing effects (Figure B.4). Figure 3.3 a) X‐ray structure of 1b⋅HSO −4 complex; thermal ellipsoids are drawn at the 25% probability level. The TBA cation is omitted for clarity. b) The coordination environment of HSO −4 showing seven hydrogen bonds (indicated by black dotted lines). Hydrogen‐bond parameters (lengths [Å], angles [°]): O1‐H1⋅⋅⋅O2: 1.63(6), 174(5), [O1⋅⋅⋅O2: 2.569(4)]; N1‐Ha⋅⋅⋅O3: 1.82(4), 149(5), [N1⋅⋅⋅O3: 2.779(4)]; C1‐Hb⋅⋅⋅O3: 2.312, 151.2, [C1⋅⋅⋅O3: 3.177]; N2‐Hc⋅⋅⋅O4: 1.82(3), 159(4), [N2⋅⋅⋅O4: 2.834(5)]; N3‐Hd⋅⋅⋅O4: 2.44(3), 139(3), [N3⋅⋅⋅O4: 3.307(6)]; N3‐Hd⋅⋅⋅O5: 2.15(3), 155(3), [N3⋅⋅⋅O5: 3.130(6)]; C6‐He⋅⋅⋅O5: 2.26, 146.3, [C6⋅⋅⋅O5: 3.096(7)]. S−O bond lengths [Å] within the HSO −4 anion: S1⋅⋅⋅O2: 1.565(3), S1⋅⋅⋅O3: 1.425(3), S1⋅⋅⋅O4: 1.436(3), S1⋅⋅⋅O5: 1.429(4). Selected atomic distances [Å]: C2⋅⋅⋅O3: 3.494; C3⋅⋅⋅O3: 3.366; C4⋅⋅⋅O4: 3.501; C5⋅⋅⋅O4: 3.472. To confirm that the P=O•••(H–O)anion hydrogen bonding observed in the solid state is retained in solution, 31P NMR measurements were performed under the same conditions on both receptors. Upon addition of TBAHSO4 to receptor 1a, the 31P signal underwent a significant downfield shift (Δδ ≈ + 3 ppm) due to the deshielding effect exerted by HSO –4 coordination to the electronegative oxygen atom of the P=O group. In contrast, small upfield signal perturbations (Δδ ≈ –0.16 ppm) were observed upon the addition of TBANO3. This reverse signal shifting is most likely due to anion-induced polarization of the N–Ha bond involved in the binding, with a concomitant increase in the electron density of the N atom sensed by the neighboring P atom. In the case of the halides, no detectable or negligible chemical shift of the 31P nucleus signal was observed for either 1a or 1b. The phosphorus NMR experiments corroborated that the P=O domain of PN heterocycle served 76 as a HB acceptor for protic anion binding and demonstrated that the PN heterocyclic framework plays an important role in the superior affinity of 1 for the HSO –4 ion over the other anions. Binding constants of the two receptors for HSO –4 and NO – 3 based on 31P NMR analysis are also given in Table 3.1 and are in good agreement with those obtained by 1H NMR titration. To further understand the interactions and structural aspects of the anionic complex, DFT calculations at the M06-2X/def2-TZVPP computational level were performed based on the geometry of the crystalline complex, where all H atoms were pre-optimized. The calculated electrostatic potential (VS) of free host 1b reveals that the preorganized cavity of the receptor possesses both electronegative and electropositive character (Figure B.50). On the basis of atoms in molecules (AIM) theory,21 the topological analysis of the electron density distinctly shows the bond critical points (BCPs) and the bond paths corresponding to those intermolecular interactions within the binary complex (Figure 3.4a). Figure 3.4 a) Snapshot showing the bond paths and BCPs for 1 b⋅HSO −4 complex based on AIM analysis. Red dots indicate BCPs, and blue dotted lines denote bond paths. Values of electron density ρ(r) are given for the relevant BCPs (in a.u.). b) Snapshot showing the NCI plot for 1 b⋅HSO −4 complex. NCI regions are represented as solid surfaces and blue‐ green‐red scaling from −0.02 < sign(λ2)ρ(r) < 0.02 (in a.u.), where red surface indicates strong repulsion, blue surface strong attraction and green surface relatively weak interactions. Isosurface cutoff for NCI=0.5. The arrows in the Figure indicate the green isosurfaces existing between anion and alkyne moieties 77 The electron density ρ(r) of P=O•••(H–O)anion as well as N–Ha•••O interactions were calculated to be 0.056 and 0.035 a.u., respectively, which are beyond the proposed range of hydrogen bond criteria (>0.034 a.u.),22 suggesting unconventionally strong HB interactions. The degree of covalency of the intermolecular HB interactions within the complex were evaluated using Wiberg Bond Indices (WBI),23 and the two higher values (0.07 and 0.05) were attributed to the P=O•••(H–O)anion and N–Ha•••O interactions, respectively (Table B.3). These computational results suggest that the interactions between phosphonamidate and guest are the dominant element in the binding events, which may partly explain the significantly greater affinities of 1 observed for HSO –4 anion. In addition, two BCPs with very small ρ(r) were observed between the oxygen atoms in the HSO –4 anion and alkyne units (i.e., C2-C3•••O3 and C4-C5•••O4 in Figure 3.3b), suggesting the existence of weak intermolecular interactions. Considering the appropriate atomic distances (3.366 to 3.501 Å) and the p-electron deficient character of acetylene units, these interactions could be suggestive of “anion-π”-type interactions.13 Indeed, the shapes and sizes of the NCI (noncovalent interaction) isosurfaces clearly indicate there are at least dispersive forces (van der Waals interactions) between the anion and the acetylene inner edges (Figure 3.4b). As receptors 1a/1b are immiscible with water and have appreciable solubility in organic solvents, we next explored the extraction behavior of 1b toward HSO –4 via liquid–liquid extraction (LLE) experiments. A 2M NaHSO4 or 2M H2SO4 aqueous solution (as the sources of HSO –4 ) containing TBANO3 (10 mm, as a cation exchanger) was layered onto a solution of 1b (10 mm) in CDCl3. The two non-miscible layers were thoroughly mixed for 30 min and allowed to settle, during which time the two layers separated and the CDCl3 78 phase was analyzed by 1H/31P NMR spectroscopy. According to the comparison experiments, the obtained spectra from the extraction experiments indicate that nearly equimolar amounts (vs. 1b) of TBAHSO4 were transferred from aqueous solution into the organic phase (Figure B.45). The apparent extraction efficiencies for a single extraction were estimated to be ca. 100% and 92% in the cases of NaHSO4 and H2SO4, respectively. In contrast, only trace amounts of HSO –4 were extracted into the CDCl3 phase in the absence of receptor (Figure B.47), primarily due to the high hydration energy of HSO –4 . The results demonstrated here are appealing since the hydrogen sulfate anion receptors could be potentially used to achieve direct extraction/removal of SO 2–4 anion from fairly acidic water without adjusting the pH. Notably, the hydrogen sulfate-bound receptor in CDCl3 can be readily returned to its free form by simple water washing, suggesting that 1b can be recycled when serving as an HSO –4 anion extractant. Compared to the extensive and well-established sulfate LLE studies,24 the release of the bound sulfate and recovery of the receptors are often not so feasible. In most cases, the sulfate-sequestering reagents were needed due to the prized strong binding affinities. Thus, the unique and efficient binding- release cycles presented here may be an added advantage for sulfate species biphasic extraction/transportation. 3.3 Conclusion In summary, we have designed receptors containing phosphonamidate and urea motifs for selective recognition of HSO –4 anion in organic solution. The geometrical complementarity in receptor-anion complexes has been unambiguously confirmed by NMR spectroscopy and single crystal X-ray analysis, as well as supported by DFT calculations. We have demonstrated that the phosphonamidate moiety of the PN-heterocycle is an HSO –4 anion 79 selective recognition motif and the cooperation of other H-bond donors can significantly enhance anion binding affinity. Given that this unique scaffold can be readily tailored, these studies point the way to the rational design of promising synthetic receptors capable of transporting/removal of sulfuric acid, HSO –4 salts, and even direct extraction of SO 2– 4 anion in highly acidic aqueous environments. 3.4 Experimental Section General Information. Tetrabutylammonium salts were dried under vacuum and stored in a desiccator over anhydrous CaSO4. All other materials were obtained from TCI-America, Sigma-Aldrich, or Acros and used as received. Reactions were performed under an inert N2 atmosphere in dried glassware. NMR spectra were obtained on an Inova 500 MHz spectrometer (1H: 500.11 MHz, 13C 125.76 MHz, 31P 202.46 MHz) or a Bruker Avance- III-HD 600 MHz (1H: 599.98 MHz, 13C: 150.87 MHz) spectrometer. Chemical shifts (δ) are expressed in ppm using residual non-deuterated solvent present in the bulk deuterated solvent (CDCl : 1H 7.26 ppm, 13C 77.16 ppm; DMSO-d : 13 6 H 2.50 ppm, 13C 39.52 ppm). 31P chemical shifts are reported against 85% H3PO4 (δ 0 ppm) as external reference. Mass spectrometry (m/z) data were acquired using atmospheric solids analysis probe (ASAP). Mixed solvent systems were referenced to the most abundant solvent. All NMR spectra were processed using MestReNova NMR processing software. IR data were collected using the Thermo Fisher Nicolet 6700 FT-IR spectrometer, the vacuum-dried solid samples were prepared by KBr pellet technique. Analytical TLC was carried out on TLC plates (5 × 10 cm with 0.25 mm thickness, silica gel 60 F254, Merck, Darmstadt, Germany) cut from the commercially available aluminum sheets. Aniline 2 and ethynylaniline 6 were synthesized following known procedures.12 80 Scheme 3.1 Synthesis of Iodoheterocycle Coupling Piece 5. Ethynylaniline 3. To an N 122-degassed solution of 4-(tert-butyl)-2-iodoaniline (2, 1.57 g, 5.70 mmol) and 4-ethynylbenzonitrile (0.86 g, 6.83 mmol) in 5:1 (v/v) THF/Et3N (30 mL) were added CuI (53 mg, 0.28 mmol) and Pd(PPh3)2Cl2 (196 mg, 0.28 mmol) at room temperature. The solution was stirred under N2 for 12h, then the reaction mixture was diluted with CH2Cl2 and filtered through a 4 cm pad of silica. The filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel to give 3 (1.29 g, 83%) as a brown solid; Rf = 0.17 (hexanes/EtOAc, 10:1). Mp 108–110 °C. 1H NMR (500 MHz, CDCl3) δ 7.61 (ABm, J = 8.1 Hz, 4H), 7.38 (d, J = 2.3 Hz, 1H), 7.24 (dd, J = 8.5, 2.3 Hz, 1H), 6.70 (d, J = 8.5 Hz, 1H), 4.19 (s, 2H), 1.29 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 145.9, 141.1, 132.1, 131.9, 128.9, 128.5, 128.2, 118.7, 114.6, 111.2, 106.3, 92.8, 91.4, 34.0, 31.4. HRMS (ASAP) m/z calcd for C +19H19N2 [M+H] 275.1548, found 275.1530. Heterocycle 4. To a solution of aniline 3 (1.3 g, 4.74 mmol) in dry pyridine (5 mL) was added triphenylphosphite (1.9 mL, 7 mmol). The reaction flask was sealed and heated to 105 °C for 24 h. After cooling, the volatiles were removed in vacuo. Analytically pure material can be obtained from recrystallization using EtOAc to give 4 (1.20 g, 61%) as a yellow solid; Rf = 0.27 (CH2Cl2/EtOAc, 2:1). Mp > 200 °C. 1H NMR (500 MHz, CDCl3) 81 δ 8.39 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 7.68 (d, J = 38.7 Hz, 1H), 7.38 (dd, J = 8.6, 2.0 Hz, 1H), 7.32 (s, 1H), 7.09 (t, J = 7.6 Hz, 2H), 6.98 (t, J = 7.5 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 1.31 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 150.3 (d, J = 9.0 Hz), 144.5, 143.9 (d, J = 5.0 Hz), 140.6 (d, J = 9.3 Hz), 137.7 (d, J = 2.0 Hz), 132.7, 129.6, 129.3, 128.4 (d, J = 6.4 Hz), 125.1, 121.2 (d, J = 4.1 Hz), 117.3 (d, J = 9.3 Hz), 111.8, 34.3, 31.5. 31P NMR (202 MHz, CDCl3) δ 10.84 (d, J = 39.3 Hz). HRMS (ASAP) m/z calcd for C25H24N2O2P [M+H] + 415.1575, found 415.1588. Iodoheterocycle 5. To a solution of 4 (106 mg, 0.256 mmol) in CH2Cl2 (2 mL) and AcOH (3 mL) was added TFA (0.05 mL). A 1.0 M solution of ICl in CH2Cl2 (0.32 mL) was added dropwise by syringe and the mixture stirred under N2 overnight. The mixture was washed with saturated NaS2O3 (2 × 150 mL) and brine (150 mL), dried (MgSO4) and evaporated. The crude product was purified by chromatography over silica gel (hexanes/CH2Cl2/EtOAc, 3:1:1) to give 5 (74 mg, 54%) as a light yellow solid; Rf = 0.32 (hexanes/CH2Cl2/EtOAc, 3:1:1). Mp > 200 °C. 1H NMR (500 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz, 2H), 7.83 (t, J = 2.1 Hz, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 39.5 Hz, 1H), 7.36 (d, J = 2.1 Hz, 1H), 7.21 (t, J = 7.7 Hz, 2H), 7.09 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 7.9 Hz, 2H), 6.55 (s, 1H), 1.32 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 149.8 (d, J = 9.2 Hz), 146.7, 142.9 (d, J = 4.8 Hz), 139.6 (d, J = 9.7 Hz), 138.4, 137.4, 132.7, 129.8, 128.7, 128.5 (d, J = 6.7 Hz), 125.8, 125.6, 124.5, 121.2 (d, J = 4.1 Hz), 120.3 (d, J = 13.7 Hz), 118.7, 112.2, 87.5 (d, J = 8.9 Hz), 34.4, 31.3. 31P NMR (202 MHz, CDCl3) δ 9.52 (d, J = 39.5 Hz). HRMS (ASAP) m/z calcd for C25H23IN2O2P [M+H] + 541.0542, found 541.0542. 82 Scheme 3.2 Synthesis of Ethynylaniline Coupling Piece 8 and Receptors 1a/1b. Ethynylaniline 7a/7b. To an N2-sparged solution of 1,3-diiodobenzene (for 7a) or 1,3- dibromo-5-nitrobenzene (for 7b) (1.2 equiv.) and terminal acetylene 612a (1.0 equiv.) in THF/Et3N (0.05 M, v/v = 1:1) was added 5 mol% Pd(PPh3)2Cl2 and 5 mol% CuI. The suspension was stirred at room temperature under an N2 atmosphere for 12 h. The reaction mixture was concentrated in vacuo and purified via flash chromatography to give product 7 as a dark orange oil. 7a. Yield: 52%; Rf = 0.47 (hexanes/EtOAc, 5:1). 1H NMR (600 MHz, CDCl3) δ 7.93 (t, J = 1.7 Hz, 1H), 7.67 (dt, J = 8.1, 1.3 Hz, 1H), 7.51 (dt, J = 7.8, 1.3 Hz, 1H), 7.41 (d, J = 2.3 Hz, 1H), 7.23 (dd, J = 8.5, 2.3 Hz, 1H), 7.09 (t, J = 7.8 Hz, 1H), 6.70 (d, J = 8.5 Hz, 1H), 4.19 (s, 2H), 1.32 (s, 9H). 13C NMR (151 MHz, CDCl3) δ 145.6, 140.9, 140.0, 137.1, 130.5, 129.9, 128.8, 127.6, 125.5, 114.5, 106.9, 93.9, 92.5, 88.1, 34.0, 31.5. HRMS (ASAP) m/z calcd for C18H19IN [M+H] + 376.0562, found 376.0555. 7b. Yield: 66%; Rf = 0.12 (hexanes/EtOAc, 10:1). 1H NMR (500 MHz, CDCl3) δ 8.33– 8.31 (m, 2H), 7.99 (d, J = 2.1 Hz, 1H), 7.40 (t, J = 2.1 Hz, 1H), 7.29–7.27 (m, 1H), 6.73 (dd, J = 8.6, 1.7 Hz, 1H), 4.21 (s, 2H), 1.33 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 148.7, 83 146.1, 141.3, 139.6, 129.1, 128.6, 127.0, 125.9, 124.8, 122.8, 114.7, 105.8, 91.2, 90.7, 34.1, 31.5. HRMS (ASAP) m/z calcd for C18H18BrN2O2 [M+H] + 373.0552, found 373.0534. Diethynylaniline 8a/8b. A ~0.1 M solution of the respective 7 (1.0 equiv.) in THF/Et3N (0.05 M, v/v = 1:1) was purged for 15 min with N2 and then TMSA (1.5 equiv.) was added via syringe. After an additional 5 min N2 purging, CuI (0.1 equiv.) and Pd(PPh3)2Cl2 (0.1 equiv.) were added to the reaction mixture. The flask was then purged for an additional 5 min, then sealed and stirred at room temperature under N2 for 12 h. The mixture was concentrated and the residue chromatographed on silica gel (10:1 hexanes/EtOAc) to afford the desired TMS-protected ethynylsilane 8 as a colorless oil. 8a. Yield: 90%; Rf = 0.32 (hexanes/EtOAc, 10:1). 1H NMR (600 MHz, CDCl3) δ 7.68 (t, J = 1.6 Hz, 1H), 7.49 (dt, J = 7.8, 1.4 Hz, 1H), 7.43 (dt, J = 7.8, 1.4 Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.31–7.28 (m, 1H), 7.21 (dd, J = 8.5, 2.3 Hz, 1H), 6.69 (d, J = 8.5 Hz, 1H), 4.17 (s, 2H), 1.31 (s, 9H), 0.29 (s, 9H). 13C NMR (151 MHz, CDCl3) δ 145.5, 140.9, 134.8, 131.4, 131.3, 128.8, 128.4, 127.4, 123.7, 123.5, 114.4, 107.2, 104.2, 95.0, 93.3, 87.2, 33.9, 31.4, 0.0. HRMS (ASAP) m/z calcd for C23H28NSi [M+H] + 346.1991, found 346.1993. 8b. Yield: 80%; Rf = 0.24 (hexanes/EtOAc, 10:1). 1H NMR (500 MHz, CDCl3) δ 8.27– 8.26 (m, 1H), 8.21–8.20 (m, 1H), 7.89–7.88 (m, 1H), 7.37 (d, J = 2.3 Hz, 1H), 7.24 (dd, J = 8.4, 2.3 Hz, 1H), 6.70 (d, J = 8.5 Hz, 1H), 4.18 (s, 2H), 1.30 (s, 9H), 0.28 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 148.2, 146.0, 141.2, 139.9, 129.1, 128.3, 125.7, 125.6, 125.6, 125.3, 114.7, 106.1, 101.7, 98.5, 91.3, 90.2, 34.1, 31.5, 0.2. HRMS (ASAP) m/z calcd for C +23H27N2O2Si [M+H] 391.1842, found 391.1854. Receptor 1a/1b. To a solution of 8 (1.0 equiv.) in MeOH (0.1 M) was added K2CO3 (3.0 equiv.). After stirring the suspension at room temperature for 3 h, the mixture was filtered 84 through a bed of Celite. After evaporation of the solvent, the crude residue was used directly in the next reaction. To an N2-sparged solution of 5 (1.2 equiv.) and the terminal acetylene in THF (0.05 M) was added 5 mol% Pd(PPh3)4 and 5 mol% CuI, followed by the addition of Et3N (1.5 equiv.). The suspension was stirred at room temperature under an N2 atmosphere for 1-2 h (monitored by TLC). The reaction mixture was concentrated in vacuo and purified via flash chromatography to give the desired crude diyne product as dark-orange oil. To a solution of the crude product in dry toluene (0.1 M) was added 4-nitrophenyl isocyanate (1.2 equiv.), and the mixture was stirred at room temperature for 24 h. The reaction was diluted with hexanes and the light yellow precipitate was isolated. The material was redissolved in a minimal amount of DMSO (to remove the insoluble impurities when necessary), and the desired product precipitated as a fine light yellow powder upon the slow addition of EtOH. 1a. Yield: 44%; Rf = 0.34 (hexanes/CH2Cl2/EtOAc, 3:1:1). Mp > 150 °C (dec.). 1H NMR (500 MHz, CDCl3/DMSO-d6, 4/1) δ 9.62 (s, 1H), 8.01 (s, 1H), 7.90–7.87 (m, 3H), 7.76 (t, J = 1.6 Hz, 1H), 7.40–7.37 (m, 2H), 7.66 (d, J = 2.8 Hz, 1H), 7.50 (d, J = 39.2 Hz, 1H), 7.49–7.44 (m, 6H), 7.38 (dt, J = 6.1, 1.7 Hz, 2H), 7.29 (d, J = 2.4 Hz, 1H), 7.19–7.16 (m, 3H), 6.93–6.90 (m, 2H), 6.81–6.78 (m, 1H), 6.72–6.70 (m, 2H), 1.12 (s, 9H), 1.11 (s, 9H). 13C NMR (126 MHz, CDCl3/DMSO-d6, 4/1) δ 151.9, 149.5 (d, J = 9.1 Hz), 145.9, 145.1, 143.7, 142.6, 141.2, 139.5 (d, J = 9.4 Hz), 137.5, 136.8, 134.4, 132.1, 131.6, 131.2 (d, J = 4.8 Hz), 129.1, 128.6, 128.3, 128.2, 127.8 (d, J = 6.5 Hz), 126.6, 124.8, 124.6, 124.1, 123.0, 122.8, 122.4, 120.6 (d, J = 4.1 Hz), 119.4, 118.9 (d, J = 13.9 Hz), 118.2, 117.3, 111.2 (d, J = 6.1 Hz), 110.0 (d, J = 8.8 Hz), 94.9, 93.6, 86.5, 84.4, 33.8, 33.8, 30.8, 30.8. 31P NMR 85 (202 MHz, CDCl3/DMSO-d6, 4/1) δ 9.13 (d, J = 39.0 Hz). IR (KBr) ν (cm –1) 3432, 2960, 2227, 1719, 1597, 1504, 1331, 1203. HRMS (ASAP) m/z calcd for C45H41N3O2P [(M−C +7H5N2O3)+H] 686.2936, found 686.2914. 1b. Yield: 41%; Rf = 0.27 (hexanes/CH2Cl2/EtOAc, 5:2:2). Mp > 150 °C (dec.). 1H NMR (500 MHz, DMSO-d6) δ 11.25 (s, 1H), 9.51 (s, 1H), 9.04 (s, 1H), 8.77 (d, J = 2.2 Hz, 1H), 8.65 (s, 1H), 8.61 (d, J = 2.3 Hz, 1H), 8.18 (d, J = 38.9 Hz), 8.17 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.1 Hz, 2H), 8.01 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.7 Hz, 2H), 7.74 (s, 1H), 7.69 (d, J = 2.3 Hz, 1H), 7.61 (d, J = 2.4 Hz, 1H), 7.48 (dd, J = 8.8, 2.4 Hz, 1H), 7.20 (t, J = 7.7 Hz, 2H), 7.03 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 1.31 (s, 9H), 1.30 (s, 9H). 13C NMR (151 MHz, DMSO-d6) δ 152.1, 150.2 (d, J = 9.2 Hz), 148.0, 146.6, 145.4, 143.3, 143.2 (d, J = 3.6 Hz), 141.0, 140.4, 140.0 (d, J = 9.7 Hz), 138.6, 137.6, 132.8, 132.4, 130.0, 129.7, 129.3, 128.1 (d, J = 6.6 Hz), 127.5, 126.1, 125.9, 125.1, 125.0, 124.5 (d, J = 12.7 Hz), 123.7, 122.6, 121.0 (d, J = 3.9 Hz), 120.5, 119.4 (d, J = 14.8 Hz), 118.8, 117.4, 111.2, 110.7, 109.2 (d, J = 8.6 Hz), 92.7, 92.1, 89.0, 87.8, 34.1, 34.0, 31.0, 30.9. 31P NMR (202 MHz, DMSO-d6) δ 9.05 (d, J = 38.7 Hz). IR (KBr) ν (cm –1) 3442, 2960, 2228, 1711, 1602, 1536, 1331, 1199. HRMS (ASAP) m/z calcd for C45H40N4O4P [(M−C +7H5N2O3)+H] 731.2787, found 731.2765. 86 CHAPTER IV AMPLIFICATION OF THE QUANTUM YIELDS OF 2‑λ5‑PHOSPHAQUINOLIN-2-ONES THROUGH PHOSPHORUS CENTER MODIFICATION This chapter includes previously published and co-authored material from Bard, J.P., Bates, H.J., Deng, C.-L., Zakharov, L.N., Johnson, D.W., Haley, M.M. “Amplification of the Quantum Yields of 2-λ5-Phosphaquinolin-2-ones Through Phosphorus Center Modification.” J. Org. Chem. 2020, 85, 85–91. This work highlights our work on understanding the effects of placing a phenyl group in place of the traditional phenoxy group on the P center of the phosphaquinolinone scaffold. It draws structure-property relationships with both the sumpramolecular and photophysical properties. 4.1 Introduction Small molecule fluorophores are used ubiquitously throughout many different fields, including chemical biology, molecular probe development, and materials for industrial and environmental sensing.1-4 In many of these applications, a fluorophore must exhibit a few characteristics to be considered optimal: large Stokes shift, high brightness, and red-shifted emission. One such example of a molecule that meets these specifications is coumarin (Figure 4.1).5-14 An impressive number of coumarin-containing compounds have been reported throughout the literature that are collected either from in-lab syntheses or by isolation from natural sources.15,16 This scaffold has been the subject of a variety of 87 synthetic modifications, diversification by adding groups onto the backbone, or incorporation of the coumarin system into larger ring networks.17-19 Through these modifications, a tremendous breadth of understanding upon the structure–activity relations has been developed20-24 that have guided the design of many useful derivatives, which have emerged for applications in chemosensing and many other areas.25-31 Figure 4.1 Well-studied coumarin and carbostyril scaffolds (top) compared to phosphaquinolinone analogues (bottom). Alongside the many derivatives of the parent coumarin scaffold, there is the nitrogen-containing structural analogue known as carbostyril (Figure 4.1).32-37 Though not as widely utilized as coumarin, carbostyril is the subject of many structure–property relationship studies, and it shows promise for use in both pharmaceutical discovery and fluorescence imaging applications.38,39 These carbostyril analogues expand on the applications of the coumarin family through modifying the lactone core to a lactam. With further alteration of this core, new applications, functionality, and fluorescent properties are expected from this widely used fluorophore. Recently, we reported a series of phosphorus- and nitrogen-containing (PN) phosphaquinolinone 1 derivatives (Figure 4.1).40,41 This scaffold, which is one of only a handful of similar heterocycles,42-52 is also an isostere to carbostyril and coumarin, with the only difference being the replacement of the lactam carbonyl with an isolobal, chiral 88 phosphorus center. We have performed a variety of structure–property studies that looked at the effects of both acene core modification and substitution at various points on the scaffold.40,41,53-56 In these studies, it was found that the emission wavelength can be moderately red-shifted through careful substitution of various groups on the backbone, affording significant Stokes shifts and modest quantum yields. On the basis of these design principles, this moiety has recently been implemented in a fluorescent receptor for HSO –4 in acidic media, showing promise for future applications of this scaffold that take advantage of both its exceptional hydrogen bonding capabilities and its inherent fluorescence.54 As clearly shown for the coumarin and carbostyril motifs, systematic modification of various structural aspects can lead to very useful derivatives. In our continuing efforts to study the 2-λ5-phosphaquinolin-2-one skeleton, the next facet that we wanted to explore was the variation of the group attached to the phosphorus center. Disclosed herein is the substitution of a phenyl ring in place of the standard phenoxy upon the phosphorus center, generating a racemic mixture of heterocycle 2 (Figure 4.1). We also hypothesize that this would increase the quantum yield through rigidifying the scaffold. With these modifications, the reported compounds could have greater potential for applications in phosphorus-containing chemosensors and fluorophores, expanding on this pre-existing group of molecules.57-65 4.2 Results and Discussion The synthesis of 2 starts from key arylethynylaniline intermediate 3, prepared following previously reported methods.40 Aniline 3 is then reacted with diphenyl phenylphosphonite (PhP(OPh)2) in pyridine at 100 °C. Subsequent hydrolysis in THF at 60 °C furnishes phenyl-appended heterocycles 2 in modest to good yields (Scheme 4.1). 89 1H, 13C, 31P, and 19F NMR spectra were collected for 2 (see Appendix C), which reveal that the direct attachment of the phenyl ring to the phosphorus center not only splits the signals of the phenyl ring (J31 1P, H and J31 13P, C values listed in the Experimental Section) but also affords coupling constants of ca. 30 Hz (3J31 1P, H) for the alkene proton signal. Scheme 4.1 Synthesis of Phosphaquinolinones 2. The photophysical properties of 2a–2f in CHCl3 are shown in Figure 4.2 and are compiled in Table 4.1. All derivatives share a common λmax at ca. 300 nm, and the lowest energy absorption peaks range from 343 to 381 nm. The absorption coefficients for this scaffold stay within the range of 1.5 × 104 (for 2a) to 2.2 × 104 M–1 cm–1 (for 2e and 2f). The λem values range from 447 (for 2a) to 515 nm (for 2f) with Stokes shifts on the order of 6350–7000 cm–1. Interestingly, the emission spectra of 2 show a ca. 20 nm bathochromic shift from those of the analogous congeners of 1,40 and the quantum yields of this scaffold show a dramatic improvement, on the order of a 4–5-fold increase in most cases. Brightness values range from 6.84 × 103 (for 2b) to 1.14 × 104 M–1 cm–1 (for 2a), which are now on par with several optimized coumarin derivatives.66 Fluorescence lifetime measurements were also performed (Figure C.6), and the radiative (kr) and nonradiative (knr) decay rate constants were determined. The kr values range from 0.06 to 0.19 ns–1, and the knr values vary from 0.06 to 0.18 ns –1, showing either equal rates or a slightly larger knr in most cases. 90 Figure 4.2 Absorption (solid lines) and fluorescence (dotted lines) spectra of 2 in CHCl3 at 298 K. Table 4.1. Photophysical Properties and HOMO–LUMO Energy Gaps of Heterocycles 2a λabs (nm)/ε λem (nm)/ Stokes shift τ b kr kn ΔEopt ΔEDFT cmpd (M–1 cm–1) ϕ (%) (cm–1) (ns) (ns–1) (ns–1) (eV) (eV)c 2a 348/15000 447/76 6360 4.1 0.19 0.06 3.19 4.40 2b 343/18000 449/38 6880 3.5 0.11 0.18 3.18 4.43 2c 360/19000 474/43 6680 4.8 0.09 0.12 3.05 4.23 2d 352/18000 467/50 7000 3.9 0.13 0.13 3.15 4.30 2e 360/22000 475/51 6730 4.2 0.12 0.12 3.04 4.21 2f 381/22000 515/35 6830 6.3 0.06 0.10 2.83 3.90 a All values collected in CHCl . b3 Decay curves fitted using a monoexponential fitting model. c Calculated at the PBE0/TZVP level of theory. These values elucidate a potential explanation for the increased quantum yields when compared to similar values of phosphaquinolinones 1.40 For 1, the kr values range from 0.10 to 0.30 ns–1, which show similar values, whereas the knr values vary from 0.30 to 3.0 ns–1, which are substantially faster in most cases. The diminished ratio of knr to kr seen for 2 may suggest that the reduced degrees of freedom may indeed be the cause of the increased quantum yields. 91 To gain further understanding of these experimental results, the frontier orbitals for heterocycles 2 were calculated (Tables 4.1 and C.1–C.7). The narrowest HOMO–LUMO gap is seen for 2f (3.90 eV), and the largest is for 2a (4.40 eV). This trend arises because of a higher magnitude of HOMO destabilization than that of the stabilization of the LUMO with more donating substituents (Table C.1). These values also follow a similar trend to the optical gaps (Tables 4.1 or C.1). TD-DFT was then used to examine the S0 to S1 transition. It was found that the S0 to S1 transition is dominated by the HOMO–LUMO transition (Table C.1). Additionally, the distributions of the HOMOs and LUMOs show a slightly more pronounced separation due to a larger HOMO localization at the phosphorus center (Figure C.4). These observations suggest that π to π* transitions are dominant, but there may be some intramolecular charge transfer (ICT) occurring in the excited state. The emission of 2 was then examined in solvents of varying polarities (Figures C.7–C.13 and Tables C.11–C.16). In these studies, bathochromatic shifting is observed in every case with more polar solvents. Compound 2f showed the greatest shifting, ranging from emission wavelengths of 504 to 531 nm and Stokes shifts of 6070 and 7070 cm–1 in cyclohexane and acetonitrile, respectively. The TD–DFT optimized S1 state near the Franck–Condon geometry of 2f shows that the dihedral angle between the parent core and appended 4-cyanophenyl substituent becomes smaller compared to the ground state (Figure 4.3). Additionally, the C–C bond connecting them is shortened by ca. 0.035 Å. The considerable geometric changes lead to a more conjugated system at the S1 state, in which the HOMO–LUMO energy gap decreases by 0.9 eV (Figure C.5); thus, the computed emission wavelength of 541 nm is 92 within the observed emission maxima (Table 4.1). These computational results could further explain the large Stokes shift for this type of PN-heterocycle. Figure 4.3 Selected bond length and dihedral angle in the optimized S0 and S1 structures of 2f calculated by DFT and TD-DFT methods at the PCM(CHCl3)-PBE0/TZVP level of theory, respectively. In addition to improved fluorescence properties, we were curious to see how phenyl substitution would affect the strength of hydrogen bond dimerization we typically observe for phosphaquinolinones. Variable concentration (VC) NMR experiments were performed in water-saturated CDCl3 to assess the strength of dimerization (Tables 4.2 and C.17–C.21, Figures C.14–C.23). Heterocycles 2 exhibit dimerization strengths of 22 (for 2e and 2f) to 82 M–1 (for 2b). While these values are roughly 70–80% smaller than those measured for the analogous congeners of 1, the strengths of dimerization for 2 again exceed those of many typical head-to-tail hydrogen bonded dimers.67 This result suggests that this new entry into the phosphaquinolinone family can still be implemented in supramolecular systems, as found in 1.54 93 Table 4.2. Dimerization Constants and Energies for 2 cmpd K (M–1dim ) ΔG –1 dim (kcal mol ) 2aa - - 2b 82 –2.6 2c 54 –2.3 2d 24 –1.8 2e 22 –1.8 2f 22 –1.8 a Not determined because of minimal solubility in H2O-saturated CDCl3. Values reported with errors less than 15%. Single crystals suitable for X-ray diffraction were grown by slowly diffusing pentane into a CHCl3 solution of 2f, and the resultant data are shown in Figures 4.4 and C.1–C.3. The structure of 2f still features the typical meso-dimer between racemates (Figure 4.4a); however, the N···O distance in the dimer of 2f (2.874 Å) is longer than those of heterocycles 1 (2.768–2.821 Å),40 which supports the observation that the molecule should form a weaker dimer in the solution-state as well. This weakened hydrogen bonding interaction can potentially be explained by examining the pseudo six-membered ring formed between the monomers. The N···O–P (115.53°), O–P–N (116.66°), and P–N···O (104.57°) angles formed between the participating atoms in the dimer formation show significant deviation from the ideal 120° orientation (Figure 4.4b), likely caused by the large O–P–N–H torsional angle of 55.35° (Figure 4.4c). With an angle so much larger than the analogous angle found in the crystal structures of several derivatives of 1 (ca. 30– 40°),40 there is a less ideal orientation for the two monomers to associate, slightly weakening the interaction overall. By comparing optimized geometries of the meso-dimer of 2f and its −OPh analogue, there are some additional steric clashes in 2f among the C–H atoms in the phenyl ring and N–H moieties, according to the noncovalent interactions 94 (NCI) plot (Figure C.24). Moreover, the natural bond orbital (NBO) analyses predict a total contribution of the n → σ * interactions of 23.1 kcal mol–1O NH for 2f and 25.0 kcal mol –1 for the respective −OPh analogue (Figure C.25). Therefore, the strength of dimerization may decrease to some degree due to the weaker primary hydrogen bonding and extra steric hindrance, in agreement with the observed diminished Kdim for 2. Figure 4.4 a) Characteristic PN-heterocycle dimer for 2f with the O···N distance (Å) shown as well as b) bond angles and c) torsional angles formed within monomers upon dimerization. Ellipsoids drawn at 30% probability. 4.3 Conclusion In summary, we have shown the effects of the attachment of a phenyl group on the phosphorus center of the phosphaquinolinone scaffold. This new class of PN-heterocycles not only has large Stokes shift values (up to 7000 cm–1) but also shows a marked 4–5-fold increase in the quantum yield when compared to previously reported phenoxy-substituted compounds. Additionally, this modification retains the strong dimerization strengths of the scaffold in both the solid and solution states. This new modification deepens the fundamental understanding of the phosphaquinolinone scaffold and allows for further 95 possibilities in the applications of this scaffold as a biologically or industrially relevant fluorophore, like the coumarin and carbostyril scaffolds. 4.4 Experimental Section General All air- or water-free reactions were performed under a N2 atmosphere using Schlenk techniques. Column chromatography was performed using silica gel (240–300 mesh), with solvent systems being referenced to the most abundant solvent. NMR spectra were acquired at room temperature on a Varian Inova 500 instrument (1H: 500 MHz, 13C: 126 MHz, 19F: 471 MHz, 31P: 202 MHz) or a Bruker Avance III HD 500 apparatus equipped with a Prodigy multinuclear cryoprobe (1H: 500 MHz, 13C: 126 MHz). 1H and 13C chemical shifts (δ) are expressed in parts per million (ppm) relative to residual CHCl3 shifts (1H: 7.26 ppm, 13C: 77.16 ppm) or residual DMSO shifts (1H: 2.50 ppm, 13C: 39.52 ppm). 31P and 19F NMR spectra are referenced to 85% H3PO4 (δ 0 ppm) and to CFCl3 (δ 0 ppm), respectively, as the external standards. UV–vis spectra were recorded using an Agilent Technologies Cary 60 UV–vis spectrophotometer in HPLC-grade CHCl3. Fluorescence emission spectra were recorded using a Horiba Jobin Yvon FluoroMax-4 fluorimeter exciting at 365 nm. Quantum yields (ϕ) were determined through a comparison of the emission and absorption intensities of the analyte to that of a 0.1 M H2SO4/quinine sulfate solution.68 Fluorescence lifetime measurements were recorded using a Horiba FluoroHub Single Photon Counting Controller with a TemPro Fluorescence Lifetime System attachment. High-resolution mass spectra (HRMS) were recorded on a Waters XEVO G2-XS mass spectrometer. 2-Ethynylanilines 3a–3f40 and phenyl diphenylphosphonite (PhP(OPh)2) 69 were prepared as previously described. 96 General Synthetic Procedure for Phosphaquinolinone 2 2-Ethynylaniline3 (1.0 equiv.) and PhP(OPh)2 (2.0 equiv.) were dissolved in pyridine (ca. 0.35 M). The vessel was sealed and heated to 100 °C for 24 h in an oil bath. The mixture was then diluted with toluene, and the solvent was removed in vacuo. This was repeated three times to remove all residual pyridine. The crude material was dissolved in THF, and ca. five drops of water were added. The solution was stirred at 60 °C for 1 h before being dried (Na2SO4), filtered, and concentrated in vacuo. The crude mixture was then purified by column chromatography on silica gel. Reported yields are given for >95% pure material (by 1H NMR spectroscopy), though subsequent recrystallization from hexanes and CH2Cl2 was used to achieve analytically pure material. Phosphaquinolinone 2a Compound 2a was synthesized from 3a (462 mg, 1.9 mmol, 1 equiv.) and PhP(OPh)2 (1.11 g, 3.8 mmol, 2 equiv.). Column chromatography (1:1 EtOAc:CH2Cl2, Rf = 0.20) gave 2a (149 mg, 21%) as a pale brown solid: mp > 250 °C; 1H NMR (500 MHz, DMSO-d6) δ 10.28 (d, J = 3.8 Hz, 1H), 8.14 (d, J = 2.0 Hz, 1H), 8.05 (d, J = 30.1 Hz, 1H), 7.82 (ABm, J = 8.4 Hz, 4H), 7.81–7.77 (m, 1H), 7.69–7.64 (m, 2H), 7.58–7.51 (m, 1H), 7.49–7.43 (m, 2H), 7.21 (d, J = 8.5 Hz, 1H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 143.1 (d, J = 3.8 Hz), 140.9 (d, J = 11.7 Hz), 139.3, 135.8, 133.8, 132.6, 132.5 (d, J = 2.7 Hz), 132.4 (d, J = 137.0 Hz), 132.2 (d, J = 10.8 Hz), 128.6 (d, J = 13.2 Hz), 128.1 (d, J = 6.1 Hz), 126.9 (d, J = 115.9 Hz), 119.2, 119.0 (d, J = 9.9 Hz), 118.5, 117.7 (d, J = 8.1 Hz), 110.6, 102.1; 31P{1H} NMR (202 MHz, DMSO-d6) δ 7.77; HRMS (ASAP) [M + H] + calcd for C22H15N3OP 368.0953, found 368.0977. Phosphaquinolinone 2b 97 Compound 2b was synthesized from 3b (700 mg, 2.4 mmol, 1 equiv.) and PhP(OPh)2 (1.40 g, 4.8 mmol, 2 equiv.). Recrystallization from CH2Cl2 and hexanes gave 2b (580 mg, 58%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, DMSO-d6) δ 10.14 (d, J = 4.1 Hz, 1H), 8.16 (d, J = 30.1 Hz, 1H), 8.06 (d, J = 2.2 Hz, 1H), 7.85 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.73–7.63 (m, 3H), 7.53 (td, J = 7.4, 1.5 Hz, 1H), 7.49–7.43 (m, 2H), 7.25 (d, J = 8.5 Hz, 1H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 142.5 (d, J = 3.7 Hz), 141.1 (d, J = 12.0 Hz), 139.9, 132.7 (d, J = 136.9 Hz), 132.6, 132.4 (d, J = 2.7 Hz), 132.2 (d, J = 10.7 Hz), 130.5, 128.5 (d, J = 13.2 Hz), 128.1 (d, J = 6.1 Hz), 127.4 (d, J = 3.7 Hz), 126.5 (d, J = 116.3 Hz), 124.5 (q, J = 271.2 Hz), 120.6 (q, J = 32.3 Hz), 118.6 (d, J = 13.0 Hz), 118.5, 117.4 (d, J = 7.9 Hz), 110.5; 31P{1H} NMR (202 MHz, DMSO-d6) δ 7.86; 19F NMR (471 MHz, DMSO-d6) δ −59.92; HRMS (ASAP) [M + H] + calcd for C22H15N2OF3P 411.0874, found 411.0909. Phosphaquinolinone 2c Compound 2c was synthesized from 3c (645 mg, 2.6 mmol, 1 equiv.) and PhP(OPh)2 (1.5 g, 5.1 mmol, 2 equiv.). Column chromatography (1:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.10) followed by two rounds of recrystallization from CH2Cl2 and hexanes gave 2c (300 mg, 31%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, DMSO-d6) δ 9.80 (d, J = 4.2 Hz, 1H), 7.99 (d, J = 29.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 2.5 Hz, 1H), 7.69–7.57 (m, 2H), 7.56–7.49 (m, 1H), 7.48–7.38 (m, 3H), 7.11 (d, J = 8.7 Hz, 1H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 141.3 (d, J = 12.0 Hz), 139.4, 138.3 (d, J = 3.7 Hz), 132.8 (d, J = 136.6 Hz), 132.5, 132.3, 132.2, 130.7, 129.9, 128.5 (d, J = 13.1 Hz), 128.1 (d, J = 6.2 Hz), 126.5 (d, J = 116.8 Hz), 123.6, 120.2 (d, J = 12.6 Hz), 98 118.6, 118.4 (d, J = 8.1 Hz), 110.3; 31P{1H} NMR (202 MHz, DMSO-d6) δ 7.69; HRMS (ASAP) [M + H]+ calcd for C21H15N2OPCl 377.0611, found 377.0641. Phosphaquinolinone 2d Compound 2d was synthesized from 3d (151 mg, 0.69 mmol, 1 equiv.) and PhP(OPh)2 (463 mg, 1.4 mmol, 2 equiv.). Column chromatography (1:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.20) gave 2d (144 mg 61%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 30.4 Hz, 1H), 7.71–7.66 (m, 2H), 7.54 (d, J = 8.2 Hz, 2H), 7.47–7.42 (m, 2H), 7.38–7.32 (m, 3H), 7.06 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.83 (br s, 1H); 13C{1H} NMR (126 MHz, CDCl3) δ 141.5 (d, J = 11.8 Hz), 141.0 (d, J = 3.0 Hz), 138.8 (d, J = 4.3 Hz), 132.7 (d, J = 10.8 Hz), 132.6 (d, J = 2.8 Hz), 132.5, 132.2 (d, J = 139.3 Hz), 131.5, 131.2, 128.6 (d, J = 13.8 Hz), 128.4 (d, J = 6.2 Hz), 126.0 (d, J = 119.5 Hz), 121.4, 119.4 (d, J = 12.1 Hz), 118.8, 117.3 (d, J = 7.7 Hz), 111.6; 31P{1H} NMR (202 MHz, CDCl3) δ 10.52; HRMS (ASAP) [M + H] + calcd for C21H16N2OP 343.1000, found 343.1030. Phosphaquinolinone 2e Compound 2e was synthesized from 3e (549 mg, 2.0 mmol, 1 equiv.) and PhP(OPh)2 (1.3 g, 4.0 mmol, 2 equiv.). Column chromatography (1:1:1 EtOAc:CH2Cl2, Rf = 0.25) gave 2e (520 mg, 65%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 2H), 7.72–7.67 (m, 2H), 7.68 (d, J = 30.3 Hz, 1H), 7.53 (d, J = 8.1 Hz, 2H), 7.48– 7.39 (m, 3H), 7.37–7.32 (m, 2H), 6.90 (d, J = 8.4 Hz, 1H), 6.48 (br s, 1H), 1.35 (s, 9H); 13C{1H} NMR (126 MHz, CDCl3) δ 144.4, 141.7 (d, J = 12.1 Hz), 141.5, 136.4, 132.7 (d, J = 10.8 Hz), 132.5, 132.5, 132.4 (d, J = 139.2 Hz), 129.1, 128.5 (d, J = 13.6 Hz), 128.4 (d, J = 6.4 Hz), 127.6, 125.8 (d, J = 119.9 Hz), 119.0, 118.9 (d, J = 8.4 Hz), 116.9 (d, J = 99 7.3 Hz), 111.4, 34.4, 31.5; 31P{1H} NMR (202 MHz, CDCl3) δ 10.44; HRMS (ASAP) [M + H]+ calcd for C25H24N2OP 399.1628, found 399.1629. Phosphaquinolinone 2f Compound 2f was synthesized from 3f (430 mg, 1.7 mmol, 1 equiv.) and PhP(OPh)2 (969 g, 3.3 mmol, 2 equiv.). Column chromatography (1:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.25) gave 2f (200 mg, 31%) as a pale yellow solid: mp > 250 °C; 1H NMR (500 MHz, CDCl3) δ 7.73–7.65 (m, 2H), 7.71 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 30.4 Hz, 1H), 7.53 (d, J = 8.2 Hz, 2H), 7.47–7.42 (m, 1H), 7.37–7.31 (m, 2H), 6.98–6.93 (m, 2H), 6.88 (d, J = 8.5 Hz, 1H), 6.60 (br s, 1H), 4.04 (q, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 153.5, 141.6 (d, J = 12.0 Hz), 140.7, 132.8 (d, J = 10.7 Hz), 132.7, 132.6 (d, J = 3.0 Hz), 132.5, 132.1 (d, J = 140.4 Hz), 128.5 (d, J = 13.8 Hz), 128.4 (d, J = 6.4 Hz), 126.7 (d, J = 119.9 Hz), 119.9, 119.8 (d, J = 11.8 Hz), 118.8, 118.2 (d, J = 7.7 Hz), 114.8, 111.5, 64.3, 15.0; 31P{1H} NMR (202 MHz, CDCl3) δ 10.51; HRMS (ASAP) [M + H]+ calcd for C23H20N2O2P 387.1261, found 387.1283. 100 CHAPTER V A HIGHLY FLUORESCENT PN-HETEROCYCLE-FUSED PYRENE DERIVATIVE WITH STRONG SELF-DIMERISATION THROUGH HYDROGEN BONDING This chapter includes previously published and co-authored material from Bard, J.P., Mancuso, J.L., Deng, C.-L., Zakharov, L.N., Johnson, D.W., Haley, M.M. “A Highly Fluorescent PN-heterocycle-fused Pyrene Derivative with Strong Self-dimerization through Hydrogen Bonding.” Supramol. Chem. 2020, 32, 49–55. This story details our synthesis and analysis of a PN-fused pyrene derivative. Interesting photophysical and supramolecular characteristics based upon the unique scaffold are detailed. 5.1 Introduction The pyrene moiety is a popular moiety in organic electronic devices because of its good hole transporting ability and excellent chemical stability.1–3 Additionally, it is inherently fluorescent and, like many polycyclic arene systems, is subject to fluorescence quenching at higher concentrations due to the formation of π–π stacked excimers.4–9 This feature provides access to switchable fluorescent behavior in the presence of analytes such as metals and anions, given appropriate molecular design.10–12 These hosts typically function through adjacent hydrogen bonding sites that coordinate with the guest and either promote or diminish intermolecular pyrene excimer formation. Similar structures featuring pyrene also exhibit switchable emission depending on environmental conditions, including 101 pressure,13 pH,14 and temperature.15 Further development of hydrogen bonding frameworks containing pyrene will enrich the library of high quantum yield hosts, while potentially providing additional fundamental insight into the complex excited state dynamics of this very interesting class of hosts. Recently, there have been several reported phosphorus- and nitrogen-containing (PN) “phosphaquinolinone” scaffolds.16–19 These molecules are members of a small family of similar PN-heterocycles,20-31 and have shown promise as hydrogen bonding fluorophores.32 One tunable parameter of these fluorescent scaffolds is the effect of increasing conjugation length of the aromatic backbones, seen with naphthalene-,16,17 anthracene-,33 and phenanthrene-like18 phosphaquinolinone structures (Figure 5.1). Ar Ar Ar P X P OPh P OPh N N N H O H O H O X = OPh or Ph Naphthalene-like Anthracene-like Phenanthrene-like Ar NH N P O P O OPh Ph R Previously Reported PN-Pyrene Scaffold 1 Target PN-Pyrene 2 Me Figure 5.1 Previously reported phosphaquinolinone scaffolds as well as new PN-fused pyrene 2. One family of particular interest is the pyrene-containing derivatives 1.19 These molecules showed a dramatic improvement in the photophysical properties compared to the parent pyrene scaffold. The increased conjugation of the arene backbone and functionalization of the phosphorus center with a phenyl group rather than the traditional phenoxy group led to not only increased quantum yields and red-shifted emissions, but also increased Stokes shifts. Though 1 holds promise for use in organic electronics, the 102 phosphaquinolinone hydrogen responsible for forming the characteristic, strong meso- dimers between enantiomers is absent due to the creation of a pyrrole motif subsequent to the formation of the phosphaquinolinone ring. Additionally, the typical pyrene excimer formation was suppressed in 1, which leads to higher quantum efficiencies, yet depletes its capacity as a switchable host molecule. Here we report the new PN-heterocycle-fused pyrene derivative 2, which retains the hydrogen bonding capabilities of the phosphaquinolinone moiety. Compound 2 couples superior fluorescent performance with the potential for supramolecular activity in a dynamic, responsive host. 5.2 Results and Discussion Synthesis of 2 begins with Sonogashira cross-coupling of nitrotriflate 319 with 4- ethynyltoluene to afford nitropyrene 4, which is then reduced to amine 5 with Zn in AcOH and EtOAc (Scheme 5.1). Finally, aminopyrene 5 is cyclized with P(OPh)3 in pyridine and subsequently hydrolyzed in THF at 60 °C for 1 h to afford heterocycle 2 in modest yield. 1H, 13C, and 31P NMR spectra were obtained, which showed the standard PN compound splitting of ~40 Hz for both the isolated alkene 1H and 31P NMR signals (See Appendix D). Me NO Pd(PPh ) Cl 23 2 2 Zn, AcOH NO2 CuI, THF, NEt3 EtOAc OTf 77% 55% 3 4 Me NH2 1. P(OPh) NH3 O pyr, 100 °C P OPh 2. THF, H2O 60 °C, 1 h 28% 5 2 Me Me Scheme 5.1 Synthesis of PN-pyrene 2. 103 Figure 5.2 X-ray crystal structure of 2 showing both pyrene π–π stacking and phosphonamidate dimer distances; ellipsoids drawn at 30% probability. Slow layering of pentane into a CHCl3 solution of 2 was used to grow single crystals suitable for x-ray diffraction; the resultant crystal structure is shown in Figure 5.2. Arguably, the two most critical aspects of the structure are the familiar PN dimerization and pyrene π–π stacking. The PN dimer distance is 2.812(2) Å, as measured by the O…N distance between P(O) and NH hydrogen bonding pairs of adjacent molecules, and is within the range of dimer distances of previously reported phosphaquinolinone structures (2.805–2.875 Å).16-18,33 Further, the pyrene moieties exhibit the typical slip-stacked face- to-face packing, with a distance of 3.591 Å between the two mean planes of each pyrene, which is similar to the packing of the previously reported anthracene-like phosphaquinolinone.33 One key difference is the near co-planarity between the pendant tolyl group and pyrene core with a dihedral angle of only 7.4°, which is smaller than the angle in previously reported phosphaquinolinone heterocycles (dihedral angles 16-46°).16- 104 18,33 This may be the result of face-to-face packing between the tolyl group of one molecule with the pyrene of another (Figure D.2). Figure 5.3 31P NMR spectra of 2 from VC NMR experiment as well as generated fit and residuals (inset). Variable concentration (VC) NMR studies were performed with a ~11 mM stock solution of 2 in H2O-saturated CDCl3 by diluting it with known amounts of solvent and tracking the 31P NMR signal after each addition (Figure 5.3).34 Typical upfield shifting (Δδ ≈ 1.2 ppm) is observed as the concentration of the sample decreases. Non-linear regression analysis was then used to determine a solution-state dimerization strength (Kdim) value for 2 of 179 M–1 (Figure 5.3 inset). This value is both consistent with the dimerization strengths of structurally similar PN-phenanthrene analogues and among the strongest reported values for similar hydrogen bonding dimers.18,36 105 Figure 5.4 a) Absorption and emission spectra of a 1 μM solution of 2 and b) emission spectra of 2 at varying concentrations, showing excimer emission at higher concentrations in CHCl3, where λex = 365 nm. The photophysical properties of 2 were studied with UV-vis and fluorescence spectroscopy. The absorbance and emission profiles of a 1 × 10–6 M solution of 2 (Figure 5.4a) demonstrate standard pyrene-like characteristics with an absorption maximum at 395 nm (ε = 2.6 × 104 M–1 cm–1) and an emission maximum of 465 nm (ϕ = 70%, τ = 3 ns) upon excitation at 365 nm (Figure D.3, a).4 Though tolyl-appended 2 was chosen based on higher yields and better stability, it is expected that more withdrawing aryl groups on the pendent phenyl should lead to a redshifting in the emission, while more donating groups should lead to a blueshifting. This is based on the results for several previously studied classes of PN heterocycles, including the aforementioned naphthalene-,16,17 anthracene-,33 and phenanthrene- like18 families. To test for the formation of pyrene excimers, the fluorescence spectra were monitored as a function of concentration by diluting a sample from 4 × 10–3 M to 1 × 10–4 M (Figure 5.4b). Below 2 × 10–3 M, only the emission profile of monomer is seen. Interestingly, at or above 2 × 10–3 M in concentration, the bands around 465 nm stay constant and a broad peak at 582 nm begins to grow in, which is coupled with a decrease 106 in the quantum efficiency of the solution and is consistent with known excimer behavior.4 A green-yellow emission is seen in the solid state, supporting the presence of a yellow fluorescing excimer mixed with the blue fluorescing monomer (Figure D.4, b). Additionally, this excimer formation is not seen when looking at 4 × 10–3 M samples in toluene, methanol, or 5% chloroform in methanol however, as shown by the emission spectra and the colors of the solutions upon excitation at 365 nm, where the chloroform solution has a more yellow emission than the others (Figures D.3, c and D.4). In an analogous 20% chloroform in methanol solution, a small shoulder begins to appear at 523 nm, potentially showing evidence for a minor formation of excimer in this solvent system as well (Figure D.4). As this excimer formation is observed only at higher concentrations in chloroform, compound 2 maintains a large quantum yield as the monomer in most concentrations yet retains promise for integration into systems that take advantage of the fluorescence quenching of the excimer. 5.3 Conclusions A new PN-pyrene derivative has been prepared that retains the enhanced photophysical properties seen in pyrene-based systems and incorporates the structural motifs that enable supramolecular assembly, as 2 exhibits strong H-bonded phosphaquinolinone dimer formation in solution and the solid state, an extended - stacking structure in the crystalline state, and monomer-excimer quenching dynamics. These structural features and concentration-dependent properties provide this highly fluorescent scaffold with the potential to be a useful supramolecular building block for 107 larger systems or networks and broaden the substrate scope and applicability of existing pyrene-containing supramolecular hosts and chemosensors. 5.4 Experimental Section General. NMR spectra were acquired at room temperature on a Varian Inova 500 (1H: 500 MHz, 13C: 126 MHz, 31P: 202 MHz) or a Bruker Avance III HD 500 equipped with a Prodigy multinuclear cryoprobe (1H: 500 MHz, 13C: 126 MHz). 1H and 13C chemical shifts (δ) are expressed in ppm relative to residual CHCl3 shifts ( 1H: 7.26 ppm, 13C: 77.16 ppm). 31P NMR are referenced to 85% H3PO4 (δ 0 ppm) as an external reference. UV-vis spectra were recorded using an Agilent Technologies Cary 60 UV-vis spectrophotometer in HPLC grade CHCl3. Fluorescence emission spectra were recorded using a Horiba Jobin Yvon FluoroMax-4 fluorimeter exciting at 365 nm. Fluorescence lifetime measurements were recorded using a Horiba FluoroHub Single Photon Counting Controller with a TemPro Fluorescence Lifetime System attachment. HRMS data were acquired on a Waters Synapt G2-Si ESI/LC-MS. All air-/water-free reactions were performed under an N2 atmosphere using Schlenk techniques. Column chromatography was performed using silica gel (240– 300 mesh), with solvent systems being referenced to the most abundant solvent. Compound 3 was prepared according to the literature;19 all other materials were used as received. Dimerization and photophysical studies. Variable concentration (VC) NMR experiments were performed by sequentially diluting a 10 mM solution of 2 with known amounts of solvent, recording the 31P NMR shift after each dilution, and fitting the peaks using non- linear regression analysis.34 Quantum yield (ϕ) was determined through comparison of the 108 emission and absorption intensities of the analyte to that of a 0.1 M quinine sulfate in H2SO4 solution. 35 Synthesis of nitropyrene 4. Nitrotriflate 319 (185 mg, 0.47 mmol, 1 equiv.) was combined with 4-ethynyltoluene (0.052 mL, 0.70 mmol, 1.5 equiv.), Pd(PPh3)2Cl2 (32 mg, 0.047 mmol, 0.1 equiv.), and CuI (9 mg, .047 mmol, 0.1 equiv.) in a round bottom flask. The vessel was then placed under N2 through atmosphere exchange before dry THF (5 mL) and Et3N (1 mL) were added. After reacting at room temperature for 24 h, the crude mixture was concentrated under reduced pressure using EtOAc to remove Et3N, and the residue was purified using silica gel chromatography (20:1 hexanes:EtOAc) to give 4 (0.130 g, 77% yield) as an orange solid; mp 169.0–170.1 °C. 1H NMR (500 MHz, CDCl3) δ 8.75 (d, J = 9.2 Hz, 1H), 8.71 (s, 1H), 8.34–8.21 (m, 3H), 8.14 (t, J = 7.8 Hz, 1H), 8.11 (d, J = 7.7 Hz, 1H), 8.04 (d, J = 8.9 Hz, 1H), 7.68 (d, J = 7.6 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 2.44 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 147.7, 139.8, 133.2, 132.1, 132.0, 131.6, 130.3, 130.3, 130.1, 129.5, 128.0, 127.3, 126.9, 126.9, 126.1, 123.7, 119.9, 119.9, 112.2, 103.2, 83.4, 77.4, 21.9. HRMS [M+H]+ calcd for C25H16NO2 362.1181, found 362.1169. Synthesis of aminopyrene 5. Nitropyrene 4 (175 mg, 0.48 mmol, 1 equiv.) was dissolved in 40 mL of EtOAc and 10 mL AcOH was added. Zn powder (317 mg, 4.8 mmol, 10 equiv.) was then added and the solution was stirred for one hour before being concentrated in vacuo. The crude mixture was purified through silica gel chromatography (15:1:1 hexanes:EtOAc:CH2Cl2), followed by recrystallization from CH2Cl2 and hexanes to afford 5 (88 mg, 0.26 mmol, 55%) as an orange solid; mp 127.4-128.1 °C. 1H NMR (500 MHz, CDCl3) δ 8.51 (d, J = 9.1 Hz, 1H), 8.18–8.05 (m, 3H), 7.98 (d, J = 9.1 Hz, 1H), 7.89 (d, J = 7.7 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 7.8 Hz, 2H), 7.49 (s, 1H), 7.24 (d, J = 109 8.4 Hz, 2H), 2.43 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 146.4, 138.8, 133.0, 132.6, 131.6, 130.1, 129.9, 129.5, 129.4, 128.8, 128.7, 126.5, 125.9, 125.7, 125.2, 124.8, 124.8, 120.6, 118.9, 110.4, 101.0, 84.4, 21.7. HRMS [M+H]+ calcd for C25H18N 332.1439, found 332.1439. Synthesis of PN-pyrene 2. Aminopyrene 5 (148 mg, 0.47 mmol, 1 equiv.) and P(OPh)3 (0.35 mL, 1.3 mmol, 3 equiv.) were dissolved in pyridine (1.5 mL). The reaction was put under a N2 atmosphere using atmosphere exchange before the mixture was heated to 100 °C and left to stir for 24 hours. The crude mixture was then dissolved in toluene and the solvent was removed in vacuo. 10 mL of THF and several drops of H2O were added to the mixture, which was then heated at 60 °C for one hour before being dried (Na2SO4), filtered, and concentrated in vacuo. This product mixture was then purified using silica gel chromatography (15:1:12:1:1 hexanes:EtOAc:CH2Cl2) and subsequent recrystallization from CH2Cl2 and hexanes to afford heterocycle 2 (62 mg, 0.13 mmol, 28%) as a yellow solid; mp >250 °C. 1H NMR (500 MHz, CDCl3) δ 8.74 (s, 1H), 8.72 (d, J = 40.1 Hz, 1H), 8.43 (d, J = 9.3 Hz, 1H), 8.14 (t, J = 7.9 Hz, 2H), 8.09 (d, J = 9.2 Hz, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.93 (t, J = 7.2 Hz, 3H), 7.83 (d, J = 8.9 Hz, 1H), 7.74 (s, 1H), 7.38 (d, J = 7.7 Hz, 2H), 7.04–6.94 (m, 4H), 6.87 (s, 1H), 2.49 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 150.7 (d, J = 9.2 Hz), 138.7, 138.5 (d, J = 2.6 Hz), 136.1 (d, J = 5.8 Hz), 133.5 (d, J = 9.3 Hz), 133.3, 130.5, 130.0, 129.9, 129.7 (d, J = 1.9 Hz), 129.5, 129.4, 129.1, 128.0 (d, J = 6.7 Hz), 126.3, 126.2, 126.2 (d, J = 164.4 Hz), 125.4, 124.9 (d, J = 1.7 Hz), 124.8, 124.1, 121.4 (d, J = 4.1 Hz), 121.2, 120.6, 113.8 (d, J = 13.2 Hz), 113.7 (d, J = 9.6 Hz), 21.5. 31P NMR (202 MHz, CDCl3) δ 10.91 (d, J = 40.2 Hz). HRMS [M+H] + calcd for C31H23NO2P 472.1466, found 472.1463. 110 Crystal data for 2. Diffraction intensities for 2 were collected at 173 K on a Bruker Apex2 CCD diffractometer using CuK radiation,  = 1.54178 Å. Space group was determined based on systematic absences. Absorption correction was applied by SADABS.37 Structure was solved by direct methods and Fourier techniques and refined on F2 using full matrix least-squares procedures. All non-H atoms were refined with anisotropic thermal parameters. H atoms were refined in calculated positions in a rigid group model except the H atom at the N atom involved in H-bond that was refined with isotropic thermal parameter. All calculations were performed by the Bruker SHELXL-2014 package.38 Compound 2: C31H22NO2P, M = 471.46, 0.12 x 0.09 x 0.03 mm, T = 173 K, Monoclinic, space group P21/n, a = 14.0132(4) Å, b = 8.3450(2) Å, c = 20.0895(6) Å,  = 97.885(2), V = 2327.06(11) Å3, Z = 4, Dc = 1.346 Mg/m 3, μ(Cu) = 1.283 mm–1, F(000) = 984, 2θmax = 133.21°, 16977 reflections, 4108 independent reflections [Rint = 0.0444], R1 = 0.0502, wR2 = 0.1351 and GOF = 1.044 for 4108 reflections (320 parameters) with I>2(I), R1 = 0.0600, wR2 = 0.1448 and GOF = 1.045 for all reflections, max/min residual electron density +1.172/–0.260 eÅ–3. CCDC 1952888 contains the supplementary crystallographic data for compound 2. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre at via www.ccdc.cam.ac.uk/data_request/cif. 111 CHAPTER VI THIONATION OF THE 2‐ λ5‐PHOSPHAQUINOLIN‐2‐ONE SCAFFOLD WITH LAWESSON'S REAGENT This chapter includes previously published and co-authored material from Bard, J.P., McNeill, J.N., Zakharov, L.N., Johnson, D.W., Haley, M.M. “Thionation of the 2-λ5- Phosphaquinolin-2-one Scaffold with Lawesson’s Reagent.” Isr. J. Chem. 2021, 61, 217– 221. This story focuses on our use of Lawesson’s Reagent to thionate the phosphorus center of the phosphaquinolinone scaffold as well as the physicochemical changes observed after doing so. 6.1 Introduction Lawesson’s reagent (LR, Figure 6.1) is a widely-used thionating reagent that converts carbonyl groups into their respective thiocarbonyls, with several authoritative reviews highlighting its utility.1,2 This reagent reacts with a wide variety of carbonyl- containing scaffolds, including, but not limited to, ketones, amides, imides, and aldehydes. These transformations, beyond being structurally interesting, often lead to changes in the physicochemical properties of the scaffolds between the oxo and thio forms. Figure 6.1 Lawesson’s Reagent and a sampling of commonly prepared thiocarbonyl compounds. 112 One framework of particular interest that has served as a substrate for LR is the well-studied fluorescent lactone coumarin.3–6 Coumarin, as well as other related fluorescent carbonyl-containing systems, exhibit red-shifted emissions and decreased quantum yields upon thionation with LR. Additionally, in many cases the thio form can be converted back to the respective oxo form through various means, a transformation which often shows a turn-on fluorescence response.5,7–9 Similarly, non-aromatic aminophosphonic esters have been converted to their respective thio forms as well.10–12 The utility of LR and the physicochemical changes it imparts upon the substrates pose the question: what other carbonyl-like systems can be modified analogously? In recent years, we have reported the synthesis and physicochemical studies of the coumarin-like 2-λ5-phosphaquinolin-2-one scaffold.13 In addition to their well-defined self-specific meso-dimerization, these phosphorus- and nitrogen-containing (PN) heterocycles have tunable emissive properties. Similar to the aforementioned analyses of coumarin derivatives, we have reported a series of studies to modify and improve the physicochemical properties of the 2-λ5-phosphaquinolin-2-ones through substituent group alteration, phosphorus center modification, and acene backbone elongation.13–15 To further explore the versatility and modularity of the phosphaquinolinone scaffold, we report herein the conversion of the phosphine oxide into the corresponding thionate form using Lawesson’s reagent and discuss in detail the resultant structural and photophysical changes. 6.2 Results and Discussion To accomplish this study, oxo-heterocycles 1a–1f were prepared as previously reported.14,15 These were treated with LR in dry toluene under N2 at reflux until only trace 113 starting material was observed via TLC (ca. 24 h), affording thioheterocycles 2a–2f in modest to very good isolated yields (Scheme 6.1). The purification of heterocycles 2 nonetheless presented some challenges, as the reaction biproducts of LR are structurally similar to the attained products and/or may coordinate with the donor-acceptor face of the PN product. In the case of 2a, this meant multiple rounds of silica gel chromatography and recrystallization, resulting in material likely being lost in purification and thus the diminished isolated yield. Scheme 6.1 Conversion of oxo-heterocycles 1 to thio-heterocycles 2 with Lawesson’s Reagent (LR). Heterocycles 2 were examined by NMR spectroscopy (Figures E.7–E.25). First, the 31P NMR signals shift significantly downfield (~ 30–35 ppm) from their respective oxo analogs 1, appearing around 40–50 ppm, which can be explained by the larger deshielding effect that the sulfur has upon the P center as seen for other examples in the literature.2 Furthermore, the proton NMR spectra show the characteristic coupling between the P center and the carbon in the isolated C=C bond along the backbone. The coupling constants range from 30.5–37.7 Hz, and correlate to the standard splitting seen in these systems; however, the N–H proton signal appears solely as a doublet (J = 6–7 Hz), which before in heterocycles 1 has been observed only as a broad singlet. While slightly confusing, examination of the 31P NMR spectra indicates that the phosphorus center is likely coupling 114 to the adjacent N–H proton, as the phosphorus peaks appear as doublet of doublets for 2a– 2c, and doublet of triplets for 2d–2f. It should be noted, however, that the coupling between the phosphorus center and the attached phenyl ring may mask this interaction. This coupling between the phosphorus center and the N–H proton could potentially be explained due to a more partially positively charged P atom resulting from the more polarized P–S bond. Furthermore, none of the characteristic shifting in any of the N–H signals was seen as a function of concentration, suggesting little to no meso-dimerization as is observed for heterocycles 1 in solution. This is likely due to the relatively large thiophosphonyl S acting as a “soft” Lewis base because of its more diffuse charge and the concurrent larger polarizability.16 This phenomenon is also observed for sulfur-containing H-bonds in proteins.17,18 Slow diffusion of pentane into CH2Cl2 solutions of heterocycles 2d and 2e furnished single crystals suitable for X-ray diffraction. In the heterocyclic core of these structures, the P–N bond distances are 1.665(1) and 1.668(1) Å, the P–C bond distances are 1.794(2) and 1.802(1) Å, the N–C bond distances are 1.394(2) and 1.395(1) Å, and the isolated C=C double bond distances are both 1.355(2) Å, respectively. All of these bond lengths are within the ranges determined for previous PN-heterocycles,13 suggesting that thionation has no significant structural effect on the conjugated backbone. The only differences in bond lengths are observed for the P–N bond distances, which are about 0.02 Å longer than those in 1,13 and, unsurprisingly, the P=S bond distances of 2d and 2e (1.959(1) and 1.958(1) Å) are ~ 0.5 Å longer than the respective P=O bonds in heterocycles 1 because of the larger sulfur atom. 115 The solid-state structures of the meso-dimers of 2d and 2e also provide some interesting observations (Figures 6.2 and E.1–E.4). The N···S intermolecular distance is 3.406(1) Å for 2d and 3.404(1) Å for 2e, which are significantly longer than any previously measured N···O bond distances (~ 2.77–2.82 Å).13 The P–N···S, N···S–P, and the S–P–N angles are 118.2°, 102.5°, and 115.7(1)° for 2d and 114.6°, 107.4°, and 116.2(1)°for 2e, respectively. These all deviate to varying degrees from the ideal 120° for the pseudo six- membered chair conformation, like their P=O analogues. Also, the S–P–N–H torsional angles for 2d and 2e are 56.5° and 60.7°, respectively. These characteristics further support the lack of solution-state dimerization since we have shown previously a correlation between solid-state distances/angles and solution-state dimerization strengths.15 Finally, the dihedral angle between the heterocyclic cores and the pendant 4-NCC6H4 groups is ca. 28–38°, illustrating good conjugation between the two π-units in the solid state. Figure 6.2 ORTEP drawing of the thioheterocycle 2e meso-dimer; thermal ellipsoids drawn at 30 % probability level. 116 We next examined the effects of thionation upon the photophysical properties of 2 (Table 6.1, Figure 6.3). First, the lowest energy absorption peaks of thio-heterocycles 2 range from 348 to 372 nm. These fall in line with the typical PN heterocycle absorbance peaks, albeit they are slightly lower energy likely due to the lowered LUMO energies and subsequently lower π to π* transitions upon introduction of the sulfur atoms in 2.19 Furthermore, the absorption coefficients for 2 range from 12,700 to 20,800 M–1 cm–1 for the λabs,max peaks around 300 nm (see Appendix E) and from 6380 to 8600 M –1cm–1 for the lowest energy absorbances. These are within the range of those seen for oxo-heterocycles 1, suggesting that there is no significant effect of the thionation upon the conjugation or absorptivity of the scaffold. Figure 6.3 Stacked absorption and emission spectra of heterocycles 2. 117 Table 6.1. Photophysical properties of heterocycles 2a λabs λem Stokes Shift cmpd ɛ (M–1 cm–1) ϕ (%)b τ (ns) (nm) (nm) (nm/cm–1) 2a 348 444 96/6213 7180 2 0.10 c 2b 352 462 110/6764 8600 6 0.24c 2c 350 470 120/7294 6520 3 0.19c 0.75 (76%), 2d 365 479 114/6520 6380 8 4.6 (24%)d 0.82 (85%), 2e 373 492 119/6484 7950 8 4.8 (15%)d 0.17 (84%), 2f 357 466 109/6552 6840 2 3.0 (16%) d a All values collected in CHCl with ca. 10–53 M solutions. b Collected using a quinine sulfate in 0.1 M H2SO4 solution. c Decay curves fitted with a monoexponential model. dDecay curves fitted with a biexponential model. When examining the emissive properties of 2, however, a few interesting, yet predictable changes were observed. For P–OPh containing heterocycles 2a–2c, ca. 20 nm redshifts in the emission are observed when compared to their respective oxo-heterocycle 1 derivatives. Similarly, the P–Ph containing heterocycles 2d–2f exhibit 12, 27, and 17 nm redshifts compared to 1d–1f, respectively. This is likely due to the weaker P–S bond in 2 compared to the P–O bond in 1 and the concurrent lower energy of the excited state (S1). With this lower energy S1 state, the S1 to S0 transition is lower in energy, as cited for thiocarbonyls vs. their parent carbonyls.20 Furthermore, all derivatives of 2 exhibited decreased quantum yields (3–8%) compared to their 1 counterparts (11–52%). This is a common phenomenon as sulfur promotes the “heavy atom effect” which acts to quench fluorescence through several electronic transitions in the excited state.21,22 This effect is most pronounced in 2d–2f, which show a dramatic reduction in quantum yield, though this 118 is likely just due to their respective 1 counterparts having higher quantum yields as previously described.14 An additional interesting difference between the P–OPh containing heterocycles 2a–2c and the P–Ph containing congeners 2d–2f is seen when determining the fluorescence lifetimes of the heterocycles. For the P–OPh heterocycles, the decays are monoexponential, and range from 0.10 to 0.24 ns, whereas the P–Ph heterocycles show biexponential lifetimes with a predominant shorter component (0.17 to 0.82 ns) as well as a longer-lived component (3.0 to 4.8 ns). This is likely due to the increased potential for charge transfer in the excited state of the P–Ph heterocycles as we have seen before.13 Examination of the absorption and emission of 2 c and 2 e in the more polar acetonitrile (Figure E.5 and Table E.1) indicate that this charge transfer is likely observed in this system as well, as 2e shows a higher energy Stokes shift in the more polar solvent, yet 2c shows a lower one. The frontier orbital geometries of the ground- and excited-state geometries were also examined by DFT and TDDFT calculations, respectively (Figure E.6 and Table E.2). A larger separation between frontier orbitals is observed in the HOMO and LUMO for the S0 state of the P–Ph containing 2e when compared to the respective P–OPh containing 2c. When looking at the respective S1 state geometries, a slightly larger orbital separation can be seen for 2e as well, though it is not as dramatic as that of the ground state. This, paired with the increased Stokes shift of 2e in a more polar solvent imply that a more prominent charge transfer event can be taking place for the P–Ph containing 2d–2f. thus leading to the biexponential decay curves. This conjecture also is corroborated by the longer lifetime components observed with the P–Ph heterocycles since charge-transfer has longer lifetime than the dominant π* to π transitions. 119 6.3 Conclusions In summary, the utility and versatility of Lawesson’s reagent has permitted the transformation of oxo-heterocycles 1a–1f into their respective thiocarbonyl derivatives 2a– 2f, affording interesting changes in physicochemical properties as well as new functionality of the compounds. With LR working well to convert the phosphaquinolinone scaffolds in the same way, and the inherent diversity of performing the transformation upon this fluorescent phosphonyl center, it opens the door for the potential utilization of these P=O(S) heterocycles as turn-on fluorescent sensors, markers, or chemodosimeters for oxidizing/reducing species. These studies will be disclosed in due course. 6.4 Experimental Section General. All oxygen- and water-free reactions were performed under an N2 atmosphere using Schlenk technique. Column chromatography was performed using silica gel (240– 300 mesh), with solvent systems being referenced to the most abundant solvent. NMR spectra were acquired at room temperature on a Bruker Avance III HD 600 equipped with a Prodigy multinuclear cryoprobe (1H: 600 MHz, 13C: 151 MHz), a Varian Inova 500 (1H: 500 MHz, 13C: 126 MHz, 31P: 202 MHz), or a Bruker Avance III HD 500 equipped with a Prodigy multinuclear cryoprobe (1H: 500 MHz, 13C: 126 MHz, 31P: 202 MHz, 19F: 471 MHz). 1H and 13C NMR chemical shifts (δ) are expressed in ppm relative to residual CHCl3 (1H: 7.26 ppm, 13C: 77.16 ppm) or DMSO (1H: 2.50 ppm, 13C: 39.52 ppm) shifts. 31P NMR shifts are referenced to 85 % H3PO4 (δ 0 ppm) as an external reference. 19F NMR shifts are referenced to CFCl3 (δ 0 ppm) as an external reference. UVvis spectra were recorded using an Agilent Technologies Cary 60 UV-vis spectrophotometer in HPLC-grade CHCl3. Fluorescence emission spectra were recorded using a Horiba Jobin Yvon FluoroMax-4 120 fluorimeter exciting at 365 nm. Quantum yields (φ) were determined through comparison of the emission and absorption intensities of the analyte to those of a 0.1 M H2SO4 quinine sulfate solution.23–25 Fluorescence lifetime measurements were recorded using a Horiba Fluoro-Hub Single Photon Counting Controller with a TemPro Fluorescence Lifetime System attachment. High-resolution mass spectra (HRMS) were recorded on a Waters XEVO G2-XS mass spectrometer. Oxo-heterocycles 1 were prepared as previously described.14,15 General procedure for thionation. Oxo-heterocycles 1 (1 equiv.) were mixed with Lawesson’s reagent (LR) (1.35–1.40 equiv.) in dry toluene (~ 0.005 M) under N2. The mixture was heated to reflux for 24 h. After cooling to room temperature, the solvent was removed in vacuo. Silica gel chromatography of the residue and subsequent recrystallization afforded the pure thio-heterocycles 2 in modest to very good yield. Heterocycle 2a: The general thionation procedure was performed on oxo-heterocycle 1a (70 mg, 0.173 mmol, 1.00 equiv.) with LR (98 mg, 0.240 mmol, 1.40 equiv.) in toluene (60 mL). Two rounds of column chromatography (2:1:1 hexanes : EtOAc : CH2Cl2, Rf=0.90 then 20:1:1 hexanes : EtOAc : CH2Cl2, Rf=0.30) and subsequent recrystallization from pentane and CH2Cl2 afforded thio-heterocycle 2a (20 mg, 27%) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 10.01 (d, J=6.0 Hz, 1H), 7.76 (d, J=37.7 Hz, 1H), 7.68 (d, J=7.8 Hz, 2H), 7.53 (s, 1H), 7.41 (d, J=8.6 Hz, 1H), 7.34 – 7.25 (m, 4H), 7.17 – 7.09 (m, 2H), 7.00 (d, J=7.9 Hz, 2H), 2.36 (s, 3H), 1.28 (s, 9H). 13C NMR (151 MHz, DMSO-d6) δ 149.9 (d, J=10.9 Hz), 143.3, 138.7 (d, J=3.4 Hz), 137.5, 137.1 (d, J=6.7 Hz), 133.0 (d, J=12.4 Hz), 129.5, 129.0, 128.0 (d, J=7.0 Hz), 127.9, 127.1 (d, J=129.9 Hz), 127.1, 124.9, 121.9 (d, J=4.5 Hz), 119.9 (d, J=13.9 Hz), 116.3 (d, J=8.3 Hz), 33.9, 31.2, 20.8. 31P NMR 121 (202 MHz, DMSO-d6) δ 56.3 (dd, J=39.4, 2.9 Hz). UV-vis (CHCl3) λmax nm (ɛ; M –1cm–1) 301 (12,700), 348 (7,180). HRMS (ASAP) [M+H]+ calcd for C25H27NOPS 420.1551, found 420.1523. Heterocycle 2b: The general thionation procedure was performed on oxo-heterocycle 1b (50 mg, 0.14 mmol, 1.00 equiv.) with LR (76 mg, 0.188 mmol, 1.35 equiv.) in toluene (25 mL). Column chromatography (2:1:1 hexanes:EtOAc: CH2Cl2, Rf=0.90) and subsequent recrystallization from hexanes and CH2Cl2afforded thio-heterocycle 2b (31 mg, 60%) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J=7.9 Hz, 2H), 7.74 (d, J=8.0 Hz, 2H), 7.54 (d, J=36.5 Hz, 1H), 7.42 (d, J=7.8 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.25 (d, J=8.1 Hz, 2H), 7.14 (t, J=7.7 Hz, 1H), 7.11 (t, J=7.7 Hz, 1H), 6.98 (d, J=7.9 Hz, 2H), 6.95 (d, J=8.1 Hz, 1H), 6.37 (d, J=6.2 Hz, 1H). 13C NMR (126 MHz, CDCl3) 149.5 (d, J=11.3 Hz), 140.6 (d, J=12.9 Hz), 140.4 (d, J=2.8 Hz), 138.9 (d, J=6.9 Hz), 132.4, 131.6, 131.4 (d, J=2.0 Hz), 129.6 (d, J=2.0 Hz), 129.3 (d, J=6.9 Hz), 128.0 (d, J=133.5 Hz), 125.7 (d, J=2.3 Hz), 122.5, 122.2 (d, J= 4.2 Hz), 121.2 (d, J=13.2 Hz), 118.8, 116.9 (d, J=7.8 Hz), 112.1. 31P NMR (202 MHz, CDCl3) 54.4 (dd, J=37.1, 4.3 Hz). UV-vis (CHCl3) λmax nm (ɛ; M–1cm–1) 302 (16,600), 352 (8,600). HRMS (ASAP) [M+H]+ calcd for C21H16N2OPS 375.0719, found 375.0721. Heterocycle 2c: The general thionation procedure was performed on oxo-heterocycle 1c (155 mg, 0.373 mmol, 1.00 equiv.) with LR (210 mg, 0.519 mmol, 1.39 equiv.) in toluene (60 mL). Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf=0.90) and subsequent recrystallization from hexanes and CH2Cl2 afforded thio-heterocycle 2c (31 mg, 60%) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J=7.8 Hz, 2H), 7.72 (d, J=8.0 Hz, 2H), 7.56 (d, J=36.5 Hz, 1H), 7.43 (dd, J=8.4, 1.9 Hz, 1H), 7.39 (s, 1H), 122 7.24 (d, J=7.6 Hz, 2H), 7.13 (t, J=7.5 Hz, 1H), 6.99 (d, J=7.9 Hz, 2H), 6.91 (d, J=8.3 Hz, 1H), 6.45 (d, J= 6.4 Hz, 1H), 1.34 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 149.6 (d, J=11.2 Hz), 145.5, 141.0 (d, J=2.8 Hz), 140.7 (d, J=13.1 Hz), 136.6 (d, J=6.8 Hz), 132.4, 129.6 (d, J= 2.0 Hz), 129.3 (d, J=7.0 Hz), 129.2, 127.8 (d, J=2.0 Hz), 127.6 (d, J=134.4 Hz), 125.6 (d, J=2.3 Hz), 122.3 (d, J= 4.4 Hz), 120.7 (d, J=13.1 Hz), 118.9, 116.7 (d, J=7.7 Hz), 111.9, 34.4, 31.4. 31P NMR (202 MHz, CDCl3) 54.9 (dd, J= 36.3, 5.1 Hz). UV-vis (CHCl3) λ nm (ɛ; M–1cm–1max ) 306 (15,900), 350 (6,520). HRMS (ASAP) [M+H] + calcd for C25H24N2OPS 431.1334, found 431.1347. Heterocycle 2d: The general thionation procedure was performed on oxo-heterocycle 1d (85 mg, 0.248 mmol, 1.00 equiv.) with LR (134 mg, 0.347 mmol, 1.40 equiv.) in toluene (50 mL). Column chromatography (5:1:1 hexanes:EtOAc:CH2Cl2, Rf=0.50) and subsequent recrystallization from CH2Cl2 and pentane afforded thio-heterocycle 2d (65 mg, 59%) as a pale yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 9.15 (d, J=6.9 Hz, 1H), 7.98 – 7.91 (m, 2H), 7.80 (d, J=30.5 Hz, 1H), 7.78 (d, J=9.0 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 7.58 – 7.49 (m, 4H), 7.34 (t, J=7.7 Hz, 1H), 7.04 (d, J=8.5 Hz, 1H), 7.00 (td, J=7.5, 1.1 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 141.2 (d, J=12.9 Hz), 139.1, 138.9 (d, J=5.2 Hz), 134.3 (d, J=106.1 Hz), 132.2 (d, J= 2.8 Hz), 132.1, 132.0 (d, J=12.3 Hz), 131.4, 131.1, 128.4 (d, J=13.4 Hz), 128.3 (d, J=6.2 Hz), 123.8 (d, J=96.8 Hz), 120.4, 119.4 (d, J=13.0 Hz), 118.6, 117.0 (d, J=8.0 Hz), 110.2. 31P NMR (202 MHz, DMSO-d6) δ 41.6 (dt, J=34.4, 15.6 Hz). UV-vis (CHCl3) λmax nm (ɛ; M –1cm–1) 301 (14,500), 365 (6,380). HRMS (ASAP) [M+H]+ calcd for C21H16N2PS 359.0762, found 359.0772. Heterocycle 2e: The general thionation procedure was performed on oxo-heterocycle 1e (199 mg, 0.500 mmol, 1.00 equiv.) with LR (283 mg, 0.700 mmol, 1.40 equiv.) in toluene 123 (100 mL). Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf=0.90) and subsequent recrystallization from hexanes and CH2Cl2 afforded thio-heterocycle 2e (185 mg, 89%) as a dark yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 9.02 (d, J=7.0 Hz, 1H), 7.97 – 7.90 (m, 2H), 7.83 (d, J=30.6 Hz, 1H), 7.79 (d, J=7.6 Hz, 2H), 7.71 (d, J=8.9 Hz, 2H), 7.57 – 7.47 (m, 4H), 7.41 (dd, J=8.3, 2.1 Hz, 1H), 6.97 (d, J=8.5 Hz, 1H), 1.30 (s, 9H). 13C NMR (126 MHz, DMSO-d6) δ 142.7, 141.3 (d, J=12.9 Hz), 139.6, 136.5 (d, J=5.1 Hz), 134.7, 133.9, 132.2 (d, J=2.9 Hz), 132.0 (d, J=9.9 Hz), 128.8, 128.4 (d, J=13.4 Hz), 128.2 (d, J=6.3 Hz), 127.5, 123.5 (d, J=97.4 Hz), 118.9 (d, J= 12.8 Hz), 118.6, 116.7 (d, J=7.9 Hz), 110.1, 33.9, 31.2. 31P NMR (202 MHz, DMSO-d6) δ 41.9 (dt, J=31.2, 15.6 Hz). UV-vis (CHCl –1 –13) λmax nm (ɛ; M cm ) 303 (20,800), 373 (7,950). HRMS (ASAP) [M+H] + calcd for C25H24N2PS 415.1422, found 414.1398. Heterocycle 2f: The general thionation procedure was performed on oxo-heterocycle 1f (100 mg, 0.240 mmol, 1.00 equiv.) with LR (138 mg, 0.341 mmol, 1.40 equiv.) in toluene (75 mL). Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf=0.90) and subsequent recrystallization from hexanes and CH2Cl2 afforded thio-heterocycle 2 f (61 mg, 59 %) as a yellow solid. 1H NMR (600 MHz, DMSO-d6) δ 9.71 (d, J=7.0 Hz, 1H), 8.00 – 7.91 (m, 3H), 7.96 (d, J=36.0 Hz, 1H), 7.80 – 7.74 (m, 4H), 7.67 (d, J=8.5 Hz, 1H), 7.58 (d, J=7.1 Hz, 1H), 7.57 – 7.51 (m, 2H), 7.19 (d, J=8.5 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 141.9, 140.7 (d, J=12.7 Hz), 138.3, 133.7 (d, J=106.1 Hz), 132.5, 132.2, 132.1 (d, J=12.5 Hz), 128.6 (d, J=13.5 Hz), 128.4 (d, J=6.1 Hz), 127.7, 126.3, 125.4 (d, J=95.2 Hz), 124.4 (q, J= 543.8, 272.9 Hz), 120.7 (q, J=32.3 Hz), 119.1 (d, J= 13.2 Hz), 118.5, 117.7 (d, J=7.8 Hz), 110.6. 31P NMR (202 MHz, DMSO-d6) δ 41.3 (dt, J=33.8, 15.9 Hz). 19F NMR (471 MHz, DMSO-d6) δ –60.02. UV-vis (CHCl3) λmax nm (ɛ; M –1cm–1) 295 124 (14,000), 357 (6,840). HRMS (ASAP) [M+H]+ calcd for C22H15N2F3PS 427.0646, found 427.0639. 125 CHAPTER VII UTILIZATION OF THE 2‐λ5‐PHOSPHAQUINOLIN‐2‐ONE SCAFFOLD AS A NON-CYTOTOXIC, pH-INSENSITIVE, AND CELL-PERMEABLE IMAGING REAGENT This chapter includes unpublished work from an ongoing study that focuses on exploiting the phosphaquinolinone as a cellular imaging reagent. This story was written by Jeremy P. Bard, synthesis and photophysical characterization were performed by Jeremy P. Bard with assistance from J. Nolan McNeill and Holden J. Howard. Cell assays were performed by Sarah G. Bolton. Editorial support was provided by Michael. D. Pluth, Michael M. Haley, and Darren W. Johnson. 7.1 Introduction Advancements in cell/tissue imaging has benefited the understanding of biological systems and mechanisms enormously, thus the development of new imaging methods, higher power scopes, and more diverse chemical dyes remains an active area of chemical biology research. While there has been significant progress in all of these areas, the development of chemical chromophores and fluorophores stands out as one of the most well-studied and broadly understood.1–10 A variety of fluorophores exist that span a series of brightnesses and emission colors, yet many are based on only a few “core” molecular scaffolds, including coumarins, xanthenes, cyanines, and BODIPY (Figure 7.1). 126 Figure 7.1 Examples of core fluorophore scaffolds and the phosphaquinolinone scaffold. Many structure-property relationships focusing on substituent group placement, heteroatom insertion, and backbone modification have been built for these compounds, which have led to a thorough understanding of their capabilities and limitations.11–18 Examples of such limitations include pH-sensitivity, low brightnesses, chemical instability, cytotoxicity, and photobleaching. The development of unique chemical structures is paramount to further expanding the toolkit of cell imaging reagents available to chemical biologists. Recently, a new phosphorus- and nitrogen-containing (PN) coumarin-like scaffold, the 2-λ5-phosphaquinolin-2-one framework, has been reported and has been shown to exhibit interesting photophysical properties (Figure 1).19,20 While a variety of P-containing heterocycles exist, relatively few contain the phosphonamidate moiety owing to difficulties in synthesis and purification, thus making this PN framework structurally unique and poised for potentially promising physicochemical properties. Primarily, this PN scaffold shows coumarin-like fluorescence, structural modularity, and very good Stokes shifts. In addition to a variety of studies examining the effect of arene core modification, several 127 structure-property relationships have been drawn for the substituent group placement along both the pendent aryl group, as well as the 6-position of the PN-naphthalene system. It was found that having electron-withdrawing groups (EWG) on the pendant aryl ring upon the carbon in the three position and/or electron-donating groups (EDG) upon the carbon in the 6-position both led to increased Stokes shifts and red shifted emissions.21 Additionally, placement of the more rigid phenyl group in place of the original phenoxy group on the phosphorus center leads to a 3- to 4-fold increase in the quantum yield of the scaffold.22 Furthermore, a vast majority of the prepared PN systems are compatible with Lipinski’s Rule of Five (Ro5), as they have less than five hydrogen bond donors, less than ten hydrogen bond acceptors, weigh less than 500 amu, and have a low octanol-water partition coeffient,23 suggesting that the scaffold should be able to permeate cell membranes. With these promising characteristics, the 2-λ5-phosphaquinolin-2-one scaffold warrants investigation as a cell imaging reagent. 7.2 Results and discussion While this system holds promise for cell imaging, several proof-of-principle studies need to be performed first to ensure that the photophysical properties seen in organic solvents hold when in more cell-like solvents, that the phosphonamidate is non-cytotoxic, and that the dyes can enter cells as suggested by the Ro5 compatibility. To first test the viability of this PN system in cell imaging applications, non- substituted PN derivative 1 was prepared through cyclization of 2-(2-phenylethynyl)- benzenamine 2 with PhP(OPh)2 following the standard cyclization procedure (Scheme 7.1). This initial derivative was chosen due to its relatively low molecular weight, simple 128 molecular structure, and minimal number of H-bond donors and acceptors in accordance with Lipinski’s Rule of 5. Scheme 7.1 Synthesis of Heterocycle 1. Upon isolation, we first examined the photophysical properties of 1 in CHCl3 (Figures F.1 and F.2, Table 7.1). The lowest energy absorption of 1 is 338 nm with an absorption maximum of 18000 M-1cm-1. The emission is at 441 nm with a 44% quantum yield. These values are in line with previously reported P-Ph heterocycles, showing a good quantum yield due to the structural rigidification caused by placing the phenyl group upon the phosphorus center instead of the traditional phenoxy. Table 7.1 Photophysical properties of new heterocycles in CHCl3 at 298 K λ aabs,max λabs εabs,max εabs λem Stokes shift Φ τ cmpd (nm) (nm) (M-1cm-1) (M-1cm-1) (nm) (nm/cm-1) (%) (ns) 1 293 338 17972 11000 441 103/6910 44 3.7 3 307 369 16201 7519 487 118/6567 24 6.1 7 306 357 24218 11886 471 114/6780 24 4.9 8 306 367 16700 7500 486 119/6671 63 5.9 9 305 368 14500 6654 487 119/6640 77 6.1 a Lowest energy absorbance maximum. To better represent the photophysical properties of 1 in an environment closer to that found in cellular assays, we next collected photophysical data in a DMSO/PBS buffer mixture (Figures F.1 and F.2, Table 7.2). Gratifyingly, relatively few changes are observed in these properties, as only a slight redshifting in the emission and moderate drop in quantum yield were observed. 129 Table 7.2 Photophysical properties of new heterocycles in ca. 5% DMSO in pH 7.4 PBS Buffer at 298 K λabs, a Stokes λabs εabs, max εabs εabs,405 λem Φ τ # max -1 -1 -1 -1 -1 -1 shift (nm) (M cm ) (M cm ) (M cm ) (nm) -1 (%) (ns) (nm) (nm/cm ) 1 290 336 17461 9140 183 452 116/7638 23 3.6 3 313 382 17506 10143 7192 499 117/6138 17 5.9 7 314 375 10711 7785 6037 485 110/6049 16 5.2 8 304 359 21000 9200 2300 500 141/7855 50 6.2 9 303 359 12980 5813 1117 493 134/7572 61 5.9 a Lowest energy absorbance maximum. With these properties, we wanted to see how 1 performed as a cell imaging reagent. For this, we first determined cell permeability of 1, which was studied by treated HeLa cells with ca. 1 × 105 M solutions of our dye in 0.5% DMSO in PBS buffer for 30 minutes and imaging them on a confocal microscope. The PN dye was excited at 405 nm and imaged on the GFP channel (Figure 7.2). While the attained images were relatively dull based upon the minimal absorbance of 1 at 405 nm, they still showed evidence for cell permeation and integration of the dye into the cytosol of the cell. We next wanted to measure the cytotoxicity of 1 and check what, if any, effect the phosphaquinolinone moiety has on cells. Live HeLa cells were treated with 1, 5, 10 and 20 μM solutions of 1 for 30 minutes. Cell death was measured using CCK-8 cell assay. Preliminary results suggest that no cytotoxicity is observed, though follow up studies need to be performed to confirm this. This proof-of-principle experiment indeed showed promise for the use of our PN derivatives for cell imaging, so our next step was to optimize the physicochemical properties of the dye. For this, we designed heterocycle 3 (Scheme 7.2). 130 Figure 7.2 Initial images of HeLa cells upon treatment with a 25 μM solution of 1 and incubation for 30 minutes. Not only does 3 retain the P-Ph substitution for improved quantum yield, but it also contains an EWG on the 3 position and an EDG on the 6 position, which leads to redshifted absorptions and emissions in these types of fluorophores. Additionally, 3 contains a methyl group upon the phosphonamide nitrogen, which removes the protic hydrogen and should impart base-insensitivity to the scaffold in addition to its inherent acid-stability. Scheme 7.2 synthesis of methylated PN 3. 131 For this synthesis of 3, 4-tert-butyl-2-((trimethylsilyl)ethynyl)aniline 4 was first protodesilylated with K2CO3 before the resultant terminal acetylene was formed by Sonogashira cross-coupling with ethyl 4-bromobenzoate 5 to afford ethynyl aniline 6. 6 was then cyclized following standard protocol with PhP(OPh)2 to give heterocycle 7 in good yield. Next, 7 was treated with MeI and DBU to afford fluorophore 3 in quantitative yield after only minimal aqueous washing. When examining the photophysical properties of heterocycle 3 in CHCl3, large red shifts in both the absorption and emission spectra are observed, which aligns with our previous studies on the PN Scaffold (Figures F.1 and F.2, Table 7.1). In ca. 5% DMSO in pH 7.4 PBS buffer, nearly 50 nm red shifts are observed in both the lower energy absorption peak and the emission wavelengths (Figures F.1 and F.2, Table 7.2). This leads to a large increase in the absorbance at 405 nm, thus increasing the effective brightness of 3 in this imaging procedure. Interestingly, methylation of the PN N–H in 3 leads to a 10 to 15 nm red shift in both the absorption and emission spectra in both solvent systems when compared to the unmethylated heterocycle 7. Furthermore, the effects of methylation on acid- and base- sensitivity for the PN heterocycles reported herein were tested by preparing ca. 1 × 104 M solutions of each fluorophore were prepared in 5% DMSO in deionized H2O or in CHCl3. UV-vis and fluorescence spectra were collected in both of these solvent systems. Then, for the base-stability studies, either a concentrated solution of NaOH or DBU was added to bring the solution to ca. pH = 13 or 5% DBU in CHCl3, respectively. The absorption and emission spectra were collected immediately after addition of the base. Then, the samples were left for 24 hours, before the absorption and emission spectra were collected again. 132 For the acid-stability studies, another set of ca. 1 × 104 M solutions of each fluorophore were prepared in 5% DMSO in deionized H2O or CHCl3, which again had their absorption and emission spectra collected. Then, either HCl or trifluoroacetic acid (TFA) was added to bring the solution to ca. pH = 2 or 5% TFA in CHCl3, respectively. Spectra were collected immediately after addition of the acid, and again after 18 hours. Compared to unmethylated heterocycles 1 and 7, which show a dramatic red shift and quench in the emission spectra after treatment with base, heterocycles, 3, 9, and 8 show relatively no change in their emission spectra upon treatment with base (Figures F.3 to F.7). To test the imaging capabilities of 3, HeLa cells were treated with the same procedure outlined for 1 (Figure 7.3). Gratifyingly images of 3 were much brighter than those of 1, likely due to the increased absorbance at 405 nm. Cytotoxicity was measured using the same CCK-8 cell assay as mentioned above, which showed no cytotoxicity even up to 150 μM dye concentration (Figure 7.4). These results present 3 as a more suitable cell imaging reagent, and further optimization and stability studies are underway to fully characterize it as such. Figure 7.3 Initial images of HeLa cells upon treatment with a 25 μM solution of 3 and incubation for 30 minutes. 133 Figure 7.4 Cytotoxicity studies on heterocycle 3 showing no significant cytotoxicity up to 150 μM. Next, we wanted to see if this new fluorophore scaffold could be further functionalized such that it could be appended to different subcellular location targeting groups. For this we designed heterocycle 8, integrating the well-known lysosome-targeting morpholine unit.24 To access 8, we first hydrolyzed the ester group of 3 to give the respective carboxylic acid 9. Peptide coupling with HBTU and 4-(2- aminoethyl)morpholine 10 is then used to afford 8 in moderate yields (Scheme 7.3). Crystals suitable for x-ray crystallography of 8 were grown, confirming the correct connectivity (Figures F.8 and F.9). Scheme 7.3 synthesis of heterocycle 8. 134 The photophysical properties of 8 are nearly identical to those of heterocycle 3 in CHCl3 (Figures F.1 and F.2, Table 7.1). This makes sense because the only difference between the structures is the ethyl ester of 8 being replaced with the morpholine-containing amide arm, but of which are moderately EWG. Interestingly, the quantum yield of 8 is 63%, which is almost triple that of 3, potentially due to solvent interaction with the hydrogen bond donating and accepting amide arm of 8 reducing thermal relaxations upon relation. This trend in the quantum yields is again seen in 5% DMSO in pH 7.4 PBS buffer. Additionally, 8 in this DMSO mixture shows a more blue-shifted absorption spectra, again suggesting that solvent coordination around the protic and polar amide arm may be influencing the photophysical properties of the scaffold (Figures F.1 and F.2, Table 7.2). While this blue-shifting in the absorbance leads to a decrease in the absorbance at 405 nm for imaging purposes, the increased quantum yield leaves the overall virtual brightness at 405 nm about the same as 3. The targeting capabilities of 8 are currently being studied through co-localization studies with lysotracker deep red (Figure 7.5). These tests were performed with three plates of HeLa cells where one is treated with 10 μM 8 (Figure 7.5, left), one is treated with 10 μM 8 and 75 nM LysoTracker Deep Red (Figure 7.5, right), and the third is treated with just DMSO and all cells are incubated for one hour. Then, cells were rinsed with FluoroBrite media and imaged on a Leica widefield scope. The probe was imaged with the DAPI long pass cube, and LysoTracker is imaged with Cy5. The images are all colored with a Red Hot filter.Similarities between the dye images and the lysotracker images can be observed, including small puncta throughout the cells indicating potential lysosome targeting. However, a large amount of both the dye as well as the lysotracker dyes are non- 135 localized throughout the cell, indicating a potential experimental, chemical, or instrumental issue during the experimental process. While this initial result is very exciting, higher resolution images must be collected to confirm the localization of 8 in the lysosome. Figure 7.5 colocalization with 8 and Lysotracker Deep Red. 7.3 Conclusions and Future Works We have prepared a series of cell imaging reagents based upon the coumarin-like phosphaquinolinone scaffold. With good solubilities, excellent Stokes shift, and moderate brightnesses in DMSO/PBS mixtures, this PN framework is poised to expand the toolkit available to both chemists and chemical biologists for live cell imaging applications. These new dyes are non-cytotoxic, cell permeable, robust, and targetable. To gain a more comprehensive understanding of these dyes and their capabilities in a variety of imaging applications, a few studies must be performed. First and foremost, efforts are underway currently to attain higher resolution images that corroborate the localization of the dye into the lysosome of the cell. Once this is confirmed, other functional groups can be appended via similar peptide coupling conditions to broaden the scope of where these dyes can be targeted, including the mitochondria, the golgi apparatus, and the nucleus. Furthermore, 136 with the permeability presented by these simple naphthalene-like PN scaffolds, it could be beneficial to explore the larger acene backbone PN derivatives that have been developed in these imaging experiments as well. While the increased size of the scaffold may inhibit cell permeation, the inherently brighter fluorophores would give much brighter images of cells if they were able to enter cells. Lastly, while this study focuses on the methylated version of the scaffold, derivatives that retain the protic N-H may be an interesting class of dyes as well, since it has been shown that the phosphaquinolinone scaffold increases in brightness and its emission red shifts dramatically upon deprotonation. While the scaffold decomposes upon deprotonation, the timescale of that decomposition has not been studied fully. If images using the deprotonated form of the dye are able to be collected before said decomposition occurs, then brighter images may be attainable. These studies, combined with the work herein, present the phosphaquinolinone framework as a promising new class of cellular imaging agents. 7.4 Experimental Section General. All oxygen- and water-free reactions were performed under an N2 atmosphere using Schlenk technique. Column chromatography was performed using silica gel (240– 300 mesh), with solvent systems being referenced to the most abundant solvent. NMR spectra were acquired at room temperature on a Varian Inova 500 (1H: 500 MHz, 13C: 126 MHz, 31P: 202 MHz) or a Bruker Avance III HD 500 equipped with a Prodigy multinuclear cryoprobe (1H: 500 MHz, 13C: 126 MHz, 31P: 202 MHz). 1H and 13C NMR chemical shifts (δ) are expressed in ppm relative to residual CHCl (13 H: 7.26 ppm, 13C: 77.16 ppm) or DMSO (1H: 2.50 ppm, 13C: 39.52 ppm) shifts. 31P NMR shifts are referenced to 85% H3PO4 (δ 0 ppm) as an external reference. 19F NMR shifts are referenced to CFCl3 (δ 0 ppm) as 137 an external reference. UV-vis spectra were recorded using an Agilent Technologies Cary 60 UV-vis spectrophotometer. Fluorescence emission spectra were recorded using a Horiba Jobin Yvon FluoroMax-4 fluorimeter exciting at 365 nm. Quantum yields (ϕ) were determined through comparison of the emission and absorption intensities of the analyte to those of a 0.1M H2SO4 quinine sulfate solution. 25 Fluorescence lifetime measurements were recorded using a Horiba FluoroHub Single Photon Counting Controller with a TemPro Fluorescence Lifetime System attachment. High-resolution mass spectra (HRMS) were recorded on a Waters XEVO G2-XS mass spectrometer. H,H PhAZP 1 was prepared by treating 2-(2-phenylethynyl)-benzenamine 2 (665 mg, 3.4 mmol, 1 equiv.) with P(Ph)(OPh)2 (2.0 g, 6.9 mmol, 2 equiv.) in pyridine (4 mL) and heating in a sand bath to 110 °C for 48 h. The reaction mixture was then cooled to room temperature before ca. 20 mL of toluene was added and the solvent was removed in vacuo. Two more analogous toluene washes were performed to fully remove pyridine from the mixture. The crude residue was then dissolved in minimal THF and 5 drops of water were added before the solution was heated to 60 °C for 1 h in a water bath. The mixture was then dried (Na2SO4), filtered, and concentrated in vacuo. Column chromatography (2:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.15) and subsequent recrystallization from CH2Cl2 and hexanes was used to give heterocycle 1 (565 mg, 52%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, Chloroform-d) δ 7.66 (d, J = 7.1 Hz, 1H), 7.65 – 7.61 (m, 1H), 7.62 (d, J = 32.7 Hz, 1H), 7.61 – 7.56 (m, 3H), 7.38 (t, J = 8.0 Hz, 2H), 7.33 – 7.17 (m, 6H), 7.01 138 (d, J = 8.1 Hz, 1H), 6.99 (t, J = 7.4 Hz, 1H). 13C NMR (126 MHz, Chloroform-d) δ 139.6 (d, J = 3.6 Hz), 139.0 (d, J = 4.0 Hz), 136.9 (d, J = 11.5 Hz), 133.2 (d, J = 138.6 Hz), 132.6 (d, J = 10.6 Hz), 132.0 (d, J = 2.8 Hz), 130.6, 130.5, 128.7, 128.3, 128.2, 127.9 (d, J = 5.9 Hz), 127.3 (d, J = 117.7 Hz), 120.8, 119.6 (d, J = 12.3 Hz), 117.2 (d, J = 7.7 Hz). 31P NMR (202 MHz, Chloroform-d) δ 11.99; HRMS (ASAP) [M + H]+ calcd for C20H17NOP 318.1048, found 318.1032. Aniline 6 was prepared by first dissolving 4-tert-Butyl-2-((trimethylsilyl)ethynyl)aniline 4 (2.18 g, 8.9 mmol, 1.0 equiv.) and K2CO3 (3.70 g, 26.7 mmol, 3.0 equiv.) in 70 mL of 1:1 MeOH:CHCl3 and stirring at room temperature for 1.5 h. Once the protodesilylation reaction was complete by TLC, the reaction mixture was reduced in vacuo. The crude mixture was then suspended in ca. 20 mL CH2Cl2 and washed 3 × with H2O. The organic layer was collected, dried (Na2SO4), and concentrated in vacuo. The crude terminal acetylene was then carried forward to the next step. Sonogashira cross-coupling was then performed by adding Ethyl 4-bromobenzoate 5 (2.04 g, 8.9 mmol, 1.0 equiv.), CuI (119 mg, 0.623 mmol, 0.07 equiv.), and Pd(PPh3)2Cl2 (437 mg, 0.623 mmol, 0.07 equiv.) to the crude terminal acetylene. This mixture was then dissolved in THF (30 mL) and the solution was made air-free using four rounds of atmosphere exchange with N2. TEA (30 mL) was then added via syringe before the reaction was heated to 50 °C and stirred for 48 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo. Three 20 mL portions of EtOAc were added to the 139 reaction mixture and subsequently removed in vacuo to remove the residual TEA. Column chromatography (16:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.20) was used to give aniline 6 (1.53 g, 53%) as an orange solid: mp > 97.5-98.8 °C; NMR 1H NMR (500 MHz, Chloroform-d) δ 8.03 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 2.4 Hz, 1H), 7.21 (dd, J = 8.5, 2.3 Hz, 1H), 6.69 (d, J = 8.5 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 4.18 (s, 2H), 1.41 (t, J = 7.2 Hz, 3H), 1.29 (s, 9H). 13C NMR (126 MHz, Chloroform-d) δ 166.1, 145.6, 141.0, 131.3, 129.7, 129.5, 128.8, 128.1, 127.7, 114.4, 106.9, 93.6, 89.6, 61.1, 33.9, 31.4, 14.3; HRMS (ASAP) [M + H]+ calcd for C21H24NO2 322.1807, found 322.1816. Heterocycle 7 was prepared by treating aniline 6 (960 mg, 2.98 mmol, 1.0 equiv.) with P(Ph)(OPh)2 ( 1.76 g, 5.96 mmol, 2.0 equiv.) in pyridine (5 mL) and heating in a sand bath to 110 °C for 48 h. The reaction mixture was then cooled to room temperature before ca. 20 mL of toluene was added and the solvent was removed in vacuo. Two more analogous toluene washes were performed to fully remove pyridine from the mixture. The crude residue was then dissolved in minimal THF and 5 drops of water were added before the solution was heated to 60 °C for 1 h in a water bath. The mixture was then dried (Na2SO4), filtered, and concentrated in vacuo. Column chromatography (5:1:1 → 1:1:1 hexanes:EtOAc:CH2Cl2, Rf = 0.15 in 3:1:1) and subsequent recrystallization from CH2Cl2 and hexanes was used to give heterocycle X (652 mg, 49%) as a yellow solid: mp > 250 °C; NMR 1H NMR (500 MHz, Chloroform-d) δ 7.90 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 3.0 Hz, 1H), 7.68 (d, J = 31.1 Hz, 1H), 7.67 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 7.3 Hz, 1H), 7.60 140 (d, J = 7.3 Hz, 1H), 7.40 (d, J = 2.3 Hz, 1H), 7.38 – 7.31 (m, 2H), 7.24 (dt, J = 7.5, 3.9 Hz, 2H), 6.99 (d, J = 8.5 Hz, 1H), 4.32 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H), 1.34 (s, 9H). 13C NMR (126 MHz, Chloroform-d) δ 166.4, 143.6, 141.5 (d, J = 11.6 Hz), 140.9 (d, J = 3.2 Hz), 132.8 (d, J = 139.4 Hz), 132.5 (d, J = 10.8 Hz), 131.9 (d, J = 2.7 Hz), 129.7, 129.4, 128.5, 128.2, 128.1, 127.6 (d, J = 6.2 Hz), 127.1, 126.0 (d, J = 119.1 Hz), 118.7 (d, J = 12.1 Hz), 117.0 (d, J = 7.6 Hz), 61.0, 34.2, 31.4, 14.3. 31P NMR (202 MHz, Chloroform- d) δ 11.79; HRMS (ASAP) [M + H]+ calcd for C27H29NO3P 446.1888, found 446.1885. Methylated heterocycle 3 was prepared by dissolving tbu ester heterocycle 7 (78 mg, 0.175 mmol, 1.0 equiv.) in dry CH2Cl2 and the mixture was put under N2 via atmosphere exchange. MeI (0.9 mL, 3.95 mmol, 22.5 equiv.) was then added before DBU (0.4 mL, 1.75 mmol, 10 equiv.) was added dropwise, which induced an immediate red-shift in both the color of solution and the emission color of the solution. The solution was let stir for 16 h, at which point the solution had returned to its original color and the reaction was complete via TLC. The reaction mixture was then reduced in vacuo, before being dissolved in CH2Cl2, washed 3 × with an aqueous NaHCO3 solution to remove excess DBU. After drying (K2CO3), filtering, and concentration in vacuo, methylated PN heterocycle 3 was afforded as a yellow solid (79 mg, 98% yield) in an excellent yield: mp 125.4-126.8 °C; NMR 1H NMR (500 MHz, Chloroform-d) δ 7.91 (d, J = 8.1 Hz, 2H), 7.83 – 7.61 (m, 5H), 7.50 (d, J = 8.7 Hz, 1H), 7.46 (s, 1H), 7.39 (t, J = 6.7 Hz, 1H), 7.34 (td, J = 7.5, 3.2 Hz, 2H), 7.04 (d, J = 8.7 Hz, 1H), 4.33 (q, J = 7.1 Hz, 2H), 3.12 (d, J = 7.7 Hz, 3H), 1.37 (s, 141 9H), 1.35 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, Chloroform-d) δ 166.4, 143.3, 141.4 (d, J = 11.7 Hz), 141.0 (d, J = 3.0 Hz), 139.5, 132.4 (d, J = 10.5 Hz), 132.2 (d, J = 138.1 Hz), 132.0 (d, J = 2.8 Hz), 129.7, 129.5, 128.7, 128.5, 128.4, 127.7 (d, J = 6.2 Hz), 125.7 (d, J = 117.8 Hz), 120.0 (d, J = 11.5 Hz), 112.9 (d, J = 5.0 Hz), 61.0, 34.1, 31.5 (d, J = 4.0 Hz), 31.4, 14.3. 31P NMR (202 MHz, Chloroform-d) δ 16.75; HRMS (ASAP) [M + H]+ calcd for C28H31NO3P 460.2042, found 460.2068. Heterocycle 9 was prepared by dissolving methylated heterocycle 3 (200 mg; 0.435 mmol, 1.0 equiv.) in 20 mL THF and 20 mL H2SO4 (30% v:v in H2O) and heating to 85 °C under a reflux condenser for 24 hr. The reaction mixture was then cooled to room temperature before the organic layer was extracted with 5 × rounds of ca. 40 mL EtOAc. The organic layer was the dried (K2CO3), filtered and concentrated in vacuo. Several round of recrystallization from CH2Cl2 and pentanes was used to remove residual EtOAc and afford carboxylic acid 9 (117 mg, 62%) as a yellow solid: mp > 250 °C; NMR 1H NMR (500 MHz, DMSO-d6) δ 8.06 (d, J = 31.2 Hz, 1H), 7.83 (d, J = 8.2 Hz, 2H), 7.79 (d, J = 8.1 Hz, 2H), 7.71 (s, 1H), 7.63 – 7.52 (m, 3H), 7.44 (dt, J = 15.9, 7.5 Hz, 3H), 7.14 (d, J = 8.8 Hz, 1H), 2.99 (d, J = 7.6 Hz, 3H), 1.33 (s, 9H). 13C NMR (126 MHz, DMSO-d6) δ 166.9, 142.6, 141.1, 141.0, 139.1, 132.3 (d, J = 134.5 Hz), 132.1, 131.8 (d, J = 10.8 Hz), 129.4, 129.3 (d, J = 105.0 Hz), 128.7, 128.6 (d, J = 8.9 Hz), 127.4 (d, J = 6.1 Hz), 124.9, 123.9, 119.5 (d, J = 11.2 Hz), 113.1, 33.8, 31.2, 31.1. 31P NMR (202 MHz, DMSO-d6) δ 15.7; HRMS (ASAP) [M + H]+ calcd for C26H27NO3P 432.1729, found 432.1758. 142 Morpholine-containing PN heterocycle 8 was prepared via peptide coupling conditions. Carboxylic acid PN 9 (314 mg; 0.730 mmol, 1.0 equiv.) and HBTU (554 mg; 1.46 mmol, 2.0 equiv.) were added to a round-bottom flask, which was then put under an N2 atmosphere via atmosphere exchange. This mixture was then dissolved in dry CH2Cl2 (18 mL) before 4-(2-aminoethyl)morpholine 10 (0.38 mL, 2.92 mmol, 4.0 equiv.) was added. Lastly, DIPEA (0.140 mL; 0.82 mmol, 1.0 equiv.) was added via Hamilton syringe. The reaction was stirred for 1 hour, at which point it showed complete conversion of starting material. The reaction mixture was then concentrated in vacuo before being suspended in MeCN and cooled in an ice bath for 1 h. Salt byproducts then crashed out and were filtered off. The organic solution was then reduced to dryness in vacuo and redissolved in minimal DCM. Pentanes was slow-layered and left overnight. This initial process led to a brown oil coating the bottom of the flask, which allowed for a cleaner product solution to be decanted, reconcentrated, and set up for another round of recrystallization following the same procedure. This led to a fluorescent, yellow oil suspending on the bottom of the flask with crystalline yellow solids dotted throughout. The organic layer was removed, and the oil/solid mixture was dried in vacuo to afford 8 (126 mg; 32% yield) as a yellow solid: mp > 234.5-235.9 °C. It is expected that the reaction yield is higher than this, however, due to structural similarities between the product and the coupling side-products, the isolation of more product presents a significant challenge. 1H NMR (500 MHz, DMSO-d6) δ 8.35 (t, J = 5.7 Hz, 1H), 8.04 (d, J = 31.4 Hz, 1H), 7.80 – 7.66 (m, 5H), 7.64 – 7.51 (m, 3H), 7.48 143 (td, J = 7.3, 1.5 Hz, 1H), 7.43 (td, J = 7.1, 3.3 Hz, 2H), 7.13 (d, J = 8.7 Hz, 1H), 3.55 (t, J = 4.6 Hz, 4H), 3.35 (d, J = 6.7 Hz, 2H), 2.99 (d, J = 7.6 Hz, 3H), 2.42 (t, J = 7.0 Hz, 2H), 2.39 (t, J = 4.0 Hz, 4H), 1.34 (s, 9H). 13C NMR (126 MHz, DMSO-d6) δ 165.6, 142.5, 140.6, 139.2 (d, J = 12.0 Hz), 139.0, 133.5, 132.4 (d, J = 134.8 Hz), 132.0, 132.0, 131.7 (d, J = 10.3 Hz), 128.6 (d, J = 13.1 Hz), 128.4, 127.3, 127.1 (d, J = 6.2 Hz), 124.5 (d, J = 116.9 Hz), 119.5 (d, J = 11.3 Hz), 113.0, 66.2, 57.3, 53.3, 36.5, 33.8, 31.2, 31.0 (d, J = 3.7 Hz). 31P NMR (202 MHz, DMSO-d6) δ 15.77; HRMS (ASAP) [M + H] + calcd for C32H39N3O3P 544.2729, found 544.2737. 144 CHAPTER VIII DEVELOPMENT OF A TRIPODAL SWITCHABLE, SELECTIVE, AND SENSITIVE HOST MOLECULE CAPABLE OF HSO –4 EXTRACTION TOWARDS NUCLEAR WASTE REMEDIATION This chapter includes unpublished work from an ongoing study that focuses on the development, synthesis, and utilization of a 3-armed, PN host molecule towards hydrogen sulfate extraction and remediation from aqueous solutions. This story was written by Jeremy P. Bard, synthesis was performed by Dr. Chun-Lin Deng and Jeremy P. Bard with assistance from J. Nolan McNeill. Titration data was collected by Jeremy P. Bard. Editorial support was provided by Michael M. Haley and Darren W. Johnson. 8.1 Introduction Anions play an important role in several areas including biology, environmental sciences, and chemistry.1–4 For this reason, a large library of compounds have been developed with the ability to detect many of these anions both selectively and sensitively.5 While halides and nitrate have a variety of hosts because of their simple shape and uniformity of charge, a majority of oxoanionic guests have relatively few hosts that are capable of binding them due to their combination of hydrogen bond donors and/or acceptors as well as their unique geometries. Of these oxoanions, the tetrahedral HSO -4 stands out because of its roles as a chemical catalyst, environmental contaminate, and aerosol nucleation initiator. Furthermore, HSO -4 acts as a major interferant in the treatment process of high-level nuclear waste by disrupting the efficient vitrification of the 145 radioactive TcO - anion.6–9 Removal of the HSO -4 4 contaminate from the aqueous nuclear waste solution prior to its treatment would allow for more efficient vitrification and subsequent storage of nuclear waste. Of the methods proposed to accomplish this task, liquid-liquid extraction (LLE) rises to the top as one of the more promising possibilities. LLE is performed by mixing an organic solution that is doped with an extractant with the aqueous nuclear waste solution. With judicious choice of extractant, the substrate of choice (HSO -4 ) is pulled into the organic solution, which upon separation of layers can be removed. Ideally, this organic layer can then be washed and recycled for future uses in LLE. These topics have built up quite an interest in HSO -4 binding, sensing, and remediation, and several groups have developed hosts for HSO - coordination.10–154 However, many of the examples shown do not exhibit excellent selectivity towards HSO -4 . This prohibits their use as a potential extractant for nuclear waste remediation based upon the variety of different anions present in the aqueous slurry. Increased selectivity must be attained in a host before it can be explored as a potential extractant. In line with our lab’s interest in both anion binding with bisurea hosts (1 in Figure 8.1) as well as exploration of the relatively new phosphorus- and nitrogen-containing (PN) phosphaquinolinone scaffold,16–19 we recently reported two-armed scaffold 2, which is capable of binding HSO -4 both selectively (ca. 50:1 binding over similar competing ions) and strongly (K -1a = 9600 M ).ref This selectivity was due in large part to both the tetrahedral geometry of the PN phosphonamidate arm as well as the complementary alignment of hydrogen bond donors and acceptors between the host and the guest. 146 Figure 8.1 Structures of the studied bisurea host 1 and hybrid PN-urea host 2 as well as the structure of proposed 3-armed host 3. Gratifyingly, this host showed promise as a potential extract in LLE experiments as well, showing the ability to extract HSO -4 even from sulfuric acid solutions. While this host performed very well as a proof of principle for the utilization of our PN scaffold as a host moiety for HSO -4 , a great deal of clean water was used to subsequently release the bound HSO -4 guest to allow for the reuse of the host. While this is not a problem on the lab-scale, the necessity to use large amounts of fresh water in the industrial scale of nuclear waste remediation diminishes some of the feasibility of this system. With this in mind, our lab has been developing a system that not only can use saline water as a way to release the bound HSO -4 instead of fresh water, but also a system that actually benefits from the use of saline water; thus, we developed hybrid host 3 (Figure 8.2). As shown in Figure 8.2, host 3 can exist in two different conformations: one where a binding pocket is composed of one urea arm and the PN arm (Conformation A) and the other where binding uses two urea arms (Conformation B). Conformation A replicates the binding pocket of the two-armed, PN-host 2, whereas conformation B replicates the binding pocket of the more traditional bisurea binding scaffold 1 that has been studied extensively in our lab.17 147 Figure 8.2 The two conformations that 3 can take when in the presence of HSO -4 (conformation A, left), or Cl- (conformation B, right). As mentioned previously, in Conformation A, 3 should exhibit strong and selective binding of HSO -4 , yet conformation B loses the geometric complementarity of the PN center from its binding pocket and therefore should also lose the ability to bind HSO -4 strongly. However, the bisurea pocket present in conformation B is identical to that of bisurea hosts 1, which have been shown to bind Cl- very strongly and selectively, indicating a potential for two separate binding modes for 3. As shown for similar aryl ethynyl systems, the acetylene linkers can freely rotate in order to access different conformations depending on solvent, guest, and host morphology. By this logic, there should be a way to control this switching of conformations based solely on the environment the host is in. So, in the presence of HSO -4 , 3 should reside in Conformation A by forming the 3•HSO - 4 complex. Conversely, in the presence of chloride, 3 should adopt conformation B, as it will then form the 3•Cl- complex. Furthermore, if the 3•HSO -4 complex is present, and the solution is mixed with Cl--containing water (e.g., sea water), then the host should both release HSO -4 into the aqueous layer as well as favor a conformational switch to Conformation B, leading 148 to an additive effect of removing HSO -4 from the host. This 3•Cl - complex could then potentially be used directly in further LLE processes, or small amounts of fresh water could also be used to release the bound chloride, leading to less fresh water overall needed in the process. 8.2 Results and Discussion To prepare host 3, as outlined in Scheme 8.1, 4-tert-butyl-2-ethynylaniline 4 was Sonogashira cross-coupled with 1-bromo-3,5-diiodobenzene 5 to give dianiline 6. Compound 6 was then Sonogashira cross-coupled with TMSA to afford TMS-protected acetylene 7, which underwent protodesilylation and subsequent cross-coupling with iododinated PN heterocycle 8 to furnish the penultimate dianiline 9. Lastly, compound 9 was treated with two equivalents of 3,5-bis(trifluoromethyl)phenyl isocyanate to afford final product 3 in good yield. While a majority of the characteristic 31P splitting is not easily observed in either the 1H or the 13C NMR spectra due to the number and complexity of the signals, the characteristic PN 31P signal is observed around 10 ppm. Upon isolation, the anion binding abilities of 3 were tested using a variety of NMR titration experiments. First, sequential additions of a TBACl solution to a ca. 1 mM host solution in 10% d6-DMSO in CDCl3 were performed and the 1H and 31P NMR signals were tracked after each addition (Figures 8.3 and 8.4, respectively). Gratifyingly, a simple pattern peak shifting can be observed, which is indicative of the typical bis-urea chloride binding that the traditional hosts in our lab have ben shown to exhibit. 149 Scheme 8.1 Synthesis of 3-armed hybrid host 3. When analyzing the 1H NMR spectra, the positions of the two urea signals were tracked and their change as a function of guest added was fit using non-linear regression analysis20 to afford a binding constant of 5000 M-1. Additionally, the 31P NMR spectra show no significant shift upon treatment with TBACl, suggesting that 3 is indeed adopting 150 conformation B when in the presence of Cl-. These shifting patterns reflect what have been seen for the analogous, previously reported bisurea systems.16–18 Figure 8.3 1H NMR titration experiment of 3 with additions of Cl-. Free host is shown on top. Figure 8.4 31P NMR titration experiment of 3 with additions of Cl-. Free host is shown on top. 151 The same experiments were then performed using TBAHSO4. When looking at the 1H NMR spectra, however, an interesting trend is seen as the HSO -4 guest concentration increases (Figure 8.5). Upon initial treatments with the guest, a consistent downfield trending shift is seen for the urea protons as well as the PN N-H, suggesting that the host is adopting conformation A. However, once a 1:1 host:guest ratio is reached, there is a change in the direction of shifting for some of the peaks. Once more guest is added after this equal ratio, the urea peak as well as the central aromatic proton begin shifting back upfield, while the PN N-H peak continues to shift consistently downfield. Figure 8.5 1H NMR titration experiment of 3 with additions of HSO -4 . Free host is shown on top and the 1:1 3:HSO -4 point is shown in the dark blue spectrum. 152 Figure 8.6 31P NMR titration experiment of 3 with additions of HSO -4 . Free host is shown on top and the 1:1 3:HSO -4 point is shown in the dark blue spectrum. These results are very intriguing, as they suggest that there is indeed a conformation switch as well as potentially a binding mode transformation once there is excess guest present. When looking at the 31P NMR spectra after each addition (Figure 8.6), there is the expected unidirectional shifting observed, suggesting that the PN center is taking place in the binding at every point of the experiment. When fitting the data from the 31P NMR peak positions using non-linear regression analysis, a bimodal 2:1 host:guest model fit very well and gave a Ka,1 = 2000 M -1 and a Ka,2 = 1000 M -1. A qualitative competition experiment was then performed, which suggests that the host can indeed switch between conformations (See Appendix G). 8.3 Conclusions and Future Works While this preliminary data suggests that our host has the potential to be used as a switchable, selective, and sensitive extractant in LLE experiments towards the remediation of high-level nuclear waste, further studies need to be performed to understand both the 153 mechanism(s) of binding for HSO -4 and Cl -, as well as the interplay between the two competing guests. First and foremost, a solid understanding of the mode of binding for HSO -4 must be established, as this has an impact upon future studies upon the host’s extraction and binding capabilities. This will be done using a multi-faceted approach. 2D- NMR experiments may help shed light on the conformation(s) that 3 is taking in solution in the presence of both one equivalent of HSO -4 as well as an excess of HSO - 4 . This can be further supported by crystal growth attempts from mixed solutions containing these ratios of host and guest to try and capture the binding geometry at those points. Computational modelling of these binding events will also be paramount to understanding how our host is binding with HSO -4 , which will help explain the complex shifting in the NMR spectra. More complex mathematical models may also be necessary to fit a more complex mode of binding than the currently hypothesized 2:1 host:guest binding ratio. Once the mechanism of HSO -4 binding is better understood, 3 will be screened against several other anions present in high-level nuclear waste. Two of the most abundant anions in high-level nuclear waste that will be tested with our host are fluoride and TcO -4 , neither of which should be suitable guests owing to their extremely high electronegativity and the large size, respectively. For testing the binding affinity for TcO -4 , ReO - 4 will be used as a non-radioactive anologue in its place as is common in these types of studies. With this library of binding data, both the selectivity and binding strength profiles will be built for host 3, and binding of HSO -4 will be attempted in mixed media with competing anions present as well, including Cl-, F-, and ReO -4 . Speciation diagrams can be built to understand the nature of the host more fully when subjected to several guests at once. 154 LLE experiments with 3 can be performed and the results of which can be compared to those of hybrid host 2. These will start with simple extraction experiments, taking HSO -4 from aqueous solutions as well as sulfuric acid solutions to confirm similar extraction capabilities as 2. In place of fresh water in the washing/recycling step after the initial HSO -4 extraction, minimal amount of saline water will be used instead to test the design principles outlined above. It is expected that minimal saline water will be needed to fully remove HSO -4 from the organic solution of 3. Then, further LLE experiments in the presence of competing anions will be performed. Initial tests will start with equimolar mixtures of Cl- and HSO -4 , then systematically approach mixtures that more closely represent the high-level nuclear waste we aim to remediate. While these studies are still underway, we have made significant progress in the development of a potentially switchable, sensitive, and selective host for HSO -4 extraction from aqueous solutions including high-level nuclear waste. Good binding strengths for HSO - -4 and Cl have been observed and potential conformational switching is corroborated by unique patterns in NMR titration experiments. Once a more complete understanding of the modes and mechanism of guest binding are achieved through a combination of experimental, computational, and mathematical methods, we will be more able to use host 3 as an extractant in LLE procedures for high-level nuclear waste remediation. 8.4 Experimental Section General. NMR spectra were obtained on a Varian Inova 500 MHz (1H: 500.11 MHz, 13C 125.76 MHz, 19F 470.53 MHz, 31P 202.46 MHz) or a Bruker Avance-III-HD 600 MHz (1H: 599.98 MHz, 13C: 150.87 MHz) spectrometer. Chemical shifts (δ) are expressed in ppm 155 using residual non-deuterated solvent present in the bulk deuterated solvent (CDCl 13: H 7.26 ppm, 13C 77.16 ppm; DMSO-d6: 1H 2.50 ppm, 13C 39.52 ppm). 19F chemical shifts are reported against CFCl3 external standard (δ 0 ppm). 31P chemical shifts are reported against 85% H3PO4 (δ 0 ppm) as external reference. Mass spectra data were acquired on a Waters SYNAPT QToF in positive ion mode with a Shimadzu LC20AD HPLC front end. The solvents were MeCN:H2O:0.1% HCO2H at a flow rate of 0.05 mL min –1 with a 5 μL injection on a loop injection. Preparative SEC was performed using a JAI Recycling Preparative HPLC (Model LC-9101) with a JAIGEL-1H preparative column with CHCl3 as solvent. Analytical TLC was carried out on TLC plates (5  10 cm with 0.25 mm thickness, silica gel 60 F254, Merck, Darmstadt, Germany) cut from the commercially available aluminium sheets. Solvents and reagents were used as purchased from suppliers, unless anhydrous conditions were employed, in which case, solvents were freshly distilled from sodium/benzophenone under N2 atmosphere (THF) or as purchased. Ethynylaniline 4, 3,5-diiodobromobenzene 5, and iodoheterocycle 8 were synthesized by their reported procedures.19 Dianiline 6. To an N2-sparged solution of 3,5-diiodobromobenzene 5 (818 mg, 2 mmol) and terminal acetylene 4 (982 mg, 4 mmol) in THF/Et3N (0.05 M, v/v = 1:1) was added 5 mol% Pd(PPh3)2Cl2 and 5 mol% CuI. The suspension was stirred at room temperature under an N2 atmosphere for 12 h. The reaction mixture was concentrated in vacuo and purified via flash chromatography to give product 6 (800 mg, 80%) as a dark orange oil. Rf = 0.27 (hexanes/EtOAc, 7:1). 1H NMR (600 MHz, CD2Cl2) δ 7.65 (d, J = 1.7 Hz, 3H), 7.39 (d, J = 2.4 Hz, 2H), 7.23 (dd, J = 8.5, 2.4 Hz, 2H), 6.70 (d, J = 8.5 Hz, 2H), 4.23 (s, 156 4H), 1.30 (s, 18H). 13C NMR (151 MHz, CD2Cl2) δ 146.4, 141.2, 133.7, 133.0, 129.2, 128.2, 126.0, 122.3, 114.7, 106.6, 92.2, 89.1, 34.2, 31.5. Ethynylsilane 7. A ~0.1 M solution of the 6 (500 mg, 1 mmol) in THF/Et3N (0.05 M, v/v = 1:1) was purged for 15 min with N2 and then TMSA (0.2 mL, 1.5 mmol) was added via syringe. After an additional 5 min N2 purging, CuI (19 mg, 0.1 mmol) and Pd(PPh3)2Cl2 (70 mg, 0.1 mmol) were added to the reaction mixture. The flask was then purged for an additional 5 min, then sealed and stirred at 80 oC (oil bath) under N2 for 12 h. The mixture was concentrated, and the residue chromatographed on silica gel (8:1 hexanes/EtOAc) to afford the desired TMS-protected ethynylsilane 7 (428 mg, 83%) as a solid. Rf = 0.27 (hexanes/EtOAc, 7:1). 1H NMR (600 MHz, CDCl3) δ 7.63 (t, J = 1.5 Hz, 1H), 7.57 (d, J = 1.6 Hz, 2H), 7.37 (d, J = 2.3 Hz, 2H), 7.21 (dd, J = 8.5, 2.3 Hz, 2H), 6.69 (d, J = 8.5 Hz, 2H), 4.19 (s, 4H), 1.29 (s, 18H), 0.26 (s, 9H). 13C NMR (151 MHz, CDCl3) δ 145.6, 141.1, 134.1, 133.9, 128.9, 127.7, 124.2, 124.0, 114.6, 107.1, 103.4, 95.9, 92.8, 87.9, 34.1, 31.5, 0.0. Host 3. To a solution of 7 (178 mg, 0.21 mmol, 1.0 equiv.) in 5 mL MeOH was added K2CO3 (86 mg, 0.62 mmol, 3.0 equiv.). After stirring the suspension at room temperature for 0.5 h, the mixture was filtered through a bed of Celite. After evaporation of the solvent, the crude residue was used directly in the next reaction. To an N2-sparged solution of 8 (135 mg, 0.25 mmol, 1.2 equiv.) and the resultant crude terminal acetylene (0.21 mmol, 1.0 equiv.) in 5 mL THF was added Pd(PPh3)4 (7 mg, 0.012 mmol, 0.05 equiv.) and 5 mol% CuI (2 mg, 0.012 mmol, 0.05 equiv.), followed by the addition of Et3N (32 mg, 0.315 mmol, 1.5 equiv.). The suspension was stirred at room temperature under an N2 atmosphere for 6 hours until completion by TLC. The reaction mixture was concentrated in vacuo and 157 purified via flash chromatography to give the desired crude diyne product 9 as dark-orange oil. To a solution 9 in 20 mL dry toluene was added 3,5-bis(trifluoromethyl)phenyl isocyanate (134 mg, 0.53 mmol, 2.5 equiv.), and the mixture was stirred at room temperature for 24 h. The reaction was diluted with hexanes and the light-yellow precipitate was isolated. The crude compounds were washed with toluene, then redissolved in CH2Cl2 (10 mL), the desired product 3 was precipitated as fine light-yellow powder upon the slow addition of hexanes. Yield: 123 mg, 43%. Rf = 0.33 (hexanes/EtOAc, 4:1). M.p. > 200 oC. 1H NMR (600 MHz, DMSO-d6) δ 10.13 (s, 2H), 9.42 (s, 1H), 8.39 (s, 2H), 8.20–8.06 (m, 12H), 7.95 (d, J = 7.9 Hz, 2H), 7.68–7.66 (m, 2H), 7.57–7.56 (m, 4H), 7.48 (dd, J = 8.9, 2.7 Hz, 2H) 7.18 (t, J = 7.6 Hz, 2H), 7.00 (t, J = 7.3 Hz, 1H), 6.93 (d, J = 7.9 Hz, 2H), 1.30 (s, 18H), 1.29 (s, 9H). 13C NMR (151 MHz, DMSO-d6) δ 152.1, 150.2 (d, J = 8.9 Hz), 145.4, 143.2, 143.2, 141.5, 140.0 (d, J = 9.9 Hz), 138.4, 137.2, 134.5, 134.3, 132.7, 132.0, 130.7 (q, J = 32.7 Hz), 129.7, 129.5, 128.9, 128.0 (d, J = 6.5 Hz), 127.3, 125.9, 124.9, 124.1, 123.8, 123.6, 123.2, 122.6, 122.3, 120.9 (d, J = 4.0 Hz), 120.5, 120.2, 119.4 (d, J = 14.6 Hz), 118.7, 117.8 (d, J = 4.4 Hz), 114.5, 111.4, 110.6, 109.5 (d, J = 8.4 Hz), 93.6, 93.1, 87.3, 86.5, 34.0, 33.9, 30.9, 30.8. 31P{1H} NMR (202 MHz, DMSO-d6) δ 10.7. 19F{1H} NMR (564 MHz, DMSO-d6) δ –61.86. NMR Titration Procedures. Roughly 1 mM solutions of 3 were prepared in 10% DMSO- d6/CDCl3. 600 μL of this stock was placed into an NMR tube to give the start point of each trial. Roughly 20 mM guest solutions were prepared using the host stock solution as the solvent. Throughout the experiment, aliquots of the guest solution were added to the NMR tube via Hamilton syringe and 31P and 1H spectra were collected after each addition. Ka values were determined by tracking the respective 31P or 1H NMR peaks and fitting them 158 using non-linear regression analysis. Each value reported is the average of at least 3 trials using the same conditions. 159 CHAPTER IX CONCLUDING REMARKS In this dissertation, I have discussed a variety of structure-property relationships performed upon the 2-λ5-phosphaquinolin-2-one scaffold. Chapter 1 highlights the context and discovery of the scaffold in our lab and overviews many of our initial studies upon the physicochemical properties of the scaffold. Chapters 2 and 4 discuss our studies specifically upon the PN-naphthalene system and our efforts towards understanding and improving both the photophysical properties and the supramolecular functionality of the framework. Chapter 3 highlights our initial work on developing a PN-containing host molecule that is capable of binding hydrogen sulfate and extracting it from aqueous solutions. Chapter 5 showcases our development of a PN-pyrene system as a part of our ongoing investigation into the effects of backbone modification. Chapter 6 covers our use of Lawesson’s reagent to thionate the phosphorus center of the PN moiety. This thionated form has the potential to serve as a responsive host for reactive oxygen species. Chapter 7 is about our ongoing studies towards utilizing a variety of PN derivatives as live cell imaging reagents. Lastly, Chapter 8 overviews our development of a 3-armed host capable of binding both chloride and hydrogen sulfate. Due to the different binding modes required to bind these two guests, only one can likely be bound at a time, thus allowing for a controllable switchability between the two depending on conditions around the host. This may have implications in the use of this host in water and nuclear waste remediation activities. 160 APPENDIX A SUPPLEMENTARY INFORMATION FOR CHAPTER 2 1. X-ray Structure Data X-ray Crystallography. Diffraction intensities for 1c and 1g were collected at 173 K on a Bruker Apex2 DUO CCD diffractometer using CuK and MoK (1b) radiations, = 1.54178 Å and 0.71073 Å, respectively. Absorption corrections were applied by SADABS.1 Space groups were determined based on systematic absences. Structures were solved by direct methods and Fourier techniques and refined on F2 using full matrix least- squares procedures. All non-H atoms were refined with anisotropic thermal parameters. H atoms in 1b and 1g were found on the residual density maps and refined with isotropic thermal parameters. H atoms in 1c were refined in calculated positions in a rigid group model. Crystals of 1c were very thin plates with weak diffraction at high angles. Diffraction data for 1c were collected only up to 2θmax = 105.2°; nonetheless, the collected data provide an appropriate number of measured reflections per refined parameters: 4048 per 470. The structure of 1c was determined in space groups P212121 with the Flack parameter of 0.55(8). Three options to get the structure of 1c in monoclinic space groups with beta angles close to 90° and refinements of them as possible twins have been checked, but the final data are given in orthorhombic space group P212121 with a pseudo-center of symmetry. The structure of 1c has been determined not precisely, but it clearly shows composition and the main features of the compound. All calculations were performed by the Bruker SHELXL- 2014/7 package.2 161 Crystallographic Data for 1b: C21H15N2O2P, M = 358.32, 0.25 x 0.23 x 0.14 mm, T = 173(2) K, Monoclinic, space group C2/c, a = 24.331(4) Å, b = 10.2408(18) Å, c = 14.540(3) Å,  = 102.686(3), V = 3534.7(11) Å3, Z = 8, Dc = 1.347 Mg/m3, μ(Mo) = 0.173 mm–3, F(000) = 1488, 2θmax = 50.0°, 11395 reflections, 3113 independent reflections [Rint = 0.0369], R1 = 0.0369, wR2 = 0.0955 and GOF = 1.049 for 3113 reflections (295 parameters) with I>2(I), R1 = 0.0568, wR2 = 0.1104 and GOF = 1.049 for all reflections, max/min residual electron density +0.246/–0.382 eÅ–3. Crystallographic Data for 1c: C21H18NO3P, M = 363.33, 0.08 x 0.06 x 0.02 mm, T = 173(2) K, Orthorhombic, space group P212121, a = 8.4621(5) Å, b = 19.7458(10) Å, c = 21.2129(10) Å, V = 3544.5(3) Å3, Z = 8, Z’=2, Dc = 1.362 Mg/m 3, μ(Cu) = 1.549 mm–1, F(000) = 1520, 2θmax = 105.20°, 17029 reflections, 4048 independent reflections [Rint = 0.0716], R1 = 0.0738, wR2 = 0.1871 and GOF = 1.066 for 4048 reflections (470 parameters) with I>2(I), R1 = 0.0849, wR2 = 0.1949 and GOF = 1.066 for all reflections, max/min residual electron density +0.979/–0.470 eÅ–3. Crystallographic Data for 1g: C25H23N2O2P, M = 414.42, 0.25 x 0.23 x 0.14 mm, T = 173(2) K, Monoclinic, space group P21/n, a = 18.5757(4) Å, b = 6.1760(2) Å, c = 18.9148(5) Å,  = 98.809(2), V = 2144.38(10) Å3, Z = 4, D 3c = 1.284 Mg/m , μ(Cu) = 1.324 mm–1, F(000) = 872, 2θmax = 133.37°, 16784 reflections, 3790 independent reflections [Rint = 0.0630], R1 = 0.0408, wR2 = 0.0999 and GOF = 1.022 for 3790 reflections (363 parameters) with I>2(I), R1 = 0.0564, wR2 = 0.1093 and GOF = 1.022 for all reflections, max/min residual electron density +0.352/–0.325 eÅ–3. 162 Figure A.1 ORTEP drawings of the (left) molecular structure of 1b and (right) hydrogen- bonded dimeric pair of enantiomers; thermal ellipsoids drawn at 30% probability. 163 Figure A.2 ORTEP drawings of the (left) molecular structure of 1c and (right) hydrogen- bonded dimeric pair of enantiomers; thermal ellipsoids drawn at 30% probability. 164 Figure A.3 ORTEP drawings of the (left) molecular structure of 1g and (right) staggered crystal packing motif, likely due to steric repulsion of the bulky alkyl groups; thermal ellipsoids drawn at 30% probability. 165 2. Photophysical Properties of Selected Heterocycles 1 1.2 1n abs 1 1n em 0.8 1a abs 0.6 1a em 0.4 1c abs 0.2 1c em 1o abs 0 275 375 475 575 1o em Wavelength (nm) 1m abs Figure A.4 Absorption and emission spectra of disparate heterocycles 1. Figure A.5 Representative fluorescence decay curve for 1p (red) plotted against Ludox background scattering curve (blue) used as a representative curve for all heterocycles 1. 166 Normalized AU 3. HOMO-LUMO Distributions of Related Subsets of Heterocycles 1 Figure A.6 HOMO and LUMO orbital distributions and energy levels for heterocycles 1g- 1l, where R2 = t-Bu. Figure A.7 HOMO and LUMO orbital distributions and energy levels for heterocycles 1d, 1m-1n, where R2 = CN. 167 Figure A.8 HOMO and LUMO orbital distributions and energy levels for heterocycles 1a, 1j, 1m, and 1o, where R1 = H. 168 4. Geometry Optimizations and Energies for Frontier Orbital Calculations Table A.1 Theoretically optimized coordinates of 1a (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 3.60625 -2.11651 -1.83390 C 4.23195 -1.91891 -0.60148 C 3.50464 -1.50718 0.50108 C 2.12996 -1.28099 0.39242 Zero-point correction = 0.313690 C 1.48134 -1.48318 -0.84139 (Hartree/Particle) C 2.24615 -1.90357 -1.94096 Thermal correction to Energy = N 1.40162 -0.88122 1.49956 P -0.21277 -0.44565 1.58662 0.333021 C -0.81586 -0.88831 -0.02998 Thermal correction to Enthalpy = C 0.05941 -1.30782 -0.97654 0.333965 C -2.25828 -0.73137 -0.31354 Thermal correction to Gibbs Free C -3.22915 -1.06329 0.63991 Energy = 0.263062 C -4.57998 -0.93784 0.34167 C -4.98772 -0.47679 -0.90464 Sum of electronic and zero-point C -4.03164 -0.13315 -1.85496 Energies = -1317.051311 C -2.68079 -0.25303 -1.56111 Sum of electronic and thermal O -0.89520 -0.95216 2.79785 Energies = -1317.031980 O -0.25751 1.18596 1.66956 Sum of electronic and thermal C 0.33803 2.01556 0.73539 C -0.42540 2.51457 -0.31196 Enthalpies = -1317.031036 C 0.15688 3.39268 -1.21821 Sum of electronic and thermal C 1.48891 3.76724 -1.07750 Free Energies = -1317.101939 C 2.23924 3.26563 -0.01970 C 1.66659 2.38842 0.89396 H 5.29891 -2.08673 -0.50047 H 3.99512 -1.35564 1.45752 H 1.74097 -2.06197 -2.88884 H 1.90514 -0.85119 2.37684 H -0.35011 -1.56730 -1.95127 H -2.91844 -1.42927 1.61198 H -5.31819 -1.20615 1.09015 H -4.33833 0.24212 -2.82578 H -1.94231 0.04664 -2.29770 H -1.46410 2.21703 -0.40101 H -0.43677 3.78745 -2.03593 H 1.93929 4.45323 -1.78657 H 3.27629 3.56006 0.10070 H 2.23462 1.99903 1.73090 H 4.18034 -2.43882 -2.69478 H -6.04376 -0.37857 -1.13265 169 Table A.2 Theoretically optimized coordinates of 1b (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 3.85295 -2.21588 -2.03236 C 4.57497 -2.03426 -0.85062 C 3.94727 -1.59519 0.30105 C 2.57650 -1.32348 0.29420 C 1.83126 -1.50973 -0.88689 Zero-point correction = 0.312508 C 2.49695 -1.95984 -2.03906 (Hartree/Particle) N 1.94751 -0.89622 1.45038 Thermal correction to Energy = P 0.36167 -0.40336 1.65599 0.333590 C -0.37593 -0.84300 0.09378 Thermal correction to Enthalpy = C 0.41086 -1.29287 -0.91608 0.334534 C -1.83077 -0.66343 -0.07672 Thermal correction to Gibbs Free C -2.72371 -0.93434 0.96935 Energy = 0.260129 C -4.08863 -0.79285 0.78812 C -4.59032 -0.37106 -0.44620 Sum of electronic and zero-point C -3.70976 -0.08307 -1.49416 Energies = -1409.214483 C -2.34749 -0.22240 -1.30358 O -0.24904 -0.87802 2.91689 Sum of electronic and thermal O 0.37093 1.22729 1.71804 Energies = -1409.193401 C 0.91327 2.02931 0.72741 Sum of electronic and thermal C 0.07552 2.56300 -0.24306 Enthalpies = -1409.192457 C 0.60724 3.41350 -1.20499 Sum of electronic and thermal C 1.96247 3.72582 -1.19493 Free Energies = -1409.266862 C 2.78763 3.19038 -0.21216 C 2.26625 2.34082 0.75661 H 5.64041 -2.23671 -0.82905 H 4.51348 -1.45697 1.21666 H 1.91693 -2.10587 -2.94502 H 2.51354 -0.88817 2.28937 H -0.07819 -1.55184 -1.85348 H -2.33986 -1.26754 1.92662 H -4.77089 -1.01339 1.60066 H -4.09697 0.26049 -2.44628 H -1.67128 0.03495 -2.11119 H -0.98021 2.31671 -0.22893 H -0.04388 3.83643 -1.96259 H 2.37309 4.39081 -1.94677 H 3.84361 3.43750 -0.19292 H 2.89376 1.92726 1.53743 C -5.99599 -0.22614 -0.63657 N -7.13434 -0.10941 -0.79343 H 4.35089 -2.55970 -2.93134 170 Table A.3 Theoretically optimized coordinates of 1c (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 4.04791 -2.18084 -1.96899 C 4.72895 -2.02832 -0.76014 C 4.05953 -1.61508 0.37836 C 2.69002 -1.34291 0.32940 C 1.98521 -1.49946 -0.87996 Zero-point correction = 0. 346376 C 2.69193 -1.92225 -2.01675 (Hartree/Particle) N 2.01859 -0.94233 1.47255 Thermal correction to Energy = 0. P 0.42904 -0.44109 1.62653 368262 C -0.25890 -0.84515 0.03356 Thermal correction to Enthalpy = C 0.56439 -1.27857 -0.95331 0. 369206 C -1.70243 -0.62778 -0.18138 Thermal correction to Gibbs Free C -2.64361 -0.89265 0.81702 Energy = 0. 293227 C -4.00461 -0.71608 0.59626 C -4.45565 -0.26029 -0.64167 Sum of electronic and zero-point C -3.52463 0.02266 -1.64675 Energies = -1431.448506 C -2.17533 -0.15387 -1.41605 O -0.22094 -0.92943 2.86347 Sum of electronic and thermal O 0.45028 1.19120 1.72278 Energies = -1431.426620 C 1.02257 2.00511 0.76106 Sum of electronic and thermal C 0.21704 2.55030 -0.23036 Enthalpies = -1431.425676 C 0.77901 3.41365 -1.16313 Sum of electronic and thermal C 2.13274 3.72761 -1.10447 Free Energies = -1431.501655 C 2.92596 3.17936 -0.10262 C 2.37397 2.31665 0.83723 H 5.79301 -2.23219 -0.70568 H 4.59270 -1.49870 1.31680 H 2.14470 -2.04568 -2.94635 H 2.55543 -0.94601 2.33019 H 0.10892 -1.51053 -1.91450 H -2.30834 -1.25435 1.78270 H -4.69978 -0.94065 1.39547 H -3.88621 0.39590 -2.59853 H -1.46930 0.10148 -2.19957 H -0.83699 2.29774 -0.25662 H 0.15275 3.84420 -1.93732 H 2.56712 4.40238 -1.83400 H 3.98085 3.42582 -0.04648 H 2.97629 1.89089 1.63136 O -5.75131 -0.05413 -0.96019 C -6.72850 -0.31170 0.03072 H -6.58329 0.32573 0.90948 H -7.68825 -0.07943 -0.42784 H -6.71890 -1.36329 0.33694 H 4.57585 -2.50403 -2.85868 171 Table A.4 Theoretically optimized coordinates of 1d (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 4.03554 -1.89142 -0.50339 C 4.55251 -1.12826 0.55670 C 3.70650 -0.40076 1.36273 C 2.32468 -0.40682 1.13397 C 1.79084 -1.17806 0.07920 Zero-point correction = 0.311380 C 2.66430 -1.91377 -0.72548 (Hartree/Particle) N 1.48978 0.32135 1.94786 Thermal correction to Energy = P -0.17112 0.54823 1.81563 0.334281 C -0.60360 -0.59713 0.51770 Thermal correction to Enthalpy = C 0.37201 -1.25614 -0.15187 0.335225 C -2.02963 -0.76501 0.17449 Thermal correction to Gibbs Free C -3.01796 -0.77985 1.16764 Energy = 0.256327 C -4.34829 -0.97043 0.83563 C -4.71700 -1.14389 -0.50100 Sum of electronic and zero-point C -3.74176 -1.11664 -1.50317 Energies = -1501.376903 C -2.41552 -0.92262 -1.16400 O -0.87670 0.48608 3.11194 Sum of electronic and thermal O -0.38741 2.04089 1.20819 Energies = -1501.354002 C 0.15889 2.46865 0.00625 Sum of electronic and thermal C -0.62194 2.42363 -1.14066 Enthalpies = -1501.353058 C -0.09804 2.90189 -2.33568 Sum of electronic and thermal C 1.19205 3.41950 -2.37957 Free Energies = -1501.431956 C 1.95817 3.46638 -1.22014 C 1.44398 2.99334 -0.01830 H 5.62055 -1.11226 0.73827 H 4.10820 0.18595 2.18142 H 2.25751 -2.51240 -1.53306 H 1.92358 0.77715 2.74172 H 0.06654 -1.94710 -0.93472 H -2.73622 -0.65168 2.20626 H -5.10494 -0.98955 1.61109 H -4.02968 -1.23502 -2.54112 H -1.67033 -0.87072 -1.95002 H -1.62958 2.02766 -1.08459 H -0.70488 2.87298 -3.23429 H 1.59694 3.79258 -3.31382 H 2.96117 3.87834 -1.24601 H 2.02379 3.03721 0.89632 C -6.08682 -1.34051 -0.84608 N -7.19526 -1.50091 -1.12768 C 4.91039 -2.64271 -1.33904 N 5.62279 -3.25023 -2.01566 172 Table A.5 Theoretically optimized coordinates of 1e (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.76888 -1.08396 -0.08227 C -4.09036 -0.10612 -1.02984 C -3.09254 0.59206 -1.67466 C -1.74716 0.33315 -1.38525 Zero-point correction = 0.313690 C -1.41241 -0.65615 -0.43936 (Hartree/Particle) C -2.44579 -1.35365 0.20051 Thermal correction to Energy = N -0.75358 1.02705 -2.04102 0.333021 P 0.90340 0.98218 -1.77564 Thermal correction to Enthalpy = C 1.06774 -0.40236 -0.66315 0.333965 C -0.04244 -0.99219 -0.15666 Thermal correction to Gibbs Free C 2.42404 -0.84145 -0.28050 C 3.47370 -0.84732 -1.20893 Energy = 0.263062 C 4.73414 -1.28970 -0.84608 C 4.97127 -1.73093 0.45846 Sum of electronic and zero-point C 3.93587 -1.71666 1.39872 Energies = -1317.051311 C 2.68075 -1.26947 1.02964 Sum of electronic and thermal O 1.69695 1.02466 -3.02169 Energies = -1317.031980 O 1.28116 2.30979 -0.91267 Sum of electronic and thermal C 0.71209 2.61654 0.31442 Enthalpies = -1317.031036 C 1.41544 2.31622 1.47312 Sum of electronic and thermal C 0.87861 2.67476 2.70380 Free Energies = -1317.101939 C -0.34933 3.32459 2.77203 C -1.03868 3.62416 1.60234 C -0.50948 3.27449 0.36539 H -5.12820 0.10378 -1.26325 H -3.34524 1.34830 -2.40998 H -2.19027 -2.11959 0.92402 H -1.05270 1.64659 -2.78415 H 0.10009 -1.83288 0.51937 H 3.29312 -0.51052 -2.22305 H 5.53772 -1.29844 -1.57304 H 4.12361 -2.04313 2.41486 H 1.89305 -1.23023 1.77369 H 2.37557 1.81825 1.39877 H 1.42642 2.44740 3.61201 H -0.76459 3.60330 3.73423 H -1.99204 4.13938 1.64841 H -1.02766 3.51616 -0.55519 C 6.26883 -2.18748 0.83484 N 7.31870 -2.55856 1.14127 C -4.87138 -1.80546 0.62193 F -4.42483 -2.83982 1.34753 F -5.78305 -2.28752 -0.24073 F -5.54155 -0.99651 1.46431 173 Table A.6 Theoretically optimized coordinates of 1f (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 3.96040 -1.76836 -0.39257 C 4.45995 -0.98124 0.64353 C 3.58879 -0.25194 1.42954 C 2.21201 -0.29294 1.19424 C 1.70778 -1.09640 0.15336 Zero-point correction = 0. 302705 C 2.60563 -1.83327 -0.63370 (Hartree/Particle) N 1.34745 0.43180 1.99279 Thermal correction to Energy = 0. P -0.30414 0.64499 1.81453 325118 C -0.70217 -0.54934 0.54999 Thermal correction to Enthalpy = C 0.29430 -1.20945 -0.08955 0. 326063 C -2.12010 -0.75342 0.19434 Thermal correction to Gibbs Free C -3.12245 -0.74745 1.17387 Energy = 0. 248120 C -4.44478 -0.97264 0.83206 C -4.79275 -1.20283 -0.50166 Sum of electronic and zero-point C -3.80421 -1.19654 -1.49115 Energies = -1868.684343 C -2.48622 -0.96718 -1.14216 O -1.04345 0.63228 3.09468 Sum of electronic and thermal O -0.52766 2.11282 1.14298 Energies = -1868.661930 C 0.05367 2.50551 -0.05268 Sum of electronic and thermal C -0.68503 2.40847 -1.22431 Enthalpies = -1868.660986 C -0.12754 2.85510 -2.41639 Sum of electronic and thermal C 1.15503 3.39259 -2.43385 Free Energies = -1868.738929 C 1.87968 3.49037 -1.25107 C 1.33128 3.04948 -0.05227 H 5.52632 -0.94006 0.82965 H 3.97695 0.36104 2.23589 H 2.22140 -2.45641 -1.43325 H 1.75898 0.89863 2.79126 H 0.01006 -1.92847 -0.85521 H -2.85678 -0.57454 2.21022 H -5.21162 -0.97487 1.59775 H -4.07586 -1.35836 -2.52767 H -1.73161 -0.93185 -1.91998 H -1.68778 1.99781 -1.18931 H -0.70218 2.78570 -3.33380 H 1.58631 3.74099 -3.36584 H 2.87691 3.91698 -1.25671 H 1.87859 3.13149 0.87963 C -6.15420 -1.43525 -0.85681 N -7.25604 -1.62465 -1.14651 Cl 5.06276 -2.68314 -1.38250 174 Table A.7 Theoretically optimized coordinates of 1g (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.78872 -1.04922 -0.08147 C -4.06468 -0.04828 -1.02947 C -3.06412 0.65178 -1.67375 C -1.72247 0.38122 -1.39455 Zero-point correction = 0.424771 C -1.40791 -0.61829 -0.45895 C -2.45478 -1.31179 0.17582 (Hartree/Particle) N -0.71497 1.06978 -2.04876 Thermal correction to Energy = P 0.93380 1.00409 -1.77488 0.451389 C 1.07789 -0.39039 -0.67440 Thermal correction to Enthalpy = C -0.04411 -0.96993 -0.17601 C 2.42576 -0.85102 -0.28950 0.452333 C 3.48384 -0.85226 -1.20908 Thermal correction to Gibbs Free C 4.73637 -1.31555 -0.84531 Energy = 0.366540 C 4.95903 -1.78509 0.45208 C 3.91616 -1.77560 1.38438 C 2.66959 -1.30602 1.01454 Sum of electronic and zero-point C -4.93596 -1.79152 0.60118 Energies = -1566.201939 O 1.74119 1.05731 -3.01360 Sum of electronic and thermal O 1.33224 2.32057 -0.89477 Energies = -1566.175321 C 0.76692 2.61953 0.33364 C 1.47022 2.30635 1.48947 Sum of electronic and thermal C 0.93881 2.65862 2.72427 Enthalpies = -1566.174377 C -0.28514 3.31513 2.80067 Sum of electronic and thermal C -0.97582 3.62641 1.63475 Free Energies = -1566.260170 C -0.45166 3.28302 0.39396 C -4.43260 -2.83417 1.59986 C -5.81522 -0.78371 1.35693 C -5.78146 -2.50820 -0.46227 H -5.09443 0.19404 -1.27209 H -3.31628 1.41873 -2.39935 H -2.17636 -2.07899 0.88977 H -1.00547 1.69226 -2.79218 H 0.08802 -1.81745 0.49434 H 3.31468 -0.49423 -2.21797 H 5.54529 -1.31971 -1.56650 H 4.09223 -2.12293 2.39576 H 1.87732 -1.27002 1.75385 H 2.42651 1.80196 1.40872 H 1.48749 2.42083 3.62938 H -0.69629 3.58933 3.76602 H -1.92669 4.14577 1.68700 H -0.97205 3.53171 -0.52351 H -5.28625 -3.33584 2.06401 H -3.82272 -3.60203 1.11397 H -3.84176 -2.37827 2.40043 H -6.64676 -1.30125 1.84597 H -6.23994 -0.03156 0.68647 H -5.23783 -0.26237 2.12629 H -5.18041 -3.23981 -1.01041 H -6.61448 -3.03705 0.01193 H -6.20263 -1.80675 -1.18781 C 6.24765 -2.26486 0.82904 N 7.29052 -2.65519 1.13607 175 Table A.8 Theoretically optimized coordinates of 1h (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.91744 -1.06325 -0.12959 C -4.18803 -0.08912 -1.09777 C -3.17538 0.60539 -1.74099 C -1.84007 0.35158 -1.43804 C -1.52900 -0.62602 -0.47453 Zero-point correction = 0.458391 C -2.57918 -1.30851 0.15345 (Hartree/Particle) N -0.82320 1.03115 -2.09156 Thermal correction to Energy = P 0.81835 0.99175 -1.77615 C 0.96229 -0.37573 -0.64217 0.485905 C -0.16329 -0.95850 -0.15975 Thermal correction to Enthalpy = C 2.31140 -0.78408 -0.20585 0.486849 C 3.40082 -0.78058 -1.08095 C 4.66208 -1.19726 -0.67116 Thermal correction to Gibbs Free C 4.86168 -1.62510 0.64060 Energy = 0.399136 C 3.78419 -1.62025 1.53272 C 2.53655 -1.20229 1.11587 O 1.64863 1.03713 -3.00115 Sum of electronic and zero-point O 1.18043 2.33650 -0.91732 Energies = -1588.435467 C 0.58693 2.65042 0.29242 Sum of electronic and thermal C 1.26308 2.35584 1.46939 Energies = -1588.407953 C 0.70238 2.72516 2.68604 C -0.52420 3.38021 2.72466 Sum of electronic and thermal C -1.18849 3.67174 1.53845 Enthalpies = -1588.407009 C -0.63483 3.31091 0.31554 Sum of electronic and thermal H -5.21199 0.14416 -1.36399 H -3.42205 1.35513 -2.48648 Free Energies = -1588.494722 H -2.31087 -2.06019 0.89037 H -1.10444 1.63909 -2.85004 H -0.03525 -1.78700 0.53476 H 3.25906 -0.45493 -2.10548 H 5.47644 -1.18650 -1.38470 H 3.95660 -1.93529 2.55590 H 1.72294 -1.17645 1.83344 H 2.21952 1.84796 1.41770 H 1.22969 2.50045 3.60713 H -0.95846 3.66730 3.67609 H -2.14214 4.18830 1.56077 H -1.13533 3.54286 -0.61729 O 6.04233 -2.04782 1.14122 C 7.16517 -2.05530 0.27980 H 7.39606 -1.04819 -0.08379 H 7.99827 -2.42216 0.87708 H 7.00916 -2.72448 -0.57314 C -5.01325 -1.84329 0.59810 C -4.83971 -3.34482 0.32448 C -4.90519 -1.58594 2.10853 C -6.41289 -1.43085 0.13940 H -4.91828 -3.55773 -0.74585 H -3.86887 -3.71093 0.66968 H -5.61623 -3.91551 0.84427 H -5.02861 -0.52220 2.33280 H -5.68319 -2.14069 2.64319 H -3.93649 -1.90269 2.50477 H -7.16102 -2.01397 0.68401 H -6.61006 -0.37269 0.33684 H -6.56211 -1.61664 -0.92862 176 Table A.9 Theoretically optimized coordinates of 1i (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.74450 -0.84961 -0.11108 C -3.93587 0.12789 -1.09515 C -2.87145 0.73303 -1.74452 C -1.56021 0.38257 -1.43190 C -1.32891 -0.60260 -0.45379 Zero-point correction = 0.453011 C -2.43002 -1.19309 0.18033 (Hartree/Particle) N -0.49368 0.97525 -2.08918 Thermal correction to Energy = P 1.14187 0.79674 -1.78807 C 1.17309 -0.55276 -0.62461 0.478948 C 0.00622 -1.03442 -0.12972 Thermal correction to Enthalpy = C 2.48537 -1.06582 -0.18109 0.479892 C 3.55735 -1.20686 -1.07243 Thermal correction to Gibbs Free C 4.77146 -1.71899 -0.64121 C 4.97098 -2.10354 0.68638 Energy = 0.395730 C 3.90490 -1.95226 1.57317 C 2.68655 -1.43763 1.15275 Sum of electronic and zero-point O 1.96025 0.74149 -3.02016 O 1.62851 2.12266 -0.96290 Energies = -1513.289529 C 1.08291 2.51124 0.24789 Sum of electronic and thermal C 1.76364 2.20478 1.41916 Energies = -1513.263592 C 1.25515 2.64446 2.63536 Sum of electronic and thermal C 0.07594 3.38107 2.67916 C -0.59284 3.68407 1.49838 Enthalpies = -1513.262648 C -0.09093 3.25345 0.27570 Sum of electronic and thermal H -4.93789 0.43531 -1.36947 Free Energies = -1513.346809 H -3.05752 1.48781 -2.50255 H -2.22120 -1.95187 0.92896 H -0.72818 1.59297 -2.85551 H 0.07061 -1.85669 0.58105 H 3.42852 -0.92112 -2.11050 H 5.58326 -1.82582 -1.35519 H 4.03357 -2.23032 2.61527 H 1.88694 -1.30175 1.87396 H 2.68173 1.63097 1.36306 H 1.78598 2.41037 3.55208 H -0.31764 3.72269 3.63030 H -1.50906 4.26427 1.52458 H -0.59495 3.49260 -0.65336 C -4.89941 -1.53100 0.62397 C -4.84649 -3.04459 0.36792 C -4.77220 -1.26557 2.13154 C -6.26128 -1.01313 0.15831 H -4.93849 -3.26293 -0.70019 H -3.90922 -3.48307 0.72140 H -5.66766 -3.54534 0.89113 H -4.81027 -0.19277 2.34316 H -5.59273 -1.74983 2.67103 H -3.83261 -1.65437 2.53373 H -7.05386 -1.52654 0.71014 H -6.37309 0.06009 0.34073 H -6.42524 -1.20151 -0.90717 C 6.29599 -2.64154 1.14124 H 6.63136 -3.46096 0.49879 H 7.06784 -1.86579 1.10314 H 6.24468 -3.01242 2.16689 177 Table A.10 Theoretically optimized coordinates of 1j (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.59840 -0.54999 -0.10998 C -3.63220 0.33034 -1.19841 C -2.47904 0.73109 -1.85409 C -1.23255 0.26530 -1.44200 C -1.15977 -0.62546 -0.35486 Zero-point correction = 0.425766 C -2.34752 -1.01061 0.28142 (Hartree/Particle) N -0.07879 0.65325 -2.10406 P 1.51034 0.28518 -1.73307 Thermal correction to Energy = C 1.33350 -0.89156 -0.40653 0.450720 C 0.09975 -1.16792 0.08324 Thermal correction to Enthalpy = C 2.55469 -1.50371 0.15870 0.451664 C 3.62735 -1.87996 -0.65954 Thermal correction to Gibbs Free C 4.75352 -2.48084 -0.11155 C 4.83426 -2.71310 1.25652 Energy = 0.369322 C 3.77982 -2.33167 2.08010 C 2.65448 -1.72693 1.53854 Sum of electronic and zero-point O 2.33097 -0.05220 -2.91796 Energies = -1474.038251 O 2.16938 1.62994 -1.07774 C 1.66167 2.26652 0.04101 Sum of electronic and thermal C 2.23284 2.00733 1.28016 Energies = -1474.013298 C 1.77069 2.69183 2.39774 Sum of electronic and thermal C 0.74624 3.62493 2.27658 Enthalpies = -1474.012354 C 0.18663 3.87754 1.02895 Sum of electronic and thermal C 0.64359 3.20144 -0.09634 H -4.57869 0.72132 -1.55217 Free Energies = -1474.094695 H -2.54397 1.41364 -2.69601 H -2.26058 -1.70219 1.11451 H -0.20967 1.20638 -2.94130 H 0.03782 -1.89821 0.88839 H 3.56793 -1.70644 -1.72818 H 5.57197 -2.77206 -0.76158 H 3.83891 -2.49356 3.15142 H 1.85195 -1.40161 2.19254 H 3.03377 1.28038 1.35305 H 2.21706 2.49505 3.36675 H 0.38894 4.15777 3.15101 H -0.60784 4.60897 0.92604 H 0.22608 3.39755 -1.07701 H 5.71619 -3.18132 1.68060 C -4.85594 -1.01104 0.62824 C -4.98799 -2.53648 0.50586 C -4.74950 -0.62731 2.11165 C -6.12307 -0.37159 0.05802 H -5.07223 -2.83762 -0.54258 H -4.12589 -3.05367 0.93606 H -5.88301 -2.88138 1.03393 H -4.65854 0.45667 2.22904 H -5.64381 -0.95577 2.65109 H -3.88264 -1.09186 2.58930 H -6.99282 -0.72432 0.61966 H -6.09802 0.71961 0.13694 H -6.27749 -0.63869 -0.99190 178 Table A.11 Theoretically optimized coordinates of 1k (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.96417 -1.13592 -0.29875 C -4.36704 0.05135 -0.92456 C -3.45540 0.97788 -1.40366 C -2.08688 0.75550 -1.27109 C -1.64436 -0.43099 -0.65490 Zero-point correction = 0.423005 C -2.59714 -1.34767 -0.18681 N -1.17191 1.67335 -1.76066 (Hartree/Particle) P 0.49109 1.66841 -1.60064 Thermal correction to Energy = C 0.79729 0.04822 -0.92094 0.451600 C -0.24523 -0.73338 -0.54050 Thermal correction to Enthalpy = C 2.19475 -0.38921 -0.75155 C 3.18150 -0.06372 -1.69205 0.452544 C 4.48535 -0.50412 -1.53800 Thermal correction to Gibbs Free C 4.84568 -1.27910 -0.43695 Energy = 0.361643 C 3.86693 -1.60086 0.52283 C 2.56130 -1.15035 0.36357 O 1.21505 2.09447 -2.81842 Sum of electronic and zero-point O 0.87177 2.73249 -0.42499 Energies = -1658.357511 C 0.35879 2.66830 0.86111 Sum of electronic and thermal C 1.13436 2.10342 1.86484 C 0.65029 2.08425 3.16746 Energies = -1658.328916 C -0.59729 2.62468 3.46051 Sum of electronic and thermal C -1.35894 3.19453 2.44637 Enthalpies = -1658.327972 C -0.88318 3.22281 1.14062 Sum of electronic and thermal H -5.42133 0.26933 -1.04555 H -3.80656 1.88541 -1.88497 Free Energies = -1658.418872 H -2.22474 -2.25542 0.27897 H -1.55477 2.44856 -2.28690 H -0.01472 -1.71505 -0.12993 H 2.91585 0.53536 -2.55547 H 5.23494 -0.25184 -2.27811 H 1.83241 -1.38187 1.13080 H 2.10977 1.69854 1.61936 H 1.25464 1.64816 3.95563 H -0.97158 2.60858 4.47816 H -2.32860 3.62610 2.67009 H -1.46013 3.67651 0.34334 C -4.95155 -2.17297 0.23804 C -4.73133 -3.50826 -0.48851 C -4.71852 -2.36686 1.74370 C -6.40478 -1.74460 0.02752 H -4.89350 -3.39801 -1.56482 H -3.71770 -3.88949 -0.33746 H -5.43094 -4.26191 -0.11301 H -4.87141 -1.42944 2.28673 H -5.41766 -3.10986 2.14060 H -3.70452 -2.71704 1.95547 H -7.07124 -2.51236 0.43050 H -6.63141 -0.80630 0.54312 H -6.64459 -1.62339 -1.03329 C 6.18919 -1.72817 -0.28903 N 7.28080 -2.08721 -0.18019 C 4.20279 -2.37389 1.67375 N 4.46001 -2.99922 2.60879 179 Table A.12 Theoretically optimized coordinates of 1l (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C -3.88485 -1.07681 -0.12885 C -4.18190 -0.06050 -1.04512 C -3.18905 0.67385 -1.67409 C -1.84565 0.42026 -1.40786 C -1.50866 -0.59919 -0.49762 Zero-point correction = 0.416338 C -2.53989 -1.32175 0.11741 (Hartree/Particle) N -0.84882 1.14085 -2.04725 P 0.79946 1.10001 -1.77113 Thermal correction to Energy = C 0.97326 -0.31963 -0.70777 0.442430 C -0.13533 -0.93424 -0.22645 Thermal correction to Enthalpy = C 2.33386 -0.75448 -0.33183 0.443374 C 3.38724 -0.73505 -1.25424 Thermal correction to Gibbs Free C 4.65390 -1.17643 -0.89936 C 4.87760 -1.63855 0.38929 Energy = 0.358508 C 3.85678 -1.65720 1.33009 C 2.59607 -1.20982 0.96639 Sum of electronic and zero-point O 1.60730 1.20235 -3.00687 Energies = -1933.510024 O 1.17220 2.40240 -0.85693 C 0.59380 2.66456 0.37303 Sum of electronic and thermal C 1.28958 2.32983 1.52746 Energies = -1933.483931 C 0.74391 2.64705 2.76556 Sum of electronic and thermal C -0.48673 3.29034 2.84695 Enthalpies = -1933.482987 C -1.17014 3.62322 1.68268 Sum of electronic and thermal C -0.63171 3.31488 0.43883 H -5.21298 0.17419 -1.28082 Free Energies = -1933.567854 H -3.45710 1.45465 -2.37911 H -2.25055 -2.10458 0.81266 H -1.15111 1.77788 -2.77317 H 0.01449 -1.79561 0.42238 H 3.20974 -0.37806 -2.26231 H 5.46104 -1.16495 -1.62196 H 1.80845 -1.19514 1.71207 H 2.25041 1.83489 1.44259 H 1.28654 2.39184 3.66961 H -0.90901 3.53697 3.81495 H -2.12664 4.13179 1.73888 H -1.14652 3.58008 -0.47719 C -4.96005 -1.89725 0.58491 C -4.76299 -3.38739 0.26911 C -4.84134 -1.67816 2.10073 C -6.37079 -1.49790 0.14939 H -4.84558 -3.57249 -0.80603 H -3.78451 -3.74767 0.59838 H -5.52654 -3.98435 0.77823 H -4.98536 -0.62377 2.35502 H -5.60116 -2.26397 2.62833 H -3.86126 -1.98359 2.47766 H -7.10304 -2.11274 0.68041 H -6.58780 -0.45087 0.38190 H -6.52394 -1.65278 -0.92305 H 4.04953 -2.00410 2.33823 Cl 6.46619 -2.19351 0.83933 180 Table A.13 Theoretically optimized coordinates of 1m (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 3.83393 -1.45704 -0.39125 C 4.15108 -0.75387 0.78211 C 3.14769 -0.23260 1.56779 C 1.80397 -0.39317 1.20655 C 1.47040 -1.10507 0.03414 Zero-point correction = 0.312635 C 2.50145 -1.62968 -0.74792 (Hartree/Particle) N 0.80858 0.12389 2.00223 Thermal correction to Energy = P -0.84556 0.18571 1.70406 0.333719 C -1.01248 -0.86872 0.27562 Thermal correction to Enthalpy = C 0.09810 -1.33539 -0.34253 0.334663 C -2.37014 -1.15667 -0.23247 Thermal correction to Gibbs Free C -3.43922 -1.39456 0.64041 Energy = 0.260387 C -4.69953 -1.69642 0.14076 C -4.91798 -1.76006 -1.23039 Sum of electronic and zero-point C -3.86554 -1.51300 -2.10596 Energies = -1409.214524 C -2.60491 -1.20856 -1.61294 O -1.66100 -0.06751 2.90988 Sum of electronic and thermal O -1.16747 1.70228 1.20598 Energies = -1409.193440 C -0.52398 2.31449 0.14123 Sum of electronic and thermal C -1.09461 2.25283 -1.12290 Enthalpies = -1409.192496 C -0.47544 2.91249 -2.17793 Sum of electronic and thermal C 0.70007 3.62557 -1.96833 Free Energies = -1409.266772 C 1.25470 3.68534 -0.69460 C 0.64357 3.03108 0.36861 H 5.18787 -0.61975 1.06676 H 3.39571 0.31227 2.47224 H 2.25128 -2.18178 -1.64717 H 1.10125 0.53267 2.88127 H -0.04492 -1.97390 -1.21191 H -3.27454 -1.35293 1.71111 H -5.51511 -1.88566 0.83062 H -4.02908 -1.54523 -3.17800 H -1.79746 -0.98757 -2.30344 H -2.01621 1.69989 -1.26476 H -0.91830 2.87043 -3.16727 H 1.17920 4.13947 -2.79440 H 2.16600 4.24799 -0.52293 H 1.05563 3.07999 1.36994 H -5.90462 -1.99357 -1.61615 C 4.86995 -1.99484 -1.20676 N 5.71256 -2.42948 -1.86698 181 Table A.14 Theoretically optimized coordinates of 1n (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 4.13012 -1.95175 -0.44566 C 4.63210 -1.20587 0.63271 C 3.77458 -0.47286 1.42249 C 2.39942 -0.45827 1.15896 C 1.87921 -1.21194 0.08489 Zero-point correction = 0.345214 C 2.76356 -1.95192 -0.70266 (Hartree/Particle) N 1.55292 0.27431 1.95815 Thermal correction to Energy = P -0.09994 0.52869 1.77884 0.368901 C -0.52186 -0.60024 0.46455 Thermal correction to Enthalpy = C 0.46379 -1.26807 -0.18169 0.369845 C -1.93974 -0.71569 0.07628 Thermal correction to Gibbs Free C -2.96649 -0.69317 1.02424 Energy = 0.289700 C -4.29776 -0.83565 0.65261 C -4.63197 -0.99716 -0.69167 Sum of electronic and zero-point C -3.61558 -1.00730 -1.65354 Energies = -1523.612105 C -2.29676 -0.86549 -1.27394 O -0.83794 0.48064 3.05870 Sum of electronic and thermal O -0.26802 2.03339 1.17759 Energies = -1523.588418 C 0.35604 2.47215 0.02016 Sum of electronic and thermal C -0.31805 2.38397 -1.19038 Enthalpies = -1523.587474 C 0.28737 2.87818 -2.33963 Sum of electronic and thermal C 1.55182 3.45394 -2.27615 Free Energies = -1523.667620 C 2.21127 3.54159 -1.05498 C 1.61515 3.05193 0.10131 H 5.69527 -1.20665 0.84144 H 4.16265 0.10137 2.25674 H 2.37003 -2.53778 -1.52614 H 1.97377 0.72577 2.76092 H 0.16927 -1.94439 -0.98144 H -2.72175 -0.57536 2.07394 H -5.06167 -0.82235 1.41982 H -3.88994 -1.11393 -2.69709 H -1.52775 -0.84690 -2.03934 H -1.30665 1.93994 -1.21876 H -0.23577 2.81515 -3.28783 H 2.01982 3.83910 -3.17541 H 3.19385 3.99742 -0.99766 H 2.10927 3.12448 1.06338 O -5.88861 -1.14093 -1.15902 C -6.95305 -1.12382 -0.22544 H -6.99538 -0.17118 0.31306 H -7.86379 -1.24899 -0.80852 H -6.86663 -1.94651 0.49220 C 5.01399 -2.70868 -1.26621 N 5.73396 -3.32112 -1.93066 182 Table A.15 Theoretically optimized coordinates of 1o (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 3.22779 -0.58397 0.10328 C 3.29633 0.31198 1.17828 C 2.14736 0.72269 1.82074 C 0.89603 0.25246 1.40443 C 0.80909 -0.65689 0.32888 Zero-point correction = 0. 385127 C 1.98972 -1.05836 -0.30093 (Hartree/Particle) N -0.24681 0.66170 2.05465 Thermal correction to Energy = P -1.84740 0.28919 1.70401 0.410346 C -1.68428 -0.90854 0.39467 Thermal correction to Enthalpy = C -0.45557 -1.19953 -0.09649 C -2.91289 -1.52223 -0.15234 0.411290 C -3.98449 -1.87217 0.67864 Thermal correction to Gibbs Free C -5.11829 -2.47392 0.14776 Energy = 0.326868 C -5.20703 -2.73238 -1.21501 C -4.15298 -2.37759 -2.05095 Sum of electronic and zero-point C -3.01973 -1.77256 -1.52689 Energies = -1583.957384 O -2.64833 -0.03189 2.90506 Sum of electronic and thermal O -2.49599 1.62988 1.04140 C -1.99375 2.25162 -0.09036 Energies = -1583.932165 C -2.55755 1.96089 -1.32543 Sum of electronic and thermal C -2.09840 2.62879 -2.45428 Enthalpies = -1583.931220 C -1.08593 3.57646 -2.34704 Sum of electronic and thermal C -0.53524 3.86130 -1.10245 Free Energies = -1584.015643 C -0.98849 3.20159 0.03406 H 4.26000 0.68393 1.50380 H 2.20536 1.41554 2.65398 H 1.94443 -1.76051 -1.12691 H -0.11131 1.23871 2.87549 H -0.39829 -1.94210 -0.89011 H -3.91867 -1.67938 1.74356 H -5.93615 -2.74504 0.80704 H -4.21816 -2.56109 -3.11834 H -2.21697 -1.46904 -2.19094 H -3.35033 1.22412 -1.38745 H -2.53795 2.40758 -3.42104 H -0.73109 4.09594 -3.23040 H 0.24904 4.60504 -1.01082 H -0.57904 3.42355 1.01269 H -6.09496 -3.20108 -1.62576 C 4.42908 -1.05511 -0.62240 O 4.40192 -1.82676 -1.55360 O 5.55696 -0.53127 -0.13384 C 6.77616 -0.93627 -0.78032 C 7.91485 -0.24063 -0.08092 H 6.71789 -0.66575 -1.83793 H 6.86014 -2.02443 -0.71818 H 8.86129 -0.52551 -0.54710 H 7.81156 0.84483 -0.15049 H 7.95462 -0.52057 0.97441 183 Table A.16 Theoretically optimized coordinates of 1p (Cartesian Coordinate in Angstrom) at PBE0/6-311G(d,p) level of theory Atom x y z C 3.85012 -1.24269 -0.01412 C 4.19156 -0.29375 0.95549 C 3.20100 0.40778 1.62691 C 1.85437 0.18653 1.35452 C 1.49835 -0.77311 0.38651 Zero-point correction = 0.373031 C 2.50871 -1.47316 -0.28156 (Hartree/Particle) N 0.86742 0.87886 2.04650 Thermal correction to Energy = P -0.77666 0.89167 1.76484 0.398261 C -0.97652 -0.46912 0.62704 Thermal correction to Enthalpy = C 0.11923 -1.07342 0.10449 0.399205 C -2.34250 -0.87124 0.23918 C -3.39214 -0.86489 1.16818 Thermal correction to Gibbs Free C -4.66291 -1.27306 0.80174 Energy = 0.315314 C -4.91233 -1.69197 -0.50802 C -3.87748 -1.68933 -1.44915 Sum of electronic and zero-point C -2.61192 -1.27626 -1.07610 Energies = -1562.859584 O -1.58878 0.94525 3.00064 Sum of electronic and thermal O -1.12635 2.24042 0.91204 Energies = -1562.834354 C -0.53783 2.55267 -0.30183 Sum of electronic and thermal C -1.23852 2.29383 -1.47264 C -0.68257 2.65981 -2.69252 Enthalpies = -1562.833410 C 0.56313 3.27678 -2.73976 Sum of electronic and thermal C 1.25092 3.53453 -1.55917 Free Energies = -1562.917302 C 0.70254 3.17674 -0.33301 H 5.22747 -0.09021 1.19527 H 3.48243 1.14137 2.37564 H 2.24654 -2.21679 -1.02654 H 1.17892 1.45484 2.81777 H -0.04479 -1.89698 -0.58779 H -3.20226 -0.54367 2.18566 H -5.46559 -1.27232 1.52985 H -4.07382 -1.99804 -2.46927 H -1.82462 -1.24626 -1.82100 H -2.21237 1.82077 -1.41490 H -1.22920 2.46396 -3.60884 H 0.99362 3.56177 -3.69346 H 2.21908 4.02287 -1.58823 H 1.22158 3.38434 0.59534 C -6.22037 -2.11326 -0.88838 N -7.27904 -2.45596 -1.19806 O 4.74111 -1.97459 -0.72460 C 6.12758 -1.77942 -0.47542 C 6.88889 -2.71136 -1.38432 H 6.34848 -1.99432 0.57802 H 6.39616 -0.73391 -0.67429 H 7.96334 -2.59255 -1.22481 H 6.62200 -3.75105 -1.18133 H 6.66848 -2.49362 -2.43189 184 5. Geometries and Methods Used for Modeling the Solution-State Dimerization of Heterocycles 1 Geometry optimizations of heterocycle 1 monomers with chloroform model: Heterocycle 1g Supporting Information: polymerdetector-s-monomer-6-c-ch3-3-0006.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-20133 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C25H23N2O2P C1[X(C25H23N2O2P)] #Atoms= 53 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1566.19434736 Predicted Change= -3.982743D-09 =============================================================== =============== Optimization completed. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00133 || 0.00180 [ YES ] 0.00133 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 1.674825 -0.719803 0.284938 C 2.860434 -1.379930 -0.128725 H 2.740609 -2.350346 -0.620399 C 4.136763 -0.846183 0.067569 C 5.426655 -1.551267 -0.392721 C 5.141342 -2.901908 -1.080078 H 4.631799 -3.608913 -0.401962 H 6.092492 -3.367588 -1.390476 H 4.520920 -2.779139 -1.985252 C 6.336966 -1.813598 0.833085 H 5.837844 -2.474733 1.562519 H 6.607019 -0.879182 1.354027 H 7.275452 -2.301014 0.513153 C 6.173642 -0.641704 -1.400567 H 6.437987 0.333253 -0.956348 185 H 5.554412 -0.449258 -2.293793 H 7.111150 -1.124949 -1.729444 C 4.208060 0.406732 0.727380 H 5.184553 0.868304 0.909135 C 3.069476 1.086315 1.154961 H 3.163091 2.054838 1.659384 C 1.788935 0.542765 0.932643 N 0.645676 1.194337 1.384711 H 0.778672 2.018474 1.974544 P -0.969221 0.853700 0.959965 O -1.916222 1.240999 2.060690 O -1.252983 1.616171 -0.490703 C -0.852545 -0.842224 0.367711 C -2.097699 -1.604173 0.131812 C 0.393031 -1.357151 0.097711 H 0.438033 -2.391236 -0.272027 C -2.165760 -2.572098 -0.900439 H -1.310409 -2.711408 -1.568721 C -3.317649 -3.327159 -1.109843 H -3.356007 -4.066105 -1.915481 C -4.454098 -3.125912 -0.293258 C -4.407773 -2.148564 0.725371 H -5.286517 -1.985649 1.356068 C -3.249177 -1.399801 0.932086 H -3.223366 -0.648080 1.726531 C -1.379884 3.009954 -0.592490 C -2.278035 3.738661 0.202818 H -2.871966 3.221188 0.959943 C -2.383311 5.123166 0.005438 H -3.080949 5.698104 0.623542 C -1.616299 5.769266 -0.974871 H -1.711238 6.849438 -1.124714 C -0.730295 5.023009 -1.766352 H -0.129683 5.517107 -2.537240 C -0.604939 3.640509 -1.576441 H 0.078562 3.038680 -2.182619 C -5.640649 -3.898086 -0.505910 N -6.614620 -4.535698 -0.680526 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1566.19434736 Predicted Change= -3.982743D-09 Zero-point correction (ZPE)= -1565.7813 0.41304 Internal Energy (U)= -1565.7536 0.44073 186 Enthalpy (H)= -1565.7526 0.44167 Gibbs Free Energy (G)= -1565.8413 0.35297 ------------------------------------------------------------------------------ Frequencies -- 14.1273 23.3695 25.7166 Single points at WB97X/6-311++G2(df,p): -1567.94 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.0351074 Heterocycle 1e Supporting Information: polymerdetector-s-monomer-6-cf3-0006.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C22H14F3N2O2P C1[X(C22H14F3N2O2P)] #Atoms= 44 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1745.88972035 Predicted Change= -2.495849D-07 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00006 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.02645 || 0.00180 [ NO ] 0.02645 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -1.620423 -0.820056 -0.230592 C -2.771036 -1.510551 0.212978 H -2.644606 -2.453240 0.754759 C -4.053596 -1.027680 -0.042202 C -5.267594 -1.748156 0.481889 F -5.737243 -1.178783 1.629257 F -5.003845 -3.053487 0.763030 F -6.291036 -1.716626 -0.417712 C -4.212443 0.171571 -0.767385 H -5.217283 0.545798 -0.983697 C -3.098774 0.877121 -1.213404 H -3.226303 1.809289 -1.774395 187 C -1.796388 0.404903 -0.942939 N -0.685570 1.093747 -1.406810 H -0.853786 1.877598 -2.041317 P 0.947877 0.857135 -0.959055 O 1.886596 1.241006 -2.062672 O 1.165778 1.696359 0.460508 C 0.906682 -0.821861 -0.305485 C 2.183497 -1.538029 -0.106099 C -0.309357 -1.388420 -0.014105 H -0.301777 -2.389290 0.439483 C 3.353353 -0.852333 0.297730 H 3.316314 0.226732 0.473731 C 4.550206 -1.536008 0.507919 H 5.445543 -0.995197 0.827131 C 4.611245 -2.934541 0.317301 C 3.452229 -3.630184 -0.095298 H 3.501046 -4.710112 -0.261605 C 2.262376 -2.936218 -0.308733 H 1.382930 -3.479080 -0.669218 C 1.148355 3.100730 0.517804 C 1.872055 3.900111 -0.380646 H 2.451320 3.430757 -1.179897 C 1.830537 5.293736 -0.224697 H 2.391484 5.924322 -0.922494 C 1.092753 5.878933 0.814226 H 1.073027 6.967158 0.929983 C 0.384270 5.061982 1.708214 H -0.192102 5.508580 2.525053 C 0.405026 3.668951 1.561960 H -0.140821 3.012869 2.246281 C 5.837389 -3.642026 0.532791 N 6.843399 -4.225734 0.712638 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1745.88972035 Predicted Change= -2.495849D-07 Zero-point correction (ZPE)= -1745.5826 0.30708 Internal Energy (U)= -1745.5568 0.33291 Enthalpy (H)= -1745.5558 0.33385 Gibbs Free Energy (G)= -1745.6435 0.24620 ------------------------------------------------------------------------------ Frequencies -- 6.3297 18.0278 19.5809 Single points at WB97X/6-311++G2(df,p): -1747.7769 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.03398828 188 Heterocycle 1b Supporting Information: 0006.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C21H15N2O2P C1[X(C21H15N2O2P)] #Atoms= 41 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1409.16315011 Predicted Change= -4.056633D-09 =============================================================== =============== Optimization completed. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00122 || 0.00180 [ YES ] 0.00122 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -1.161693 2.676854 -0.174198 C -1.489591 3.935296 -0.736421 H -0.700497 4.491200 -1.255651 C -2.772521 4.467839 -0.638130 H -3.003125 5.439836 -1.083419 C -3.767282 3.745034 0.047921 H -4.779155 4.153191 0.137253 C -3.479278 2.503729 0.617245 H -4.256844 1.943021 1.148177 C -2.186165 1.953101 0.507049 N -1.883963 0.733173 1.103069 H -2.598056 0.319961 1.706799 P -0.487790 -0.219804 0.877442 O -0.164842 -1.011590 2.113049 O -0.750347 -1.142306 -0.479635 C 0.672190 0.969966 0.186084 C 2.092629 0.581383 0.050274 C 0.192647 2.181837 -0.247773 189 H 0.922177 2.885962 -0.672016 C 2.869980 1.061414 -1.032048 H 2.398741 1.674124 -1.806837 C 4.219168 0.735592 -1.153610 H 4.804396 1.108572 -1.999144 C 4.834783 -0.099684 -0.193390 C 4.066020 -0.602048 0.879691 H 4.537387 -1.252481 1.622135 C 2.716769 -0.267871 0.997106 H 2.131152 -0.659561 1.834130 C -1.600099 -2.260197 -0.477841 C -1.443648 -3.311968 0.437930 H -0.672914 -3.245787 1.209327 C -2.295846 -4.421427 0.341993 H -2.181113 -5.245289 1.054240 C -3.279490 -4.486759 -0.655686 H -3.935542 -5.360259 -0.725205 C -3.415563 -3.429211 -1.567365 H -4.177841 -3.472485 -2.352311 C -2.578664 -2.308638 -1.480822 H -2.664914 -1.473529 -2.182234 C 6.219977 -0.439889 -0.316694 N 7.359475 -0.716650 -0.419082 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1409.16315011 Predicted Change= -4.056633D-09 Zero-point correction (ZPE)= -1408.8602 0.30292 Internal Energy (U)= -1408.8382 0.32487 Enthalpy (H)= -1408.8373 0.32581 Gibbs Free Energy (G)= -1408.9142 0.24893 ------------------------------------------------------------------------------ Frequencies -- 11.8031 19.0278 32.5940 Single points at WB97X/6-311++G2(df,p): -1410.6769 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.03306504 Heterocycle 1p Supporting Information: 1-cn-2-eto-monomer-3.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman 190 #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C23H19N2O3P C1[X(C23H19N2O3P)] #Atoms= 48 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1562.82081034 Predicted Change= -6.168975D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00235 || 0.00180 [ NO ] 0.00235 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 1.902599 0.651089 0.358334 C 3.110139 1.290998 -0.030062 H 3.037643 2.268633 -0.514250 C 4.350779 0.691334 0.202012 C 4.397420 -0.567978 0.846452 H 5.374411 -1.025541 1.027057 C 3.226865 -1.209702 1.235014 H 3.278816 -2.186405 1.728752 C 1.967995 -0.621725 0.991479 N 0.795363 -1.245452 1.417050 H 0.892909 -2.069369 2.013513 P -0.794883 -0.865794 0.948811 O -1.785807 -1.252600 2.010684 O -1.052612 -1.588913 -0.527611 C -0.622284 0.839110 0.395679 C -1.841038 1.640571 0.154798 C 0.641638 1.326115 0.159817 H 0.719866 2.366141 -0.186665 C -1.865253 2.630754 -0.858286 H -0.995574 2.759555 -1.510046 C -2.992407 3.421401 -1.070950 H -2.997165 4.176986 -1.861932 C -4.147395 3.235745 -0.276995 C -4.144939 2.237137 0.721966 H -5.038220 2.086021 1.334944 C -3.011251 1.452040 0.931618 H -3.019461 0.683023 1.709688 191 C -1.196428 -2.977454 -0.667205 C -0.420027 -3.591311 -1.660610 H 0.276148 -2.981926 -2.244386 C -0.559101 -4.966833 -1.887535 H 0.042984 -5.447605 -2.665680 C -1.460097 -5.723390 -1.123136 H -1.565465 -6.798228 -1.301653 C -2.228377 -5.094182 -0.132950 H -2.937721 -5.677023 0.464110 C -2.109703 -3.716456 0.101119 H -2.705315 -3.211725 0.865589 C -5.308253 4.045195 -0.492494 N -6.260860 4.713771 -0.669252 C 5.574509 2.501106 -0.789404 H 5.094613 3.255799 -0.133516 O 5.566860 1.221097 -0.140652 C 7.024047 2.864431 -1.070662 H 7.600953 2.921096 -0.133235 H 7.494530 2.112354 -1.724798 H 7.075804 3.845030 -1.572431 H 4.987814 2.447204 -1.729178 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1562.82081034 Predicted Change= -6.168975D-09 Zero-point correction (ZPE)= -1562.4585 0.36230 Internal Energy (U)= -1562.4323 0.38841 Enthalpy (H)= -1562.4314 0.38935 Gibbs Free Energy (G)= -1562.5177 0.30306 ------------------------------------------------------------------------------ Frequencies -- 13.2719 21.5509 23.2439 Single points at WB97X/6-311++G2(df,p): -1564.5292 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.03528503 Heterocycle 1j Supporting Information: 0002.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 192 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C24H24NO2P C1[X(C24H24NO2P)] #Atoms= 52 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1474.04821420 Predicted Change= -3.066499D-09 =============================================================== =============== Optimization completed on the basis of negligible forces. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00269 || 0.00180 [ NO ] 0.00269 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -1.876040 0.170058 0.262835 C -3.145920 0.619356 -0.179591 H -3.198459 1.639351 -0.573373 C -4.295926 -0.173475 -0.128568 C -5.675702 0.309803 -0.614395 C -6.168478 -0.612171 -1.757854 H -5.476691 -0.579631 -2.617391 H -7.166197 -0.289994 -2.106818 H -6.251101 -1.662837 -1.430949 C -5.634394 1.757374 -1.144955 H -4.953928 1.859391 -2.008711 H -5.315521 2.471513 -0.365455 H -6.642131 2.058658 -1.479345 C -6.684046 0.252976 0.560360 H -6.782147 -0.767118 0.969513 H -7.685083 0.575429 0.221706 H -6.368911 0.917047 1.383807 C -4.145758 -1.477991 0.404214 H -5.014250 -2.142445 0.468121 C -2.916901 -1.956885 0.854251 H -2.837738 -2.972389 1.259520 C -1.766344 -1.146990 0.786933 N -0.541683 -1.612361 1.259092 H -0.540277 -2.536615 1.695654 P 0.981994 -0.874132 1.136205 O 1.837794 -1.033462 2.361737 O 1.574329 -1.686081 -0.195306 193 C 0.563671 0.774769 0.554142 C 1.651468 1.770865 0.401839 C -0.735479 1.053222 0.205065 H -0.949277 2.075242 -0.138402 C 2.725427 1.842944 1.320383 H 2.764510 1.134249 2.152841 C 3.719824 2.817647 1.174838 H 4.538996 2.860752 1.900462 C 3.670556 3.735038 0.115823 H 4.452157 4.494042 0.005369 C 2.618915 3.664338 -0.810375 H 2.580919 4.361378 -1.654407 C 1.625243 2.690156 -0.673608 H 0.831087 2.617111 -1.424373 C 2.907371 -1.627015 -0.622842 C 3.992964 -1.784206 0.252977 H 3.809794 -1.903336 1.323499 C 5.291991 -1.769592 -0.274599 H 6.143421 -1.887952 0.404205 C 5.508663 -1.614152 -1.651416 H 6.527508 -1.609246 -2.051796 C 4.411145 -1.467688 -2.512639 H 4.567372 -1.346258 -3.589746 C 3.106839 -1.470958 -2.002369 H 2.236303 -1.356037 -2.654794 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1474.04821420 Predicted Change= -3.066499D-09 Zero-point correction (ZPE)= -1473.6336 0.41456 Internal Energy (U)= -1473.6077 0.44041 Enthalpy (H)= -1473.6068 0.44136 Gibbs Free Energy (G)= -1473.6920 0.35612 ------------------------------------------------------------------------------ Frequencies -- 6.5156 17.0003 21.9082 Single points at WB97X/6-311++G2(df,p): -1475.6946 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.0323201 Heterocycle 1m Supporting Information: 0005.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== 194 # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C21H15N2O2P C1[X(C21H15N2O2P)] #Atoms= 41 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1409.16290164 Predicted Change= -6.773340D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00346 || 0.00180 [ NO ] 0.00346 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 2.187149 0.496204 -0.118091 C 3.508238 0.710855 0.323185 H 3.746167 1.640121 0.850814 C 4.523776 -0.233778 0.097155 C 4.214269 -1.425861 -0.605347 H 5.000127 -2.163697 -0.788807 C 2.918936 -1.657625 -1.053392 H 2.683430 -2.581772 -1.592310 C 1.892392 -0.718094 -0.811702 N 0.610362 -0.939709 -1.284476 H 0.469415 -1.753007 -1.888035 P -0.815535 -0.074829 -0.888468 O -1.780112 -0.086315 -2.038939 O -1.392941 -0.751871 0.511646 C -0.153358 1.458409 -0.215860 C -1.086881 2.575712 0.055331 C 1.183243 1.519758 0.084402 H 1.558541 2.464144 0.502033 C -2.192674 2.831351 -0.789969 H -2.374506 2.178623 -1.648970 C -3.041007 3.916110 -0.538706 H -3.887106 4.101968 -1.208494 C -2.812322 4.760936 0.556382 H -3.480573 5.606217 0.750797 C -1.728377 4.507706 1.411018 195 H -1.553069 5.147691 2.282161 C -0.878104 3.425032 1.167556 H -0.060298 3.211252 1.863714 C -1.956275 -2.037721 0.549550 C -1.490571 -2.892944 1.558303 H -0.703909 -2.542829 2.233076 C -2.049678 -4.171299 1.684492 H -1.691230 -4.839821 2.474155 C -3.058665 -4.592989 0.805599 H -3.492428 -5.592982 0.905594 C -3.512428 -3.724688 -0.197825 H -4.304057 -4.044532 -0.883591 C -2.971733 -2.437478 -0.332924 H -3.320263 -1.747429 -1.105147 C 5.854568 0.007499 0.563836 N 6.950241 0.202770 0.947392 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1409.16290164 Predicted Change= -6.773340D-09 Zero-point correction (ZPE)= -1408.8599 0.30294 Internal Energy (U)= -1408.8379 0.32491 Enthalpy (H)= -1408.8370 0.32585 Gibbs Free Energy (G)= -1408.9137 0.24919 ------------------------------------------------------------------------------ Frequencies -- 14.9694 21.1450 29.8218 Single points at WB97X/6-311++G2(df,p): -1410.677 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.0344051 Heterocycle 1a Supporting Information: 0005.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C20H16NO2P C1[X(C20H16NO2P)] #Atoms= 40 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ 196 SCF Energy= -1317.01704642 Predicted Change= -8.137098D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00002 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00560 || 0.00180 [ NO ] 0.00560 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -0.242448 2.635088 0.144449 C -0.308901 3.933329 0.705682 H -1.212457 4.210781 1.260748 C 0.733657 4.847035 0.563680 H 0.659859 5.842878 1.010281 C 1.878725 4.477381 -0.166316 H 2.704563 5.185460 -0.289655 C 1.977027 3.206546 -0.736237 H 2.871182 2.919422 -1.301216 C 0.931191 2.274593 -0.582149 N 1.006179 1.019756 -1.180170 H 1.796868 0.848532 -1.804660 P 0.010681 -0.331897 -0.881121 O -0.079593 -1.219088 -2.091160 O 0.627790 -1.086162 0.471376 C -1.446121 0.423959 -0.144087 C -2.656720 -0.404313 0.061942 C -1.364190 1.731008 0.267337 H -2.264628 2.166075 0.723461 C -3.482380 -0.192489 1.191396 H -3.184618 0.543395 1.945781 C -4.650510 -0.938106 1.376779 H -5.270148 -0.761263 2.262452 C -5.016001 -1.922105 0.445442 H -5.927889 -2.509873 0.594015 C -4.196476 -2.156321 -0.667649 H -4.468652 -2.926248 -1.397386 C -3.027286 -1.410948 -0.861198 H -2.393382 -1.597166 -1.733364 C 1.879939 -1.711950 0.475661 C 2.690370 -1.471340 1.595363 H 2.327445 -0.799013 2.378291 C 3.939724 -2.097592 1.687404 H 4.571189 -1.912664 2.562817 C 4.381986 -2.950989 0.665135 197 H 5.360040 -3.437166 0.738340 C 3.560603 -3.181644 -0.447663 H 3.894783 -3.852653 -1.246257 C 2.301465 -2.571942 -0.551776 H 1.644874 -2.753528 -1.406549 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1317.01704642 Predicted Change= -8.137098D-08 Zero-point correction (ZPE)= -1316.7125 0.30454 Internal Energy (U)= -1316.6924 0.32457 Enthalpy (H)= -1316.6915 0.32552 Gibbs Free Energy (G)= -1316.7633 0.25371 ------------------------------------------------------------------------------ Frequencies -- 15.8757 23.5736 41.1169 Single points at WB97X/6-311++G2(df,p): -1318.4317 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.02998695 Heterocycle 1o* Supporting Information: 1-h-2-co2me-monomer-5.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C22H18NO4P C1[X(C22H18NO4P)] #Atoms= 46 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1544.65655049 Predicted Change= -1.649204D-09 =============================================================== =============== Optimization completed. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00127 || 0.00180 [ YES ] 0.00127 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ 198 P 1.458613 0.104155 -0.898194 O 2.000550 0.776463 0.521835 C 2.566406 2.058230 0.584181 O 2.450087 0.149071 -2.025865 C 0.813023 -1.447903 -0.259001 C 1.765433 -2.543225 0.038187 N 0.028890 0.950759 -1.311906 H 0.170357 1.779461 -1.893950 C -0.532156 -1.546801 -0.009055 H -0.898027 -2.504712 0.385585 C -1.555401 -0.549525 -0.237611 C -1.265976 0.685346 -0.896122 C 2.083018 2.905139 1.592172 H 1.280207 2.550711 2.245338 C 2.644148 4.179653 1.744983 H 2.271013 4.840764 2.534199 C 3.673581 4.607287 0.893046 H 4.108959 5.604381 1.013576 C 4.145114 3.748127 -0.110070 H 4.952567 4.072363 -0.775141 C 3.602563 2.464831 -0.271319 H 3.964179 1.782293 -1.044122 C -2.307380 1.601483 -1.161578 H -2.074405 2.542551 -1.672425 C -3.613526 1.321695 -0.770994 H -4.411001 2.041331 -0.972854 C -3.918487 0.110860 -0.107701 C -2.888406 -0.804687 0.140750 H -3.141254 -1.745467 0.641712 C 1.537806 -3.407723 1.134806 H 0.687734 -3.222627 1.799811 C 2.406837 -4.469781 1.402563 H 2.214648 -5.122135 2.261003 C 3.529916 -4.686457 0.589566 H 4.212965 -5.515150 0.803360 C 3.777297 -3.825980 -0.489163 H 4.653487 -3.982846 -1.127093 C 2.909356 -2.762888 -0.765397 H 3.106082 -2.098425 -1.612137 C -5.290864 -0.250301 0.336934 O -5.590491 -1.292960 0.909868 O -6.201023 0.724505 0.032665 C -7.548207 0.419389 0.443827 H -7.909757 -0.494343 -0.055558 H -7.597252 0.267853 1.534457 H -8.149473 1.289122 0.144441 199 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1544.65655049 Predicted Change= -1.649204D-09 Zero-point correction (ZPE)= -1544.3103 0.34616 Internal Energy (U)= -1544.2855 0.37098 Enthalpy (H)= -1544.2846 0.37192 Gibbs Free Energy (G)= -1544.3681 0.28837 ------------------------------------------------------------------------------ Frequencies -- 14.5204 20.6541 27.0101 Single points at WB97X/6-311++G2(df,p): -1546.336 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.0318351 Heterocycle 1h Supporting Information: polymerdetector-s-monomer-1-ome-2-c-ch3-3-0010.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C25H26NO3P C1[X(C25H26NO3P)] #Atoms= 56 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1588.44569629 Predicted Change= -2.458265D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00224 || 0.00180 [ NO ] 0.00224 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -1.732515 -0.790906 -0.290861 C -2.882769 -1.505540 0.128833 H -2.713150 -2.457125 0.642247 C -4.186513 -1.048685 -0.088497 C -5.438345 -1.816682 0.377823 200 C -6.254817 -0.925433 1.347088 H -5.661581 -0.668463 2.241754 H -7.166305 -1.454954 1.678424 H -6.570280 0.018064 0.869707 C -5.082586 -3.125987 1.111117 H -4.525196 -3.822809 0.460746 H -6.008086 -3.636427 1.429072 H -4.478857 -2.938800 2.016634 C -6.313023 -2.171034 -0.850855 H -5.763259 -2.822172 -1.552344 H -6.628891 -1.270098 -1.404294 H -7.226264 -2.703890 -0.529865 C -4.324812 0.182610 -0.775235 H -5.324251 0.583950 -0.974389 C -3.220716 0.915870 -1.207140 H -3.362709 1.867596 -1.732261 C -1.914690 0.448801 -0.964483 N -0.803255 1.153256 -1.422201 H -0.976960 1.965163 -2.017957 P 0.820599 0.916979 -0.965550 O 1.757961 1.357117 -2.056188 O 1.035660 1.723055 0.479767 C 0.802315 -0.771885 -0.345414 C 2.090280 -1.441381 -0.067060 C -0.416030 -1.351013 -0.082029 H -0.405446 -2.377446 0.310910 C 2.202945 -2.391453 0.979972 H 1.343713 -2.582932 1.631009 C 3.396571 -3.061213 1.228005 H 3.481481 -3.784017 2.045057 C 4.536218 -2.797057 0.438806 O 5.659599 -3.507270 0.766485 C 6.838726 -3.253369 0.005134 H 6.692779 -3.496382 -1.064766 H 7.612857 -3.911511 0.426048 H 7.163411 -2.199307 0.096579 C 4.454207 -1.844043 -0.592870 H 5.320922 -1.613368 -1.217158 C 3.246660 -1.177823 -0.835246 H 3.196064 -0.442827 -1.644379 C 1.045445 3.118204 0.579867 C 1.773483 3.937778 -0.298418 H 2.336103 3.483039 -1.117534 C 1.758579 5.325709 -0.096178 H 2.323815 5.969148 -0.779050 C 1.042514 5.890524 0.969082 201 H 1.043200 6.974706 1.120501 C 0.329212 5.056033 1.842907 H -0.231177 5.485076 2.680358 C 0.323658 3.668843 1.649976 H -0.227866 2.999898 2.317153 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1588.44569629 Predicted Change= -2.458265D-09 Zero-point correction (ZPE)= -1587.9992 0.44641 Internal Energy (U)= -1587.9708 0.47488 Enthalpy (H)= -1587.9698 0.47582 Gibbs Free Energy (G)= -1588.0606 0.38507 ------------------------------------------------------------------------------ Frequencies -- 8.4463 20.2689 25.2397 Single points at WB97X/6-311++G2(df,p): -1590.2295 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.03308909 Heterocycle 1c Supporting Information: 0006.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C21H18NO3P C1[X(C21H18NO3P)] #Atoms= 44 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1431.41483237 Predicted Change= -5.835733D-09 =============================================================== =============== Optimization completed. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00002 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00140 || 0.00180 [ YES ] 0.00140 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ 202 C 1.433626 2.630608 0.146780 C 1.859537 3.860849 0.703689 H 1.122554 4.465520 1.244821 C 3.172869 4.309268 0.574235 H 3.476686 5.262390 1.016961 C 4.101174 3.527162 -0.137554 H 5.135531 3.867528 -0.250905 C 3.715702 2.309345 -0.702004 H 4.440498 1.699407 -1.253364 C 2.392275 1.846526 -0.561721 N 1.991530 0.652064 -1.155172 H 2.664314 0.187357 -1.768411 P 0.553572 -0.216132 -0.868561 O 0.155176 -1.010696 -2.081524 O 0.815094 -1.142027 0.493293 C -0.518345 1.041423 -0.157168 C -1.950466 0.727478 0.028780 C 0.050566 2.222662 0.253650 H -0.620481 2.972298 0.695882 C -2.680662 1.281282 1.111128 H -2.163124 1.897198 1.853748 C -4.037884 1.026150 1.277219 H -4.594193 1.445006 2.121166 C -4.720420 0.192144 0.365995 O -6.051683 0.003270 0.621216 C -6.771396 -0.856833 -0.260344 H -6.359364 -1.883937 -0.252813 H -6.768109 -0.471934 -1.297983 H -7.803860 -0.875056 0.118103 C -4.012609 -0.384068 -0.704717 H -4.512158 -1.038502 -1.423231 C -2.647260 -0.117781 -0.863903 H -2.109617 -0.568053 -1.703996 C 1.615506 -2.290938 0.483052 C 1.429858 -3.326292 -0.447323 H 0.668321 -3.221351 -1.223673 C 2.239826 -4.467548 -0.358688 H 2.101147 -5.277262 -1.083105 C 3.211536 -4.583155 0.646061 H 3.834640 -5.481041 0.709328 C 3.377460 -3.542913 1.572752 H 4.130862 -3.623887 2.363464 C 2.583697 -2.391153 1.493370 H 2.695826 -1.567833 2.205020 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis 203 Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1431.41483237 Predicted Change= -5.835733D-09 Zero-point correction (ZPE)= -1431.0785 0.33628 Internal Energy (U)= -1431.0558 0.35901 Enthalpy (H)= -1431.0548 0.35995 Gibbs Free Energy (G)= -1431.1330 0.28175 ------------------------------------------------------------------------------ Frequencies -- 13.3909 23.0996 31.2795 Single points at WB97X/6-311++G2(df,p): -1432.9668 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.03086346 Geometry optimizations of heterocycle 1 dimers with chloroform model: R-S-Heterodimers Dimeric heterocycle 1g Supporting Information: polymerdetector-r-s-dimer-6-c-ch3-3-25-0004.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C50H46N4O4P2 C1[X(C50H46N4O4P2)] #Atoms= 106 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -3132.42114258 Predicted Change= -1.859898D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00444 || 0.00180 [ NO ] 0.00444 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -4.254132 -0.810428 0.290434 C -5.356290 -1.705764 0.261682 H -6.350106 -1.265182 0.131788 C -5.211752 -3.088080 0.389654 204 C -6.399881 -4.068504 0.371835 C -7.751792 -3.345605 0.205616 H -7.945260 -2.640989 1.033475 H -8.569764 -4.086522 0.202297 H -7.805709 -2.787912 -0.745916 C -6.432658 -4.857890 1.704510 H -5.501700 -5.426969 1.868728 H -7.269483 -5.579248 1.700792 H -6.568402 -4.178155 2.563482 C -6.231127 -5.059340 -0.807105 H -6.227097 -4.526557 -1.773914 H -7.063697 -5.785414 -0.818028 H -5.290151 -5.630733 -0.732308 C -3.887650 -3.580404 0.537562 H -3.721238 -4.658720 0.637133 C -2.778552 -2.740210 0.567545 H -1.767980 -3.145534 0.682443 C -2.943915 -1.342816 0.456847 N -1.834349 -0.509132 0.463397 H -0.896655 -0.971242 0.430023 P -1.835262 1.174706 0.521459 O -0.688159 1.756607 -0.285654 O -1.765058 1.647653 2.112400 C -3.529487 1.608759 0.131427 C -3.882261 3.029732 -0.073891 C -4.467310 0.600866 0.100348 H -5.501659 0.891114 -0.132590 C -5.149926 3.521541 0.323092 H -5.848639 2.857535 0.841279 C -5.512974 4.848729 0.103291 H -6.493492 5.213988 0.422295 C -4.604503 5.738591 -0.514090 C -3.329217 5.266811 -0.896791 H -2.622440 5.952882 -1.372675 C -2.975957 3.935281 -0.678749 H -1.989427 3.577840 -0.987871 C -0.547911 1.595191 2.814414 C -0.378980 0.590304 3.775927 H -1.172818 -0.146915 3.926927 C 0.803405 0.559205 4.528474 H 0.940931 -0.222271 5.282893 C 1.804143 1.518852 4.316512 H 2.726636 1.488637 4.904994 C 1.619444 2.517776 3.348865 H 2.398571 3.267080 3.174408 C 0.439656 2.564903 2.593526 205 H 0.276325 3.335735 1.836398 C -4.970002 7.104304 -0.738415 N -5.270877 8.227091 -0.924292 P 1.835260 -1.174714 -0.521463 O 1.765070 -1.647669 -2.112401 C 0.547930 -1.595219 -2.814427 O 0.688154 -1.756616 0.285644 C 3.529485 -1.608754 -0.131417 C 3.882269 -3.029724 0.073907 N 1.834336 0.509124 -0.463408 H 0.896636 0.971225 -0.430032 C 4.467301 -0.600854 -0.100335 H 5.501651 -0.891095 0.132610 C 4.254115 0.810437 -0.290427 C 2.943895 1.342817 -0.456851 C 0.379011 -0.590350 -3.775961 H 1.172853 0.146864 -3.926967 C -0.803365 -0.559262 -4.528521 H -0.940881 0.222200 -5.282957 C -1.804109 -1.518903 -4.316552 H -2.726595 -1.488696 -4.905044 C -1.619422 -2.517808 -3.348884 H -2.398552 -3.267107 -3.174421 C -0.439642 -2.564925 -2.593531 H -0.276321 -3.335742 -1.836387 C 2.778524 2.740209 -0.567558 H 1.767950 3.145525 -0.682466 C 3.887616 3.580410 -0.537570 H 3.721198 4.658724 -0.637153 C 5.211720 3.088096 -0.389647 C 6.399843 4.068527 -0.371836 C 6.231100 5.059355 0.807113 H 6.227089 4.526566 1.773919 H 5.290119 5.630743 0.732333 H 7.063665 5.785435 0.818027 C 6.432596 4.857920 -1.704507 H 6.568332 4.178190 -2.563484 H 7.269417 5.579283 -1.700797 H 5.501632 5.426993 -1.868709 C 7.751760 3.345633 -0.205640 H 7.805704 2.787960 0.745903 H 8.569730 4.086552 -0.202358 H 7.945206 2.641001 -1.033489 C 5.356267 1.705781 -0.261673 H 6.350085 1.265206 -0.131776 C 2.975970 -3.935280 0.678761 206 H 1.989436 -3.577848 0.987876 C 3.329242 -5.266806 0.896807 H 2.622469 -5.952883 1.372689 C 4.604536 -5.738574 0.514118 C 5.513003 -4.848705 -0.103259 H 6.493527 -5.213954 -0.422254 C 5.149942 -3.521521 -0.323065 H 5.848654 -2.857508 -0.841247 C 4.970049 -7.104282 0.738451 N 5.270918 -8.227071 0.924328 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -3132.42114258 Predicted Change= -1.859898D-08 Zero-point correction (ZPE)= -3131.5942 0.82689 Internal Energy (U)= -3131.5370 0.88412 Enthalpy (H)= -3131.5360 0.88507 Gibbs Free Energy (G)= -3131.6958 0.72529 ------------------------------------------------------------------------------ Frequencies -- 4.8989 8.6250 9.7633 Single points at WB97X/6-311++G2(df,p): -3135.9149 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05950948 Dimeric heterocycle 1e Supporting Information: polymerdetector-r-s-dimer-6-cf3-25-0014.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C44H28F6N4O4P2 C1[X(C44H28F6N4O4P2)] #Atoms= 88 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -3491.81477091 Predicted Change= -9.627271D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? 207 Force 0.00001 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00211 || 0.00180 [ NO ] 0.00211 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -4.307926 -0.842193 0.340389 C -5.428085 -1.706567 0.314631 H -6.427782 -1.274365 0.205984 C -5.280707 -3.085610 0.430042 C -6.472034 -4.002569 0.358180 F -6.416583 -4.968086 1.318584 F -6.533134 -4.651375 -0.841453 F -7.646439 -3.332560 0.512554 C -3.987276 -3.638922 0.569555 H -3.871129 -4.722197 0.672871 C -2.865974 -2.818230 0.591924 H -1.862460 -3.239869 0.706900 C -3.007955 -1.414816 0.480508 N -1.882030 -0.612298 0.482558 H -0.955718 -1.098652 0.462976 P -1.811876 1.075990 0.468163 O -0.736466 1.589266 -0.471578 O -1.546179 1.579533 2.022563 C -3.519612 1.554820 0.217023 C -3.838516 2.995340 0.103393 C -4.489579 0.579870 0.200892 H -5.525784 0.908398 0.039720 C -2.953069 3.897883 -0.535310 H -2.013329 3.523174 -0.951920 C -3.271232 5.251158 -0.653914 H -2.583033 5.936558 -1.157061 C -4.488968 5.744909 -0.135863 C -5.375908 4.856056 0.513138 H -6.310589 5.237426 0.934248 C -5.047301 3.506951 0.633869 H -5.723400 2.840167 1.177879 C -0.271205 1.984077 2.456843 C 0.692273 1.025954 2.798441 H 0.472966 -0.039330 2.677976 C 1.934202 1.459344 3.285174 H 2.694123 0.717424 3.551471 C 2.201294 2.828059 3.435177 H 3.171529 3.159367 3.818370 C 1.220988 3.772014 3.094040 H 1.422906 4.841675 3.211156 208 C -0.022342 3.354329 2.599701 H -0.801527 4.071553 2.325141 C -4.817308 7.133352 -0.256767 N -5.086302 8.274768 -0.356769 P 1.787213 -1.324966 -0.504910 O 1.697241 -1.910851 -2.055968 C 0.478699 -1.848633 -2.761932 O 0.651557 -1.840417 0.357670 C 3.479742 -1.725803 -0.072817 C 3.817556 -3.105809 0.339643 N 1.792045 0.362094 -0.586798 H 0.852449 0.824072 -0.586152 C 4.419640 -0.722134 -0.113672 H 5.458437 -1.004551 0.107605 C 4.207874 0.671756 -0.413730 C 2.895352 1.197327 -0.613085 C -0.529046 -2.788729 -2.509881 H -0.382992 -3.539735 -1.728994 C -1.708072 -2.739710 -3.266699 H -2.502476 -3.467493 -3.072253 C -1.870941 -1.765558 -4.263083 H -2.792388 -1.733794 -4.852883 C -0.850018 -0.834408 -4.503791 H -0.970907 -0.073632 -5.281620 C 0.332873 -0.868951 -3.751915 H 1.143345 -0.155749 -3.927389 C 2.714957 2.587525 -0.796567 H 1.698458 2.978251 -0.904291 C 3.814873 3.436658 -0.826359 H 3.668220 4.511546 -0.968383 C 5.123095 2.926281 -0.666725 C 6.301567 3.857003 -0.769018 F 6.594659 4.157890 -2.066869 F 7.426417 3.321656 -0.219055 F 6.057344 5.041664 -0.139712 C 5.306358 1.562439 -0.455766 H 6.315594 1.166066 -0.305495 C 3.210233 -4.230417 -0.267194 H 2.482030 -4.083113 -1.069843 C 3.555108 -5.526589 0.114422 H 3.085730 -6.387691 -0.369734 C 4.523362 -5.736701 1.121539 C 5.132314 -4.622229 1.741087 H 5.870315 -4.780700 2.532642 C 4.775133 -3.330533 1.356905 H 5.223148 -2.475100 1.872305 209 C 4.879676 -7.066179 1.516508 N 5.173433 -8.158696 1.840783 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -3491.81477091 Predicted Change= -9.627271D-09 Zero-point correction (ZPE)= -3491.1993 0.61542 Internal Energy (U)= -3491.1460 0.66868 Enthalpy (H)= -3491.1451 0.66963 Gibbs Free Energy (G)= -3491.2990 0.51575 ------------------------------------------------------------------------------ Frequencies -- 5.2568 6.9680 11.8537 Single points at WB97X/6-311++G2(df,p): -3495.5933 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05570801 Dimeric heterocycle 1b Supporting Information: 0015.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C42H30N4O4P2 C1[X(C42H30N4O4P2)] #Atoms= 82 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2818.35838883 Predicted Change= -2.252437D-07 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.02410 || 0.00180 [ NO ] 0.02410 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -2.447119 -3.499944 0.909628 C -2.633343 -4.894051 1.094337 210 H -3.650528 -5.295644 1.018412 C -1.563283 -5.740766 1.364866 H -1.728574 -6.812434 1.508548 C -0.262631 -5.201882 1.454394 H 0.586414 -5.857919 1.673054 C -0.040592 -3.836935 1.276613 H 0.965964 -3.413078 1.353671 C -1.124330 -2.972433 1.004713 N -0.889167 -1.621399 0.796489 H 0.110230 -1.323712 0.721199 P -2.027084 -0.393261 0.597346 O -2.262172 0.338089 2.067287 C -1.630647 1.535094 2.435182 O -1.601391 0.608215 -0.460107 C -3.568948 -1.288214 0.416081 C -4.805625 -0.523998 0.142498 C -3.568905 -2.652040 0.602119 H -4.529742 -3.171691 0.480234 C -6.049097 -0.957532 0.664068 H -6.084676 -1.834317 1.318015 C -7.228179 -0.265007 0.395959 H -8.179109 -0.609980 0.812275 C -7.197729 0.904264 -0.397901 C -5.961924 1.359144 -0.908863 H -5.933493 2.264576 -1.522073 C -4.787430 0.655230 -0.642673 H -3.837590 1.010590 -1.053242 C -0.234282 1.630157 2.516873 H 0.398422 0.776891 2.251857 C 0.337380 2.837301 2.944110 H 1.427615 2.919648 3.004254 C -0.472940 3.925740 3.297900 H -0.018411 4.862663 3.635043 C -1.868674 3.808043 3.220031 H -2.509012 4.652274 3.496015 C -2.454930 2.612452 2.783831 H -3.540368 2.498968 2.709156 C -8.404528 1.624479 -0.670566 N -9.396812 2.216517 -0.895256 P 2.211381 0.207720 -0.607235 O 2.477935 -0.600641 -2.038228 C 1.486009 -1.447786 -2.567229 O 1.779767 -0.737147 0.499345 C 3.741428 1.126644 -0.443435 C 4.945197 0.449809 0.082898 N 1.061795 1.406922 -0.882817 211 H 0.063189 1.123406 -0.749763 C 3.741932 2.454503 -0.808943 H 4.704412 2.983127 -0.756699 C 2.625549 3.247903 -1.254705 C 1.297667 2.722716 -1.257977 C 0.744927 -0.997358 -3.667532 H 0.924523 0.007024 -4.061750 C -0.206783 -1.851441 -4.242042 H -0.788321 -1.507061 -5.103340 C -0.416335 -3.135481 -3.717329 H -1.163509 -3.796555 -4.167694 C 0.334068 -3.570690 -2.614934 H 0.171492 -4.568486 -2.194655 C 1.294695 -2.730031 -2.035803 H 1.887562 -3.051469 -1.175688 C 0.211411 3.556258 -1.601260 H -0.801614 3.142734 -1.565929 C 0.438824 4.880799 -1.971674 H -0.412626 5.514141 -2.241302 C 1.746338 5.409005 -2.004370 H 1.915156 6.448114 -2.301418 C 2.817631 4.598767 -1.642850 H 3.838480 4.998177 -1.644603 C 5.208418 -0.912597 -0.195763 H 4.516035 -1.477360 -0.826586 C 6.356631 -1.538027 0.288253 H 6.551423 -2.589196 0.057042 C 7.283766 -0.814398 1.071202 C 7.030407 0.544971 1.363276 H 7.736607 1.104469 1.983512 C 5.875009 1.158029 0.881306 H 5.669702 2.198874 1.150792 C 8.463972 -1.452896 1.570296 N 9.434862 -1.977555 1.979602 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2818.35838883 Predicted Change= -2.252437D-07 Zero-point correction (ZPE)= -2817.7513 0.60700 Internal Energy (U)= -2817.7057 0.65262 Enthalpy (H)= -2817.7048 0.65356 Gibbs Free Energy (G)= -2817.8396 0.51873 ------------------------------------------------------------------------------ Frequencies -- 4.2468 8.3317 13.2541 212 Single points at WB97X/6-311++G2(df,p): -2821.3888 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05543327 Dimeric heterocycle 1p Supporting Information: 1-cn-2-eto-5.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C46H38N4O6P2 C1[X(C46H38N4O6P2)] #Atoms= 96 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -3125.67367442 Predicted Change= -1.462814D-07 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00017 || 0.00045 [ YES ] 0.00003 || 0.00030 [ YES ] Displ 0.00200 || 0.00180 [ NO ] 0.00200 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -4.139498 -1.885553 0.263789 C -4.950636 -3.044729 0.408778 H -6.031258 -2.933358 0.285107 C -4.381540 -4.286589 0.696620 C -2.974453 -4.387785 0.831333 H -2.543433 -5.368967 1.051489 C -2.163325 -3.268582 0.692751 H -1.076873 -3.351076 0.799722 C -2.729302 -2.002778 0.420673 N -1.903580 -0.894893 0.252523 H -0.874950 -1.070571 0.197562 P -2.395901 0.712210 0.195430 O -1.447843 1.547001 -0.646408 O -2.523045 1.286491 1.750447 C -4.133963 0.597161 -0.230026 213 C -4.871458 1.816815 -0.621314 C -4.746041 -0.629980 -0.101083 H -5.817328 -0.679267 -0.341813 C -4.245332 2.850874 -1.360618 H -3.189994 2.751429 -1.630414 C -4.957902 3.982248 -1.757535 H -4.464082 4.767857 -2.336890 C -6.323480 4.119600 -1.423167 C -6.955736 3.102774 -0.671556 H -8.006843 3.214366 -0.389867 C -6.235962 1.977499 -0.275535 H -6.729729 1.220335 0.341379 C -1.365858 1.611793 2.478982 C -0.733906 2.845983 2.276169 H -1.124037 3.530533 1.518566 C 0.388047 3.171457 3.050665 H 0.892984 4.129377 2.889223 C 0.865159 2.275420 4.019072 H 1.740812 2.535159 4.622482 C 0.217215 1.046694 4.214139 H 0.584214 0.344720 4.970036 C -0.902672 0.705729 3.442354 H -1.424190 -0.246042 3.579367 C -7.057235 5.279400 -1.830095 N -7.661326 6.232447 -2.165617 C -6.498953 -5.413693 0.728141 H -6.767422 -5.047382 -0.283791 O -5.071371 -5.458997 0.863669 C -7.025943 -6.821659 0.957063 H -6.757995 -7.178980 1.964762 H -8.124605 -6.833321 0.862903 H -6.604555 -7.520668 0.216302 H -6.922367 -4.704194 1.468219 P 1.852321 -0.408350 -0.555758 O 1.997016 -0.690075 -2.187917 C 2.349160 -1.933559 -2.734722 O 0.879319 -1.370117 0.103803 C 3.526878 -0.327962 0.089012 C 4.258393 -1.574240 0.404650 N 1.345399 1.185353 -0.534544 H 0.315244 1.345916 -0.617723 C 4.117168 0.912181 0.199770 H 5.147296 0.939390 0.582288 C 3.526242 2.197134 -0.072418 C 2.151684 2.314624 -0.419866 C 3.382402 -1.929663 -3.682435 214 H 3.885987 -0.987106 -3.916225 C 3.739903 -3.128968 -4.311997 H 4.545470 -3.128533 -5.053632 C 3.074105 -4.321989 -3.993798 H 3.357177 -5.258083 -4.485356 C 2.041102 -4.308170 -3.045392 H 1.512560 -5.234605 -2.797016 C 1.665261 -3.115074 -2.412141 H 0.858210 -3.087272 -1.676509 C 1.589355 3.597295 -0.605389 H 0.528899 3.677601 -0.864237 C 2.372499 4.736750 -0.468689 H 1.945318 5.732276 -0.622125 C 3.746866 4.637991 -0.136944 C 4.309916 3.376523 0.062752 H 5.364087 3.263757 0.330004 C 3.601002 -2.701133 0.956974 H 2.523871 -2.653957 1.138753 C 4.309639 -3.857207 1.283052 H 3.790061 -4.716531 1.716944 C 5.703343 -3.926854 1.063375 C 6.369262 -2.814957 0.498983 H 7.444528 -2.870669 0.305806 C 5.653198 -1.665546 0.171768 H 6.176279 -0.830022 -0.303830 C 6.432425 -5.112104 1.398791 N 7.032598 -6.086006 1.676568 C 5.806764 5.787455 0.298631 H 5.940145 5.284043 1.278088 O 4.412939 5.832143 -0.036985 C 6.313290 7.220498 0.347938 H 7.385713 7.232880 0.604525 H 6.182251 7.714190 -0.628817 H 5.765818 7.801725 1.107802 H 6.356166 5.196533 -0.462568 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -3125.67367442 Predicted Change= -1.462814D-07 Zero-point correction (ZPE)= -3124.9479 0.72574 Internal Energy (U)= -3124.8940 0.77966 Enthalpy (H)= -3124.8930 0.78061 Gibbs Free Energy (G)= -3125.0475 0.62611 ------------------------------------------------------------------------------ 215 Frequencies -- 3.6817 6.6552 11.4552 Single points at WB97X/6-311++G2(df,p): -3129.0918 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05959069 Dimeric heterocycle 1j Supporting Information: 0018.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C48H48N2O4P2 C1[X(C48H48N2O4P2)] #Atoms= 104 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2948.13012412 Predicted Change= -1.531703D-08 =============================================================== =============== Optimization completed. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00001 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00168 || 0.00180 [ YES ] 0.00168 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 4.253562 -0.886991 0.254948 C 5.609251 -0.463912 0.267596 H 6.364477 -1.213928 0.010874 C 5.991513 0.841169 0.582211 C 7.457515 1.313851 0.590671 C 7.822566 1.837490 2.002218 H 7.173028 2.674339 2.311058 H 8.866506 2.199662 2.019006 H 7.723634 1.038208 2.756985 C 7.632659 2.457599 -0.440139 H 6.978855 3.317147 -0.214023 H 7.391047 2.109446 -1.459669 H 8.676631 2.819968 -0.438377 C 8.439608 0.182318 0.226601 216 H 9.474212 0.566252 0.248783 H 8.253212 -0.212347 -0.787768 H 8.380304 -0.657182 0.941438 C 4.949657 1.754760 0.893132 H 5.195980 2.794003 1.136849 C 3.609684 1.382838 0.896924 H 2.824695 2.112360 1.120822 C 3.240765 0.057181 0.583225 N 1.900904 -0.302085 0.571784 H 1.206882 0.468218 0.706588 P 1.236189 -1.801600 0.185312 O 0.097414 -1.690992 -0.816531 O 0.709236 -2.472699 1.609911 C 2.666590 -2.801449 -0.204897 C 2.456569 -4.225465 -0.559282 C 3.919154 -2.237228 -0.116825 H 4.770807 -2.879675 -0.382942 C 1.327396 -4.643761 -1.303405 H 0.592148 -3.899484 -1.625482 C 1.156354 -5.991647 -1.642953 H 0.278369 -6.291764 -2.225127 C 2.103128 -6.950269 -1.254993 H 1.966659 -8.003039 -1.523551 C 3.222937 -6.550083 -0.510252 H 3.960369 -7.291541 -0.184370 C 3.393614 -5.206801 -0.159403 H 4.247590 -4.912532 0.459898 C -0.648842 -2.583136 1.936359 C -1.335026 -1.481638 2.465756 H -0.824762 -0.518136 2.560848 C -2.674587 -1.636766 2.849895 H -3.220083 -0.777373 3.253079 C -3.313477 -2.878365 2.715975 H -4.360191 -2.992088 3.016060 C -2.608935 -3.972039 2.190704 H -3.101771 -4.944383 2.084921 C -1.271612 -3.830110 1.794971 H -0.703025 -4.667155 1.378415 P -1.236214 1.801395 -0.185467 O -0.709106 2.472295 -1.610094 C 0.649050 2.582681 -1.936418 O -0.097518 1.690706 0.816458 C -2.666505 2.801501 0.204525 C -2.456257 4.225556 0.558644 N -1.901156 0.301942 -0.571890 H -1.207309 -0.468559 -0.706400 217 C -3.919152 2.237467 0.116540 H -4.770708 2.880127 0.382453 C -4.253739 0.887185 -0.254908 C -3.241068 -0.057170 -0.583018 C 1.335188 1.481153 -2.465784 H 0.824831 0.517711 -2.560993 C 2.674814 1.636219 -2.849740 H 3.220333 0.776809 -3.252854 C 3.313763 2.877772 -2.715676 H 4.360525 2.991440 -3.015618 C 2.609229 3.971481 -2.190461 H 3.102121 4.943785 -2.084587 C 1.271848 3.829620 -1.794898 H 0.703257 4.666669 -1.378362 C -3.610168 -1.382868 -0.896366 H -2.825282 -2.112522 -1.120208 C -4.950176 -1.754645 -0.892375 H -5.196640 -2.793917 -1.135823 C -5.991915 -0.840856 -0.581613 C -7.457976 -1.313362 -0.589939 C -7.633270 -2.456914 0.441051 H -8.677300 -2.819117 0.439362 H -7.391592 -2.108642 1.460524 H -6.979616 -3.316612 0.215067 C -7.823110 -1.837183 -2.001405 H -7.724040 -1.038041 -2.756300 H -8.867109 -2.199189 -2.018136 H -7.173696 -2.674185 -2.310090 C -8.439917 -0.181644 -0.226036 H -8.380526 0.657731 -0.941013 H -8.253443 0.213162 0.788263 H -9.474572 -0.565446 -0.248135 C -5.609479 0.464258 -0.267364 H -6.364592 1.214437 -0.010784 C -3.393000 5.207000 0.158346 H -4.246910 4.912770 -0.461065 C -3.222107 6.550325 0.508934 H -3.959305 7.291872 0.182727 C -2.102381 6.950429 1.253842 H -1.965744 8.003228 1.522199 C -1.155909 5.991686 1.642242 H -0.277999 6.291741 2.224561 C -1.327168 4.643762 1.302950 H -0.592155 3.899395 1.625355 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis 218 Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2948.13012412 Predicted Change= -1.531703D-08 Zero-point correction (ZPE)= -2947.3000 0.83009 Internal Energy (U)= -2947.2465 0.88353 Enthalpy (H)= -2947.2456 0.88447 Gibbs Free Energy (G)= -2947.3943 0.73574 ------------------------------------------------------------------------------ Frequencies -- 4.3339 12.4357 15.4786 Single points at WB97X/6-311++G2(df,p): Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: Dimeric heterocycle 1m Supporting Information: 0005.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C42H30N4O4P2 C1[X(C42H30N4O4P2)] #Atoms= 82 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2818.36002288 Predicted Change= -1.463986D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00255 || 0.00180 [ NO ] 0.00255 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -4.163177 -1.208498 0.535223 C -5.185352 -2.173970 0.646497 H -6.223624 -1.870526 0.476891 C -4.899309 -3.510646 0.965807 C -3.548741 -3.898689 1.176011 H -3.322160 -4.938504 1.428414 219 C -2.524596 -2.967470 1.068657 H -1.482411 -3.259835 1.231411 C -2.811581 -1.617739 0.752794 N -1.777025 -0.712324 0.629527 H -0.805202 -1.098932 0.667313 P -1.884049 0.956234 0.365021 O -1.705668 1.699771 1.832935 C -0.490145 2.282075 2.230176 O -0.843864 1.431397 -0.631766 C -3.626475 1.211663 0.037844 C -4.089460 2.579553 -0.296316 C -4.488408 0.151313 0.174281 H -5.550226 0.343704 -0.033130 C -3.315465 3.441407 -1.108685 H -2.352126 3.094145 -1.494353 C -3.783167 4.720104 -1.435004 H -3.173301 5.369688 -2.071746 C -5.024628 5.166568 -0.960392 H -5.386519 6.167578 -1.216926 C -5.796203 4.325054 -0.144674 H -6.758513 4.670199 0.247828 C -5.332040 3.048799 0.189659 H -5.921117 2.415441 0.861302 C 0.590907 1.479171 2.618242 H 0.514680 0.388686 2.564103 C 1.766618 2.098763 3.066665 H 2.617439 1.478680 3.367517 C 1.853455 3.496987 3.135375 H 2.773182 3.973159 3.489395 C 0.757534 4.283386 2.749443 H 0.818217 5.375344 2.802248 C -0.421108 3.679170 2.290750 H -1.287802 4.270383 1.980660 C -5.953829 -4.471337 1.072926 N -6.818801 -5.265432 1.158726 P 1.915469 -1.215377 -0.352615 O 1.771292 -1.979332 -1.820955 C 0.503866 -2.066513 -2.430607 O 0.867259 -1.692731 0.634773 C 3.653547 -1.444082 0.017355 C 4.120869 -2.754313 0.528823 N 1.782307 0.447375 -0.639511 H 0.805404 0.824785 -0.669091 C 4.500453 -0.373581 -0.139440 H 5.565128 -0.552739 0.064926 C 4.162349 0.973596 -0.536239 220 C 2.805866 1.367647 -0.751744 C -0.386304 -3.079612 -2.051090 H -0.106293 -3.772882 -1.253374 C -1.624257 -3.175312 -2.701815 H -2.328609 -3.959335 -2.405666 C -1.961131 -2.271665 -3.720637 H -2.928530 -2.351985 -4.226301 C -1.055286 -1.267214 -4.092204 H -1.312271 -0.560889 -4.888069 C 0.184592 -1.156867 -3.446882 H 0.906132 -0.382610 -3.722628 C 2.500475 2.716893 -1.049267 H 1.451882 3.004123 -1.174876 C 3.514947 3.656769 -1.168209 H 3.274532 4.697480 -1.403009 C 4.872633 3.279044 -0.987148 C 5.175454 1.946160 -0.668010 H 6.218239 1.652984 -0.508324 C 3.611047 -3.971702 0.022916 H 2.859597 -3.952499 -0.772177 C 4.088014 -5.197362 0.500956 H 3.686725 -6.129332 0.089310 C 5.079252 -5.235892 1.492162 H 5.448925 -6.196427 1.865458 C 5.588455 -4.035048 2.008336 H 6.351400 -4.053123 2.793637 C 5.110335 -2.807689 1.537350 H 5.483845 -1.874828 1.973236 C 5.916871 4.248634 -1.113349 N 6.773332 5.049958 -1.215766 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2818.36002288 Predicted Change= -1.463986D-09 Zero-point correction (ZPE)= -2817.7528 0.60718 Internal Energy (U)= -2817.7072 0.65277 Enthalpy (H)= -2817.7063 0.65371 Gibbs Free Energy (G)= -2817.8401 0.51983 ------------------------------------------------------------------------------ Frequencies -- 6.6629 8.2195 11.1622 Single points at WB97X/6-311++G2(df,p): -2821.3924 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05603817 Dimeric heterocycle 1a 221 Supporting Information: 0003.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C40H32N2O4P2 C1[X(C40H32N2O4P2)] #Atoms= 80 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2634.06625433 Predicted Change= -3.719026D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00001 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00447 || 0.00180 [ NO ] 0.00447 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -3.334148 2.486946 -1.202693 C -3.836091 3.720881 -1.687434 H -4.910672 3.916458 -1.592765 C -2.997633 4.671938 -2.261933 H -3.406029 5.617326 -2.631264 C -1.615220 4.409787 -2.350797 H -0.944137 5.156483 -2.788027 C -1.085494 3.205294 -1.889094 H -0.011999 2.998177 -1.946092 C -1.936411 2.227169 -1.330508 N -1.399758 1.032442 -0.866584 H -0.356291 0.966668 -0.821943 P -2.254391 -0.324444 -0.351229 O -1.518729 -1.058965 0.754758 O -2.510459 -1.306139 -1.675872 C -3.908254 0.300423 -0.062506 C -4.882552 -0.526781 0.685069 C -4.213374 1.552865 -0.542304 H -5.249094 1.894946 -0.405494 C -5.808962 0.081753 1.562894 222 H -5.762065 1.163945 1.725591 C -6.756683 -0.683584 2.250856 H -7.461003 -0.190581 2.929429 C -6.790973 -2.076707 2.089934 H -7.527503 -2.676713 2.634375 C -5.868343 -2.695535 1.234014 H -5.887256 -3.782283 1.099907 C -4.923959 -1.932320 0.538547 H -4.227902 -2.423014 -0.148879 C -1.417876 -1.948298 -2.283774 C -0.919159 -1.424361 -3.484046 H -1.364441 -0.515212 -3.898429 C 0.138772 -2.081691 -4.127212 H 0.532922 -1.677175 -5.065224 C 0.693538 -3.244436 -3.572304 H 1.523674 -3.750435 -4.075413 C 0.183357 -3.756243 -2.369995 H 0.616419 -4.657984 -1.925030 C -0.879486 -3.113300 -1.720596 H -1.287793 -3.495479 -0.781540 P 2.111310 0.077483 0.439919 O 2.249749 0.957885 1.842556 C 1.423687 2.048649 2.140721 O 1.405744 0.874771 -0.641123 C 3.799602 -0.469033 0.200476 C 4.820879 0.529145 -0.196486 N 1.291183 -1.348998 0.810491 H 0.248619 -1.275292 0.820246 C 4.112871 -1.782292 0.461272 H 5.157803 -2.083650 0.300640 C 3.229131 -2.831517 0.903727 C 1.832262 -2.598235 1.075749 C 0.044725 1.885924 2.335783 H -0.419548 0.902113 2.212209 C -0.725954 3.003503 2.686588 H -1.804936 2.883875 2.830515 C -0.126123 4.259768 2.856945 H -0.734699 5.126222 3.134978 C 1.257066 4.401190 2.669778 H 1.733507 5.378400 2.801671 C 2.038656 3.296561 2.306164 H 3.117288 3.383070 2.145613 C 0.987956 -3.653265 1.488490 H -0.079622 -3.450859 1.623954 C 1.517697 -4.920851 1.728115 H 0.851658 -5.726396 2.054975 223 C 2.895792 -5.169790 1.562857 H 3.304823 -6.166098 1.755077 C 3.730730 -4.133292 1.155078 H 4.804435 -4.309418 1.020286 C 4.514611 1.588845 -1.082972 H 3.498544 1.678012 -1.479543 C 5.500513 2.507893 -1.462228 H 5.242764 3.317174 -2.153825 C 6.808646 2.393979 -0.970779 H 7.576663 3.115103 -1.269533 C 7.122813 1.354192 -0.082536 H 8.135704 1.265723 0.324885 C 6.140160 0.438022 0.306161 H 6.385352 -0.342367 1.034301 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2634.06625433 Predicted Change= -3.719026D-08 Zero-point correction (ZPE)= -2633.4560 0.61017 Internal Energy (U)= -2633.4142 0.65198 Enthalpy (H)= -2633.4133 0.65292 Gibbs Free Energy (G)= -2633.5386 0.52763 ------------------------------------------------------------------------------ Frequencies -- 4.8961 8.0606 12.5771 Single points at WB97X/6-311++G2(df,p): -2636.899 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.04980344 Heterocycle 1o* Supporting Information: 1-h-2-co2me-dimer-8.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C44H36N2O8P2 C1[X(C44H36N2O8P2)] #Atoms= 92 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -3089.34722096 Predicted Change= -5.808904D-08 224 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00001 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00619 || 0.00180 [ NO ] 0.00619 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 4.232766 0.927589 -0.118239 C 5.591898 0.544079 -0.114126 H 6.347117 1.277097 0.186344 C 5.989513 -0.747026 -0.478860 C 5.001343 -1.689340 -0.853941 H 5.324982 -2.697190 -1.130311 C 3.656298 -1.344510 -0.870450 H 2.890679 -2.075345 -1.148899 C 3.253876 -0.036579 -0.510203 N 1.908992 0.288913 -0.515747 H 1.233748 -0.480203 -0.734732 P 1.196445 1.771005 -0.138743 O 0.015782 1.661674 0.807245 O 0.736878 2.316530 -1.635714 C 2.585849 2.782810 0.368178 C 2.331384 4.185500 0.777197 C 3.852754 2.255920 0.297937 H 4.679707 2.904612 0.619715 C 1.199136 4.536979 1.549543 H 0.491176 3.757755 1.847093 C 0.990285 5.864875 1.940967 H 0.110952 6.115008 2.543864 C 1.897554 6.868046 1.571888 H 1.729371 7.905496 1.879133 C 3.018444 6.534530 0.796328 H 3.724920 7.312066 0.486727 C 3.230577 5.210068 0.397836 H 4.087286 4.964225 -0.238781 C -0.412522 3.098468 -1.835890 C -0.285321 4.491627 -1.909335 H 0.692902 4.953895 -1.748277 C -1.422407 5.263483 -2.185581 H -1.330751 6.353017 -2.244446 C -2.667542 4.648427 -2.384176 H -3.552146 5.256582 -2.598759 C -2.776009 3.251769 -2.309571 225 H -3.744426 2.764273 -2.461265 C -1.646002 2.467317 -2.038951 H -1.707412 1.376442 -1.989230 P -1.214962 -1.854269 0.080288 O -0.757324 -2.420805 1.570093 C 0.380080 -3.224121 1.756195 O -0.033580 -1.734109 -0.863328 C -2.609442 -2.853975 -0.438215 C -2.359149 -4.246195 -0.884045 N -1.920382 -0.373166 0.473810 H -1.242623 0.394748 0.687419 C -3.875782 -2.331079 -0.336136 H -4.707551 -2.972292 -0.659827 C -4.250305 -1.012914 0.117140 C -3.266152 -0.052308 0.505207 C 1.620404 -2.614081 1.980999 H 1.695946 -1.523108 1.959021 C 2.739489 -3.419252 2.235985 H 3.713553 -2.948307 2.402834 C 2.613545 -4.815878 2.273541 H 3.489996 -5.440301 2.474077 C 1.361635 -5.409752 2.054426 H 1.256276 -6.499199 2.084211 C 0.235198 -4.616983 1.794023 H -0.747777 -5.063531 1.618044 C -3.664362 1.247325 0.896555 H -2.893772 1.975392 1.168782 C -5.011379 1.590468 0.922304 H -5.311869 2.595802 1.228496 C -6.003575 0.648675 0.555156 C -5.607630 -0.632121 0.154764 H -6.383222 -1.348529 -0.137606 C -3.254690 -5.279911 -0.521001 H -4.105295 -5.050388 0.129679 C -3.046807 -6.593964 -0.954484 H -3.750490 -7.378828 -0.657343 C -1.934050 -6.907988 -1.749656 H -1.769257 -7.937427 -2.084410 C -1.030437 -5.895929 -2.103048 H -0.157285 -6.130866 -2.720820 C -1.234861 -4.578258 -1.676300 H -0.529508 -3.792173 -1.961556 O 8.262028 -0.184437 -0.108200 C 7.408952 -1.187562 -0.482360 O 7.791489 -2.314604 -0.780801 C 9.650282 -0.569408 -0.094095 226 H 10.199338 0.327243 0.225882 H 9.817384 -1.400414 0.610628 H 9.976661 -0.888137 -1.097584 C -7.458282 0.954460 0.565030 O -8.344808 0.165073 0.253736 O -7.709432 2.238782 0.966083 C -9.108231 2.582030 0.994613 H -9.555026 2.480830 -0.008049 H -9.656039 1.926841 1.691519 H -9.146278 3.626934 1.332988 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -3089.34722096 Predicted Change= -5.808904D-08 Zero-point correction (ZPE)= -3088.6536 0.69353 Internal Energy (U)= -3088.6023 0.74491 Enthalpy (H)= -3088.6013 0.74585 Gibbs Free Energy (G)= -3088.7485 0.59870 ------------------------------------------------------------------------------ Frequencies -- 4.7697 11.2384 12.1183 Single points at WB97X/6-311++G2(df,p): -3092.7102 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05165733 Dimeric heterocycle 1h Supporting Information: 1-ome-2-c-ch3-3-0016.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C50H52N2O6P2 C1[X(C50H52N2O6P2)] #Atoms= 112 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -3176.92196624 Predicted Change= -1.433711D-07 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? 227 Force 0.00002 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.13324 || 0.00180 [ NO ] 0.13324 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 4.134783 -1.300405 -0.473561 C 5.097701 -2.338685 -0.569618 H 6.147294 -2.054579 -0.442619 C 4.753407 -3.672230 -0.802438 C 3.369995 -3.962797 -0.928702 H 3.047243 -4.996144 -1.096282 C 2.392209 -2.975067 -0.848520 H 1.329906 -3.224204 -0.939167 C 2.760265 -1.629488 -0.640399 N 1.780584 -0.646267 -0.552406 H 0.788447 -0.974215 -0.501625 P 2.033297 1.016312 -0.498035 O 0.974064 1.717485 0.335029 O 2.052775 1.590947 -2.066095 C 3.764157 1.171243 -0.062285 C 4.284532 2.477205 0.392300 C 4.548543 0.043079 -0.149306 H 5.619845 0.169254 0.062740 C 3.802980 3.695489 -0.131901 H 3.032040 3.680556 -0.908549 C 4.311931 4.929802 0.289179 H 3.914415 5.847640 -0.150971 C 5.330008 4.972219 1.260199 O 5.901001 6.116584 1.749508 C 5.409979 7.357896 1.248127 H 4.332238 7.486607 1.464844 H 5.574108 7.451093 0.157415 H 5.982836 8.138186 1.770223 C 5.820514 3.765695 1.801697 H 6.596933 3.814530 2.571112 C 5.300082 2.546174 1.378285 H 5.664502 1.622052 1.839514 C 0.879571 1.596484 -2.836812 C -0.144147 2.518882 -2.577943 H -0.048147 3.206945 -1.734601 C -1.279064 2.526256 -3.400594 H -2.087213 3.234642 -3.190646 C -1.382517 1.631631 -4.476000 H -2.270589 1.642710 -5.116010 C -0.345916 0.720392 -4.727195 228 H -0.420885 0.018623 -5.564403 C 0.789664 0.694822 -3.906081 H 1.607958 -0.009661 -4.081196 C 5.793117 -4.804098 -0.909532 C 5.672262 -5.484706 -2.296108 H 6.397659 -6.314253 -2.380760 H 5.875883 -4.765447 -3.108271 H 4.664741 -5.903231 -2.461442 C 7.237791 -4.288499 -0.750336 H 7.400449 -3.820114 0.236384 H 7.498181 -3.551803 -1.530599 H 7.944941 -5.131392 -0.838609 C 5.527900 -5.853994 0.198762 H 5.622240 -5.401800 1.201226 H 6.255673 -6.682257 0.123934 H 4.516627 -6.287958 0.119231 P -1.925348 -0.823822 0.519363 O -1.878379 -1.288826 2.116376 C -0.713894 -1.752416 2.738663 O -0.878537 -1.560943 -0.295859 C -3.669805 -1.036073 0.166993 C -4.210520 -2.409053 0.059626 N -1.709767 0.845112 0.438901 H -0.716259 1.167995 0.400550 C -4.461844 0.084913 0.080380 H -5.527428 -0.077504 -0.136255 C -4.061687 1.465232 0.211436 C -2.693499 1.824050 0.386405 C -0.767164 -3.020954 3.331644 H -1.683559 -3.611142 3.239401 C 0.352533 -3.501595 4.023247 H 0.313816 -4.492060 4.488983 C 1.517584 -2.725050 4.112470 H 2.392832 -3.106167 4.648314 C 1.555718 -1.458380 3.511856 H 2.460602 -0.844914 3.575351 C 0.438846 -0.958072 2.827494 H 0.466733 0.035584 2.369153 C -2.344267 3.186156 0.465461 H -1.292288 3.454281 0.609291 C -3.327156 4.174344 0.376922 H -3.011721 5.218787 0.450154 C -4.695860 3.859281 0.207338 C -5.023776 2.499193 0.127068 H -6.069568 2.197320 -0.009638 C -3.458929 -3.465967 -0.514803 229 H -2.445958 -3.267236 -0.877896 C -3.992920 -4.746744 -0.635159 H -3.413693 -5.558238 -1.086047 C -5.299679 -5.022525 -0.184647 O -5.727515 -6.313038 -0.352778 C -7.046764 -6.627548 0.085971 H -7.808309 -6.026564 -0.447307 H -7.162320 -6.473613 1.176167 H -7.193592 -7.692123 -0.148148 C -6.058868 -3.991957 0.402062 H -7.064999 -4.180023 0.785200 C -5.509320 -2.710137 0.522695 H -6.097328 -1.930851 1.019117 C -5.798403 4.933640 0.113089 C -6.820370 4.726999 1.258887 H -6.333007 4.820335 2.244776 H -7.293104 3.731202 1.210116 H -7.623364 5.483883 1.198138 C -5.231411 6.363796 0.226035 H -6.054996 7.095573 0.158629 H -4.519086 6.589151 -0.587147 H -4.718853 6.527489 1.190254 C -6.526693 4.808699 -1.248517 H -6.984162 3.812955 -1.378304 H -5.826776 4.969289 -2.086985 H -7.332767 5.561080 -1.324581 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -3176.92196624 Predicted Change= -1.433711D-07 Zero-point correction (ZPE)= -3176.0280 0.89387 Internal Energy (U)= -3175.9693 0.95262 Enthalpy (H)= -3175.9684 0.95356 Gibbs Free Energy (G)= -3176.1320 0.78995 ------------------------------------------------------------------------------ Frequencies -- 1.7009 5.6735 8.6199 Single points at WB97X/6-311++G2(df,p): -3180.4925 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05649918 Dimeric heterocycle 1c Supporting Information: 0006.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 230 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C42H36N2O6P2 C1[X(C42H36N2O6P2)] #Atoms= 88 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2862.86173312 Predicted Change= -1.891495D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00449 || 0.00180 [ NO ] 0.00449 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -2.552034 3.522551 -0.887574 C -2.634502 4.907993 -1.174413 H -3.616487 5.391881 -1.114498 C -1.507392 5.649463 -1.520029 H -1.596060 6.717347 -1.741154 C -0.251245 5.012714 -1.572973 H 0.643642 5.586989 -1.834677 C -0.130029 3.650544 -1.295906 H 0.843613 3.150555 -1.322065 C -1.273870 2.892538 -0.964174 N -1.139184 1.542274 -0.658199 H -0.166257 1.155887 -0.651008 P -2.383058 0.426609 -0.425195 O -1.998610 -0.612405 0.613424 O -2.737918 -0.275645 -1.891624 C -3.833734 1.450920 -0.190767 C -5.105786 0.812331 0.210250 C -3.726673 2.792704 -0.473356 H -4.633011 3.400364 -0.339549 C -5.140391 -0.275950 1.109723 H -4.200700 -0.670916 1.507667 C -6.350865 -0.850864 1.517119 H -6.331250 -1.685398 2.222556 231 C -7.568463 -0.346595 1.024231 O -8.808354 -0.827483 1.350486 C -8.865066 -1.929904 2.253178 H -8.430829 -1.673022 3.238386 H -8.342056 -2.816641 1.846694 H -9.933396 -2.160937 2.375265 C -7.552742 0.730305 0.112980 H -8.505347 1.095434 -0.282565 C -6.343873 1.291902 -0.286432 H -6.351598 2.100884 -1.024311 C -1.876958 -1.248361 -2.424646 C -0.951171 -0.865330 -3.404771 H -0.890964 0.184287 -3.706537 C -0.124948 -1.840980 -3.979904 H 0.601210 -1.548259 -4.745292 C -0.221959 -3.180495 -3.575378 H 0.429495 -3.937526 -4.023564 C -1.153745 -3.547658 -2.592919 H -1.226973 -4.589747 -2.265390 C -1.989813 -2.583298 -2.013603 H -2.722400 -2.846568 -1.246200 P 1.829632 -0.546270 0.486157 O 2.014090 0.150715 1.987566 C 2.362805 1.497835 2.153568 O 1.479494 0.499673 -0.556843 C 3.290744 -1.548016 0.222449 C 4.576535 -0.867843 -0.052366 N 0.619174 -1.678041 0.757955 H -0.352529 -1.294027 0.789930 C 3.191744 -2.912320 0.366796 H 4.107456 -3.496194 0.195170 C 2.017158 -3.682146 0.692254 C 0.749439 -3.055516 0.877605 C 1.380142 2.492361 2.055897 H 0.353354 2.215318 1.800926 C 1.734491 3.827571 2.293738 H 0.970921 4.607748 2.208724 C 3.053303 4.161959 2.635779 H 3.324120 5.205969 2.823907 C 4.023598 3.153856 2.737568 H 5.054875 3.407503 3.004741 C 3.684383 1.815593 2.495230 H 4.428270 1.016308 2.562317 C -0.389449 -3.839471 1.164435 H -1.353352 -3.337327 1.295933 C -0.276056 -5.225174 1.274524 232 H -1.167223 -5.819321 1.503172 C 0.969630 -5.861911 1.100198 H 1.052762 -6.949165 1.190316 C 2.093235 -5.092518 0.810764 H 3.068727 -5.571905 0.666688 C 4.655697 0.287817 -0.871196 H 3.740727 0.696206 -1.310476 C 5.878492 0.900314 -1.134104 H 5.938190 1.787553 -1.771598 C 7.070774 0.382969 -0.587918 O 8.216223 1.060280 -0.911235 C 9.444172 0.556808 -0.390477 H 10.228360 1.223673 -0.777679 H 9.639114 -0.477066 -0.734444 H 9.458916 0.579489 0.716260 C 7.014723 -0.755972 0.238377 H 7.918120 -1.167127 0.695829 C 5.778880 -1.360011 0.500357 H 5.745523 -2.222331 1.174956 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2862.86173312 Predicted Change= -1.891495D-09 Zero-point correction (ZPE)= -2862.1879 0.67382 Internal Energy (U)= -2862.1408 0.72089 Enthalpy (H)= -2862.1398 0.72184 Gibbs Free Energy (G)= -2862.2767 0.58501 ------------------------------------------------------------------------------ Frequencies -- 5.2586 8.0191 15.3657 Single points at WB97X/6-311++G2(df,p): -2865.9697 Solvation Correction at PBE/6-31+G(d,p)/auto/Chloroform: -0.05096194 Homodimeric S-S heterocycle 1g: Supporting Information: polymerdetector-s-s-dimer-6-c-ch3-3-0008.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== # pbepbe/6-31G*/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman iop(1/8=18) Temperature=298.15 #N Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ 233 Pointgroup= C1 Stoichiometry= C50H46N4O4P2 C1[X(C50H46N4O4P2)] #Atoms= 106 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -3132.42079857 Predicted Change= -1.709265D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.01361 || 0.00180 [ NO ] 0.01361 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -2.360729 3.056319 -0.915451 C -2.487288 4.330514 -1.520618 H -3.408915 4.526672 -2.081811 C -1.500531 5.319511 -1.432022 C -1.705908 6.690247 -2.108202 C -2.955005 7.378333 -1.502956 H -3.865663 6.771313 -1.644040 H -3.125946 8.357118 -1.986447 H -2.827239 7.547903 -0.419792 C -1.918519 6.490470 -3.629662 H -2.080747 7.465269 -4.123860 H -2.797015 5.857345 -3.842024 H -1.038547 6.012084 -4.093411 C -0.495919 7.626087 -1.908697 H -0.687430 8.589687 -2.411382 H 0.427763 7.203666 -2.341831 H -0.312686 7.839806 -0.840965 C -0.333364 4.987137 -0.703702 H 0.474631 5.717181 -0.606241 C -0.166649 3.743751 -0.092074 H 0.750101 3.512025 0.459673 C -1.175209 2.765976 -0.179814 N -0.995474 1.526096 0.423554 H -0.054033 1.340633 0.837755 P -2.065347 0.234944 0.453016 O -1.433645 -1.103555 0.109337 O -2.589655 0.270520 2.025927 C -3.434913 0.794143 -0.564743 C -4.589127 -0.106876 -0.780611 C -3.399581 2.072287 -1.075599 H -4.243502 2.379287 -1.709527 234 C -4.430651 -1.512123 -0.866385 H -3.431657 -1.945691 -0.763499 C -5.526562 -2.345928 -1.088116 H -5.388363 -3.428917 -1.154976 C -6.821097 -1.800058 -1.233947 C -6.995229 -0.400426 -1.139182 H -7.998427 0.026138 -1.230157 C -5.896507 0.424649 -0.908028 H -6.054663 1.501595 -0.793611 C -3.236803 -0.822570 2.628980 C -4.575844 -0.654364 3.007112 H -5.082888 0.287222 2.777034 C -5.234424 -1.697398 3.671972 H -6.281142 -1.572108 3.967615 C -4.558605 -2.893717 3.954994 H -5.076285 -3.706970 4.473701 C -3.216295 -3.041198 3.575652 H -2.677179 -3.966815 3.802911 C -2.542132 -2.006081 2.912770 H -1.494675 -2.107381 2.620681 C -7.947219 -2.653605 -1.463438 N -8.873741 -3.354418 -1.653425 P 2.324795 -0.343488 0.872231 O 2.767623 -1.328251 2.131634 C 1.889286 -1.706723 3.158971 O 1.602301 0.902698 1.355859 C 3.904022 -0.217059 0.029997 C 4.961265 0.649413 0.594441 N 1.371443 -1.220880 -0.202031 H 0.339241 -1.206042 -0.034417 C 4.105536 -0.996287 -1.086479 H 5.083370 -0.914205 -1.581841 C 3.167108 -1.883211 -1.726131 C 1.814096 -1.973569 -1.284900 C 1.701224 -3.081441 3.359721 H 2.191501 -3.791033 2.686902 C 0.902837 -3.513631 4.428002 H 0.760878 -4.586768 4.593843 C 0.292995 -2.579867 5.279344 H -0.332573 -2.919393 6.110753 C 0.486243 -1.207846 5.059382 H 0.010346 -0.474495 5.718369 C 1.289845 -0.758681 4.001929 H 1.453394 0.305602 3.818341 C 0.914184 -2.791526 -1.993542 H -0.129704 -2.836659 -1.666877 235 C 1.349911 -3.528578 -3.095983 H 0.619461 -4.157684 -3.611819 C 2.688817 -3.483206 -3.553130 C 3.191580 -4.297146 -4.762959 C 4.327660 -5.245881 -4.305195 H 4.707199 -5.831337 -5.161895 H 3.968558 -5.953481 -3.537935 H 5.178419 -4.688146 -3.877461 C 3.735068 -3.332544 -5.845999 H 4.114500 -3.905213 -6.711340 H 4.564605 -2.712105 -5.465792 H 2.942191 -2.653448 -6.204229 C 2.074343 -5.151462 -5.396566 H 1.662159 -5.886945 -4.683452 H 2.480968 -5.713684 -6.254744 H 1.243057 -4.529415 -5.772534 C 3.563875 -2.645074 -2.851883 H 4.609050 -2.556770 -3.172368 C 6.326408 0.291936 0.470232 H 6.594964 -0.663908 0.010119 C 7.338680 1.115530 0.958244 H 8.387407 0.820826 0.858862 C 7.013705 2.328928 1.606613 C 5.655903 2.687057 1.758655 H 5.399392 3.622106 2.265100 C 4.649091 1.859748 1.261449 H 3.601729 2.151543 1.380614 C 8.049355 3.178139 2.112014 N 8.901504 3.877471 2.524831 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -3132.42079857 Predicted Change= -1.709265D-08 Zero-point correction (ZPE)= -3131.5936 0.82715 Internal Energy (U)= -3131.5364 0.88432 Enthalpy (H)= -3131.5355 0.88527 Gibbs Free Energy (G)= -3131.6949 0.72587 ------------------------------------------------------------------------------ Frequencies -- 4.0915 7.9697 10.1404 Geometries for the Testing of Stereoelectronic Effect: R-S-dimer, no phenyl group, phenoxy replaced with methoxy, R2 = H Supporting Information: r-s-paired-down-9-1.log ------------------------------------------------------------------------------ 236 Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C18H20N2O4P2 C1[X(C18H20N2O4P2)] #Atoms= 46 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1789.52557403 Predicted Change= -1.144653D-06 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00002 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.02018 || 0.00180 [ NO ] 0.02018 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -4.321048 0.508797 -0.275566 C -5.637427 -0.012893 -0.299174 H -6.438325 0.620962 -0.697961 C -5.922805 -1.293788 0.165463 H -6.947438 -1.676170 0.141231 C -4.874138 -2.093701 0.663758 H -5.084343 -3.104051 1.030332 C -3.565504 -1.614981 0.702113 H -2.748680 -2.231629 1.092589 C -3.271316 -0.309938 0.243036 N -1.960414 0.142351 0.274023 H -1.230589 -0.546398 0.571687 P -1.388452 1.685379 -0.132567 O -1.151755 2.524313 1.259666 C 0.066305 2.280198 2.000608 H 0.952502 2.537341 1.396119 H 0.130531 1.223655 2.317881 H 0.017225 2.927866 2.888251 O -0.115626 1.614291 -0.961915 C -2.831995 2.454364 -0.808695 H -2.718711 3.453846 -1.239175 C -4.045177 1.828550 -0.796883 237 H -4.903951 2.360573 -1.229543 P 1.388473 -1.685416 0.132494 O 1.151824 -2.524367 -1.259737 C -0.066243 -2.280317 -2.000687 H -0.952434 -2.537425 -1.396174 H -0.017165 -2.928048 -2.888285 H -0.130480 -1.223796 -2.318033 O 0.115626 -1.614349 0.961811 C 2.832014 -2.454367 0.808665 H 2.718740 -3.453859 1.239124 N 1.960414 -0.142382 -0.274095 H 1.230585 0.546344 -0.571804 C 4.045176 -1.828513 0.796926 H 4.903947 -2.360514 1.229620 C 4.321030 -0.508746 0.275636 C 3.271299 0.309954 -0.243024 C 3.565467 1.615007 -0.702084 H 2.748644 2.231627 -1.092606 C 4.874082 2.093773 -0.663652 H 5.084273 3.104133 -1.030211 C 5.922748 1.293899 -0.165294 H 6.947366 1.676316 -0.140999 C 5.637388 0.012991 0.299320 H 6.438287 -0.620837 0.698151 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1789.52557403 Predicted Change= -1.144653D-06 Zero-point correction (ZPE)= -1789.1749 0.35058 Internal Energy (U)= -1789.1493 0.37622 Enthalpy (H)= -1789.1484 0.37716 Gibbs Free Energy (G)= -1789.2337 0.29187 ------------------------------------------------------------------------------ Frequencies -- 11.7392 22.4312 25.2322 Single Points at WB97X/6-311++G2(df,p)= -1791.3035 S-S-dimer, no phenyl group, phenoxy replaced with methoxy, R2 = H Supporting Information: s-s-paired-down-2.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman 238 #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C18H20N2O4P2 C1[X(C18H20N2O4P2)] #Atoms= 46 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1789.52544372 Predicted Change= -7.797984D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00001 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.01478 || 0.00180 [ NO ] 0.01478 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C 3.980661 0.983034 0.321143 C 4.994916 1.868411 -0.118888 H 5.794373 2.129743 0.584596 C 4.989231 2.401754 -1.404364 H 5.783174 3.082475 -1.725363 C 3.944087 2.057412 -2.286387 H 3.924984 2.473255 -3.299358 C 2.928518 1.190057 -1.888981 H 2.113485 0.923428 -2.570073 C 2.934747 0.635885 -0.587885 N 1.909048 -0.217213 -0.207946 H 1.143738 -0.366852 -0.904190 P 1.736228 -1.040694 1.263012 O 0.321743 -0.943548 1.815187 O 2.155933 -2.610238 1.025309 C 3.090425 -0.405856 2.207591 H 3.177666 -0.735510 3.247260 C 3.993744 0.465335 1.669761 H 4.810771 0.823176 2.311799 C 1.142856 -3.522823 0.540604 H 0.865450 -3.283972 -0.501260 H 0.244319 -3.480587 1.178010 H 1.592551 -4.525977 0.583392 P -1.644201 -0.792562 -1.382676 O -1.969534 -2.403717 -1.283365 C -3.181879 -2.829586 -0.630300 H -4.073221 -2.374449 -1.099271 239 H -3.163016 -2.570843 0.442917 H -3.225625 -3.922719 -0.748284 O -0.253420 -0.684986 -1.969732 C -2.979779 0.008854 -2.231223 H -3.101009 -0.213289 -3.296427 N -1.810576 -0.178386 0.186926 H -1.045369 -0.451936 0.851944 C -3.801293 0.904720 -1.606639 H -4.592829 1.383911 -2.199938 C -3.720006 1.308582 -0.221842 C -2.712199 0.776498 0.639140 C -2.629245 1.223975 1.977993 H -1.839376 0.818047 2.618846 C -3.536716 2.165685 2.459409 H -3.458479 2.499810 3.499358 C -4.546804 2.689738 1.626338 H -5.255603 3.427873 2.012972 C -4.625740 2.262501 0.304235 H -5.396599 2.667303 -0.362266 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1789.52544372 Predicted Change= -7.797984D-08 Zero-point correction (ZPE)= -1789.1749 0.35053 Internal Energy (U)= -1789.1492 0.37624 Enthalpy (H)= -1789.1482 0.37718 Gibbs Free Energy (G)= -1789.2343 0.29112 ------------------------------------------------------------------------------ Frequencies -- 8.2965 21.6464 23.4530 Single Points at WB97X/6-311++G2(df,p)= -1791.3029 Monomer, no phenyl group, phenoxy replaced with methoxy, R2 = H Supporting Information: monomer-paired-down-4-1.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C9H10NO2P C1[X(C9H10NO2P)] #Atoms= 23 240 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -894.744992190 Predicted Change= -1.581251D-09 =============================================================== =============== Optimization completed. {Found 2 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00059 || 0.00180 [ YES ] 0.00059 || 0.00180 [ YES ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ P 1.587328 0.016446 0.360501 O 2.443100 -0.431675 -0.977249 C 3.885448 -0.388680 -0.919804 H 4.253046 -1.160602 -1.613758 H 4.244836 -0.593222 0.101687 H 4.249267 0.600331 -1.252074 O 2.369488 -0.177215 1.629911 C 0.885330 1.622055 0.062804 H 1.578047 2.470214 0.064811 N 0.208414 -0.967557 0.135945 H 0.374798 -1.973499 0.212026 C -0.455388 1.827697 -0.071551 H -0.816803 2.858343 -0.191975 C -1.473129 0.799229 -0.071501 C -1.124030 -0.580207 0.038346 C -2.142602 -1.557835 0.028424 H -1.868676 -2.615831 0.113972 C -3.481802 -1.184711 -0.084855 H -4.254870 -1.960049 -0.087655 C -3.841643 0.172117 -0.192582 H -4.892912 0.461357 -0.279932 C -2.841245 1.141534 -0.185700 H -3.101887 2.203102 -0.269015 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -894.744992190 Predicted Change= -1.581251D-09 Zero-point correction (ZPE)= -894.5705 0.17440 Internal Energy (U)= -894.5583 0.18662 Enthalpy (H)= -894.5574 0.18757 Gibbs Free Energy (G)= -894.6097 0.13519 241 ------------------------------------------------------------------------------ Frequencies -- 31.6694 56.6009 90.8014 Single Points at WB97X/6-311++G2(df,p)= -895.63309 R-S-dimer, no phenyl group, with phenoxy, R2 = H Supporting Information: r-s-no-ph-oph-8.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C28H24N2O4P2 C1[X(C28H24N2O4P2)] #Atoms= 60 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2172.53686587 Predicted Change= -8.193969D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00002 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00560 || 0.00180 [ NO ] 0.00560 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -3.959543 -1.820499 0.212476 C -5.340573 -1.828097 -0.103624 H -6.006684 -2.456746 0.499096 C -5.852031 -1.059536 -1.144728 H -6.921247 -1.081024 -1.375249 C -4.977194 -0.245045 -1.893266 H -5.369221 0.373214 -2.707635 C -3.612715 -0.213760 -1.613082 H -2.931576 0.425132 -2.184628 C -3.084734 -1.008348 -0.570401 N -1.721781 -0.961184 -0.305480 H -1.173051 -0.237694 -0.823914 P -0.861304 -1.846354 0.847501 O -0.112978 -3.120856 0.085904 242 C 1.205472 -3.060101 -0.381525 O 0.150234 -0.996835 1.596197 C -2.153783 -2.673617 1.725540 H -1.867796 -3.272425 2.595580 C -3.457923 -2.586684 1.329111 H -4.211061 -3.136443 1.910688 C 2.120681 -3.981366 0.145274 H 1.790827 -4.672129 0.926726 C 3.434430 -3.998989 -0.341678 H 4.151098 -4.718803 0.067661 C 3.831994 -3.097836 -1.340448 H 4.861148 -3.108470 -1.713117 C 2.904247 -2.182867 -1.858652 H 3.204800 -1.474173 -2.637401 C 1.582321 -2.162624 -1.391160 H 0.858630 -1.451605 -1.801550 P 0.861730 1.846950 -0.847132 O 0.111969 3.119424 -0.083481 C -1.206890 3.057290 0.382645 O -0.148785 0.997179 -1.596914 C 2.153111 2.677306 -1.723901 H 1.866311 3.277314 -2.592846 N 1.723423 0.961090 0.304360 H 1.175519 0.236276 0.821822 C 3.457350 2.591580 -1.327520 H 4.209725 3.143436 -1.908097 C 3.959995 1.824275 -0.212111 C 3.086268 1.009713 0.569461 C -1.583356 2.159899 1.392492 H -0.859058 1.449928 1.803632 C -2.905668 2.178730 1.858949 H -3.205947 1.470088 2.637858 C -3.834184 3.092230 1.339506 H -4.863638 3.101754 1.711376 C -3.437018 3.993296 0.340504 H -4.154284 4.711954 -0.069826 C -2.122851 3.977089 -0.145395 H -1.793283 4.667873 -0.926952 C 3.615270 0.214248 1.610965 H 2.934931 -0.426342 2.181567 C 4.979692 0.246940 1.891250 H 5.372527 -0.372017 2.704698 C 5.853456 1.063753 1.143983 H 6.922634 1.086324 1.374575 C 5.341008 1.833236 0.104048 H 6.006299 2.463706 -0.497673 243 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2172.53686587 Predicted Change= -8.193969D-08 Zero-point correction (ZPE)= -2172.0843 0.45248 Internal Energy (U)= -2172.0526 0.48425 Enthalpy (H)= -2172.0516 0.48520 Gibbs Free Energy (G)= -2172.1519 0.38491 ------------------------------------------------------------------------------ Frequencies -- 11.5080 17.8701 18.7386 Single Points at WB97X/6-311++G2(df,p)= -2174.7879 S-S-dimer, no phenyl group, with phenoxy, R2 = H Supporting Information: s-s-no-ph-oph-14.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C28H24N2O4P2 C1[X(C28H24N2O4P2)] #Atoms= 60 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -2172.53781442 Predicted Change= -7.759443D-08 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00002 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00836 || 0.00180 [ NO ] 0.00836 || 0.00180 [ NO ] ------------------------------------------------------------------------------ Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ C -2.514247 -3.153270 -0.020475 C -3.159726 -4.213336 -0.703166 H -3.781325 -4.902670 -0.119677 C -3.015331 -4.389245 -2.076117 H -3.522836 -5.213892 -2.585102 244 C -2.204246 -3.493812 -2.802945 H -2.080233 -3.622767 -3.883316 C -1.554117 -2.438796 -2.165158 H -0.923336 -1.741208 -2.726118 C -1.703238 -2.251180 -0.772701 N -1.042352 -1.195095 -0.156282 H -0.422300 -0.607841 -0.763156 P -1.082094 -0.755012 1.471110 O 0.273203 -0.481705 2.091330 O -1.897329 0.690932 1.579560 C -2.095672 -2.023214 2.174833 H -2.247232 -1.999391 3.258664 C -2.659399 -3.003939 1.408595 H -3.274803 -3.763355 1.910719 C -3.058307 0.947186 0.838246 C -4.309354 0.772471 1.445462 H -4.360392 0.393763 2.470506 C -5.468808 1.098410 0.727941 H -6.449235 0.966193 1.197492 C -5.374530 1.592742 -0.581258 H -6.282245 1.846769 -1.138176 C -4.114308 1.764906 -1.173743 H -4.035018 2.155385 -2.193567 C -2.946116 1.445729 -0.468264 H -1.954203 1.582326 -0.909933 P 2.088183 0.714035 -1.101476 O 2.367525 2.320113 -0.788110 C 1.379094 3.215648 -0.362624 O 0.666405 0.502114 -1.592479 C 3.463019 0.327210 -2.145272 H 3.444045 0.720400 -3.166288 N 2.433721 -0.182910 0.288077 H 1.664217 -0.262716 0.992235 C 4.517058 -0.415950 -1.697396 H 5.345730 -0.608740 -2.392884 C 4.649363 -0.997651 -0.381816 C 3.600263 -0.881853 0.579052 C 1.284514 4.430774 -1.054888 H 1.941255 4.608200 -1.911520 C 0.353214 5.389069 -0.633529 H 0.278814 6.339995 -1.171678 C -0.483876 5.130575 0.462348 H -1.217339 5.877378 0.782650 C -0.376471 3.910203 1.144387 H -1.026356 3.691179 1.997458 C 0.563048 2.948744 0.745519 245 H 0.653781 2.008575 1.297745 C 3.728960 -1.514388 1.836283 H 2.905857 -1.431686 2.553679 C 4.885148 -2.229066 2.144378 H 4.970961 -2.708538 3.125167 C 5.938626 -2.338050 1.213495 H 6.843895 -2.898282 1.465220 C 5.809812 -1.730826 -0.032115 H 6.612719 -1.814562 -0.774032 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -2172.53781442 Predicted Change= -7.759443D-08 Zero-point correction (ZPE)= -2172.0850 0.45274 Internal Energy (U)= -2172.0534 0.48439 Enthalpy (H)= -2172.0524 0.48533 Gibbs Free Energy (G)= -2172.1521 0.38564 ------------------------------------------------------------------------------ Frequencies -- 11.2709 14.3932 21.3146 Single Points at WB97X/6-311++G2(df,p)= -2174.7875 Monomer, no phenyl group, with phenoxy, R2 = H Supporting Information: monomer-no-ph-oph-1.log ------------------------------------------------------------------------------ Using Gaussian 09: AM64L-G09RevD.01 24-Apr-2013 =============================================================== =============== #PBEPBE/6-31G(d)/auto gfprint gfinput scf=(direct,tight,maxcycle=300,xqc) opt=(maxcycle=250) freq=noraman #P Geom=AllCheck Guess=TCheck SCRF=Check Test GenChk RPBEPBE/6- 31G(d)/Auto Freq ------------------------------------------------------------------------------ Pointgroup= C1 Stoichiometry= C14H12NO2P C1[X(C14H12NO2P)] #Atoms= 30 Charge = 0 Multiplicity = 1 ------------------------------------------------------------------------------ SCF Energy= -1086.25102464 Predicted Change= -6.309716D-09 =============================================================== =============== Optimization completed. {Found 1 times} Item Max Val. Criteria Pass? RMS Val. Criteria Pass? Force 0.00000 || 0.00045 [ YES ] 0.00000 || 0.00030 [ YES ] Displ 0.00242 || 0.00180 [ NO ] 0.00242 || 0.00180 [ YES ] ------------------------------------------------------------------------------ 246 Atomic Coordinates (Angstroms) Type X Y Z ------------------------------------------------------------------------------ P -0.141238 1.383577 -0.293497 O -1.159878 0.706874 0.837693 C -2.317458 -0.004087 0.496968 O -0.849078 2.191585 -1.341450 C 1.071704 2.114360 0.779002 H 0.810450 3.068487 1.246884 N 0.753592 0.087098 -0.961338 H 0.319092 -0.379185 -1.760637 C 2.278266 1.526623 1.012518 H 2.979079 2.033814 1.689970 C 2.750373 0.284359 0.436630 C 1.984697 -0.411773 -0.546921 C -3.267564 0.491166 -0.411002 H -3.088613 1.446520 -0.910017 C -4.422034 -0.265237 -0.659477 H -5.165416 0.114938 -1.368337 C -4.635084 -1.488511 -0.007354 H -5.542636 -2.067836 -0.205205 C -3.679985 -1.963378 0.903962 H -3.837258 -2.915686 1.421424 C -2.516187 -1.225899 1.157647 H -1.757986 -1.577294 1.863741 C 2.503033 -1.589767 -1.126369 H 1.912635 -2.116763 -1.884692 C 3.747319 -2.083291 -0.732986 H 4.127363 -3.002079 -1.191437 C 4.508738 -1.414575 0.244123 H 5.483129 -1.805690 0.550564 C 4.008099 -0.244380 0.810707 H 4.591729 0.296110 1.564937 ------------------------------------------------------------------------------ Statistical Thermodynamic Analysis Temperature= 298.150 Kelvin Pressure= 1.00000 Atm =============================================================== =============== SCF Energy= -1086.25102464 Predicted Change= -6.309716D-09 Zero-point correction (ZPE)= -1086.0255 0.22546 Internal Energy (U)= -1086.0103 0.24062 Enthalpy (H)= -1086.0094 0.24157 Gibbs Free Energy (G)= -1086.0701 0.18086 ------------------------------------------------------------------------------ Frequencies -- 17.1823 18.8685 36.2698 Single Points at WB97X/6-311++G2(df,p)= -1087.3754 247 Computational Methods Attempted for Solution-state Dimer Strength Predictions: • Optimizations at PBE/6-31G(d)/Auto using Gaussian 09 o Single points in gas phase at PBE/6-311++G(2df,p)/auto using Gaussian 09 ▪ Solvation Correction in chloroform and gas at PBE/6-31+G(d,p) with D3 and D3BJ corrections using Gaussian 09 o Single points at M062X/ 6-311++G(2df,p)/CPCM/H2O using Gaussian 09 o Single points at M062X/ 6-311++G(2df,p)/CPCM/Choroform using Gaussian 09 o Single points at M062X/ 6-311++G(2df,p)/SMD/H2O using Gaussian 09 o Single points at M062X/ 6-311++G(2df,p)/SMD/Chloroform using Gaussian 09 o Single points at M062X/ 6-311++G(2df,p)/CPCM/H2O using Gaussian 16 o Single points at M062X/ 6-311++G(2df,p)/CPCM/Choroform using Gaussian 16 o Single points at M062X/ 6-311++G(2df,p)/SMD/H2O using Gaussian 16 o Single points at M062X/ 6-311++G(2df,p)/SMD/Chloroform using Gaussian 16 o Single points in gas phase at PBE/6-311++G(2df,p)/auto in Gaussian 16 o Single points in gas phase at PBE/def2TZVPP/auto using Gaussian 09 o Single points in gas phase at PBE/ def2-QZVPP/RIJCOSX/auto using ORCA o Single points in gas phase at PBE/ def2-TZVPP/RIJCOSX/auto using ORCA o Single points in gas phase at WB97X/6-311++G(2df,p) using Gaussian 09 ▪ Solvation Correction in chloroform and gas at PBE/6-31+G(d,p) using Gaussian 09 • Optimizations at PBE/6-31G(d) using Gaussian 09 o No single points or solvation correction • Optimizations at B3LYP/6-31G(d) using Gaussian 09 o No single points or solvation correction 248 Representative Drawings of R-S and S-S Dimer Orientations: Figure A.9 Chemical structures and predicted geometries of the a) S-S homodimer and b) R-S heterodimer of 1g. 249 Gas-Phase Free Energy Values Compared to Experimental Values: Table A.17 Comparison between gas phase free energy predictions and experimental free energy values collected in H2O-saturated CHCl3 Computed ΔG Exp. ΔG Entry (R1,R2) (gas phase) (kcal/mol) (kcal/mol) 1b (4-CN,H) -8.8 -2.9 1e (4-CN,CF3) -10.1 -3.4 1p (4-CN,EtO) -8.5 -2.6 1m (H,CN) -10.7 -3.7 1a (H,H) -9.7 -2.4 1o (H,CO2Et) -10.2 -3.1 1h (4-OMe,t-Bu) -8.5 -2.1 1c (4-OMe,H) -9.2 -2.4 Data for Figure 2.9: Table A.18 Data for the construction and validation of Hammett parameter-based prediction of Keq Entry (R1,R2) σR1 σR2 Keq Predicted Dataset 1h (4-OMe,t-Bu) -0.27 -0.2 -2.12 -2.138783 Training 1i (4-Me,t-Bu) -0.17 -0.2 -2.15 -2.181648 Training 1c (4-OMe,H) -0.27 0 -2.38 -2.424156 Training 1a (H,H) 0 0 -2.44 -2.539892 Training 1g (4-CN,t-Bu) 0.66 -0.2 -2.52 -2.537431 Training 1p (4-CN,EtO) 0.66 -0.24 -2.64 -2.480356 Training 1b (4-CN,H) 0.66 0 -2.88 -2.822803 Training 1e (4-CN,CF3) 0.66 0.54 -3.36 -3.59331 Training 1m (H,CN) 0 0.66 -3.71 -3.481622 Training 1j (H,t-Bu) 0 -0.2 -2.24 -2.254519 Validation 1o (H,CO2Et) 0 0.45 -3.14 -3.181981 Validation 250 6. Data for Dimerization Constant (Kdim) Values for 1a-p Figure A.10 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1a stacked top to bottom with initial and final peak positions marked. 251 Figure A.11 Representative 31P NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 31P NMR spectra (bottom) for solution-state dimerization strength studies of 1a stacked top to bottom with initial and final peak positions marked. 252 Figure A.12 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1c stacked top to bottom with initial and final peak positions marked. 253 Figure A.13 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1e stacked top to bottom with initial and final peak positions marked. 254 Figure A.14 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1g stacked top to bottom with initial and final peak positions marked. 255 Figure A.15 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1h stacked top to bottom with initial and final peak positions marked. 256 Figure A.16 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1i stacked top to bottom with initial and final peak positions marked. 257 Figure A.17 Representative 31P NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 31P NMR spectra (bottom) for solution-state dimerization strength studies of 1i stacked top to bottom with initial and final peak positions marked. 258 Figure A.18 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1j stacked top to bottom with initial and final peak positions marked. 259 Figure A.19 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1m stacked top to bottom with initial and final peak positions marked. 260 Figure A.20 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1o stacked top to bottom with initial and final peak positions marked. 261 Figure A.21 Representative 1H NMR binding isotherm with residuals inset (top left), dilution data (top right), and stacked 1H NMR spectra (bottom) for solution-state dimerization strength studies of 1p stacked top to bottom with initial and final peak positions marked. 262 7. Cyclic Voltammetry Studies Cyclic voltammetry (CV) measurements taken with a Bio-Logic SP-50 potentiostat. Samples were prepared as ca. 1 mM solutions in air- and water-free dichloromethane with 0.1 M TBA-PF6 electrolyte solution. Samples were referenced using Fc/Fc+ as an external reference. Figure A.22 shows the voltammogram of 1j as a representative voltammogram for heterocycles 1 and shows several oxidation and reduction peaks. Of interest, the difference of 4.003 eV between the lowest energy oxidation event (1.682 eV vs Fc/Fc+) and the lowest energy reduction event (-2.319 eV vs Fc/Fc+) corresponds nicely with the energy gaps determined by theoretical and spectroscopic methods. 0.15 0.1 0.05 0 -3 -2 -1 0 1 2 -0.05 -0.1 -0.15 -0.2 Ewe (V) vs. SCE Figure A.22 Cyclic voltammogram showing oxidation and reduction potentials for 1j as a representative curve for heterocycles 1. 263 Current (mA) 9. NMR Spectra of New Compounds 1H NMR spectrum of arylethynylaniline 4d (in CDCl3) 13C NMR spectrum of arylethynylaniline 4d (in CDCl3) 264 1H NMR spectrum of arylethynylaniline 4e (in CDCl3) 13C NMR spectrum of arylethynylaniline 4e (in CDCl3) 265 19F NMR spectrum of arylethynylaniline 4e (in CDCl3) 1H NMR spectrum of arylethynylaniline 4f (in CDCl3) 266 13C NMR spectrum of arylethynylaniline 4f (in CDCl3) 1H NMR spectrum of arylethynylaniline 4g (in CDCl3) 267 13C NMR spectrum of arylethynylaniline 4g (in CDCl3) 1H NMR spectrum of arylethynylaniline 4h (in CDCl3) 268 13C NMR spectrum of arylethynylaniline 4h (in CDCl3) 1H NMR spectrum of arylethynylaniline 4i (in CDCl3) 269 13C NMR spectrum of arylethynylaniline 4i (in CDCl3) 1H NMR spectrum of arylethynylaniline 4j (in CDCl3) 270 13C NMR spectrum of arylethynylaniline 4j (in CDCl3) 1H NMR spectrum of arylethynylaniline 4k (in CDCl3) 271 13C NMR spectrum of arylethynylaniline 4k (in CDCl3) 1H NMR spectrum of arylethynylaniline 4l (in CDCl3) 272 13C NMR spectrum of arylethynylaniline 4l (in CDCl3) 1H NMR spectrum of arylethynylaniline 4m (in CDCl3) 273 13C NMR spectrum of arylethynylaniline 4m (in CDCl3) 1H NMR spectrum of arylethynylaniline 4n (in CDCl3) 274 13C NMR spectrum of arylethynylaniline 4n (in CDCl3) 1H NMR spectrum of arylethynylaniline 4o (in CDCl3) 275 13C NMR spectrum of arylethynylaniline 4o (in CDCl3) 1H NMR spectrum of arylethynylaniline 4p (in CDCl3) 276 13C NMR spectrum of arylethynylaniline 4p (in CDCl3) 1H NMR spectrum of phosphaquinolinone 1d (in CDCl3) 277 13C NMR spectrum of phosphaquinolinone 1d (in CDCl3) Coupled 31P NMR spectrum of phosphaquinolinone 1d (in CDCl3) 278 1H NMR spectrum of phosphaquinolinone 1e (in CDCl3) 13C NMR spectrum of phosphaquinolinone 1e (in CDCl3) 279 Coupled 31P NMR spectrum of phosphaquinolinone 1e (in CDCl3) 19F NMR spectrum of phosphaquinolinone 1e (in CDCl3) 280 1H NMR spectrum of phosphaquinolinone 1f (in C2D6OS) 13C NMR spectrum of phosphaquinolinone 1f (in C2D6OS) 281 Coupled 31P NMR spectrum of phosphaquinolinone 1f (in C2D6OS) 1H NMR spectrum of phosphaquinolinone 1g (in CDCl3) 282 13C NMR spectrum of phosphaquinolinone 1g (in CDCl3) Coupled 31P NMR spectrum of phosphaquinolinone 1g (in CDCl3) 283 1H NMR spectrum of phosphaquinolinone 1h (in CDCl3) 13C NMR spectrum of phosphaquinolinone 1h (in CDCl3) 284 Coupled 31P NMR spectrum of phosphaquinolinone 1h (in CDCl3) 1H NMR spectrum of phosphaquinolinone 1i (in CDCl3) 285 13C NMR spectrum of phosphaquinolinone 1i (in CDCl3) Coupled 31P NMR spectrum of phosphaquinolinone 1i (in CDCl3) 286 1H NMR spectrum of phosphaquinolinone 1j (in CDCl3) 13C NMR spectrum of phosphaquinolinone 1j (in CDCl3) 287 Coupled 31P NMR spectrum of phosphaquinolinone 1j (in CDCl3) 1H NMR spectrum of phosphaquinolinone 1k (in C2D6OS) 288 13C NMR spectrum of phosphaquinolinone 1k (in C2D6OS) Coupled 31PNMR spectrum of phosphaquinolinone 1k (in C2D6OS) 289 1H NMR spectrum of phosphaquinolinone 1l (in CDCl3) 13C NMR spectrum of phosphaquinolinone 1l (in CDCl3) 290 Coupled 31P NMR spectrum of phosphaquinolinone 1l (in CDCl3) 1H NMR spectrum of phosphaquinolinone 1m (in CDCl3) 291 13C NMR spectrum of phosphaquinolinone 1m (in CDCl3) Coupled 31P NMR spectrum of phosphaquinolinone 1m (in CDCl3) 292 1H NMR spectrum of phosphaquinolinone 1n (in CDCl3) 13C NMR spectrum of phosphaquinolinone 1n (in CDCl3) 293 Coupled 31P NMR spectrum of phosphaquinolinone 1n (in CDCl3) 1H NMR spectrum of phosphaquinolinone 1o (in CDCl3) 294 13C NMR spectrum of phosphaquinolinone 1o (in CDCl3) Coupled 31P NMR spectrum of phosphaquinolinone 1o (in CDCl3) 295 1H NMR spectrum of phosphaquinolinone 1p (in CDCl3) 13C NMR spectrum of phosphaquinolinone 1p (in CDCl3) 296 Coupled 31P NMR spectrum of phosphaquinolinone 1p (in CDCl3) 297 APPENDIX B SUPPLEMENTARY INFORMATION FOR CHAPTER 3 1. CCDC Search Results Search criteria for monomeric HSO −4 solid-state complexes were made by drawing the chemical structure of HSO −4 and using the “exact” designation. 450 results were found showing chains, metal-containing species, water/solvent-bridged, homodimers and oligomers; only monomer species with synthetic receptors were selected. For numerous HSO −4 homodimers, see: E. M. Fatila, E. B. Twum, A. Sengupta, M. Pink, J. A. Karty, K. Raghava-chari, A. H. Flood, Angew. Chem. Int. Ed. 2016, 55, 14057–14062.1 Table B.1 CCDC results of selected monomeric HSO –4 solid-state complexes Database Identifier Reference BURKAB CrystEngComm 2010, 12, 413 ISOWAP Org. Biomol. Chem. 2011, 9, 4444 J. Am. Chem. Soc. 2007, 129, 8692 MIJTAB Inorg. Chem. 2012, 51, 4833 NELWAE Polyhedron 2013, 50, 622 XIBCOB Inorg. Chem. 2007, 46, 2846 FAZCEP New J. Chem. 2004, 28, 1301 UMOHIN J. Med. Chem. 2003, 46, 3865 DALRIT Cryst. Growth Des. 2011, 11, 4463 ASOXEN Chem. Commun. 2016, 52, 11139 3. X-ray Crystallographic Data X-ray Crystallography. Diffraction intensities for 1a, 1b and 1b•HSO –4 were collected at 173 K on a Bruker Apex2 CCD diffractometer using CuKα radiation, λ= 1.54178 Å. Space groups were determined based on systematic absences (1a) and intensity statistics (1b and 1b•HSO –4 ). Absorption corrections were applied by SADABS.2 Structures were solved by 298 direct methods and Fourier techniques and refined on F2 using full matrix least-squares procedures. All non-H atoms were refined with anisotropic thermal parameters. H atoms in all structures were refined in calculated positions in a rigid group model, except the H atoms at the N atoms and the H atoms in MeOH and HSO4 groups (in 1a and 1b•HSO –4 , respectively) involved in H-bonds. Positions of these H atoms were found on the residual density map and refined with isotropic thermal parameters with restrictions on its bond distance; the standard N–H and O–H bond lengths were used in the refinements as the targets for corresponding bonds. Terminal t-Bu groups in all structures and a counterion NBu +4 in 1b•HSO –4 are disordered. Thermal ellipsoids for these groups and some other terminal groups and solvent molecules as well in the structures are significantly elongated. Some solvent molecules (expecting a mixture of CHCl3/(CH3)2SO/pentane) in 1b•HSO –4 are highly disordered around an inversion canter and was treated by SQUEEZE;3 the correction of the X-ray data by SQUEEZE is 127 electron/cell. These not resolved solvent molecules have not been included in the total formula of the compound. Due to a lot of disordered groups in the structures, X-ray diffraction from crystals of 1b and 1b•HSO –4 at high angles is very weak and reflection statistics at high angles are poor. Even using a strong Incoatec IμS Cu source. it was possible to collected data only up to 2θmax = 100.75° (1b) and 104.42° (1b•HSO –4 ); thus, the resolution for these X-ray structures is not very high. Nonetheless, diffraction data collected for these structures provide appropriate numbers of measured reflections per refined parameters (5160/631 in 1b and 8208/818 in 1b•HSO –4 ) and the X-ray structures clearly show the chemical results. All calculations were performed by the Bruker SHELXL-2014 package.4 299 Crystallographic Data for 1a: C54H50Cl2N5O5P, M = 966.86, 0.07 x 0.04 x 0.04 mm, T = 173(2) K, Monoclinic, space group P21/n, a = 12.8174(11) Å, b = 29.801(3) Å, c = 13.9869(11) Å, β = 114.808(3)°, V = 4849.6(8) Å3, Z = 4, Dc = 1.324 Mg/m 3, μ(Cu) = 1.974 mm–3, F(000) = 2024, 2θmax = 135.50°, 31807 reflections, 8432 independent reflections [Rint = 0.0702], R1 = 0.1002, wR2 = 0.2512 and GOF = 1.086 for 8432 reflections (627 parameters) with I>2σ(I), R1 = 0.1414, wR2 = 0.2902 and GOF = 1.086 for all reflections, max/min residual electron density +0.853/–1.205 eÅ–3. CCDC 1884079. 300 Figure B.1 X-ray structure of 1a a) and the dimer of 1a b), showing the coordination of MeOH solvent molecules; thermal ellipsoids drawn at the 30% probability level. The dotted lines denote hydrogen-bonding interactions with distances shown in Å. The t-Bu groups are disordered. In the solid-state structure, the oxygen atom of the MeOH solvent guest accepts a hydrogen bond from both a phosphonamidate N−H moiety and an aromatic hydrogen atom in the phenyl backbone, while the P=O motif accepts H-bonds from the two urea N−H units of an adjacent molecule. As a result, two molecules are stacked in a head- to-tail fashion through these hydrogen bond interactions to form a dimeric structure and the monomer exhibits an open ‘S’ conformation. 301 Crystallographic Data for 1b: C54H49N6O8PS, M = 973.02, 0.11 x 0.02 x 0.01 mm, T = 173(2) K, Triclinic, space group P-1, a = 13.4164(10) Å, b = 13.7420(12) Å, c = 14.3491(11) Å, α = 107.705(6)°, β = 98.455(6)°, γ = 93.057(6)°, V = 2479.3(4) Å3, Z = 2, Dc = 1.303 Mg/m3, μ(Cu) = 1.388 mm–1, F(000) = 1020, 2θmax = 100.75°, 15858 reflections, 5160 independent reflections [Rint = 0.0833], R1 = 0.0749, wR2 = 0.1904 and GOF = 1.012 for 5160 reflections (631 parameters) with I>2σ(I), R1 = 0.1303, wR2 = 0.2326 and GOF = 1.012 for all reflections, max/min residual electron density +0.530/– 0.523 eÅ–3. CCDC 1884080. 302 Figure B.2 X-ray structure of 1b a) and the dimer of 1b b), showing the coordination of DMSO solvent molecules; thermal ellipsoids drawn at the 30% probability level. The dotted lines denote hydrogen-bonding interactions with distances shown in Å. Receptor 1b adopts a slightly twisted ‘U’ conformation and donates two hydrogen bonds through the urea moiety and another weak C−H hydrogen bond through the nitrophenyl core to provide an electropositive pocket, which accommodates the electronegative oxygen atom of DMSO solvent. The PN-heterocycle unit interacts with another host molecule through N−H and P=O hydrogen bonding interactions to form a centrosymmetrical dimer. 303 Crystallographic Data for 1b•HSO – [TBA]+4 complex: C68H80N7O11PS, M = 1234.42, 0.17 x 0.05 x 0.01 mm, T = 173(2) K, Triclinic, space group P-1, a = 11.3009(5) Å, b = 18.4309(8) Å, c = 19.7252(10) Å, α = 108.978(3)°, β = 102.353(3)°, γ = 97.591(3)°, V = 3703.7(3) Å3, Z = 2, Dc = 1.107 Mg/m3, μ(Cu) = 1.057 mm–1, F(000) = 1312, 2θmax = 104.42°, 28307 reflections, 8208 independent reflections [Rint = 0.0652], R1 = 0.0688, wR2 = 0.1822 and GOF = 1.001 for 8208 reflections (818 parameters) with I>2σ(I), R1 = 0.1059, wR2 = 0.2024 and GOF = 1.005 for all reflections, max/min residual electron density +0.462/–0.292 eÅ–3. CCDC 1884081. Figure B.3 X-ray structure of 1b·HSO −4 [TBA] + complex; thermal ellipsoids drawn at the 30% probability level. The dotted lines denote hydrogen-bonding interactions. 304 Figure B.4 Snapshot showing 2:2 dimeric complex provided by additional C−H⋯O contacts. The dotted lines denote hydrogen-bonding interactions with distances shown in Å. 4. 2D NMR Spectroscopic Data for 1 Figure B.5 1H-1H gradient COSY spectrum of 1a in 10% DMSO-d6/CDCl3. 305 Figure B.6 1H-13C HSQC NMR spectrum of 1a in 10% DMSO-d6/CDCl3. This result supports that Ha, Hc and Hd are N−H protons. 306 Figure B.7 1H-1H NOESY (top: whole spectrum; bottom: partial spectrum showing the cross peak/correlation of Hc and Hd) of 1a in 10% DMSO-d6/CDCl3. 307 Figure B.8 1H-1H gradient COSY spectrum of 1b in 10% DMSO-d6/CDCl3. Figure B.9 1H-13C HSQC spectrum of 1b in 10% DMSO-d6/CDCl3. This result supports that Ha, Hc and Hd are N−H protons. 308 Figure B.10 1H-1H NOESY (top: whole spectrum; bottom: partial spectrum showing the cross peak/correlation of Hc and Hd) of 1b in 10% DMSO-d6/CDCl3. 309 5. Interaction of 1a with Various Anions Figure B.11 Partial 1H NMR (top) and 31P NMR (bottom) spectra of 1a (1.0 mM) in 10 vol% DMSO-d6/CDCl3 in the absence and the presence of 10 equiv. of various anions. All anions were used as their respective TBA salts. 310 6. Representative NMR Titration Data Solutions of host (10 ~ 20 mg) were prepared using 10% DMSO-d6/CDCl3 in a volumetric flask to a final concentration of approximately 0.0005-0.0015 M. In each case, 600 μL of this solution was transferred to an NMR tube, and the remainder of the solution was used to generate the guest stock solution to a concentration of 0.005–0.060 M to maintain a constant host concentration throughout the titration. Aliquots of the guest solution were added via Hamilton gas tight syringes to the host solution in the NMR tube, and a spectrum was obtain via a Varian Inova 500 at 298 K after thorough mixing. Association constants (Ka) were calculated by nonlinear curve fitting of the obtained titration isotherms (Δδ > ± 0.2 ppm) using the reported 1:1 binding model.5 The reported association constants were the average of triplicate titrations, which were calculated from the simultaneous fitting of downfield shifting proton resonances (Hb, Hc and Hd for hydrogen sulfate, Ha, Hc and Hd for nitrate, Hc and Hd for halides. The Ha, He resonances may not be explicitly determined due to the slow exchange regime problems with disappearing or overlapping peaks during 1H NMR studies in the case of hydrogen sulfate). Similarly, the chemical shifts change (Δδ > ± 0.1 ppm) of the P atom resonances during titrations were also recorded and fitted. 311 Figure B.12 Representative 1H NMR titration of 1a (1.0 mM in 10% DMSO-d6/CDCl3) with tetrabutylammonium hydrogen sulfate as stacked spectra with hydrogen sulfate equivalents increasing bottom to top. 312 Figure B.13 Representative binding isotherm and fit curves for HSO –4 titration of 1a in 10% DMSO-d6/CDCl3 by 1H NMR. Figure B.14 Representative 31P NMR titration of 1a (1.0 mM) with tetrabutylammonium hydrogen sulfate as stacked spectra with hydrogen sulfate equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 313 Figure B.15 Representative binding isotherm and fit curves for HSO –4 titration of 1a in 10% DMSO-d6/CDCl3 by 31P NMR. Figure B.16 Representative 1H NMR titration of 1a (1.38 mM) with tetrabutylammonium nitrate as stacked spectra with nitrate equivalents increasing bottom to top in 10% DMSO- d6/CDCl3. 314 Figure B.17 Representative binding isotherm and fit curves for NO –3 titration of 1a in 10% DMSO-d6/CDCl3 by 1H NMR. 315 Figure B.18 Representative 31P NMR titration of 1a (1.38 mM) with tetrabutylammonium nitrate as stacked spectra with nitrate equivalents increasing bottom to top in 10% DMSO- d6/CDCl3. Figure B.19 Representative binding isotherm and fit curves for NO –3 titration of 1a in 10% DMSO-d6/CDCl3 by 31P NMR. 316 Figure B.20 Representative 1H NMR titration of 1a (1.37 mM) with tetrabutylammonium chloride as stacked spectra with chloride equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 317 Figure B.21 Representative binding isotherm and fit curves for Cl– titration of 1a in 10% DMSO-d6/CDCl3 by 1H NMR. Figure B.22 Representative 31P NMR titration of 1a (1.37 mM) with tetrabutylammonium chloride as stacked spectra with chloride equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 318 Figure B.23 Representative 1H NMR titration of 1a (1.37 mM) with tetrabutylammonium bromide as stacked spectra with bromide equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 319 Figure B.24 Representative binding isotherm and fit curves for Br– titration of 1a in 10% DMSO-d6/CDCl3 by 1H NMR. Figure B.25 Representative 31P NMR titration of 1a (1.37 mM) with tetrabutylammonium bromide as stacked spectra with bromide equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 320 Figure B.26 Representative 1H NMR titration of 1b (0.56 mM) with tetrabutylammonium hydrogen sulfate as stacked spectra with hydrogen sulfate equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 321 Figure B.27 Representative binding isotherm and fit curves for HSO –4 titration of 1b in 10% DMSO-d6/CDCl by 1 3 H NMR. Figure B.28 Representative 31P NMR titration of 1b (1.66 mM) with tetrabutylammonium hydrogen sulfate as stacked spectra with hydrogen sulfate equivalents increasing bottom to top in 10% DMSO-d6/CDCl3 (discernible 31P NMR resonance signals cannot be detected when [1b]≤ 1 mM). 322 Figure B.29 Representative binding isotherm and fit curves for HSO –4 titration of 1b in 10% DMSO-d6/CDCl3 by 31P NMR. Figure B.30 Representative 1H NMR titration of 1b (1.08 mM) with tetrabutylammonium nitrate as stacked spectra with nitrate equivalents increasing bottom to top in 10% DMSO- d6/CDCl3. 323 Figure B.31 Representative binding isotherm and fit curves for NO –3 titration of 1b in 10% DMSO-d6/CDCl 1 3 by H NMR. Figure B.32 Representative 31P NMR titration of 1b (1.08 mM) with tetrabutylammonium nitrate as stacked spectra with nitrate equivalents increasing bottom to top in 10% DMSO- d6/CDCl3. 324 Figure B.33 Representative binding isotherm and fit curves for NO –3 titration of 1b in 10% DMSO-d6/CDCl3 by 31P NMR. 325 Figure B.34 Representative 1H NMR titration of 1b (1.24 mM) with tetrabutylammonium chloride as stacked spectra with chloride equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. Figure B.35 Representative binding isotherm and fit curves for Cl– titration of 1b in 10% DMSO-d6/CDCl3 by 1H NMR. 326 Figure B.36. Representative 31P NMR titration of 1b (1.24 mM) with tetrabutylammonium chloride as stacked spectra with chloride equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. Figure B.37 Representative 1H NMR titration of 1b (1.09 mM) with tetrabutylammonium bromide as stacked spectra with bromide equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 327 Figure B.38 Representative binding isotherm and fit curves for Br– titration of 1b in 10% DMSOd6/CDCl3 by 1H NMR. Figure B.39 Representative 31P NMR titration of 1b (1.09 mM) with tetrabutylammonium bromide as stacked spectra with bromide equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 328 Figure B.40 Representative 1H NMR titration of 1b (1.12 mM) with tetrabutylammonium iodide as stacked spectra with bromide equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 329 Figure B.41 Representative binding isotherm and fit curves for I– titration of 1b in 10% DMSO-d6/CDCl3 by 1H NMR. Figure B.42 Representative 31P NMR titration of 1b (1.12 mM) with tetrabutylammonium iodide as stacked spectra with bromide equivalents increasing bottom to top in 10% DMSO-d6/CDCl3. 7. Competition Experiments of 1b with Anions Figure B.43 Partial 1H NMR spectra of receptor 1b (1.5 mM) in the presence of one equivalent of Cl− and NO −3 anions (added as TBA salts) in 10% DMSO-d6/CDCl3. 330 8. Hydrogen Sulfate Extraction Experiments For this initial study, the hydrogen sulfate extraction behavior of 1b was examined with 1H NMR and 31P NMR spectroscopy. 8.1 Extraction experiments Liquid-liquid extractions using 1b as the extractant were undertaken as follows: 1b (10 mM) in 0.8 mL CDCl3 and 0.8 mL NaHSO4 (2 M) (HSO − 4 is characterized as a weak acid and will dissociate in either non-pH buffered or dilute aqueous solution, thus higher concentration of HSO −4 sources were employed in this study, [HSO − 4 ]/[1b] ≈ 184 in theory) or H2SO − 4 (2 M, [HSO4 ]/[1b] ≈ 200 in theory) in deionized H2O solution (containing 10 mM TBANO3) were placed in a vial. The two phases were mixed thoroughly by stirring at rt. After 30 min, the stirring was stopped and the vial was allowed to stand for 1 h to fully separate the two phases. The CDCl3 phase (0.7 mL) were carefully separated and dried (Na2SO4). After filtration, the spectra of the resulting CDCl3 phase (0.6 mL) were then recorded. The purity and nature of the extracted product were determined by 1H NMR and 31P NMR spectroscopy (Figure B.45). 331 To estimate the apparent extraction efficiency (i.e., the molar percent of extractant containing TBAHSO4 after contact with a corresponding concentrated aqueous solution), 1,3,5-trimethoxybenzene (TMB) was used as an internal standard (10 mM, pre-dissolved in CDCl3) and TBAHSO4 as the cation exchanger, the results were obtained via calculation of the integration ratio of the peaks from 1H NMR spectroscopy (Figure B.46). 8.2 Blank experiment 1b (10 mM) in 0.8 mL CDCl3 and 0.8 mL deionized H2O solution (containing 10 mM TBANO3) were placed in a vial. The two phases were mixed thoroughly by stirring at rt. After 30 min, the stirring was stopped and the vial was allowed to stand for 1 h to fully separate the two phases. The CDCl3 phase (0.7 mL) was carefully separated and dried (Na2SO4). After filtration, the spectra were recorded (Figure B.45). The extraction efficiency was ca. 67%, determined by using TMB as an internal standard via 1H NMR. Unfortunately, our attempt to extract TBAHSO4 from water using 1b in the presence of equal molar amounts of TBANO3 was unsuccessful. This result is not surprising. We found that even pure CDCl3 (without receptor) is capable of capturing considerable amount of TBANO3 (ca. 43% extraction) from water solution, probably due to the small hydration energy of TBANO3. Since all the studied interfering anion TBA salts are somewhat hydrophobic compared to bisulfate anion based on the Hofmeister sequence, which prelude the potential selective extraction in the presence of competitive anions at this stage. 332 8.3 Comparison experiments Comparison experiments were conducted by directly adding aliquots of TBAHSO4 to the CDCl3 solution of 1b (10 mM). The spectra of 1b in the presence of 0.7, 0.8, 0.9, 0.95, 1.0, 1.2 and 2.0 equivalents of TBAHSO4 were recorded (Figure B.44). 8.4 Control experiments 0.8 mL neat CDCl3 (i.e. without host 1b) and 0.8 mL NaHSO4 (2 M) or H2SO4 (2 M) in deionized H2O solution (containing 10 mM TBAHSO4) were placed in a vial. The two phases were mixed thoroughly by stirring at rt. After 1 h, the stirring was stopped and the vial was allowed to stand for 1 h to fully separate the two phases. The CDCl3 phase (0.7 mL) was carefully separated and dried (Na2SO4). After filtration, the spectra of the resulting CDCl3 phase (0.6 mL) was then recorded (Figure B.47). 333 8.5 Recycling experiments The resulting CDCl3 phases in NMR tubes from extraction experiments were evaporated, and redissolved in 1 mL CDCl3, and 20 mL deionized H2O was also added to the same vial. After thoroughly mixing the two phases for 1 h by stirring at rt. The guest was released in the form of sulfate anion from the receptor and transferred to the H2O phase due to the chemical dissociation of bisulfate in dilute aqueous solution. The recycled receptors were ascertained by 1H NMR spectra (Figure B.48). 334 Figure B.44 Partial 1H NMR (500 MHz) (left) and 31P NMR (202 MHz) (right) spectra (in CDCl3, 298 K) of 1b with TBAHSO4 as stacked spectra with TBAHSO4 equivalents increasing bottom to top. Figure B.45 Partial 1H NMR (500 MHz) (left) and 31P NMR (202 MHz) (right) spectra (in CDCl3, 298 K) of a) receptor 1b (10 mM); b) the CDCl3 phase after extraction from 2 M H2SO4; c) the CDCl3 phase after extraction from 2 M NaHSO4; d) 1b in the comparison experiment by direct adding 1.0 eq. of TBAHSO4; e) blank experiment. 335 Figure B.46 Partial 1H NMR spectra (500 MHz) of a) the CDCl3 phase (containing TMB internal standard) after extraction from 2 M H2SO4 in the extraction experiment, showing ca. 92% uptake of TBAHSO4; b) the CDCl3 phase (containing TMB internal standard) after extraction from 2 M NaHSO4 in the extraction experiment, showing ca. 100% uptake of TBAHSO4. All the relevant peaks for each spectrum are integrated at the same scale. The TBA+ counterion is marked with pink squares. The TMB standard is marked with blue stars. 336 Figure B.47 Partial 1H NMR spectra (500 MHz, CDCl3) of a) the CDCl3 phase after extraction from 2 M H2SO4 in the control experiment; b) TBAHSO4; c) the CDCl3 phase after extraction from 2 M NaHSO4 in the control experiment. The spectral intensities of a) and c) were zoomed-in by 10 times, showing only trace amounts of bisulfate anion were extracted into CDCl3 phase. Figure B.48 Partial 1H NMR spectra (500 MHz, CDCl3) of a) receptor 1b and the recycled 1b from the extraction experiments of b) NaHSO4 aqueous solution and c) H2SO4 aqueous solution. 337 9. Computational Details For 1b•Cl− and 1b•NO −3 complexes (The t-Bu groups in receptors were omitted to reduce computational costs) were built manually by placing corresponding anions in the tentatively proposed conformations of receptors and optimized by the PM6-D3H46 semi- empirical method. Afterwards, all the obtained structures were further optimized by carrying out the DFT calculations using the M06-2X functional7 along with the 6-31G(d,p) basis set. The solvent effects are included using the polarizable continuum model (PCM)8 (solvent: CHCl3). The frequency calculations were also performed on the structures to ensure no imaginary frequency. A constrained optimization in gas phase was performed to the single crystal structure of 1b•HSO −4 , where non-H atoms were frozen and only H atoms were fully optimized at M06- 2X/Def2-TZVPP9 level of theory. The distribution of electrostatic potential, V(r), on the molecular surfaces of 1b were computed at the M06-2X/6-31G(d,p) level in gas phase from previously optimized structures of their complexes with HSO −4 anion, after removal of HSO −4 anion of the corresponding complex. The V(r) was evaluated on the 0.001 e/Bohr 3 contour of ρ(r) to generate the VS(r). The most negative and most positive VS(r) values (i.e. VS,min and VS,max, respectively) for electrostatic potential surface energies were calculated (Figure B.50). The QTAIM10 analyses were conducted based on the optimized geometries of 1b•HSO −4 . QTAIM topological parameter G(r) is the Lagrangian kinetic energy and V(r) is the local potential electron energy density. A negative Laplacian of electron density [∇2ρ(r)] shows the excess potential energy at the BCP which means that the electronic charge is contracted between two nuclei (covalent interaction), while a positive ∇2ρ(r) reveals that the kinetic energy contribution is greater than the potential energy (closed-shell electrostatic 338 interaction). The sign of electronic energy H(r) on the Hamiltonian at BCP determines whether the accumulation of charge at a given point is stabilizing [H(r) < 0] or destabilizing [H(r) > 0]. The nature of hydrogen bond can be evaluated by means of the −[G(r)/V(r)]. If −[G(r)/V(r)] > 1, then the hydrogen bond has non-covalent character while for the 0.5 < −[G(r)/V(r)] < 1, the hydrogen bond has partly covalent character (Table B.2).11 To visualize the position and different types of non-covalent interactions in 3D space, the gradient isosurfaces (cutoff = 0.5 a.u.) of the reduced density gradient (RDG)12 at low densities, colored on a blue–green–red scale according to values of sign(λ2)ρ(r) (ranging from −0.02 to 0.02 a.u.) were obtained. The PM6-D3H4 optimizations were performed with MOPAC201613 and all the DFT calculations were carried out by Gaussian 09 software package.14 The Wiberg bond indices15 (WBI) were calculated based on the DFT optimized structures of the complexes of 1•HSO −4 , which were performed using the Natural Bond Orbital (NBO) program, within the Gaussian 09 suite. The Multiwfn package program16 was employed for obtaining electrostatic potential surface energy extremes (VS,min and VS,max) and visualizing the bond paths and to calculate the bond critical points (BCPs). Also, this program has been used to obtain the RDG function. 339 Figure B.49 DFT-optimized complexes (at M06-2X/6-31G(d,p) level of theory) of 1b•Cl− (left) and 1b•NO −3 (right). In the structures, the anions are shown in CPK model, and host molecules are depicted in stick representation. The t-Bu groups were omitted to reduce computational costs. Figure B.50 The electrostatic potential (ESP) surfaces (isosurface = 0.001 a.u.) of free 1b calculated at M06-2X/6-31G(d,p) level of theory in gas phase. Red indicates negative charge density, and blue positive charge density. Surface minima (VS,min) and maxima (VS,max) of ESP energies (in kcal mol −1) are represented as orange and cyan dots, respectively. Table B.2 Values of the density of all electrons ρ(r), Laplacian of electron density 2ρ(r), local potential electron energy density V(r), energy density H(r), Lagrangian kinetic energy G(r) (in a.u.) at the bond critical points (BCPs) for selected significant H-bond interactions in the crystal structure of 1b•HSO −4 complex, calculated at M06-2X/Def2-TZVPP level of theory 1b•HSO −4 ρ(r) 2ρ(r) V(r) H(r) G(r) −[G(r)/V(r)] N‒Ha•••Oanion 0.03501 0.10936 −0.03403 0.00335 0.03068 0.90169 C‒Hb•••Oanion 0.01603 0.06265 −0.01151 0.00208 0.01359 1.18049 N‒Hc•••Oanion 0.03007 0.10555 −0.02845 0.00103 0.02742 0.96372 d 0.00945; 0.03881; −0.00612; 0.00179; 0.00791; 1.29290; N‒H •••Oanion 0.01559 0.05915 −0.01131 0.01739 0.01305 1.15372 N‒He•••Oanion 0.01662 0.06994 −0.01260 0.00244 0.01504 1.19378 P=O•••(H‒ 0.05616 0.12312 −0.06416 0.01669 0.04747 0.73986 O)anion 340 Table B.3 Wiberg Bond Indices (WBIs) for the relevant HB interactions in the crystal structure of 1b•HSO −4 complex, calculated at M06-2X/Def2-TZVPP level of theory HB interactions WBI N‒Ha•••Oanion 0.0493 C‒Hb•••Oanion 0.0094 N‒Hc•••Oanion 0.0356 N‒Hd•••Oanion 0.0049; 0.0155 N‒He•••Oanion 0.0069 P=O•••(H‒O)anion 0.0717 Table B.4 Cartesian coordinates for 1b•HSO − 4 X Y Z S 0.85947400 0.90394500 -0.60559800 O 0.00452700 -0.19498400 -0.30070800 O 2.20135700 0.49929400 -0.91811500 O 0.77574900 1.98521500 0.32367400 O 0.34269600 1.50294000 -1.95708400 H -0.63960100 1.57543300 -1.92876500 P -3.23196300 0.52596500 -1.41259100 O -2.22039500 1.50747400 -1.81300400 O -3.43699600 -0.40343500 -2.70314300 O 1.49820000 -7.46860000 1.99392300 O 3.57329500 -7.14365000 1.57628100 O 6.02092000 2.92488300 0.65292200 O 1.33746900 7.39577500 4.35208800 O 3.30954800 7.95098800 4.42820300 N -2.76190900 -0.42069900 -0.16124500 N -8.08589700 5.97457500 -4.51060900 N 2.43192200 -6.74786100 1.66466900 N 4.87006900 1.16458500 -0.23243100 N 3.74667100 2.78974100 0.89940100 N 2.48406300 7.23955600 4.01215100 C 1.62195500 -2.73276000 0.71780800 H 1.39059100 -1.70975400 0.44718500 C 0.59852800 -3.53975500 1.23632600 C 0.88331200 -4.86349400 1.56658400 H 0.12522300 -5.52129100 1.96258700 C 2.16025900 -5.33599500 1.34849100 C 3.17391000 -4.56264000 0.82988300 H 4.15652300 -4.98447100 0.68348700 C 2.90639600 -3.22266400 0.51509200 C -0.71537400 -3.02110500 1.38080200 C -1.82856700 -2.56847200 1.49282200 341 C -3.15587300 -2.04450400 1.62167500 C -4.03544100 -2.57944900 2.58125500 H -3.64320800 -3.37182200 3.20299600 C -5.34338400 -2.12957400 2.73898400 C -5.76270300 -1.13115000 1.88609700 H -6.77637200 -0.75664900 1.94377500 C -4.93332100 -0.56891900 0.92495100 C -3.60724900 -1.01659700 0.78682900 C -5.46837900 0.49477200 0.08091600 H -6.47374000 0.79709000 0.33634400 C -4.81680000 1.09274500 -0.96009400 C -5.51580600 2.17917700 -1.75225400 C -6.78229100 2.61076400 -1.38704600 H -7.29911400 2.20040900 -0.53521300 C -7.42262700 3.58070400 -2.11750500 H -8.41210900 3.90523100 -1.82429000 C -6.81902800 4.14842800 -3.18838800 C -5.56344800 3.74450500 -3.56300100 H -5.07863000 4.20118800 -4.41452600 C -4.90444100 2.77638800 -2.83145200 H -3.90104400 2.49164000 -3.11753900 C -7.51007000 5.16224600 -3.93579800 C -4.30295300 -1.49661400 -2.65953200 C -5.53974100 -1.34617200 -3.20996400 H -5.80453600 -0.38538400 -3.63358000 C -6.42186100 -2.40399100 -3.21584300 H -7.40873000 -2.29886700 -3.64399200 C -6.01842300 -3.60031700 -2.64893000 H -6.70455400 -4.43820900 -2.64116700 C -4.74736200 -3.77359500 -2.11942300 H -4.44328900 -4.72266900 -1.70190100 C -3.85925100 -2.68146700 -2.11945800 H -2.85840300 -2.75528400 -1.71671000 C -6.27721900 -2.71916300 3.77209200 C -5.79594500 -2.28691000 5.12234400 H -4.75517600 -2.56294900 5.29304200 H -6.39536700 -2.74454600 5.91179400 H -5.86008000 -1.20207700 5.25248100 C -7.64781800 -2.31609200 3.68114000 H -7.76937100 -1.23653500 3.79297200 H -8.23469800 -2.78016400 4.47571400 H -8.11872300 -2.59783300 2.73342700 C -6.09906800 -4.18935600 3.90494100 H -5.08423000 -4.46099600 4.18317500 H -6.33560900 -4.72997100 2.98216600 H -6.76002000 -4.57893900 4.68078600 342 C 3.94826900 -2.38349000 0.02980900 C 4.84077800 -1.68264000 -0.34392800 C 5.93600400 -0.90553700 -0.87631900 C 7.01760000 -1.59020400 -1.47132200 H 6.95737000 -2.66945900 -1.47816600 C 8.09232000 -0.94308600 -2.02091900 C 8.07830800 0.43964100 -1.96796000 H 8.89096400 1.00988700 -2.39998500 C 7.03934600 1.14511000 -1.38425700 H 7.06571700 2.22273000 -1.35030600 C 5.96442100 0.48828700 -0.81038800 C 9.27930000 -1.67112700 -2.65318000 C 9.25169300 -3.16049900 -2.37970300 H 9.22653600 -3.36167800 -1.30816300 H 10.14619800 -3.62936300 -2.79314900 H 8.38720700 -3.64545400 -2.83743400 C 9.33008600 -1.36054400 -4.12483500 H 9.40712700 -0.28675200 -4.29678200 H 8.43230400 -1.71301000 -4.63767200 H 10.19486300 -1.83872400 -4.59176700 C 10.61157000 -1.13575600 -2.04769300 H 10.63739700 -1.29018200 -0.96824600 H 10.74409900 -0.07268300 -2.24188200 H 11.45235600 -1.66781000 -2.49638600 C 4.95779000 2.33683400 0.44968800 C 3.50939800 3.92136800 1.65560700 C 2.19158000 4.09878600 2.08947600 H 1.43657000 3.38231300 1.79782800 C 1.84665000 5.21676700 2.84077000 H 0.82993800 5.37528700 3.16584800 C 2.82581200 6.09200700 3.19307200 C 4.11411300 5.93920000 2.78813500 H 4.85674500 6.66712900 3.08083600 C 4.46445300 4.85427100 2.02653900 H 5.48350600 4.72397100 1.70526200 H 3.94528400 0.75206100 -0.37220300 H 2.90999200 2.27895100 0.62346500 H -1.73388100 -0.51903900 -0.06839700 Table B.5 Cartesian coordinates for 1b•Cl− X Y Z N -3.81011800 -0.34394800 -0.73864900 N -12.95812800 1.59925300 -1.11656200 343 N 6.46259900 -0.78094900 0.59344100 N 6.02799900 1.41598200 0.15237800 N 6.38616900 6.81935000 -1.29820000 N 0.39687400 -6.01243900 -2.09282100 C 1.80634800 -2.42848300 -0.36116000 C 0.46429200 -2.53525800 -0.74884600 C -0.01005500 -3.71823000 -1.32498100 C 0.88595300 -4.76411700 -1.48906000 C 2.21856900 -4.69425800 -1.11356500 C 2.68375300 -3.50383300 -0.54073300 C -0.39735000 -1.41406500 -0.52717500 C -1.03897300 -0.41445100 -0.28582600 C -1.79269200 0.75742400 0.02449000 C -1.16856000 1.87729800 0.58101600 C -1.90995700 3.00435400 0.92670700 C -3.27960700 3.01203400 0.71474700 C -3.93961400 1.90532500 0.16038500 C -3.18725100 0.76731700 -0.18670800 C -5.37444600 1.94397800 -0.04653500 C -6.16047200 0.90519800 -0.41355500 C -7.62177400 1.04181400 -0.58945000 C -8.16769700 2.22371300 -1.10978000 C -9.53918700 2.37376900 -1.24284800 C -10.38826500 1.32715700 -0.86637800 C -9.85891700 0.13485300 -0.36196900 C -8.48570800 -0.00268500 -0.22675000 C -11.81210500 1.47649800 -1.00647500 C -5.09162200 -0.83552200 1.99072300 C -5.90065400 -0.01345500 2.76714500 C -5.35356900 0.60598700 3.88781500 C -4.01474700 0.40595600 4.21805900 C -3.22117300 -0.43095900 3.43564200 C -3.75867800 -1.06209000 2.31764300 C 4.04898400 -3.38064300 -0.12975600 C 5.20302000 -3.27885000 0.22552200 C 6.56882400 -3.19761100 0.63899000 C 7.28353400 -4.38132800 0.87566000 C 8.61593800 -4.34275100 1.25403100 C 9.24217700 -3.10618800 1.40725300 C 8.55148800 -1.92104900 1.18999100 C 7.20726100 -1.94692400 0.79757000 C 6.99454600 0.43490900 0.20925200 C 6.19440900 2.73772300 -0.21927300 C 7.39959700 3.28599900 -0.69731200 C 7.45261400 4.62479100 -1.04890700 C 6.31618000 5.41643000 -0.92803900 344 C 5.11131300 4.89531300 -0.45965300 C 5.05481000 3.56207100 -0.10855200 O -5.94691300 -1.62281900 -1.64926500 O -5.63152900 -1.44174700 0.85695400 O 8.17653000 0.61227300 -0.04929500 O 5.37594500 7.49837700 -1.18252600 O 7.45155700 7.25708700 -1.70840900 O -0.77066100 -6.05772000 -2.43685100 O 1.18644100 -6.93183000 -2.21497700 P -5.43408700 -0.71998300 -0.59906500 H -3.19239400 -1.08933400 -1.05073700 H 5.44696600 -0.84706900 0.67484000 H 5.08202000 1.15349500 0.47138100 H 2.17267600 -1.50811100 0.09071600 H -1.04130700 -3.82750100 -1.63512200 H 2.87414000 -5.54220900 -1.26466000 H -0.09704400 1.84073900 0.74790800 H -1.41713700 3.86552100 1.36207000 H -3.86886700 3.88476800 0.98075900 H -5.85111700 2.90535200 0.14316000 H -7.50878500 3.02216000 -1.43467700 H -9.95578100 3.28901700 -1.64828800 H -10.52206300 -0.67363400 -0.07566900 H -8.08408000 -0.92806700 0.17502700 H -6.93721300 0.13804900 2.48151500 H -5.97562500 1.25090500 4.49966900 H -3.59016300 0.89775000 5.08669200 H -2.17867300 -0.59202700 3.68911000 H -3.15417800 -1.70913900 1.68954100 H 6.76919300 -5.32809900 0.74936100 H 9.15986800 -5.26406100 1.43035000 H 10.28305900 -3.05927400 1.71134300 H 9.04289300 -0.96734600 1.31666800 H 8.27491200 2.66095000 -0.78277400 H 8.37127400 5.06293100 -1.41886200 H 4.24248600 5.53645200 -0.37857800 H 4.13046700 3.12753200 0.26150600 Cl 3.28140300 0.35454800 1.18561400 Table B.6 Cartesian coordinates for 1b•NO − 3 X Y Z P 2.24133900 -0.89001400 -0.63371700 N 1.17179900 -2.16783200 -0.51063900 345 C 1.42637800 -3.37301500 0.11996800 C 2.75021600 -3.79844400 0.35868600 C 3.87944200 -2.98920300 -0.05309800 C 3.82313200 -1.72844400 -0.53664300 C 0.35761700 -4.21032800 0.51714600 C 0.62242800 -5.43640100 1.13206900 C 1.92908200 -5.85350400 1.36743500 C 2.97703500 -5.03479000 0.97934300 C -0.98706600 -3.78258400 0.30367800 C -2.11628000 -3.39306900 0.10540000 C 5.04507400 -1.00580000 -0.95346100 C 6.05462700 -1.68846400 -1.64737700 C 7.22559100 -1.04403100 -2.01420000 C 7.39454700 0.30841700 -1.69836200 C 6.39180100 1.00953400 -1.02027600 C 5.22582100 0.35221500 -0.65289000 O 2.02760800 0.02213600 -1.77943500 N -3.61326100 3.25344100 -0.04975300 C -2.44703900 3.94934100 0.20872300 N -1.33570700 3.19291600 -0.08373200 O -2.41094200 5.09193900 0.64136700 C -0.00625600 3.57492900 0.03001000 C 0.43020900 4.74526700 0.67837800 C 1.78686000 5.01646300 0.75868000 C 2.70017700 4.13082600 0.19536600 C 2.28637700 2.97550500 -0.46277100 C 0.93728300 2.70246000 -0.54094500 C -5.69749000 -3.40425100 -0.84213900 C -4.42015000 -3.87378700 -0.58003400 C -3.45303400 -2.95621500 -0.15425600 C -5.08712700 -1.16047300 -0.29042600 C -6.05933600 -2.07253200 -0.71818900 C -4.91371100 3.73436900 0.11263800 C -5.96980500 2.79215900 0.08657500 C -5.22942800 5.09067900 0.26745500 C -6.55533700 5.48812800 0.39381600 C -7.59821000 4.56384700 0.36179000 C -7.29853100 3.21972600 0.20528000 C -5.40578800 0.22613400 -0.15953400 C -5.68056400 1.40101400 -0.04935000 C -3.79357100 -1.60806600 0.00101900 N 4.11914500 4.40643300 0.31406400 C 8.60781000 0.98107200 -2.07949800 N 9.58834000 1.51532100 -2.38582900 O 4.47016500 5.46247800 0.81736200 O 4.90582800 3.55952200 -0.09271900 346 N -6.71912700 -4.36714000 -1.27973100 O -7.83687700 -3.94303400 -1.51263200 O -6.39141700 -5.53574500 -1.38141000 H 0.19901800 -1.94275100 -0.76334700 H 4.85918800 -3.45255900 0.06193600 H -0.21775800 -6.05470800 1.42954900 H 2.12071700 -6.80580500 1.84774800 H 4.00455800 -5.34319400 1.15066800 H 5.90550100 -2.72821800 -1.91961800 H 8.00241300 -1.57518900 -2.55294800 H 6.52394000 2.05750800 -0.77797000 H 4.46172900 0.90151300 -0.10964500 H -3.51901600 2.28554700 -0.35217300 H -1.49740100 2.26621200 -0.48181900 H -0.29009300 5.42078700 1.11373200 H 2.14542900 5.90476100 1.26408600 H 2.99912100 2.29846500 -0.91643100 H 0.61739800 1.78909100 -1.03000000 H -4.18440800 -4.92214500 -0.70829900 H -7.06737400 -1.75424600 -0.94982900 H -4.43312600 5.81881700 0.28986700 H -6.77259000 6.54502100 0.51259400 H -8.62848700 4.88772800 0.45718200 H -8.08507500 2.47296400 0.17687200 H -3.05257400 -0.90475800 0.36549600 O 2.15504700 -0.02784100 0.75125000 C 2.11166800 -0.69620600 1.96941000 C 0.89410500 -1.18426500 2.43560700 C 3.28677900 -0.85202900 2.69603700 C 0.86542100 -1.85560400 3.65437700 H 0.00481900 -1.03891500 1.82909200 C 3.24107300 -1.51997800 3.91728900 H 4.21560400 -0.45504900 2.29806400 C 2.03427700 -2.02648000 4.39483600 H -0.07635400 -2.24681900 4.02578200 H 4.15254500 -1.64629600 4.49258000 H 2.00403400 -2.55158000 5.34386100 O -0.83603400 0.09744800 -0.05808800 O -2.26919500 0.80511600 -1.51457900 O -1.27832400 -1.09551200 -1.80517200 N -1.45338100 -0.06925100 -1.13355300 347 11. Copies of NMR Spectra 1H-NMR spectrum of compound 3 (CDCl3, 298K) 13C-NMR spectrum of compound 3 (CDCl3, 298K) 348 1H-NMR spectrum of compound 4 (CDCl3, 298K) 13C-NMR spectrum of compound 4 (CDCl3, 298K) 349 31P-NMR spectrum of compound 4 (CDCl3, 298K) 1H-NMR spectrum of compound 5 (CDCl3, 298K) 350 13C-NMR spectrum of compound 5 (CDCl3, 298K) 31P-NMR spectrum of compound 5 (CDCl3, 298K) 351 1H-NMR spectrum of compound 7a (CDCl3, 298K) 13C-NMR spectrum of compound 7a (CDCl3, 298K) 352 1H-NMR spectrum of compound 7b (CDCl3, 298K) 13C-NMR spectrum of compound 7b (CDCl3, 298K) 353 1H-NMR spectrum of compound 8a (CDCl3, 298K) 13C-NMR spectrum of compound 8a (CDCl3, 298K) 354 1H-NMR spectrum of compound 8b (CDCl3, 298K) 13C-NMR spectrum of compound 8b (CDCl3, 298K) 355 1H-NMR spectrum of compound 1a (CDCl3/DMSO-d6= 4/1, 298K) 13C-NMR spectrum of compound 1a (CDCl3/DMSO-d6 = 4/1, 298K) 356 31P-NMR spectrum of compound 1a (CDCl3/DMSO-d6 = 4/1, 298K) 1H-NMR spectrum of compound 1b (DMSO-d6, 298K) 357 13C-NMR spectrum of compound 1b (DMSO-d6, 298K) 31P-NMR spectrum of compound 1b (DMSO-d6, 298K) 358 APPENDIX C SUPPLEMENTARY INFORMATION FOR CHAPTER 4 1. Crystallographic Data for 2f General. Diffraction intensities for 2f were collected at 173 K on a Bruker Apex2 CCD diffractometer using CuK radiation, = 1.54178 Å. Space group was determined based on systematic absences. Absorption correction was applied by SADABS.1 Structure was solved by direct methods and Fourier techniques and refined on F2 using full matrix least- squares procedures. All non-H atoms were refined with anisotropic thermal parameters. H atoms were refined in calculated positions in a rigid group model except the H atom at the N atom involved in H-bond which was found on the residual density map and refined with isotropic thermal parameter. In the crystal structure the main molecules form a dimer unit via N-H•••O H-bonds which are packed in columns. Solvent molecules CHCl3 fill out empty space between such the columns and are highly disordered. These disordered solvent molecules were treated by SQUEEZE.2 The corrections of the X-ray data by SQUEEZE are 220 electron/cell; the required values are 232 electron/cell for four CHCl3 molecules in the full unit cell. All calculations were performed by the Bruker SHELXL-2014 package.3 Crystallographic Data for 2f: C24H20Cl3O2P, M = 505.74, 0.15 x 0.08 x 0.06 mm, T = 173(2) K, Monoclinic, space group P21/c, a = 17.7865(8) Å, b = 8.1543(4) Å, c = 18.4012(8) Å,  = 117.199(3), V = 2373.7(2) Å3, Z = 4, Dc = 1.415 Mg/m3, μ(Cu) = 4.335 mm–1, F(000) = 1040, 2θmax = 133.15°, 13893 reflections, 4116 independent reflections [Rint = 0.0465], R1 = 0.0570, wR2 = 0.1562 and GOF = 1.021 for 4116 reflections (257 359 parameters) with I>2(I), R1 = 0.0699, wR2 = 0.1630 and GOF = 1.021 for all reflections, max/min residual electron density +0.588/–0.275 eÅ–3. CCDC 1944053. Figure C.1 ORTEP drawing of 2f with selected bond lengths listed; thermal ellipsoids drawn at 30% probability. Crystals grown with slow diffusion of pentane into a solution of 2 in CHCl3. Figure C.2 ORTEP drawing of the racemic dimer of 2f; thermal ellipsoids drawn at 30% probability. 360 Figure C.3 ORTEP drawing of the crystal packing of 2f looking down the b-axis. 361 2. Frontier Orbital Values and TD-DFT Excitations Ground state calculations Table C.1 Calculated Frontier Orbitals and First Excitation Values for 2a S0 → S1 cmpd EHOMO ELUMO ΔEDFT computed (nm), osc. Strength 2a –6.800 –2.405 4.395 341, 0.505 2b –6.750 –2.319 4.431 337, 0.535 2c –6.531 –2.296 4.235 354, 0.392 2d –6.510 –2.294 4.303 348, 0.486 2e –6.481 –2.178 4.207 358, 0.361 2f –6.353 –2.146 3.896 389, 0.195 a Calculated at the PBE0/TZVP level of theory; values reported in eV. Figure C.4 Frontier orbital shapes (isovalue = 0.3) of heterocycles 2; calculated at the PBE0/TZVP level of theory. Excited state calculations These initial structures were optimized using the functional PBE04,5 (25% full-range HF exchange) and TZVP basis set6 as implemented in Gaussian 09.7 In addition, all the optimized structures were confirmed by frequency analysis and the number of imaginary frequencies was zero. TD-DFT vertical excitation calculations and geometry optimization of the first excited state (S1) were performed at the same level of theory. The PCM solvation model8,9 was used to account for the solvent effects of the chloroform. 362 Figure C.5 HOMO-LUMO pictorial representations (isovalue = 0.3), energies and their differences (ΔE) in the optimized S0 and S1 structures of 2f calculated by the DFT and TD- DFT methods at the PCM(CHCl3)-PBE0/TZVP level of theory, respectively. 363 3. Geometry Optimizations and Coordinates Ground state geometries Table C.2 Cartesian coordinates of the optimized geometry of 2a determined at the PBE0/TZVP level of theory Atom x y z C -4.85224 -0.99453 0.24314 C -5.06467 0.36876 -0.01362 C -3.99796 1.19772 -0.26557 C -2.68944 0.69768 -0.26948 C -2.46321 -0.67090 -0.00881 C -3.55816 -1.49676 0.24538 N -1.62915 1.54068 -0.48129 P -0.05268 1.09981 -0.96544 C 0.01373 -0.57214 -0.28708 C -1.13106 -1.21587 0.02816 C 1.32888 -1.22391 -0.17733 C 2.32937 -1.00360 -1.13093 C 3.55719 -1.62907 -1.02594 C 3.81064 -2.48996 0.04330 C 2.82419 -2.71342 1.00652 C 1.60209 -2.08011 0.89538 O 0.24116 1.20873 -2.43673 H -6.07224 0.76605 -0.01630 H -4.16680 2.24964 -0.46799 H -3.38832 -2.54835 0.44662 H -1.86453 2.51486 -0.62006 H -1.06114 -2.25919 0.32868 H 2.13135 -0.35505 -1.97675 H 4.32091 -1.45850 -1.77493 H 3.02505 -3.37115 1.84342 H 0.85418 -2.23445 1.66438 C 5.07615 -3.13557 0.15614 N 6.10029 -3.65817 0.24771 C 1.00594 2.19506 0.01314 C 1.97814 2.94304 -0.64517 C 0.86604 2.29013 1.39720 C 2.80595 3.78889 0.08033 H 2.07444 2.85806 -1.72158 C 1.69724 3.13388 2.11728 H 0.10786 1.70840 1.91080 C 2.66562 3.88319 1.45833 H 3.56138 4.37440 -0.43113 H 1.59006 3.20904 3.19339 H 3.31411 4.54305 2.02388 C -5.95519 -1.85468 0.50419 N -6.85123 -2.54976 0.71725 364 Zero-point correction = 0.306046 (Hartree/Particle); Thermal correction to energy = 0.328311; Thermal correction to enthalpy = 0.329256; Thermal correction to Gibbs free energy = 0.252414; Sum of electronic and zero-point energies = -1426.281789; Sum of electronic and thermal energies = -1426.259523; Sum of electronic and thermal enthalpies = -1426.258579; Sum of electronic and thermal free energies = -1426.335421. Table C.3 Cartesian coordinates of the optimized geometry of 2b determined at the PBE0/TZVP level of theory Atom x y z C 4.33256 0.25239 0.07266 C 4.36740 -1.12574 -0.14433 C 3.19680 -1.82533 -0.36097 C 1.96424 -1.16425 -0.36534 C 1.91814 0.22872 -0.13593 C 3.11747 0.91433 0.07864 N 0.79435 -1.87023 -0.54497 P -0.71412 -1.24659 -1.00223 C -0.55995 0.42532 -0.35685 C 0.66485 0.93655 -0.08900 C -1.78476 1.23382 -0.22255 C -2.83620 1.11740 -1.14210 C -3.97972 1.88534 -1.01112 C -4.09599 2.78768 0.05013 C -3.05815 2.90828 0.97984 C -1.92102 2.13323 0.84339 O -1.06879 -1.33987 -2.44972 H 5.31560 -1.64935 -0.14765 H 3.22816 -2.89645 -0.53066 H 3.08031 1.98498 0.25349 H 0.90195 -2.87056 -0.65853 H 0.72898 1.98857 0.18318 H -2.74143 0.43697 -1.98120 H -4.78302 1.79523 -1.73288 H -3.15443 3.59763 1.81044 H -1.13530 2.20738 1.58703 C -5.27351 3.57973 0.18954 N -6.22685 4.22181 0.30316 C -1.87332 -2.16682 0.02964 C -2.99233 -2.74612 -0.56830 C -1.67521 -2.28375 1.40740 C -3.90785 -3.44425 0.21021 H -3.13095 -2.64787 -1.63956 C -2.59376 -2.97976 2.18044 H -0.80363 -1.83295 1.87151 C -3.70888 -3.55955 1.58133 365 H -4.77702 -3.89756 -0.25393 H -2.44117 -3.07162 3.25034 H -4.42561 -4.10321 2.18781 C 5.58540 1.02927 0.31687 F 5.71872 2.05264 -0.54614 F 6.68573 0.27257 0.20460 F 5.60776 1.57440 1.54852 Zero-point correction = 0.312616 (Hartree/Particle); Thermal correction to energy = 0.335712; Thermal correction to enthalpy = 0.336656; Thermal correction to Gibbs free energy = 0.257793; Sum of electronic and zero-point energies = -1670.857410; Sum of electronic and thermal energies = -1670.834315; Sum of electronic and thermal enthalpies = -1670.833370; Sum of electronic and thermal free energies = -1670.912234. Table C.4 Cartesian coordinates of the optimized geometry of 2c determined at the PBE0/TZVP level of theory Atom x y z C 4.76530 -0.84753 -0.21352 C 4.95235 0.51406 0.01777 C 3.85707 1.32309 0.25213 C 2.56393 0.79136 0.25768 C 2.37737 -0.58478 0.01677 C 3.49994 -1.39313 -0.21621 N 1.46788 1.61180 0.44837 P -0.06873 1.13040 0.96633 C -0.10263 -0.53610 0.28870 C 1.05876 -1.16265 -0.01869 C -1.40505 -1.21599 0.17783 C -2.41834 -1.00066 1.12223 C -3.63596 -1.64912 1.01591 C -3.86748 -2.52873 -0.04558 C -2.86886 -2.74659 -1.00019 C -1.65681 -2.09032 -0.88811 O -0.35888 1.22487 2.42868 H 5.95108 0.93373 0.01736 H 4.00140 2.38257 0.43708 H 3.36185 -2.45261 -0.39989 H 1.67299 2.59782 0.54848 H 1.01106 -2.21043 -0.31023 H -2.23659 -0.33867 1.96189 H -4.40883 -1.48285 1.75717 H -3.05318 -3.41765 -1.83095 H -0.90062 -2.23953 -1.65088 C -5.12144 -3.19771 -0.15958 N -6.13694 -3.74019 -0.25236 C -1.17198 2.18283 0.00032 C -2.19830 2.86079 0.65770 366 C -1.02047 2.31216 -1.38225 C -3.06654 3.67011 -0.06545 H -2.30167 2.75103 1.73180 C -1.89224 3.11874 -2.10022 H -0.22075 1.78506 -1.89284 C -2.91380 3.79763 -1.44141 H -3.86269 4.20063 0.44554 H -1.77547 3.22002 -3.17380 H -3.59348 4.42828 -2.00484 Cl 6.14889 -1.86580 -0.50514 Zero-point correction = 0.298482 (Hartree/Particle); Thermal correction to energy = 0.320018; Thermal correction to enthalpy = 0.320963; Thermal correction to Gibbs free energy = 0.245463; Sum of electronic and zero-point energies = -1793.507492; Sum of electronic and thermal energies = -1793.485956; Sum of electronic and thermal enthalpies = -1793.485012; Sum of electronic and thermal free energies = -1793.560511. Table C.5 Cartesian coordinates of the optimized geometry of 2d determined at the PBE0/TZVP level of theory Atom x y z C 4.87957 -2.33820 -0.55510 C 5.40340 -1.07460 -0.27234 C 4.56839 -0.01982 0.04974 C 3.18339 -0.20570 0.09586 C 2.63866 -1.47362 -0.19415 C 3.51235 -2.52485 -0.51570 N 2.34180 0.85710 0.37539 P 0.75066 0.75975 0.93800 C 0.26395 -0.80418 0.19669 C 1.21640 -1.68909 -0.18898 C -1.17160 -1.12470 0.11863 C -2.06875 -0.69107 1.10523 C -3.41442 -1.00319 1.02777 C -3.89511 -1.75842 -0.04594 C -3.01376 -2.19077 -1.04236 C -1.67175 -1.86848 -0.95930 O 0.53974 0.85819 2.41437 H 6.47569 -0.91258 -0.30076 H 4.98133 0.95935 0.27178 H 3.08676 -3.49915 -0.73586 H 2.80016 1.74837 0.51685 H 0.89018 -2.67426 -0.51917 H -1.69940 -0.12656 1.95449 H -4.09666 -0.67053 1.80128 H -3.38796 -2.76407 -1.88250 H -1.00217 -2.17782 -1.75409 367 C -5.28099 -2.08196 -0.12992 N -6.40367 -2.34505 -0.19896 C -0.07738 2.10620 0.06374 C -0.88916 2.97892 0.78798 C 0.06664 2.26802 -1.31618 C -1.55170 4.01136 0.13447 H -0.98883 2.84211 1.85939 C -0.59871 3.29914 -1.96466 H 0.70009 1.58949 -1.87873 C -1.40739 4.16985 -1.23917 H -2.18113 4.69171 0.69792 H -0.48711 3.42552 -3.03617 H -1.92673 4.97494 -1.74843 H 5.53887 -3.16167 -0.80375 Zero-point correction = 0.308146 (Hartree/Particle); Thermal correction to energy = 0.328403; Thermal correction to enthalpy = 0.329347; Thermal correction to Gibbs free energy = 0.257198; Sum of electronic and zero-point energies = -1334.037270; Sum of electronic and thermal energies = -1334.017013; Sum of electronic and thermal enthalpies = -1334.016068; Sum of electronic and thermal free energies = -1334.088218. Table C.6 Cartesian coordinates of the optimized geometry of 2e determined at the PBE0/TZVP level of theory Atom x y z C 4.35248 0.21049 0.07235 C 4.33995 -1.17064 -0.16139 C 3.16166 -1.86961 -0.36931 C 1.93366 -1.21055 -0.35366 C 1.90847 0.17770 -0.11411 C 3.12016 0.85067 0.09372 N 0.74735 -1.90753 -0.51892 P -0.74060 -1.26142 -0.99010 C -0.56897 0.40515 -0.33619 C 0.66375 0.89745 -0.06005 C -1.78056 1.23340 -0.20894 C -2.83472 1.12515 -1.12718 C -3.96518 1.91354 -1.00623 C -4.06710 2.83118 0.04353 C -3.02744 2.94420 0.97248 C -1.90413 2.14776 0.84649 O -1.09672 -1.34365 -2.43972 H 5.27024 -1.72536 -0.18728 H 3.19132 -2.94032 -0.54750 H 3.06805 1.91990 0.27852 H 0.84423 -2.90826 -0.63491 H 0.73924 1.94775 0.21772 368 H -2.75058 0.43374 -1.95842 H -4.76930 1.82839 -1.72779 H -3.11227 3.64495 1.79488 H -1.11817 2.21716 1.59035 C -5.22999 3.64586 0.17141 N -6.17152 4.30702 0.27540 C -1.92693 -2.16603 0.02901 C -3.05613 -2.71550 -0.57772 C -1.73891 -2.29931 1.40660 C -3.99141 -3.39891 0.19059 H -3.18671 -2.60599 -1.64895 C -2.67669 -2.98045 2.17009 H -0.85902 -1.87219 1.87731 C -3.80214 -3.52974 1.56168 H -4.86839 -3.82863 -0.28143 H -2.53109 -3.08441 3.23994 H -4.53410 -4.06162 2.16049 C 5.63766 1.00664 0.30357 C 5.74841 2.11833 -0.75049 H 5.77949 1.69730 -1.75979 H 4.90443 2.81180 -0.70109 H 6.66472 2.69643 -0.59303 C 6.88485 0.12698 0.20409 H 6.88632 -0.66501 0.95924 H 6.97790 -0.33603 -0.78307 H 7.77572 0.74011 0.36767 C 5.60079 1.63565 1.70446 H 5.53400 0.86334 2.47670 H 6.51095 2.21793 1.88161 H 4.74564 2.30666 1.82388 Zero-point correction = 0.420029 (Hartree/Particle); Thermal correction to energy = 0.445957; Thermal correction to enthalpy = 0.446901; Thermal correction to Gibbs free energy = 0.362564; Sum of electronic and zero-point energies = -1491.024374; Sum of electronic and thermal energies = -1490.998446; Sum of electronic and thermal enthalpies = -1490.997502; Sum of electronic and thermal free energies = -1491.081839. Table C.7 Cartesian coordinates of the optimized geometry of 2f determined at the PBE0/TZVP level of theory Atom x y z C 4.47588 -0.49543 -0.11516 C 4.55087 0.88383 0.10641 C 3.39489 1.62204 0.31345 C 2.14145 1.01628 0.30167 C 2.05466 -0.37183 0.06988 C 3.22937 -1.10406 -0.13277 369 N 0.98169 1.76709 0.45969 P -0.51584 1.18392 0.96994 C -0.42817 -0.48686 0.30598 C 0.77737 -1.03553 0.01956 C -1.67841 -1.25610 0.18321 C -2.71804 -1.10476 1.11169 C -3.88606 -1.83701 0.99485 C -4.04100 -2.73965 -0.06140 C -3.01604 -2.89482 -1.00048 C -1.85444 -2.15464 -0.87810 O -0.83990 1.26621 2.42738 H 5.50541 1.39434 0.12376 H 3.46976 2.69084 0.48664 H 3.17401 -2.17336 -0.30815 H 1.11904 2.76509 0.55595 H 0.80395 -2.08652 -0.26323 H -2.59360 -0.42479 1.94740 H -4.67904 -1.71914 1.72410 H -3.14145 -3.58368 -1.82771 H -1.07896 -2.25603 -1.62926 C -5.24310 -3.49585 -0.18623 N -6.21661 -4.10928 -0.28810 C -1.68565 2.14206 -0.01896 C -2.78685 2.71979 0.61264 C -1.51424 2.28933 -1.39736 C -3.71017 3.44529 -0.13109 H -2.90542 2.59902 1.68402 C -2.44008 3.01266 -2.13633 H -0.65624 1.84030 -1.88745 C -3.53719 3.59020 -1.50293 H -4.56501 3.89692 0.36070 H -2.30706 3.12759 -3.20671 H -4.25970 4.15509 -2.08268 O 5.54569 -1.30193 -0.32098 C 6.84268 -0.72057 -0.29182 C 7.84268 -1.82535 -0.52364 H 7.01082 -0.23888 0.68006 H 6.92205 0.04825 -1.07137 H 8.85712 -1.41944 -0.50995 H 7.76385 -2.58608 0.25638 H 7.67376 -2.30144 -1.49231 Zero-point correction = 0.368617 (Hartree/Particle); Thermal correction to energy = 0.393025; Thermal correction to enthalpy = 0.393970; Thermal correction to Gibbs free energy = 0.312175; Sum of electronic and zero-point energies = -1487.682390; Sum of electronic and thermal energies = -1487.657981; Sum of electronic and thermal enthalpies = -1487.657037; Sum of electronic and thermal free energies = -1487.738831. 370 Representative excited state geometry Table C.8 Cartesian coordinates for compound 2f (S1) Atom x y z C 4.19754 0.83011 0.04258 C 4.43859 -0.30536 -0.75296 C 3.34960 -0.99099 -1.24675 C 2.02893 -0.57501 -0.98158 C 1.76910 0.59205 -0.18219 C 2.87518 1.25433 0.31293 N 0.98402 -1.27177 -1.48236 P -0.70551 -1.07234 -1.17069 C -0.75456 0.54008 -0.40889 C 0.43970 1.06313 0.08325 C -2.03546 1.16742 -0.22284 C -3.26152 0.49519 -0.47023 C -4.47749 1.09997 -0.26071 C -4.54758 2.42475 0.21555 C -3.34562 3.11750 0.45118 C -2.13156 2.50968 0.23727 O -1.47016 -1.33310 -2.42262 H 5.44102 -0.64467 -0.97311 H 3.50091 -1.87627 -1.85654 H 2.75354 2.14216 0.92323 H 1.20261 -2.08660 -2.04452 H 0.38969 1.94048 0.71954 H -3.25594 -0.52378 -0.83955 H -5.39269 0.55342 -0.45885 H -3.38120 4.14509 0.79654 H -1.23161 3.09014 0.40068 C -5.79638 3.04886 0.44241 N -6.82004 3.56105 0.62818 C -1.02320 -2.31567 0.10097 C -1.88954 -3.36767 -0.20702 C -0.43713 -2.24196 1.36922 C -2.16463 -4.33891 0.74848 H -2.34218 -3.41212 -1.19192 C -0.71523 -3.21626 2.31544 H 0.22229 -1.41627 1.61968 C -1.57745 -4.26674 2.00635 H -2.84004 -5.15319 0.50835 H -0.26328 -3.15571 3.29972 H -1.79397 -5.02592 2.75041 O 5.14428 1.57982 0.58991 C 6.52855 1.25640 0.38195 C 7.34720 2.28195 1.12018 371 H 6.73510 1.27453 -0.69282 H 6.71378 0.24638 0.76081 H 8.40933 2.06646 0.98366 H 7.14692 3.28556 0.73949 H 7.12518 2.25966 2.18909 Geometries of 2 meso-dimer and analogous 1 meso-dimer Table C.9 Cartesian coordinates for compound 2f·2f (meso-dimer) Atom x y z P -1.95724 0.60235 -0.15810 O -1.13426 0.91794 1.07453 O -4.86819 -5.45211 -0.32378 N -1.72792 -0.90711 -0.85743 N -6.92721 6.54145 1.19270 C -3.73766 0.57706 0.11224 C -4.39950 -0.59867 0.11116 H -5.45545 -0.58653 0.37173 C -3.84837 -1.89655 -0.20763 C -2.54204 -2.01925 -0.69556 C -2.07237 -3.28570 -1.07125 H -1.07359 -3.37896 -1.48229 C -2.86947 -4.39809 -0.93597 H -2.50799 -5.37646 -1.22553 C -4.17029 -4.28817 -0.42388 C -4.65455 -3.04354 -0.07520 H -5.65812 -2.91755 0.30781 C -4.41821 1.86371 0.36187 C -5.70140 2.08442 -0.14977 H -6.17936 1.31735 -0.74569 C -6.35626 3.28249 0.06722 H -7.34684 3.44695 -0.33573 C -5.72281 4.29106 0.79408 C -4.43772 4.09287 1.29858 H -3.95194 4.87940 1.86064 C -3.79259 2.88822 1.08154 H -2.80197 2.72981 1.49055 C -6.39194 5.54025 1.01540 C -1.60300 1.78258 -1.48582 C -0.61820 2.74784 -1.31084 H -0.06610 2.78759 -0.38140 C -0.34559 3.65095 -2.33102 H 0.42602 4.39841 -2.19596 C -1.06490 3.59304 -3.51740 H -0.85633 4.29959 -4.31093 C -2.05424 2.62939 -3.69172 372 H -2.61274 2.58634 -4.61790 C -2.32146 1.72118 -2.67885 H -3.08473 0.96234 -2.81326 C -6.18694 -5.38880 0.20600 H -6.80431 -4.74129 -0.42516 H -6.15489 -4.95833 1.21243 C -6.73651 -6.79556 0.23574 H -7.74918 -6.78877 0.63901 H -6.76584 -7.21498 -0.76966 H -6.11603 -7.43412 0.86410 H -0.75384 -1.07946 -1.13391 P 1.95156 -0.64866 0.19274 O 1.08688 -0.96110 -1.01172 O 4.69506 5.48289 0.53051 N 1.68726 0.83535 0.93440 N 7.06869 -6.35013 -1.57736 C 3.71838 -0.55160 -0.13926 C 4.34473 0.64290 -0.10761 H 5.39135 0.67402 -0.40224 C 3.76786 1.90828 0.28504 C 2.47046 1.97330 0.80554 C 1.97625 3.20980 1.24574 H 0.98434 3.25755 1.68084 C 2.74001 4.34850 1.13996 H 2.35923 5.30349 1.47902 C 4.03159 4.29657 0.59628 C 4.54060 3.08158 0.18481 H 5.53862 2.99783 -0.22352 C 4.43069 -1.80350 -0.46702 C 5.73087 -2.00838 0.00685 H 6.19822 -1.25657 0.63004 C 6.41634 -3.17373 -0.28147 H 7.41988 -3.32672 0.09277 C 5.79805 -4.16492 -1.04428 C 4.49709 -3.98263 -1.51265 H 4.02348 -4.75542 -2.10340 C 3.82065 -2.81055 -1.22348 H 2.81680 -2.66345 -1.60302 C 6.50213 -5.37893 -1.34047 C 1.69613 -1.88524 1.49285 C 0.64469 -2.78840 1.38896 H -0.01285 -2.74941 0.53080 C 0.44143 -3.73291 2.38765 H -0.38232 -4.43095 2.30814 C 1.29730 -3.78013 3.48005 H 1.14343 -4.52010 4.25539 373 C 2.35300 -2.87906 3.58311 H 3.01798 -2.91732 4.43630 C 2.55094 -1.92835 2.59314 H 3.36803 -1.21946 2.67405 C 6.00897 5.47632 -0.01461 H 6.65036 4.82286 0.58592 H 5.97823 5.08342 -1.03618 C 6.51872 6.89823 0.00350 H 7.52896 6.93518 -0.40423 H 6.54128 7.28223 1.02310 H 5.87721 7.54089 -0.59909 H 0.70937 0.98002 1.21499 Table C.10 Cartesian coordinates for compound 2f‘·2f‘ (meso-dimer for -OPh analogue) Atom x y z P 1.92141 0.79131 -0.26147 O 0.78543 1.51236 -0.92423 O 6.53956 -3.99151 -1.19988 N 2.02262 -0.82536 -0.62475 N 4.97709 8.03803 0.16496 C 3.59102 1.36451 -0.52551 C 4.57382 0.46252 -0.73510 H 5.58336 0.84492 -0.86408 C 4.43734 -0.97249 -0.81836 C 3.18131 -1.58317 -0.74275 C 3.09026 -2.97766 -0.82535 H 2.11643 -3.44875 -0.76712 C 4.22370 -3.74153 -0.97276 H 4.15972 -4.82045 -1.03252 C 5.48901 -3.14105 -1.05234 C 5.58959 -1.76691 -0.97746 H 6.54735 -1.26819 -1.03595 C 3.87197 2.80945 -0.37778 C 5.03179 3.22763 0.28458 H 5.69956 2.49146 0.71451 C 5.32555 4.57143 0.42127 H 6.22247 4.88754 0.93716 C 4.44618 5.52323 -0.09631 C 3.27888 5.12301 -0.74537 H 2.60112 5.86640 -1.14344 C 2.99450 3.77540 -0.88166 H 2.09196 3.46511 -1.39128 C 4.74073 6.91971 0.04861 C 7.83932 -3.42380 -1.31227 H 8.06387 -2.84264 -0.41180 H 7.86840 -2.74857 -2.17381 374 C 8.82206 -4.55834 -1.48203 H 9.83191 -4.16050 -1.58264 H 8.79387 -5.22113 -0.61745 H 8.58521 -5.13637 -2.37497 H 1.13240 -1.32490 -0.52414 P -1.83870 -0.83501 -0.24159 O -0.58006 -1.54000 0.16537 O -6.03526 4.24836 0.94534 N -1.79480 0.81008 -0.03092 N -4.96926 -7.90305 1.34215 C -3.39028 -1.28890 0.51650 C -4.28646 -0.31809 0.79650 H -5.24232 -0.62508 1.21435 C -4.11342 1.10510 0.61877 C -2.88448 1.63685 0.21450 C -2.74464 3.02402 0.08792 H -1.78912 3.43301 -0.21776 C -3.81060 3.85580 0.33656 H -3.71118 4.92879 0.23273 C -5.05144 3.33451 0.73214 C -5.19474 1.96973 0.87834 H -6.13228 1.53222 1.19349 C -3.71128 -2.72292 0.68277 C -4.99895 -3.18586 0.38912 H -5.74136 -2.49828 0.00330 C -5.33121 -4.51660 0.56144 H -6.32798 -4.86844 0.33091 C -4.36480 -5.41187 1.02114 C -3.07251 -4.96965 1.30158 H -2.32861 -5.67016 1.65720 C -2.74907 -3.63508 1.12870 H -1.74774 -3.29074 1.35074 C -4.70057 -6.79521 1.19888 C -7.30470 3.76745 1.37118 H -7.69766 3.06517 0.62875 H -7.19240 3.23607 2.32210 C -8.21923 4.96014 1.52189 H -9.20286 4.63183 1.85789 H -8.33183 5.47687 0.56903 H -7.81697 5.65942 2.25452 H -0.90390 1.25228 -0.29356 O 1.65012 0.93158 1.34869 O -2.03326 -1.14197 -1.84182 C 2.42198 0.19621 2.24001 C 3.51657 0.80032 2.83895 C 2.06499 -1.11320 2.52760 375 C 4.27398 0.07137 3.74738 H 3.75515 1.82865 2.59475 C 2.83279 -1.83172 3.43459 H 1.19713 -1.54270 2.04046 C 3.93610 -1.24381 4.04341 H 5.12751 0.53465 4.22565 H 2.56580 -2.85461 3.66811 H 4.52892 -1.80929 4.75059 C -3.06789 -0.51671 -2.52823 C -4.25761 -1.20300 -2.71875 C -2.88728 0.76802 -3.01906 C -5.29228 -0.58260 -3.40703 H -4.35624 -2.20940 -2.33039 C -3.93080 1.38009 -3.70142 H -1.94065 1.27030 -2.86233 C -5.13323 0.70995 -3.89317 H -6.22390 -1.11125 -3.56359 H -3.80062 2.38351 -4.08590 H -5.94271 1.19250 -4.42543 376 4. Photophysical Properties in Different Solvents Figure C.6 Fluorescence decay curve of 2d vs Ludox Prompt sample. Solvent effects on fluorescence Figure C.7 Emission spectra of 2a in various solvents. 377 Table C.11 Photophysical properties of 2a in various solvents Cyclohexane Toluene Chloroform DCM THF Acetonitrile λabs 353 351 348 349 358 350 λem 445 446 452 448 456 456 Stokes 92 95 104 99 98 106 Shift (nm) Figure C.8 Emission spectra of 2b in various solvents. Table C.12 Photophysical properties of 2b in various solvents Cyclohexane Toluene Chloroform DCM THF Acetonitrile λabs 346 346 343 344 358 345 λem 442 442 447 445 453 458 Stokes 96 96 104 101 95 113 Shift (nm) 378 Figure C.9 Emission spectra of 2c in various solvents. Table C.13 Photophysical properties of 2c in various solvents Cyclohexane Toluene Chloroform DCM THF Acetonitrile λabs 366 365 360 365 367 363 λem 467 466 474 472 480 486 Stokes 101 101 114 107 113 123 Shift (nm) 379 Figure C.10 Emission spectra of 2d in various solvents. Table C.14 Photophysical properties of 2d in various solvents Cyclohexan Toluen Chlorofor AcetonitrilDCM THF e e m e λabs 355 353 352 365 361 357 λem 458 461 467 465 473 475 Stokes Shift 103 108 115 100 112 118 (nm) 380 Figure C.11 Emission spectra of 2e in various solvents. Table C.15 Photophysical properties of 2e in various solvents Cyclohexane Toluene Chloroform DCM THF Acetonitrile λabs 365 361 360 362 368 365 λem 467 469 473 478 488 493 Stokes 102 108 113 116 120 128 Shift (nm) 381 Figure C.12 Emission spectra of 2f in various solvents. Table C.16 Photophysical properties of 2f in various solvents Cyclohexane Toluene Chloroform DCM THF Acetonitrile λabs 386 384 381 386 387 386 λem 504 508 515 518 524 531 Stokes 118 124 134 132 137 145 Shift (nm) Figure C.13 Fluorescent image of 2f in Acetonitrile, THF, DCM, Chloroform, Toluene, Cyclohexane (left to right). 382 5. Experimental and Computational Examination of the Dimer Solution-state studies of dimer strength General procedure for variable concentration (VC) NMR experiments. CDCl3 was added in a 1:1 ratio to H2O, shaken vigorously, then allowed to separate. The organic phase was then separated and used to prepare ca. 10 mM solutions of heterocycle 2. These solutions were then diluted through addition of known amounts of the H2O-saturated CDCl3 solvent, with 31P NMR spectra being collected after each addition. The 31P NMR spectra were chosen over those of 1H NMR for these experiments since they give comparable results to 1H NMR signals and the 1H NMR signals become impossible to track at lower concentrations due to complex splitting of multiple signals by the phosphorus center. The chemical shift of the phosphorus signal was tracked and fitted to generate the dimerization values.10 383 Figure C.14 Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2b. Table C.17 Experimental and fitting data for VC NMR experiment of 2b Concentration Experimental Fit δ (ppm) (mM) δ (ppm) 8.60 11.3755 11.37636588 8.32 11.3583 11.35553759 8.06 11.3315 11.33535491 7.48 11.2871 11.28750165 6.97 11.2465 11.24300097 6.14 11.1654 11.16255996 5.49 11.09 11.09160143 4.96 11.0247 11.02836421 4.16 10.918 10.92008376 3.58 10.8299 10.83033275 2.96 10.7164 10.72063772 2.53 10.6342 10.6324564 2.11 10.5421 10.53825939 1.76 10.4816 10.44649514 1.46 10.3465 10.36343269 1.25 10.2875 10.29857999 1.10 10.2345 10.24644727 0.877 10.1592 10.16767483 0.731 10.1191 10.11087501 0.585 10.0577 10.05013847 384 Figure C.15 Representative 31P NMR spectra for VC NMR of 2b. Figure C.16 Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2c. 385 Table C.18 Experimental and fitting data for VC NMR experiment of 2c Concentration Experimental Fit δ (ppm) (mM) δ (ppm) 14.0 11.2039 11.2064793 13.6 11.1831 11.1885475 13.2 11.1672 11.1711442 12.2 11.1341 11.1297717 11.4 11.0951 11.0911563 10.0 11.0212 11.0209934 8.96 10.9617 10.9586984 8.09 10.9091 10.9028468 6.79 10.8023 10.8064342 5.84 10.7176 10.7257245 4.84 10.6209 10.6260187 4.12 10.5419 10.5449533 3.45 10.4777 10.4573812 2.86 10.4277 10.3710209 2.39 10.2748 10.2918817 2.04 10.1932 10.2294034 1.79 10.1464 10.1787126 1.43 10.0982 10.1012771 1.19 10.0425 10.0447712 0.954 10.0123 9.98368372 Figure C.17 Representative 31P NMR spectra for VC NMR of 2c. 386 Figure C.18 Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2d. Table C.19 Experimental and fitting data for VC NMR of 2d Concentration Experimental Fit δ (mM) δ (ppm) (ppm) 12.6 10.7014 10.694546 12.2 10.6799 10.679281 11.8 10.6658 10.664594 10.9 10.6234 10.630185 10.2 10.5926 10.598709 9.00 10.5362 10.543093 8.03 10.5069 10.495405 7.25 10.4546 10.453992 6.09 10.3830 10.385454 5.24 10.3280 10.330913 4.34 10.2696 10.267033 3.70 10.2173 10.217883 3.09 10.1697 10.167531 2.57 10.1452 10.120592 2.14 10.0711 10.079881 1.83 10.0379 10.049254 1.60 10.0143 10.025362 1.28 9.9839 9.9904767 1.07 9.9667 9.9662182 0.856 9.9540 9.9410965 387 Figure C.19 Representative 31P NMR spectra for VC NMR of 2d. Figure C.20 Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2e. 388 Table C.20 Experimental and fitting data for VC NMR of 2e Concentration Experimental Fit δ (ppm) (mM) δ (ppm) 11.6 10.7552 10.75070613 11.2 10.7379 10.73691784 10.9 10.7255 10.72367435 10.1 10.6966 10.69273486 9.39 10.6656 10.66454316 8.27 10.609 10.61499453 7.39 10.5668 10.57278564 6.68 10.5217 10.53634355 5.60 10.4786 10.47648406 4.83 10.4291 10.42926445 3.99 10.3749 10.37444554 3.41 10.3314 10.33263873 2.85 10.3066 10.29015441 2.36 10.2735 10.25087549 1.97 10.2087 10.21706939 1.69 10.1835 10.19180097 1.48 10.1671 10.17218912 1.18 10.1399 10.14371351 0.985 10.1185 10.12402601 0.788 10.109 10.1037383 Figure C.21 Representative 31P NMR spectra for VC NMR of 2e. 389 Figure C.22 Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2f. Table C.21 Experimental and fitting data for VC NMR of 2f Concentration Experimental Fit δ (ppm) (mM) δ (ppm) 11.8 10.7356 10.7285531 11.4 10.7052 10.712116 11.0 10.689 10.6963319 10.3 10.6654 10.6594712 9.59 10.6183 10.6259015 8.45 10.5703 10.5669423 7.55 10.5243 10.51676 6.83 10.4787 10.4734671 5.72 10.4056 10.4024241 4.93 10.3464 10.3464462 4.08 10.2772 10.2815335 3.48 10.2254 10.2320847 2.91 10.1666 10.1818864 2.41 10.1348 10.1355237 2.01 10.1038 10.0956594 1.72 10.0768 10.0658868 1.51 10.0456 10.0427937 1.21 10.01 10.0092865 1.01 9.9864 9.98613666 0.805 9.9561 9.96229545 390 Figure C.23 Representative 31P NMR spectra for VC NMR experiment of 2f. Computational studies on dimer interactions The geometries for dimeric complexes of 2f and its -OPh counterpart were fully optimized without symmetry constraint by using the functional M06-2X11 (accounting for the contributions of H-bond/dispersion forces) and TZVP basis set as implemented in Gaussian 09. The PCM solvation model was used to account for the effects of the chloroform environment. All of the optimized structures were confirmed by frequency calculations to be minima using the same level of theory. The solution-phase optimized geometries were used in the following calculations. The natural bond order (NBO) analyses were carried out using NBO 3.1 embedded in Gaussian 09 package. The NCI plot were performed by using the Multiwfn program.12 391 Figure C.24 The NCI plots for a) 2f and b) its -OPh analogue meso-dimeric motifs at the PCM(CHCl3)-M06-2X/TZVP equilibrium geometries. NCI regions are represented as solid surfaces and blue−green−red scaling from −0.02 < sign(2)(r) < 0 (in a.u.), where red surface indicates strong repulsion, blue surface strong attraction and green surface relatively weak interactions. Isosurface cutoff for NCI = 0.5. 392 Figure C.25 The NBO charge transfer stabilization energy [second-order perturbation energies E(2), in kcal/mol] for the indicated H-bond interactions in a) 2f and b) its -OPh analogue at PCM(CHCl3)-M06-2X/TZVP equilibrium geometries of the meso-dimeric motifs. The indicated H-bond interactions shown by the broken line, and H-bond distances in Å. 393 7. Copies of NMR Spectra Figure C.26 1H NMR spectrum of 2a in DMSO-d6. Figure C.27 13C NMR spectrum of 2a in DMSO-d6. 394 Figure C.28 31P NMR spectrum of 2a in DMSO-d6. Figure C.29 1H NMR spectrum of 2b in DMSO-d6. 395 Figure C.30 13C NMR spectrum of 2b in DMSO-d6. Figure C.31 31P NMR spectrum of 2b in DMSO-d6. 396 Figure C.32 19F NMR spectrum of 2b in DMSO-d6. Figure C.33 1H NMR spectrum of 2c in DMSO-d6. 397 Figure C.34 13C NMR spectrum of 2c in DMSO-d6. Figure C.35 31P NMR spectrum of 2c in DMSO-d6. 398 Figure C.36 1H NMR spectrum of 2d in CDCl3. Figure C.37 13C NMR spectrum of 2d in CDCl3. 399 Figure C.38 31P NMR spectrum of 2d in CDCl3. Figure C.39 1H NMR spectrum of 2e in CDCl3. 400 Figure C.40 13C NMR spectrum of 2e in CDCl3. Figure C.41 31P NMR spectrum of 2e in CDCl3. 401 Figure C.42 1H NMR spectrum of 2f in CDCl3. Figure C.43 13C NMR spectrum of 2f in CDCl3. 402 Figure C.44 31P NMR spectrum of 2f in CDCl3. 403 APPENDIX D SUPPLEMENTARY INFORMATION FOR CHAPTER 5 Additional Crystallographic Figures Figure D.1 ORTEP drawing of PN-fused pyrene 2; thermal ellipsoids drawn at 30% probability. Crystals grown from slow layering of pentane into a concentrated solution of 2 in chloroform. Figure D.2 ORTEP drawing of the crystal packing of 2. Crystals grown from slow layering of pentane into a concentrated solution of 2 in chloroform. 404 Photophysical Studies in Different Solvents and the Solid state Figure D.3 Fluorescence images of 2 in a) chloroform (ca. 1 μM), b) the solid state, and c) (left to right) toluene, chloroform, and methanol at ca. 4 mM in concentration. All samples were excited at 365 nm. Figure D.4 Fluorescence spectra of 4 mM solutions of 2 in a variety of solvents. Samples excited at 365 nm. 405 Copies of NMR Spectra for New Compounds Figure D.5 1H NMR spectrum of 4 in CDCl3. Figure D.6 13C NMR spectrum of 4 in CDCl3. 406 Figure D.7 1H NMR spectrum of 5 in CDCl3. Figure D.8 13C NMR spectrum of 5 in CDCl3. 407 Figure D.9 1H NMR spectrum of 2 in CDCl3. Figure D.10 13C NMR spectrum of 2 in CDCl3. 408 Figure D.11 31P NMR spectrum of 2 in CDCl3. 409 APPENDIX E SUPPLEMENTARY INFORMATION FOR CHAPTER 6 1. X-ray Crystallographic Details General. Diffraction intensities for 2d and 2e were collected at 173 K on a Bruker Apex2 CCD diffractometer using MoK radiation, = 0.71073 Å. Space groups were determined based on intensity statistics (2d) and systematic absences (2e). Absorption corrections were applied by SADABS.[1] Structures were solved by direct methods and Fourier techniques and refined on F2 using full matrix least-squares procedures. All non-H atoms were refined with anisotropic thermal parameters. H atoms in both structures were refined in calculated positions in a rigid group model except the H atoms at the N atoms involved in forming H-bonds. These H atoms were found from the diffraction data and refined with isotropic thermal parameters. The standard N–H bond distance was used in the refinement as the target for corresponding bond length. In both structures the main molecules form dimer units via N–H···S H-bonds. Crystal structure of 2d includes also solvent molecule CH2Cl2. Terminal Me-groups in 2e are disordered over two positions in ratio 1:1. All calculations were performed by the Bruker SHELXL-2014 package.[2] Crystallographic Data for 2d: C22H17Cl2N2PS, M = 443.30, 0.24 x 0.18 x 0.12 mm, T = 173(2) K, Triclinic, space group P-1, a = 8.8716(14) Å, b = 10.6480(16) Å, c = 11.6935(18) Å, α = 83.063(2),  = 80.956(2), γ = 86.672(2), V = 1082.0(3) Å3, Z = 2, Dc = 1.361 Mg m –3, μ(Mo) = 0.481 mm–1, F(000) = 456, 2θmax = 60.18°, 17797 reflections, 6236 independent reflections [Rint = 0.0291], R1 = 0.0454, wR2 = 0.1283 and GOF = 1.058 for 6236 reflections (257 parameters) with I>2(I), R1 = 0.0537, wR2 = 0.1354 and GOF = 1.060 for all reflections, max/min residual electron density +1.155/–0.652 eÅ–3. CCDC 2034968. Crystallographic Data for 2e: C25H23N2PS, M = 414.48, 0.23 x 0.23 x 0.11 mm, T = 173(2) K, Monoclinic, space group C2/c, a = 19.716(4) Å, b = 12.307(2) Å, c = 18.192(3) Å,  = 99.272(3), V = 4356.5(14) Å3, Z = 8, Dc = 1.264 Mg m–3, μ(Mo) = 0.236 mm–1, F(000) = 1744, 2θmax = 60.042°, 24992 reflections, 6375 independent reflections [Rint = 0.0366], R1 = 0.0378, wR2 = 0.1027 and GOF = 1.020 for 6375 reflections (293 410 parameters) with I>2(I), R1 = 0.0450, wR2 = 0.1078 and GOF = 1.026 for all reflections, max/min residual electron density +0.458/–0.256 eÅ–3. CCDC 2034967. Figure E.1 ORTEP drawing of thio-heterocycle 2d; thermal ellipsoids drawn at 30% probability. Figure E.2 ORTEP drawing of the racemic dimer of thio-heterocycle 2d; thermal ellipsoids drawn at 30% probability. 411 Figure E.3 ORTEP drawing of thio-heterocycle 2e; thermal ellipsoids drawn at 30% probability. Figure E.4 ORTEP drawing of the racemic dimer of thio-heterocycle 2e; thermal ellipsoids drawn at 30% probability. 412 2. Comparison of the Photophysical Properties of 2c and 2e in CHCl3 vs. MeCN Table E.1 Photophysical properties of heterocycles 2c and 2e in CHCl3 and MeCN a Stokes Stokes shift cmpd solvent λabs (nm) λem (nm) shift (cm–1) (nm) MeCN 371 497 26 6834 2c CHCl3 373 492 19 6484 MeCN 360 484 24 7116 2e CHCl3 350 470 20 7304 aAll values collected using ca. 10–5 M solutions. Figure E.5 Stacked absorption and emission spectra of 2c and 2e in MeCN. 413 3. TD-DFT studies and coordinates for selected heterocycles 2 Ground state calculations: The initial structures were optimized at the ground state using the functional PBE03,4 (25% full-range HF exchange) and TZVP basis set5 as implemented in Gaussian 09.6 In addition, all the ground state optimized structures were confirmed by frequency analysis and the number of imaginary frequencies was zero. TD-DFT vertical excitation calculations and geometry optimization of the first excited state (S1) were performed at the same level of theory and the PCM solvation model7,8 was used to account for the solvent effects of chloroform. Figure E.6 Frontier orbital plots (isovalue = 0.2) of heterocycles 2c and 2e in the optimized S0 and S1 structures calculated by DFT and TD-DFT methods at the PCM(CHCl3)- PBE0/TZVP level of theory, respectively. Table E.2 Calculated frontier orbitals and first excitation values for compounds 2c and 2ea S0 to S1 computed (nm), osc. Compound EHOMO ELUMO ΔEDFT strength 2c -6.385 -2.995 3.390 366, 0.3008 2e -6.266 -2.996 3.270 379, 0.2913 aCalculated at the PCM(CHCl3)-PBE0/TZVP level of theory, energy values reported in eV. Ground state geometries: Cartesian coordinates for compound 2c: Zero-point correction = 0.421712 (Hartree/Particle) Thermal correction to Energy = 0.449176 Thermal correction to Enthalpy = 0.450120 414 Thermal correction to Gibbs Free Energy = 0.361543 Sum of electronic and zero-point Energies = -1889.158422 Sum of electronic and thermal Energies = -1889.130957 Sum of electronic and thermal Enthalpies = -1889.130013 Sum of electronic and thermal Free Energies = -1889.218591 C 5.9109860000 -1.0127790000 1.1533730000 C 5.0355570000 -1.8264830000 0.1914770000 C 5.8782310000 -2.2674180000 -1.0123200000 C 4.5534540000 -3.0772420000 0.9234020000 C 3.8750230000 -0.9607620000 -0.2912030000 C 4.1298800000 0.2285300000 -0.9900630000 C 3.1157770000 1.0456670000 -1.4423340000 C 1.7816580000 0.7081810000 -1.2116480000 N 0.7623840000 1.5129150000 -1.6795590000 P -0.9026400000 1.3908620000 -1.4009190000 C -1.0061200000 -0.2540390000 -0.6674560000 C -2.3262920000 -0.8359160000 -0.3580790000 C -3.3835040000 -0.8088680000 -1.2726080000 C -4.5954720000 -1.4010130000 -0.9689250000 C -4.7803940000 -2.0320500000 0.2615900000 C -6.0290760000 -2.6445490000 0.5766760000 N -7.0368070000 -3.1420540000 0.8343530000 C -3.7362490000 -2.0562460000 1.1881880000 C -2.5300550000 -1.4590360000 0.8792290000 C 0.1312770000 -0.9026690000 -0.3258710000 O -1.2645780000 2.4235910000 -0.1630650000 C -0.7323110000 2.3172380000 1.1083410000 C 0.5478280000 2.7796580000 1.3788630000 C 1.0316030000 2.7193560000 2.6783080000 C 0.2401010000 2.2157260000 3.7010410000 C -1.0455880000 1.7721210000 3.4204710000 C -1.5373290000 1.8222950000 2.1245000000 S -1.9364900000 1.9272820000 -2.9483300000 C 1.4890200000 -0.4795060000 -0.5275740000 C 2.5481010000 -1.2863390000 -0.0827700000 H 6.7510340000 -1.6187540000 1.5047120000 H 5.3363510000 -0.6881710000 2.0245830000 H 6.3226080000 -0.1225060000 0.6724890000 H 6.7174460000 -2.8853170000 -0.6803300000 H 6.2898970000 -1.4132420000 -1.5546170000 H 5.2798940000 -2.8533350000 -1.7145290000 H 5.4155870000 -3.6633620000 1.2506640000 H 3.9468950000 -3.7180320000 0.2778810000 H 3.9686850000 -2.8280810000 1.8129310000 H 5.1535950000 0.5278980000 -1.1865150000 415 H 3.3519020000 1.9591990000 -1.9789680000 H 1.0148430000 2.2389420000 -2.3353090000 H -3.2475000000 -0.3279230000 -2.2329560000 H -5.4050740000 -1.3814320000 -1.6884960000 H -3.8824770000 -2.5329880000 2.1500590000 H -1.7361450000 -1.4493370000 1.6170950000 H 0.0155770000 -1.8839840000 0.1309170000 H 1.1504390000 3.1905500000 0.5785580000 H 2.0315340000 3.0802630000 2.8916370000 H 0.6203960000 2.1775430000 4.7153260000 H -1.6762230000 1.3921060000 4.2166050000 H -2.5419540000 1.4919570000 1.8890350000 H 2.2871050000 -2.1993170000 0.4395920000 Cartesian coordinates for compound 2e: Zero-point correction = 0.417734 (Hartree/Particle) Thermal correction to Energy = 0.444242 Thermal correction to Enthalpy = 0.445186 Thermal correction to Gibbs Free Energy = 0.359416 Sum of electronic and zero-point Energies = -1813.978974 Sum of electronic and thermal Energies = -1813.952466 Sum of electronic and thermal Enthalpies = -1813.951522 Sum of electronic and thermal Free Energies = -1814.037292 C -5.5134060000 -2.5541420000 -0.3364810000 C -5.7067050000 -1.0403170000 -0.2763330000 C -6.4388910000 -0.5979280000 -1.5498110000 C -6.5737670000 -0.7140440000 0.9466330000 C -4.3789170000 -0.2953860000 -0.1682330000 C -4.3630320000 1.1053570000 -0.1094380000 C -3.1889360000 1.8214890000 -0.0055380000 C -1.9601230000 1.1636360000 0.0437700000 N -0.7727910000 1.8749150000 0.0828850000 P 0.6771600000 1.2807940000 0.7773640000 C 0.5353370000 -0.4516120000 0.2524370000 C 1.7461860000 -1.2836930000 0.1754320000 C 2.7880400000 -1.1676940000 1.1022840000 C 3.9099890000 -1.9690870000 1.0104470000 C 4.0192120000 -2.9096580000 -0.0150450000 C 5.1762550000 -3.7369800000 -0.1124530000 N 6.1114950000 -4.4067090000 -0.1932350000 C 2.9901670000 -3.0313820000 -0.9504710000 C 1.8753710000 -2.2217880000 -0.8555390000 C -0.6930050000 -0.9575440000 0.0037130000 C 1.9441970000 2.0719940000 -0.2697400000 C 3.0220780000 2.7235510000 0.3176920000 416 C 3.9902660000 3.3150210000 -0.4819300000 C 3.8826180000 3.2541400000 -1.8639200000 C 2.8048500000 2.6030560000 -2.4522650000 C 1.8349930000 2.0117300000 -1.6584450000 S 0.9329160000 1.5958390000 2.6935360000 C -1.9389530000 -0.2382240000 -0.0130420000 C -3.1527770000 -0.9332340000 -0.1209270000 H -6.4873560000 -3.0434320000 -0.4146000000 H -5.0240540000 -2.9378290000 0.5626400000 H -4.9238130000 -2.8545050000 -1.2068760000 H -7.3959390000 -1.1204100000 -1.6368640000 H -5.8453570000 -0.8225280000 -2.4397250000 H -6.6457810000 0.4746140000 -1.5471510000 H -7.5317180000 -1.2381960000 0.8821530000 H -6.7845460000 0.3552260000 1.0203620000 H -6.0773920000 -1.0217260000 1.8703510000 H -5.2969050000 1.6559260000 -0.1408660000 H -3.2171070000 2.9057080000 0.0404230000 H -0.8792140000 2.8773600000 0.1634100000 H 2.7009890000 -0.4586020000 1.9178120000 H 4.7060270000 -1.8767210000 1.7395250000 H 3.0790830000 -3.7505850000 -1.7558930000 H 1.0983310000 -2.2967700000 -1.6076070000 H -0.7640590000 -2.0266980000 -0.1886550000 H 3.0856060000 2.7640590000 1.4001820000 H 4.8301430000 3.8244290000 -0.0231240000 H 4.6408550000 3.7153430000 -2.4871630000 H 2.7207010000 2.5567080000 -3.5322540000 H 0.9900340000 1.5072400000 -2.1143230000 H -3.0997850000 -2.0149650000 -0.1631400000 Excited state geometries: Cartesian coordinates for compound 2c: C -6.0817380000 -0.6876210000 -1.3217830000 C -5.1841790000 -1.7042300000 -0.5995640000 C -5.9842810000 -2.3765590000 0.5264430000 C -4.7676490000 -2.7777690000 -1.6023920000 C -3.9939660000 -0.9738650000 0.0026500000 C -4.2163960000 0.0404470000 0.9624980000 C -3.1623760000 0.7246390000 1.5238190000 C -1.8476450000 0.4407970000 1.1410920000 N -0.8143850000 1.1775720000 1.6479910000 P 0.8565340000 0.8901360000 1.4861420000 C 0.9519070000 -0.4693090000 0.3531570000 C 2.2395580000 -1.0185130000 0.0618810000 C 3.4524530000 -0.3454340000 0.3753850000 417 C 4.6791450000 -0.8912070000 0.0895890000 C 4.7744910000 -2.1428310000 -0.5450510000 C 6.0350380000 -2.7020610000 -0.8532660000 N 7.0678480000 -3.1614550000 -1.1049920000 C 3.5879890000 -2.8264390000 -0.8714610000 C 2.3639850000 -2.2827880000 -0.5802090000 C -0.2558430000 -0.9713650000 -0.1610030000 O 1.4310340000 2.2723410000 0.8177200000 C 1.0092160000 2.7149340000 -0.4369120000 C 0.0040700000 3.6666870000 -0.5014020000 C -0.3790000000 4.1591260000 -1.7414810000 C 0.2402670000 3.7022200000 -2.8976240000 C 1.2494360000 2.7520500000 -2.8130240000 C 1.6435280000 2.2527040000 -1.5788190000 S 1.6567120000 0.7221410000 3.2698870000 C -1.5725120000 -0.6010580000 0.2002740000 C -2.6833290000 -1.2646170000 -0.3491330000 H -6.9462250000 -1.2003300000 -1.7527470000 H -5.5388830000 -0.1936700000 -2.1314950000 H -6.4536410000 0.0825540000 -0.6431070000 H -6.8462720000 -2.8999350000 0.1036170000 H -6.3574170000 -1.6515220000 1.2525220000 H -5.3698920000 -3.1059700000 1.0600470000 H -5.6608620000 -3.2655470000 -1.9994860000 H -4.1486190000 -3.5499100000 -1.1384630000 H -4.2194490000 -2.3546800000 -2.4480110000 H -5.2247590000 0.2909860000 1.2674530000 H -3.3427670000 1.5071100000 2.2539420000 H -1.0504800000 1.8715370000 2.3484210000 H 3.4318520000 0.6350500000 0.8359850000 H 5.5819520000 -0.3479400000 0.3424570000 H 3.6464840000 -3.7978100000 -1.3489130000 H 1.4780250000 -2.8569780000 -0.8183230000 H -0.1855550000 -1.7558450000 -0.9055440000 H -0.4596600000 4.0215190000 0.4112480000 H -1.1611610000 4.9073520000 -1.8007000000 H -0.0604840000 4.0900740000 -3.8640070000 H 1.7411830000 2.3977600000 -3.7117600000 H 2.4356880000 1.5179920000 -1.4992750000 H -2.4799650000 -2.0472510000 -1.0689210000 Cartesian coordinates for compound 2e: C -5.2454010000 -2.5083080000 -1.2165510000 C -5.5172560000 -1.2050930000 -0.4686420000 C -6.3164670000 -0.2728020000 -1.3922770000 C -6.3575390000 -1.5261800000 0.7770540000 418 C -4.2408030000 -0.5011010000 -0.0376460000 C -4.3272730000 0.7241320000 0.6625370000 C -3.1919690000 1.3923610000 1.0550970000 C -1.9217980000 0.8739350000 0.7653650000 N -0.8084620000 1.5748220000 1.1024290000 P 0.8466420000 1.1241470000 0.9314330000 C 0.7323760000 -0.5223570000 0.2341720000 C 1.9362480000 -1.2799130000 0.0910280000 C 3.2283240000 -0.6954830000 0.1699200000 C 4.3716320000 -1.4425130000 0.0338080000 C 4.2961200000 -2.8266270000 -0.2073050000 C 5.4701920000 -3.5968550000 -0.3648760000 N 6.4323650000 -4.2288720000 -0.4921100000 C 3.0269420000 -3.4290720000 -0.2941030000 C 1.8868680000 -2.6811520000 -0.1515210000 C -0.5269840000 -0.9798410000 -0.1660090000 C 1.4745330000 2.2877820000 -0.3153180000 C 2.3029150000 3.3387390000 0.0697510000 C 2.7833580000 4.2216160000 -0.8875860000 C 2.4348640000 4.0599080000 -2.2214390000 C 1.6097020000 3.0069500000 -2.6054300000 C 1.1308250000 2.1177040000 -1.6585070000 S 1.6803210000 1.3182690000 2.7125620000 C -1.7893170000 -0.3845480000 0.0941930000 C -2.9764120000 -1.0163050000 -0.3019070000 H -6.1960000000 -2.9642360000 -1.5026280000 H -4.7076540000 -3.2295580000 -0.5959740000 H -4.6712120000 -2.3407450000 -2.1313620000 H -7.2406580000 -0.7674230000 -1.7035190000 H -5.7428770000 -0.0256730000 -2.2890830000 H -6.5881590000 0.6603930000 -0.8948850000 H -7.2814370000 -2.0284710000 0.4773370000 H -6.6311290000 -0.6248960000 1.3291730000 H -5.8133400000 -2.1880330000 1.4552500000 H -5.2941490000 1.1526000000 0.8948110000 H -3.2655560000 2.3384680000 1.5809250000 H -0.9461540000 2.4579950000 1.5809120000 H 3.3358220000 0.3725710000 0.3171240000 H 5.3406600000 -0.9617140000 0.0972110000 H 2.9540470000 -4.4971370000 -0.4642090000 H 0.9304800000 -3.1872320000 -0.1872400000 H -0.5639620000 -1.9149580000 -0.7140930000 H 2.5735100000 3.4529730000 1.1141680000 H 3.4314280000 5.0375120000 -0.5884830000 H 2.8119400000 4.7503830000 -2.9673750000 H 1.3464420000 2.8745870000 -3.6486270000 419 H 0.5035180000 1.2861080000 -1.9622240000 H -2.8797190000 -1.9595250000 -0.8247590000 420 5. Copies of NMR Spectra Figure E.7 1H NMR spectrum of 2a in DMSO-d6. Figure E.8 13C NMR spectrum of 2a in DMSO-d6. 421 Figure E.9 31P NMR spectrum of 2a in DMSO-d6. Figure E.10 1H NMR spectrum of 2b in CDCl3. 422 Figure E.11 13C NMR spectrum of 2b in CDCl3. Figure E.12 31P NMR spectrum of 2b in CDCl3. 423 Figure E.13 1H NMR spectrum of 2c in CDCl3. Figure E.14 13C NMR spectrum of 2c in CDCl3. 424 Figure E.15 31P NMR spectrum of 2c in CDCl3. Figure E.16 1H NMR spectrum of 2d in DMSO-d6. 425 Figure E.17 13C NMR spectrum of 2d in DMSO-d6. Figure E.18 31P NMR spectrum of 2d in DMSO-d6. 426 Figure E.19 1H NMR spectrum of 2e in DMSO-d6. Figure E.20 13C NMR spectrum of 2e in DMSO-d6. 427 Figure E.21 31P NMR spectrum of 2e in DMSO-d6. Figure E.22 1H NMR spectrum of 2f in DMSO-d6. 428 Figure E.23 13C NMR spectrum of 2f in DMSO-d6. Figure E.24 31P NMR spectrum of 2f in DMSO-d6. 429 Figure E.25 19F NMR spectrum of 2f in DMSO-d6. 430 APPENDIX F SUPPLEMENTARY INFORMATION FOR CHAPTER 7 Photophysical Properties Figure F.1 UV-vis absorption spectra of new heterocycles in (left) CHCl3 and (right) ~5% DMSO in pH 7.4 PBS buffer. Figure F.2 Emission spectra of new heterocycles in (left) CHCl3 and (right) ~5% DMSO in pH 7.4 PBS buffer. 431 Acid base stabilities studies Figure F.3 (left) absorption spectra of 1 before and after addition of acid or base. 432 Figure F.4 (left) absorption spectra of 3 before and after addition of acid or base. 433 Figure F.5 (left) absorption spectra of 7 before and after addition of acid or base. 434 Figure F.6 (left) absorption spectra of 8 before and after addition of acid or base. 435 Figure F.7 (left) absorption spectra of 9 before and after addition of acid or base. 436 Crystallographic Structures of 8 Figure F.8 ORTEP drawing of heterocycle 8; thermal ellipsoids drawn at 30% probability. 437 Figure F.9 ORTEP drawing of amide-directed hydrogen bonding seen in the solid state for heterocycle 8; thermal ellipsoids drawn at 30% probability. 438 Copies of NMR Spectra 439 440 441 442 443 444 445 446 447 APPENDIX G SUPPLEMENTARY INFORMATION FOR CHAPTER 8 Copies of NMR spectra: 1H NMR spectrum of 6 in CD2Cl2. 448 13C NMR spectrum of 6 in CD2Cl2. 1H NMR spectrum of 7 in CDCl3. 449 13C NMR spectrum of 7 in CDCl3. 1H NMR spectrum of 3 in DMSO-d6. 450 13C NMR spectrum of 3 in DMSO-d6. 451 31P {1H} NMR spectrum of 3 in DMSO-d6. 19F {1H} NMR spectrum of 3 in DMSO-d6. 452 453 APPENDIX H NAPHTHO[2,1‑e]‑1,2-AZAPHOSPHORINE 2‑OXIDE DERIVATIVES: SYNTHESIS, OPTOELECTRONIC PROPERTIES, AND SELF-DIMERIZATION PHENOMENA (WITH SUPPLEMENTARY INFORMATION) This Appendix includes previously published and co-authored material from Deng, C.-L., Bard, J.P., Zakharov, L.N., Johnson, D.W., Haley, M.M. “Naphtho[2,1-e]-1,2- azaphosphorine-2-oxides Derivatives: Synthesis, Optoelectronic Properties, and Self- Dimerization Phenomena.” J. Org. Chem. 2019, 84, 8131–8139 and the associated Supplementary Information document. The bulk of the writing and synthesis for this study was performed by Dr. Chun-Lin Deng, with assistance from Jeremy P. Bard. Editorial support was provided by Michael M. Haley and Darren W. Johnson. Introduction Six-membered phosphorus- and nitrogen-containing (PN-) heterocycles based on the azaphosphinine/azaphosphorine scaffold have been studied for over half a century. Phosphinamidate 1 and phosphonamidate2 (Figure H.1) represent two of the earliest known examples, disclosed in 1960 by the groups of Dewar1 and Campbell,2 respectively. Nonetheless, such molecules were scarcely explored in the following 45+ years, mainly because of the lack of viable and reliable synthetic methods to prepare them. This has changed in the past decade, however, as significant efforts have been devoted to metal- mediated C–H functionalization routes to relevant analogues such as 33 and 4,4 molecules 454 that have emerged as versatile building blocks for the modular syntheses of organocatalysts and chiral ligands. Figure H.1 Chemical structures of selected, known six-membered PN-heterocycles 1–7. Despite these efforts, feasible construction of N-unsubstituted phosphonamidates remains underexplored. Such systems are appealing as the phosphonamide motif features a hydrogen-bond-donating N–H moiety and one strong hydrogen-bond-accepting phosphonyl group.5,6 The latter not only provides a source of chirality but also functions as an electron-withdrawing group to increase the acidity of the N–H motif. The hydrogen bond donor/acceptor results in intermolecular self-association events, which could trigger the formation of various well-ordered supramolecular complexes, leading to novel supramolecular polymers7 and programmable molecular architectures.8 In addition, scant attention has been paid to the electronic properties of these heterocycles, as the unique nature of the phosphorus-containing frameworks would make them particularly attractive skeletons for new classes of phosphorus-containing electronic materials, fluorophores, and chemosensors.9,10 We reported a metal-free, one-pot tandem synthetic method that provides 2-λ5- phosphaquinolines 5 and 2-λ5-phosphaquinolin-2-ones 6 in good yields, thus allowing for 455 the facile preparation of diversiform PN-heterocycles with tunable emission properties.11 More recently, we described the preparation of a series of linearly fused naphtho[2,3-e]- 1,2-azaphosphorine-2-oxides 7 exhibiting considerably large Stokes shifts;12 however, their low quantum efficiencies could limit optoelectronic applications to some extent. Also, it is of fundamental importance to unravel the factors that influence H-bonding within these systems, not only to predict their self-association behavior but also to provide insights into elaborating these compounds as molecular recognition motifs.13 Herein, we report the synthesis, electronic characterization, and self-dimerization behavior of a series of angular naphtho-fused PN-heterocyclic systems that exhibit enhanced quantum yields over their linearly fused congeners. Results and Discussion As shown in Scheme H.1, the synthesis of the requisite alkyne precursors 11 for our study started by cross-coupling (trimethylsilyl)acetylene (TMSA) with iodonaphthalenamine 9. Protodesilylation of 10 and a second cross-coupling utilizing the appropriate para- substituted haloarene afforded a series of tolane derivatives 11 containing various aryl substituents in moderate to good yield (see the Supplementary Information section below). In all cases, the P(OPh)3-mediated cyclization of 11 proceeded smoothly to give the corresponding phosphinimidates, which were subsequently hydrolyzed with minimal amounts of water to provide the desired phosphonamidates 8. The crude materials were purified by silica gel column chromatography followed by preparative size-exclusion chromatography (SEC) and then recrystallization to furnish the analytically pure products in modest overall yields. Compounds 8a–f are air- and thermally-stable solids and were 456 fully characterized by conventional techniques (1H, 13C, and 31P NMR spectroscopy as well as HRMS). Scheme H.1 Synthesis of PN-Heterocycles 8. Characteristic to these molecules in their proton NMR spectra in CDCl3 are the N–H singlet and the 31P-coupled doublet (J ∼ 40 Hz) in the 9.3–9.7 and 7.7–7.9 ppm range, respectively. These peaks shift downfield progressively as the pendant aryl group becomes more electron deficient. Alternatively, this same effect results in the 31P peaks shifting upfield, though there is a definite concentration dependence on their chemical shift (due to dimerization, vide infra). Single crystals of 8c and 8d suitable for X-ray diffraction were obtained by slow evaporation of their CHCl3 or CH2Cl2 solutions, respectively. Various depictions of the structures are shown in Figure H.2 and Figure H.7 (for 8d), as well as Figure H.8 (for 8c), and select bond lengths and angles are compiled in Table H.4. As expected, both the N–H donor and P═O acceptor groups in 8c and 8d are involved in hydrogen bond formation to crystallize meso-dimeric complexes in the solid state. Both 8c (H···O 1.90(3) Å/160(5)°, 457 1.86(3) Å/154(4)°, respectively) and 8d (H···O 2.06(3) Å/166(2)°) display short H-bond interactions. Notably, a pair of weak intermolecular C–H H-bonds (H···O 2.45 Å/165°, 2.43 Å/165° for 8c, H···O 2.41 Å/ 163° for 8d, respectively) were observed in the crystalline lattice, which are supported by the observed light red circles in the Hirshfeld surface analysis of 8d (Figure H.2b). Examination of the packing diagram of 8c reveals that two antiparallel naphthalene moieties are stacked to form a face-to-face π-interaction at a distance of 3.38 Å. For 8d, effective π–π interactions occur between the p-cyanophenyl units and naphthalene cores (see the Supplementary Information section below). Figure H.2 (a) ORTEP drawing of the dimer structure of 8d via hydrogen bonds; thermal ellipsoids drawn at 50% probability. (b) dnorm (red: −0.502 to blue: 1.427 Å) mapped on the Hirshfeld surface of 8d. The surface regions with intermolecular H-bond interactions 458 are drawn in red. (c) Intermolecular π contacts. (d) Molecular packing diagram viewed along the a-axis. All hydrogen atoms not involved in the interactions are omitted for clarity. Optoelectronic Properties As shown in Figure H.3, the UV/vis absorption spectra of 8a–f exhibit two weaker bands at ca. 320–450 nm with the strongest bands in the 275–310 nm range. The lowest energy absorption bands in 8a–e are red-shifted with increasing electron-withdrawing ability of the terminal para-substituents with regard to 8f. Figure H.3 Electronic absorption (solid line) and emission spectra (dotted line) of 8 in CHCl3 at 298 K. To elucidate the origin of the low energy absorption bands and electronic structures of the new PN-heterocycles, TD-DFT calculations at the PBE0/6-311G(d) level of theory were performed on the previously optimized geometries of 8. As shown in Figure H.4, the calculated excitation energies for all compounds were found to be in good agreement with the experimentally obtained lowest energy absorption bands (Table H.1). The lowest energy absorption bands correspond to the S0 → S1 electronic transitions, which are dominated by the transitions from HOMO → LUMO. Figure H.4 shows that the LUMO and HOMO of 8f encompass the entire molecular system; therefore, its absorption bands appear to be π → π* transitions. With respect to 8a, the HOMO coefficients reside mainly 459 on the naphthalene and PN heterocyclic moiety, whereas the terminal phthalonitrile substituent dominates the LUMO; thus, the S0 → S1 transition of 8a appears to have some charge-transfer (CT) character. As with the other four compounds, from 8e to 8b, the orbital coefficients in the LUMO gradually shift to the pendant phenyl units, whereas the contributions of the naphthalene-fused PN-heterocyclic rings to the HOMOs remain almost unchanged. This suggests that the effect of CT in the S0 → S1 transition becomes more prominent with stronger EWG. These calculations suggest that the attachment of the pendant phenyl units to the parent core can significantly change the electronic structure of these molecules. Table H.1 Photophysical Data of PN-Heterocycles 8 in CHCl3 at 298 K cmpd λ amax (nm) λ c d em (nm) ΦF τ (ns) 8a 404 (4.07) 493 0.93 1.0/4.4 (3/97) 8b 397 (3.72) 490 0.80 1.0/4.0 (4/96) 8c 389 (4.01) 469 0.36 1.8/3.9 (28/72) 8d 388 (3.87) 470 0.66 2.6 8e 380 (3.84) 457 0.29 1.7 8f 372b (3.83) 441 0.19 0.8 a The longest absorption maximum wavelengths; molar absorption coefficients as log ε (M–1 cm–1) given in parentheses. b A broad absorption band. c The relative fluorescence quantum yield determined with quinine sulfate in 0.1 M H2SO4 as a standard (λex= 360 nm, ΦF = 0.54). d For 8a–c, fitted with biexponential model and the amplitudes of two lifetimes given in parentheses; for 8d–f, fitted with monoexponential model. 460 Figure H.4 Kohn–Sham molecular orbitals, excitation energies, and oscillator strengths for 8, calculated at the TD-PBE0/6-311G(d) level of theory. In contrast, the fluorescence maxima (λem) are red-shifted significantly following the same trend as the absorption spectra (FigureH.3). As shown in Table H.1, the compounds appended with the electron-withdrawing substituents possess moderate to excellent emission quantum efficiencies (0.29–0.93), compared to those small values (ΦF < 0.1) observed among the relevant PN-heterocycles.10,11 The TD-DFT calculations show that the S0 → S1 excitations in linear analogues 7 11 have very small oscillator strengths (Figure H.15), which may partly account for the lower quantum yields of 7 relative to 8. The emission peak for 8f is unaffected by solvents of varying polarity; however, the emission peaks for 8a–d were bathochromically shifted and broadened in varying degrees with the increasing solvent polarity (see Supplementary information section below), which is 461 consistent with the involvement of CT transitions.14 The fluorescence decay histograms of 8d–f were fitted with a single exponential function with the fluorescence lifetimes ranging from 0.8 to 2.6 ns (Table H.1). By contrast, only the biexponential model can be reasonably applied to 8a–c, indicating that different emissive species exist in the excited state. There is a trend in the amplitudes of the two components; as the para-substituent becomes more electron-withdrawing, the longer-lived excited state becomes dominant. Considering the different electronic structures of 8, the excitations for 8d–f seem to take place locally within the phenanthrene-like heterocyclic fragment, whereas some added intramolecular charge transfer (ICT) occurred between the central core and 3-aryl moieties in 8a–c, which correspond to the mixed π → π*/ICT states. Additionally, the TD-DFT-optimized geometry of the S1 state of 8a–f show that the whole molecular system becomes more conjugated compared to the ground state, as a result of decreasing the dihedral angle and shortening the length of the connecting C–C bond between the plane of the 3-phenyl group and the plane of the tricyclic core (Table H.5). These geometric relaxations favor the electron delocalization and eventually lower the HOMO–LUMO energy gaps, thereby contributing to their Stokes shifts; thus, the TD-DFT predicted emission wavelength with increased oscillator strength is within the observed emission maxima (Tables H.1 and H.6). Self-Dimerization Unlike the linear-fused regioisomers 7, compounds 8 ( aside from 8a) exhibit appreciable solubility in CHCl3, which allows for the investigation of their dimerization behavior in solution by variable concentration (VC) NMR spectroscopy experiments. When a water- saturated CDCl3 solution of 8b was diluted from 17 mM, the resonances of the P atom showed upfield shifts of ca. 1 ppm, indicating disassociation of dimer 8b·8b (Figure H.5a). 462 Meanwhile, the proton of the phosphonamide NH also gradually shifted upfield with decreasing concentration. Nonlinear regression analysis of the chemical shift data of the NH proton and P atom yielded the dimerization constant (Kdim) values of 308 and 289 M – 1, respectively. The results are consistent with the expected strong N–H/P═O head-to-tail hydrogen bond pairs. Additional Kdim data for the dimerization of the other phosphonamidates are summarized in Table H.2. The dimerization constants for 8b and 8d, with their electron-withdrawing substituent in the 3-aryl position were measured to be over 200 M–1. In contrast, both compound 8e, with a less electron-poor group, and 8f, bearing an electron-donating group, show K –1dim values less than 100 M . It is noteworthy that the obtained self-association constants are significantly larger than those of structurally related C═O/N–H motifs.15 Figure H.5 (a) Stacked partial 31P NMR spectra of 8b at various concentrations. (b) Chemical shifts of phosphonamidate NH proton and P atom resonances in 8b during the dilution NMR experiments. Table H.2 Dimerization Constants (Kdim) of 8 in H2O-Saturated CDCl3 at 298 K a cmpd Kdim (M –1) cmpd K –1dim (M ) 8a b 8d 246 8b 306 (290) 8e 84 8c 117 8f 77 463 a All of the reported dimerization constants represent the average value from triplicate titrations. Uncertainties are less than 10%. The values derived from 31P NMR titrations are given in parentheses.b Not determined due to the insolubility in H2O-saturated CDCl3. To gain insight into the self-association properties, the calculated electrostatic potential (ESP) showed that the domain with the largest global positive ESP (Vs,max) is located on the N–H moiety of 8b, accompanied by the most negative ESP (Vs,min) on the P═O local surface (Figure H.6a). Similar distribution patterns of ESP are found within all other molecular systems. According to the “best donor-best acceptor” empirical rule proposed by Etter,16 we posit that the assembly via the N–H/P═O hydrogen bonds would cancel out their surface global extremes to form stable self-complementary dimers. As suggested in the solid structure, another important aspect of self-association is that a monomer always adopts an “edge to edge” antiparallel orientation with respect to its enantiomer, while the dimer consisting of two homochiral monomers was never observed. We note that the distribution of positive and negative charge across the PN-heterocycle core is uneven and would give rise to a permanent dipole moment (μg), which was calculated to be 6.5 D (Figure H.6b). On the other hand, the dipole moment for the anticipated (R,S)-meso-dimer is negligible (μg ≈ 0 D). The result is not surprising since the dipole moment vectors in the two monomers are also in an antiparallel arrangement because of the centrosymmetric structure of meso-dimer. In contrast, the suggested (S,S)-dimer would still possess a small dipole moment (0.4 D) relative to the monomer. It seems that this unique antiparallel alignment feature for self-association is directly related to the most favorable orientation for dipolar anisotropy, in which the dipole moments for two monomers are effectively canceled. Furthermore, the noncovalent interactions (NCI) plot reveals that additional long-range repulsive domains appear between the −OPh moieties in the (S,S)-dimer (Figure 464 6d), which could act as some kind of destabilizing steric clash. Meanwhile, the predicted interaction energy (ΔEint) in the gas phase for the resulting (R,S)-meso-dimer is 3 kJ mol –1 more negative than that of the proposed (S,S)-dimer counterpart, although their H-bond parameters are comparable (Figure H.6c). Therefore, these findings indicate PN- heterocycles 8 have greater propensity for formation of the meso-dimer compared to the (S,S)- or (R,R)-dimer. Figure H.6 (a) Electrostatic potential surface (isovalue = 0.001 au) of 8b. Surface global minima (Vs,min) and maxima (Vs,max) are represented as cyan and orange dots, respectively. (b) Molecular dipole moment (in debye) for the PN-heterocycle core is denoted by the light orange arrow pointing from the negative pole to the positive pole. (c) Optimized structures with hydrogen bond distances (in Å), molecular dipole moments, and the interaction energies (ΔEint, kJ mol –1) for the (R,S)-dimer and (S,S)-dimer. The electrostatic potential surface was obtained at the M06-2X/TZVP level of theory. All the dipole moments were calculated at the M06-2X/ma-def2-TZVP level. The interaction energy (ΔEint) is defined as the gas-phase electronic energy difference between dimer and its isolated monomers and calculated at the M06-2X/ma-def2-TZVP//M06-2X/TZVP level of theory, which was corrected for the basis set superposition error (BSSE) in both complexes. (d) NCI plots for two dimeric motifs at the M06-2X/TZVP equilibrium geometries. NCI regions are represented as solid surfaces and blue–green–red scaling from −0.03 < sign(λ2)ρ(r) < 0.01 (in au), where red surface indicates strong repulsion, blue surface strong attraction and green surface relatively weak interactions. Isosurface cutoff for NCI = 0.5. To understand the energetic differences on dimerization, we analyzed the geometric aspects of the hydrogen bonds of each dimer. The DFT optimizations on these meso- 465 dimeric complexes at the PCM(CHCl3) M06-2X/TZVP level of theory revealed that the two H-bond distances near N–H/P═O moieties are nearly identical to each other. The values of electron density ρ(r) at the hydrogen bond critical points (BCPs) derived from the atoms in molecules (AIM) topological analysis fall within a narrow window (0.029– 0.031 au). Meanwhile, the total hydrogen-bonding energies for the N–H···O═P H-bonds are estimated to be ca. −74.5 kJ mol–1 for each dimer complex, suggesting they have similar primary H-bond strengths regardless of the appended p-substituents (Table H.23). By comparing computationally derived Vs,max (related to H-bond acidity of N–H) and Vs,min (related to H-bond basicity of P═O) values17 across this series of compounds, there is a general increase in Vs,max absolute values and a concurrent decrease in Vs,min absolute values with the increasing electron-withdrawing abilities of the 3-aryl substituents (as judged by the increasing Hammett substituent parameters,18 σp = ∼1.22 for 8a, 0.96 for 8b, 0.66 for 8c, 0.72 for 8d, 0.54 for 8e, and −0.27 for 8f) (Figure H.17). Presumably, the comparable hydrogen bond lengths could be interpreted by the balance between the increased H-bond donor ability of N–H and the reduced H-bond acceptor ability of P═O from 8f to 8a; however, the total interaction energy (ΔEint) for the dimerization in the gas phase computed at the M06-2X/ma-def2-TZVP//PCM(CHCl3)-M06-2X/TZVP level of theory shows the order of 8a > 8b > 8d > 8c > 8e > 8f and agrees qualitatively well with the respective experimentally determined Gibbs free association energies (Table H.3). Table H.3 Theoretical Interaction Energies in the Gas Phase (ΔEint), Experimental Binding Gibbs Free Energy Change (ΔGexp) of the Self-Dimerization of 8, Total SAPT0 Energy (ESAPT), Electrostatic Term (Eele), Non-electrostatic Components (ΔEnonele) (the Sum of Contributions from the Dispersion, Exchange and Induction Terms, Enonele) in the SAPT0 Energy Partitions, and the Calculated Molecular Dipole Moments of Monomer (μg,mono) and Their Respective Dimer (μg,di) of 8 a cmpd ΔEintb ΔGexpc ESAPTd Eele Enonele μg,mono μg,di 8a –124.3 –170.2 –176.4 6.2 13.5 0 466 8b –123.1 –14.3 –156.3 –166.4 10.2 11.2 0.8 8c –122.4 –11.9 –154.8 –165.3 10.5 10.1 0 8d –122.7 –13.7 –154.8 –164.5 9.7 10.4 0 8e –121.1 –11.1 –152.8 –163.3 10.5 8.4 0 8f –119.6 –10.8 –152.3 –162.7 10.4 4.2 0.2 a Energies in kJ mol–1, molecular dipole moments in debye. b With BSSE corrections. c ΔGexp= −RT ln Kdim. d SAPT0 calculations with jun-cc-pVDZ basis set. To determine the fundamental factors of energy differences, symmetry-adapted perturbation theory (SAPT) was utilized to decompose the binding energies into different energy terms. The total SAPT0/jun-cc-pVDZ energies (ESAPT) demonstrate the same trend found in gas-phase interaction energies. According to the SAPT0 energy decomposition, the electrostatic interactions are the leading contributors to stabilization, followed by induction and dispersion, whereas the exchange energies appear repulsive (Table H.25). We further note that the sum of contributions from nonelectrostatic components (Enonele) are similar for all of the considered systems expect 8a and vary within the narrow range of +9.7 to +10.5 kJ mol–1 (Table H.3), acting as the destabilizing term for overall interacting energies. Hence, the induction and dispersion energies are heavily outweighed by the large positive exchange energies. Consequently, the electrostatics alone are comparable to the total interaction energies of these dimeric complexes (Eele ≈ ESAPT). Notably, the electrostatic components also display a distinct trend with the order of 8a > 8b > 8c > 8d > 8e > 8f. This analysis supports the conclusion that the higher interaction energies for these types of molecular systems are mainly due to the pronounced electrostatic interactions. In the context of structural similarities among the monomers and their dimers as well as the dipolar properties for this type of compound, we assumed that the dimers were stabilized by some additional intermolecular stabilizations such as possible permanent 467 dipole–dipole/atomic charge–dipole interactions (accounted in Eele term). To further gauge the effect of dipolar interactions, we performed calculations for the dipole moments of 8 and their corresponding meso-dimers at the M06-2X/ma-def2-TZVP level of theory, and the results are shown in Table H.3 and Figure H.18. The magnitude of dipole moment for the monomeric compound (μg,mono) increases with the order of 8f < 8e < 8c < 8d < 8b < 8a (ranging from 4.2 to 13.5 D), which is in line with the trend for the calculated ΔEint. As expected, the nearly quenched molecular dipole moments were found among all of the examined dimer systems. The larger μg,mono would result in more pronounced electrostatic interactions. These results suggest that the monomeric polarity difference model suitably describes the experimental tendencies for all the addressed dimeric adducts and the enhanced dipolar/charge-dipole interactions between the (R)- and (S)-monomers could be one of the influential factors for the increased overall dimeric stabilization, though it should be noted that many other considerations, including solvation and dispersive elements such as π–π interactions could also play a role during the actual dimerization events, at least in chloroform solution. Conclusions In summary, we have prepared a new type of fluorescent naphtho-fused PN-heterocycle via the P(OPh)3-mediated cyclization protocol. Both the experimental results and the DFT calculations have revealed that the pendant phenyl rings have a significant impact on their optical properties, electronic structure, and self-association behaviors. The incorporation of a strong electron-withdrawing group leads to a redshift in the spectrum with good photoluminescence quantum yields, as well as strong dimerization in solution state. The monomeric polarity model can successfully explain the overall dimerization stabilities, and 468 it suggests that appreciable tuning of the self-association ability would be possible by modifying the dipole moment of the monomer, i.e., by further tuning the 3-aryl substituents among these PN-heterocycles. These results provide not only an understanding of the nature of the π-extended PN-heterocyclic skeletons but also a basis for designing intriguing motifs for constructing fluorescent probes and sensors. Furthermore, the strong self- dimerizaton patterns suggest that this class of molecules could be useful as novel monomeric components for supramolecular assemblies. Experimental Section General Methods NMR spectra were obtained on a Varian Inova 500 MHz spectrometer (1H: 500.11 MHz, 13C 125.76 MHz, 19F 470.53 MHz, 31P 202.46 MHz) or a Bruker Avance-III-HD 600 MHz (1H: 599.98 MHz, 13C: 150.87 MHz) spectrometer. Chemical shifts (δ) are expressed in ppm using residual nondeuterated solvent present in the bulk deuterated solvent (CDCl3: 1H 7.26 ppm, 13C 77.16 ppm; DMSO-d6: 1H 2.50 ppm, 13C 39.52 ppm). 19F chemical shifts are reported against CFCl3 external standard (δ 0 ppm). 31P chemical shifts are reported against 85% H3PO4 (δ 0 ppm) as external reference. Mass spectra data were acquired on a Waters SYNAPT QToF in positive ion mode with a Shimadzu LC20AD HPLC front end. The solvents were MeCN/H2O/0.1% HCO2H at a flow rate of 0.05 mL min –1 with a 5 μL injection on a loop injection. Preparative SEC was performed using a JAI Recycling Preparative HPLC (Model LC-9101) with a JAIGEL-1H preparative column with CHCl3 as solvent. Analytical TLC was carried out on TLC plates (5 × 10 cm with 0.25 mm thickness, silica gel 60 F254, Merck, Darmstadt, Germany) cut from commercially available aluminum sheets. Solvents and reagents were used as purchased from suppliers, unless 469 anhydrous conditions were employed, in which case solvents were freshly distilled from sodium/benzophenone under N2 atmosphere (THF) or as purchased. 2- Iodonaphthalenamine 919 was synthesized according to the literature method. 2-(Trimethylsilylethynyl)naphthalenamine 10: A ∼0.1 M solution of iodonaphthalenamine 9 (150 mg, 0.6 mmol) in toluene (4 mL) and (i-Pr)2NH (4 mL) was purged for 15 min with N2. TMSA (88 mg, 0.125 mL, 0.9 mmol) was added via syringe. After an additional 5 min of N2 purging, CuI (11.4 mg, 0.06 mmol) and [Pd(PPh3)2Cl2] (42 mg, 0.06 mmol) were added to the reaction mixture. The flask was then purged for an additional 5 min, sealed, and stirred at room temperature under N2 for 12 h. The mixture was then concentrated and the residue chromatographed on silica gel to afford the desired ethynylsilane 10 (131 mg, 98%) as a colorless oil: R = 0.4 (hexanes/EtOAc, 8:1); 1f H NMR (500 MHz, CDCl3) δ 7.79–7.73 (m, 2H), 7.47–7.45 (m, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 8.5 Hz, 1H), 4.87 (s, 2H), 0.31 (s, 9H); 13C{1H} NMR (126 MHz, CDCl3) δ 145.6, 134.3, 128.7, 128.5, 126.8, 125.5, 122.5, 121.1, 118.0, 103.0, 102.0, 100.6, 0.39; HRMS (ESI) m/z calcd for C15H18NSi [M + H +] 240.1209, found 240.1206. General Procedure for Synthesis of 2-(Phenylethynyl)naphthalenamines 11: To a solution of alkyne 10 (1.0 equiv.) in MeOH/CH2Cl2 (1:1, ∼0.01 M) was added K2CO3 (3.0 equiv.). The suspension was stirred at room temperature for 2–3 h and then filtered through a bed of Celite. After evaporation of the solvent, the crude residue was used directly in the next reaction. To an N2-sparged solution of bromoarene (for 11a–e) or iodoarene (for 11f) (1.2 equiv.) and terminal acetylene (1.0 equiv.) in 1:1 THF/DIPA was added 5 mol % of [Pd(PPh3)2Cl2] and 5 mol % of CuI. The suspension was stirred at room temperature under an N2 atmosphere for 24 h. In the case of the 4-bromobenzonitrile starting material, the 470 solution was heated to 60 °C (oil bath) for 12 h. The reaction mixture was cooled, concentrated in vacuo, and purified via flash chromatography to give the desired product 11 as a dark-orange oil. 4-((1-Aminonaphthalen-2-yl)ethynyl)phthalonitrile 11a: The general procedure was followed using 4-iodophthalonitrile (254 mg, 1.0 mmol). Purification by column chromatography (silica gel, hexanes/EtOAc 3:1) gave 11a (249 mg, 85%) as a waxy solid: Rf = 0.28 (hexanes/EtOAc, 3:1); 1H NMR (600 MHz, DMSO-d6) δ 8.49 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.14–8.09 (m, 2H), 7.76 (d, J = 8.1 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H), 6.54 (s, 2H); 13C{1H} NMR (151 MHz, DMSO-d6) δ 148.4, 135.7, 135.3, 134.6, 134.0, 129.2, 128.6, 128.1, 127.6, 125.0, 123.0, 121.8, 116.0, 115.7, 115.6, 115.0, 112.1, 96.6, 95.8, 92.5; HRMS (ESI) m/z calcd for C +20H12N3 [M + H ] 294.1031, found 294.1052. 2-((4-((Trifluoromethyl)sulfonyl)phenyl)ethynyl)naphthalen-1-amine 11b: The general procedure was followed using 1-bromo-4-[(trifluoromethyl)sulfonyl]-benzene (722 mg, 2.5 mmol). Purification by column chromatography (silica gel, hexanes/EtOAc, 5:1) gave 11b (779 mg, 83%) as a dark-orange oil: Rf = 0.29 (hexanes/EtOAc, 4:1); 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 8.1 Hz, 2H), 7.83–7.77 (m, 4H), 7.54–7.49 (m, 2H), 7.42 (d, J = 8.5 Hz, 1H), 7.25 (d, J = 8.7 Hz, 1H), 4.99 (s, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 146.0, 134.8, 132.7, 132.3, 130.9, 129.6, 128.9, 128.3, 127.6, 125.9, 121.2, 119.9 (q, J = 327.0 Hz), 118.5, 100.2, 94.1, 93.8; 19F NMR (471 MHz, CDCl3) δ −78.24; HRMS (ESI) m/z calcd for C +19H13F3NO2S [M + H ] 376.0619, found 376.0626. 2-(2-(4-Cyanophenyl)ethynyl)naphthalen-1-amine 11c: The general procedure was followed using 4-bromobenzonitrile (154 mg, 0.8 mmol). Purification by column 471 chromatography (silica gel, hexanes/EtOAc, 5:1) gave 11c (130 mg, 61%) as a tan oil: Rf = 0.18 (hexanes/EtOAc, 5:1); 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz, 1H), 7.80 (d, J = 7.1 Hz, 1H), 7.68–7.64 (m, 4H), 7.55–7.50 (m, 2H), 7.43 (d, J = 8.5 Hz, 1H), 7.27 (m, 1H), 4.97 (s, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 145.5, 134.6, 132.2, 131.8, 128.9, 128.6, 128.3, 127.3, 125.8, 122.5, 121.1, 118.7, 118.4, 111.3, 100.8, 94.2, 91.9; HRMS (ESI) m/z calcd for C19H13N2 [M + H +] 269.1079, found 269.1076. 2-((4-(Methylsulfonyl)phenyl)ethynyl)naphthalen-1-amine 11d: The general procedure was followed using 1-bromo-4-(methylsulfonyl)benzene (235 mg, 1.0 mmol). Purification by column chromatography (hexanes/CH2Cl2/EtOAc, 3:1:1) gave 11d (266 mg, 83%) as a waxy solid: Rf = 0.12 (hexanes/EtOAc, 2:1); 1H NMR (500 MHz, DMSO-d6) δ 8.26 (d, J = 8.2 Hz, 1H), 7.96–7.90 (m, 4H), 7.76 (d, J = 7.9 Hz, 1H), 7.51–7.44 (m, 2H), 7.34 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.37 (s, 2H), 3.24 (s, 3H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 147.6, 139.4, 134.4, 131.8, 128.8, 128.2, 127.4, 127.3, 125.1, 123.0, 122.0, 116.0, 97.8, 93.7, 92.2, 43.6; HRMS (ESI) m/z calcd for C19H16NO2S [M + H +] 322.0902, found 322.0916. 2-(2-(4-(Trifluoromethyl)phenyl)ethynyl)naphthalen-1-amine 11e: The general procedure was followed using 1-bromo-4-(trifluoromethyl)benzene (450 mg, 2.0 mmol). Purification by column chromatography (hexanes/EtOAc, 10:1) gave 11e (386 mg, 62%) as a tan oil: Rf = 0.42 (hexanes/EtOAc, 10:1); 1H NMR (500 MHz, CDCl3) δ 7.83–7.81 (m, 1H), 7.79– 7.77 (m, 1H), 7.67–7.62 (m, 4H), 7.52–7.48 (m, 2H), 7.43 (d, J = 8.5 Hz, 1H), 7.25 (d, J = 8.5 Hz, 1H), 4.93 (s, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 145.2, 134.5, 131.6, 129.8 (q, J = 32.8 Hz), 128.8, 128.4, 127.4 (q, J = 1.3 Hz), 127.2, 125.7, 125.5 (q, J = 3.8 Hz), 472 124.1 (q, J = 272 Hz), 122.5, 121.1, 118.4, 101.2, 94.3, 89.7; 19F NMR (471 MHz, CDCl3) δ −62.68; HRMS (ESI) m/z calcd for C19H13F3N [M + H +] 312.1000, found 312.1008. 2-(2-(4-Methoxyphenyl)ethynyl)naphthalen-1-amine 11f: The general procedure was followed using 4-iodoanisole (357 mg, 1.5 mmol). Purification by column chromatography (hexanes/EtOAc, 10:1) gave 11f (241 mg, 59%) as a tan oil: Rf = 0.39 (hexanes/EtOAc, 5:1); 1H NMR (500 MHz, CDCl3) δ 7.84–7.79 (m, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.50–7.45 (m, 3H), 7.27 (m, 1H), 6.93 (d, J = 8.2 Hz, 2H), 4.91 (s, 2H), 3.87 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 159.7, 144.5, 134.1, 133.0, 128.8, 128.6, 126.6, 125.5, 122.7, 121.1, 118.2, 115.7, 114.2, 102.6, 95.5, 85.6, 55.5; HRMS (ESI) m/z calcd for C19H16ON [M + H+] 274.1232, found 274.1245. General Procedure for Synthesis of PN-Heterocycles 8 To a solution of amine 11 (0.5 mmol) in dry pyridine (1 mL) was added triphenyl phosphite (171 mg, 0.55 mmol). The reaction vessel was sealed and heated to 100 °C (oil bath) for 18–24 h. After cooling, the volatiles were removed in vacuo. The residue was purified through flash chromatography on silica gel (eluting with CH2Cl2/EtOAc, 15/1–3/1 (v/v) containing 0.05% MeOH) to give the crude product, which then was further purified via preparative SEC (if necessary). In most cases, the desired fractions were accompanied by a small amount of unknown persistent aromatic impurities. Analytically pure product can be obtained from recrystallization by slow evaporation of its CHCl3 solution at room temperature. The reported yields are overall yields. (Note: The chemical shifts of 31P resonances can vary with concentration; thus, we reported the H coupled 31P NMR spectra). 2-Phenoxy-3-(3,4-dicyanophenyl)-1H-naphtho[2,1-e][1,2]azaphosphinine 2-oxide 8a: yellow solid (69 mg, 32%); Rf = 0.57 (hexanes/CH2Cl2/EtOAc, 1:2:2); mp > 200 °C; 1H 473 NMR (600 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.66 (m, 1H), 8.61 (m, 1H), 8.47 (m, 1H), 8.43 (d, J = 37.9 Hz, 1H), 8.25 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 7.3 Hz, 1H), 7.66–7.61 (m, 2H), 7.57–7.52 (m, 2H), 7.16 (t, J = 7.7 Hz, 2H), 7.18–7.14 (m, 2H), 7.03 (m, 1H), 6.92– 6.90 (m, 2H); 13C{1H} NMR (151 MHz, DMSO-d6) δ 149.9 (d, J = 9.0 Hz), 145.1 (d, J = 3.7 Hz), 141.0 (d, J = 10.5 Hz), 138.0, 134.5, 131.8 (d, J = 5.9 Hz), 131.5 (d, J = 8.1 Hz), 129.6, 128.4 (d, J = 16.5 Hz), 128.0, 126.5, 125.1, 123.1 (d, J = 8.2 Hz), 122.7, 121.1, 120.93 (d, J = 3.9 Hz), 119.7 (d, J = 12.9 Hz), 118.6, 115.98 (d, J = 19.6 Hz), 115.4, 114.90 (d, J = 15.2 Hz), 112.8; 31P NMR (202 MHz, DMSO-d6) δ 10.43 (d, J = 37.7 Hz); UV/vis (CHCl3) λmax (log ε) 404 (4.07), 343 (4.17) nm; HRMS (ESI) m/z calcd for C26H17N3O2P [M + H+] 434.1058, found 434.1047. 2-Phenoxy-3-(4-((trifluoromethyl)sulfonyl)phenyl)-1H-naphtho[2,1- e][1,2]azaphosphinine 2-oxide 8b: yellow solid (77 mg, 30%); Rf = 0.43 (hexanes/CH2Cl2/EtOAc, 1:2:2); mp > 200 °C; 1H NMR (500 MHz, CDCl3) δ 9.71 (s, 1H), 8.52 (d, J = 8.5 Hz, 1H), 8.23–8.21 (m, 2H), 8.14 (d, J = 8.2 Hz, 2H), 7.91 (d, J = 38.7 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.64–7.61 (m, 1H), 7.51–7.47 (m, 2H), 7.39 (d, J = 8.5 Hz, 1H), 7.00–6.97 (m, 2H), 6.93–6.89 (m, 3H); 13C{1H} NMR (151 MHz, CDCl3) δ 149.9 (d, J = 8.9 Hz), 144.9 (d, J = 4.8 Hz), 144.6 (d, J = 9.8 Hz), 138.1 (d, J = 2.8 Hz), 135.0, 131.4, 130.1, 129.6, 128.8 (d, J = 6.7 Hz), 128.6 (d, J = 19.0 Hz), 127.5, 126.7, 125.3, 123.9 (d, J = 8.1 Hz), 122.7, 122.0, 121.4, 121.2 (d, J = 4.1 Hz), 121.1, 120.4, 120.0 (q, J = 325.9 Hz), 115.4 (d, J = 14.9 Hz); 31P NMR (202 MHz, CDCl3) δ 11.72 (d, J = 38.9 Hz); 19F NMR (471 MHz, CDCl3) δ −78.22; UV/vis (CHCl3): λmax (log ε) 375 (3.72), 338 (3.90) nm; HRMS (ESI) m/ z calcd for C25H18NO4F3PS [M + H +] 516.0646, found 516.0648. 474 2-Phenoxy-3-(4-cyanophenyl)-1H-naphtho[2,1-e][1,2]azaphosphinine 2-oxide 8c: yellow solid (33 mg, 16%); R 1f = 0.58 (hexanes/CH2Cl2/EtOAc, 1:2:2); mp > 200 °C; H NMR (500 MHz, CDCl3) δ 9.76 (s, 1H), 8.56 (d, J = 8.5 Hz, 1H), 8.09 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 39.3 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.65 (m, 1H), 7.54 (m, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.39 (d, J = 8.5 Hz, 1H), 7.02–6.99 (m, 2H), 6.95–6.90 (m, 3H); 13C{1H} NMR (151 MHz, CDCl3) δ 150.1 (d, J = 8.9 Hz), 143.7, 140.5, 137.6, 134.8, 132.7, 129.5, 128.7, 128.2, 128.2, 127.5, 126.6, 125.2, 123.8, 122.6, 121.8, 121.2 (d, J = 4.2 Hz), 119.0, 115.5 (d, J = 16.7 Hz), 111.7; 31P NMR (202 MHz, CDCl3) δ 12.09 (d, J = 39.3 Hz); UV/vis (CHCl3) λmax (log ε) 389 (4.01), 340 (4.09) nm; HRMS (ESI) m/z calcd for C25H18N2O2P [M + H +] 409.1106, found 409.1106. 2-Phenoxy-3-(4-(methylsulfonyl)phenyl)-1H-naphtho[2,1-e][1,2]azaphosphinine 2-oxide 8d: yellow solid (90 mg, 39%); Rf = 0.27 (hexanes/CH2Cl2/EtOAc, 1:2:2); mp > 200 °C; 1H NMR (500 MHz, CDCl3) δ 9.40 (s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.1 Hz, 2H), 8.08–8.06 (m, 2H), 7.85 (d, J = 39.2 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 7.38 (d, J = 8.5 Hz, 1H), 7.01– 6.97 (m, 2H), 6.93–6.89 (m, 2H), 3.14 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3) δ 150.0 (d, J = 9.1 Hz), 144.0 (d, J = 5.1 Hz), 141.6 (d, J = 9.7 Hz), 139.8, 137.5 (d, J = 2.8 Hz), 134.8, 129.5, 128.7, 128.5 (d, J = 6.7 Hz), 128.3, 128.1, 127.5, 126.7, 125.21, 123.8 (d, J = 8.0 Hz), 122.4, 122.3, 121.9, 121.24 (d, J = 4.2 Hz), 121.2, 115.5 (d, J = 14.9 Hz), 44.8; 31P NMR (202 MHz, CDCl3) δ 11.92 (d, J = 38.9 Hz); UV/vis (CHCl3) λmax (log ε) 388 (3.87), 337 (3.96) nm; HRMS (ESI) m/z calcd for C25H21NO4PS [M + H +] 462.0929, found 462.0933. 475 2-Phenoxy-3-(4-(trifluoromethyl)phenyl)-1H-naphtho[2,1-e][1,2]azaphosphinine 2-oxide 8e: yellow solid (40 mg, 18%); Rf = 0.74 (hexanes/CH2Cl2/EtOAc, 1:2:2); mp > 200 °C; 1H NMR (500 MHz, CDCl3) δ 9.38 (s, 1H), 8.47 (d, J = 8.5 Hz, 1H), 8.05 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 39.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.59 (dd, J = 8.2, 6.7 Hz, 1H), 7.50 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.37 (d, J = 8.5 Hz, 1H), 7.00–6.97 (m, 2H), 6.94–6.88 (m, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 150.2 (d, J = 9.1 Hz), 143.3 (d, J = 5.2 Hz), 139.5 (d, J = 9.6 Hz), 137.3, 134.7, 130.2 (q, J = 32.8 Hz), 129.5, 128.6, 128.1, 128.1, 128.0, 127.5, 126.6, 126.0 (q, J = 3.8 Hz), 125.1, 124.3 (q, J = 273 Hz), 123.8 (d, J = 8.0 Hz), 123.1, 122.3, 121.8, 121.7, 121.3 (d, J = 4.2 Hz), 115.6 (d, J = 14.9 Hz); 31P NMR (202 MHz, CDCl3) δ 12.14 (d, J = 39.4 Hz); 19F NMR (471 MHz, CDCl3) δ −62.51; UV/vis (CHCl3) λmax (log ε) 380 (3.84), 337 (3.91) nm; HRMS (ESI) m/z calcd for C H NO +25 18 2F3P [M + H ] 452.1027, found 452.1030. 2-Phenoxy-3-(4-methoxyphenyl)-1H-naphtho[2,1-e][1,2]azaphosphinine 2-oxide 8f: colorless waxy solid (33 mg, 16%); Rf = 0.53 (hexanes/CH2Cl2/EtOAc, 1:2:2); mp > 200 °C; 1H NMR (500 MHz, CDCl3) δ 9.29 (s, 1H), 8.51 (d, J = 8.1 Hz, 1H), 7.94–7.92 (m, 2H), 7.82 (m, 1H), 7.69 (d, J = 40.6 Hz, 1H), 7.58–7.52 (m, 2H), 7.44 (d, J = 8.5 Hz, 1H), 7.36 (d, J = 8.5 Hz, 1H), 7.08 (d, J = 8.5 Hz, 2H), 7.01–6.96 (m, 4H), 6.90 (m, 1H), 3.94 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3) δ 160.0, 150.5 (d, J = 9.2 Hz), 140.4 (d, J = 6.3 Hz), 136.4, 134.2, 129.3, 129.1 (d, J = 6.9 Hz), 128.4, 128.3 (d, J = 9.3 Hz), 127.5, 127.4, 126.4, 124.8, 124.0, 123.9 (d, J = 8.0 Hz), 122.9, 122.3, 121.4 (d, J = 4.2 Hz), 121.3, 115.9 (d, J = 15.1 Hz), 114.5, 55.6; 31P NMR (202 MHz, CDCl3) δ 13.07 (d, J = 40.7 Hz); UV/vis (CHCl3) λmax (log ε) 372 (3.86), 356 (3.87) nm; HRMS (ESI) m/z calcd for C25H21NO3P [M + H+] 414.1259, found 414.1261. 476 Supplementary Information 1. X-ray Structure Data and Molecular Packing Diffraction intensities for 8c and 8d were collected at 173 K on a Bruker Apex2 CCD diffractometer using CuKa radiation, λ = 1.54178 A. Space groups were determined based on intensity statistics. Absorption corrections were applied by SADABS.20 Structures were solved by direct methods and Fourier techniques and refined on F2 using full matrix least- squares procedures. All non-H atoms were refined with anisotropic thermal parameters. All H atoms in 8d and H atoms at the N atoms in 8c involved in H-bonds were found on the residual density maps and refined with isotropic thermal parameters. Other H atoms in 8c were refined in calculated positions in a rigid group model. Solvent molecules CHCl3 in 8c fill out in the packing a space between main molecules and its positions appear to be partially occupied or highly disordered. As a result, diffraction intensities at high angles are very weak. These solvents molecules on 8c were treated by SQUEEZE.21 The correction of the X-ray data by SQUEEZE is 228 electron/cell; the required value is 232 electron/cell for four CHCl3 molecules in the full unit cell. All calculations were performed by the Bruker SHELXL-2014 package22 The ORTEP drawings were made with the Diamond23 and Ortep-324 programs. The visualization and exploration of the intermolecular close contacts of the structure was achieved by the Hirshfeld surface analysis with the Crystal Explorer software.25 CCDC 1900247 and 1900248 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre at www.ccdc.cam.ac.uk/data_request/cif. 477 Crystallographic data for 8c: C25H17N2O2P•CHCl3, M = 527.74, 0.11 × 0.03 × 0.02 mm, T = 173(2) K, Triclinic, space group P-1, a = 12.7196(6) A, b = 14.8501(7) A, c = 15.4304(7) A, α = 117.135(3)°, β = 106.977(3)°, γ = 94.402(3)°, V = 2404.1(2) A3, Z = 4, Dc = 1.458 Mg m–3, μ(Cu)= 4.310 mm–1, F(000) = 1080, 2θmax = 133.44°, 30824 reflections, 8446 independent reflections [Rint = 0.0546], R1 = 0.1027, wR2 = 0.2856 and GOF = 1.115 for 8446 reflections (549 parameters) with I>2σ(I), R1 = 0.1241, wR2 = 0.3052 and GOF = 1.119 for all reflections, max/min residual electron density +1.335/– 0.332 eA–3. CCDC 1900247. Crystallographic data for 8d: C25H20NO4PS, M = 461.45, 0.12 × 0.09 × 0.07 mm, T = 173(2) K, Triclinic, space group P-1, a = 8.3012(3) A, b = 11.3430(4) A, c = 13.0055(5) A, α = 93.515(2)°, b = 103.769(2)°, γ = 110.518(2)°, V = 1099.77(7) A3, Z = 2, Dc = 1.393 Mg m–3, S3 μ(Cu) = 2.273 mm–1, F(000) = 480, 2θmax = 133.10°, 12225 reflections, 3871 independent reflections [Rint = 0.0453], R1 = 0.0370, wR2 = 0.0993 and GOF = 1.029 for 3871 reflections (369 parameters) with I>2s(I), R1 = 0.0424, wR2 = 0.1039 and GOF = 1.029 for all reflections, max/min residual electron density +0.399/–0.342 eA–3. CCDC 1900248. 478 Figure H.7. ORTEP drawing of the structure of 8d (thermal ellipsoids drawn at 30% probability). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of CH2Cl2 solution at room temperature. Figure H.8 (a) ORTEP drawing of the dimer structure of 8c via hydrogen-bonding (thermal ellipsoids drawn at 30% probability). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of CHCl3 solution at room temperature; (b) Intermolecular π contacts; (c) The molecular packing diagram viewed along the a-axis. All hydrogen atoms not involved in H-bonding interactions are omitted for clarity; the distances of contacts are in A. 479 Table H.4. Selected bond lengths, bond angles, and dihedral angles of PN-heterocycles 8c and 8d. There are no significant differences of the selected bond angles and lengths among the two structures. The dihedral angle between the tricyclic cores and their intersections with the pendant phenyl plane exhibit the value of 7° for 8c and 40° in 8d, respectively, which is likely attributable to the packing effects in the solid state. ________________________________________________________________________ cmpd 8c 8d Bond Length (Å) a 1.632/1.635 1.648 b 1.771/1.760 1.762 c 1.353/1.351 1.347 Bond angle (°) α 128.2/128.9 127.4 β 128.1/128.2 127.8 Deviation of P atom (Å)a 0.05/0.11 0.25 Dihedral angle A/B θ (°)b 7.1/7.6 40.2 a The average distance of the P atom from the mean plane A defined by the other 13 non- H atoms in the tricyclic core. b Dihedral angles between the mean plane A defined by the other 13 non-H atoms and the pendant phenyl plane B. 480 2. Photophysical Properties UV/Vis data were obtained on an HP 8453 UV/Vis spectrometer. Fluorescence data were acquired with a Horiba Jobin-Yvon FluoroMax-4 fluorescence spectrophotometer. Dilute solutions in degassed spectral grade CHCl3 in a 1 cm quartz cell were used for measurements. Quantum yields were calculated by comparison with freshly prepared quinine sulfate in 0.1M H2SO4 with excitation at 360 nm using an excitation slit width of 2.5 nm for all samples, and emission integrated across the range 380–650 nm. To minimize the re-absorption effects, the absorbance in the 10 mm fluorescence cuvette was about 0.05- 0.07 at 360 nm. Fluorescence lifetimes were measured using time correlated single photon counting (TCSPC). Dilute solutions were prepared and placed in a 1 cm optical path quartz cuvette. A pulsed nanoLED was used to excite the samples at 344 nm at a 1 MHz repetition rate. The emission was detected via a longpass filter. The decay profiles of were fitted reasonably well using the bi-exponential (for 8a-c) and mono-exponential functions (for 8d-f). Figure H.9 Fluorescence spectra of 8a in various solvents. 481 Figure H.10 Fluorescence spectra of 8b in various solvents. Figure H.11 Fluorescence spectra of 8c in various solvents. Figure H.12 Fluorescence spectra of 8d in various solvents. 482 Figure H.13 Fluorescence spectra of 8e in various solvents. Figure H.14 Fluorescence spectra of 8f in various solvents. 483 3. Theoretical calculations This work benefited from access to the University of Oregon high performance computer, Talapas. The initial structures of 7, 8c and 8d were generated from the above X-ray crystallography data. Other similar structures are adjusted according to the structures in the single crystal. 3.1 TD-DFT calculations These initial structures were optimized using the functional PBE07 and 6-311G(d) basis set as implemented in Gaussian 09.27 In addition, all the optimized structures were confirmed by frequency analysis and the number of imaginary frequencies was zero. TD- DFT vertical excitation calculations and geometry optimization of the first excited state (S1) were performed at the same level of theory. The PCM solvation model 28 was used to account for the solvent effects of the chloroform. 484 Figure H.15 Kohn-Sham molecular orbitals, excitation energies, and oscillator strengths for PN-heterocycles 7a-d, calculated at the TD-PBE0/6-311G(d) level of theory. For 7a-c, the S0→S1 electronic transitions are dominated by the transitions from HOMO→LUMO with very small oscillator strengths (f < 0.1), while the transitions from HOMO-1→LUMO contribute the S0→S2 electronic transitions with large oscillator strengths (f ≈ 1). For 7d, the S0→S1 electronic transitions mainly correspond to the transitions from HOMO- 1→LUMO, while the S0→S2 electronic transitions is predominated by the transitions from HOMO→LUMO. 485 Table H.5 The S0/S1 geometries of 8 ________________________________________________________________________ S0 S1 θ (°)a d (Å) θ (°)a d (Å) 8a 32.93 1.473 12.70 1.440 8b 34.23 1.474 8.90 1.438 8c 32.77 1.474 7.17 1.436 8d 34.82 1.476 7.91 1.437 8e 33.77 1.476 11.04 1.439 8f 33.82 1.475 14.26 1.434 a Dihedral angles between the mean plane A defined by the other 13 non-H atoms and the pendant phenyl plane B. Table H.6 The frontier molecular orbital energies in the S1 states and TD-DFT predicted emission wavelengths of 8. HOMO LUMO (eV) EH-L (eV)  a em,cal (nm) em,exp (nm) (eV) 8a −6.144 −2.948 3.196 485 (0.6025) 493 8b −6.124 −2.86 3.264 477 (0.6002) 490 8c −6.023 −2.721 3.302 468 (0.7179) 469 8d −6.042 −2.68 3.362 461 (0.6329) 470 8e −5.98 −2.569 3.411 452 (0.5917) 457 8f −5.592 −2.305 3.287 461 (0.9252) 441 a The calculated oscillator strength (f) given in parentheses. 486 Table H.7 Cartesian coordinates for compound 8a (S0) X Y Z C -3.35271900 -1.20420200 2.53300500 C -2.00606500 -1.14125900 2.35750400 C -4.22602400 -1.08607300 1.41893800 C -3.69077000 -0.89475000 0.11278200 C -2.26894600 -0.84593400 -0.04256000 C -1.43143400 -0.96170300 1.06865300 N -1.71933000 -0.70538700 -1.29922200 P -0.11889700 -0.43998600 -1.72505300 C 0.72457600 -0.77490500 -0.19769700 C -0.00503900 -0.95929700 0.93481100 O 0.28286000 -1.14480500 -2.96141600 C 2.19697100 -0.80638500 -0.18933100 C 2.90576700 -0.30244100 0.90712000 C 4.29465400 -0.35462200 0.94599400 C 5.01025000 -0.90607100 -0.13436900 C 4.30590600 -1.38831500 -1.23642400 C 2.92235600 -1.33665000 -1.26534100 C -5.62753400 -1.14792400 1.58124800 C -6.47254400 -1.02166000 0.50731500 C -5.94612600 -0.81825400 -0.78126800 C -4.58803400 -0.75466000 -0.97185700 O 0.03899600 1.15615200 -2.00919200 C -0.27586800 2.13487200 -1.07858700 C -1.58530700 2.58133300 -0.95811100 C -1.87333300 3.60036900 -0.05744800 C -0.86157200 4.16953800 0.70809200 C 0.44713200 3.71957800 0.56861400 C 0.74589600 2.69858200 -0.32581700 C 6.43288500 -0.96755300 -0.11363100 N 7.58579900 -1.02406300 -0.10777500 H -3.77670500 -1.34565800 3.52182700 H -1.33787800 -1.23336800 3.20848900 H -2.34428500 -0.80180400 -2.08693400 H 0.54400900 -1.16380900 1.85277400 H 2.37779700 0.15847600 1.73386400 H 4.85006700 -1.81113200 -2.07275300 H 2.39189700 -1.72135800 -2.12874700 H -6.02784800 -1.29689400 2.57972800 H -7.54716800 -1.07167100 0.64978200 H -6.61475800 -0.70588500 -1.62817700 H -4.22565600 -0.57795000 -1.97980500 H -2.36366000 2.14011600 -1.57070400 H -2.89513200 3.95265200 0.04006500 H -1.09117700 4.96744100 1.40660700 H 1.24364100 4.16664600 1.15473700 487 H 1.76299800 2.34545800 -0.45811700 C 4.98087700 0.17131800 2.08058100 N 5.52306600 0.59947600 3.00481400 Table H.8 Cartesian coordinates for compound 8a (S1) X Y Z C -3.39447600 -2.12734200 1.75355100 C -2.02528300 -2.03930100 1.59915400 C -4.27675300 -1.51497200 0.83190700 C -3.73039200 -0.79758600 -0.27517300 C -2.31187500 -0.74729100 -0.42997500 C -1.43492500 -1.35307100 0.52811900 N -1.75001000 -0.15357300 -1.51464900 P -0.12124800 0.26906500 -1.77801700 C 0.75173900 -0.66481500 -0.54281800 C -0.01344400 -1.32565400 0.41045600 O 0.20981400 0.15284300 -3.21226200 C 2.19062500 -0.60187600 -0.52644900 C 2.91774600 -0.99630100 0.62227200 C 4.29830700 -0.94713600 0.66366100 C 5.04517300 -0.49710900 -0.45929100 C 4.32601600 -0.09651400 -1.60345100 C 2.95469800 -0.14534700 -1.64003100 C -5.66833100 -1.59125500 0.99522700 C -6.52744800 -0.97478600 0.09997700 C -5.99720500 -0.25894400 -0.97570300 C -4.62653900 -0.16853900 -1.16052300 O -0.02208100 1.83396500 -1.35360300 C -0.26250000 2.31781200 -0.07481200 C -1.54839700 2.70981100 0.27179300 C -1.77463400 3.24417400 1.53535100 C -0.72427600 3.38403800 2.43550200 C 0.55979100 2.99253700 2.06913100 C 0.79810700 2.45550600 0.81004000 C 6.45416900 -0.44525000 -0.43628400 N 7.61298300 -0.39646400 -0.42898000 H -3.80704800 -2.67336800 2.59554300 H -1.37681100 -2.52309600 2.32220300 H -2.36032300 0.12362600 -2.27251800 H 0.50901900 -1.90364800 1.16590000 H 2.39902300 -1.31616100 1.51747200 H 4.87369400 0.24689100 -2.47399100 H 2.45137700 0.14512500 -2.55516000 H -6.06478900 -2.14278700 1.84209900 H -7.60086100 -1.04170800 0.23633500 H -6.66013400 0.23804400 -1.67568500 H -4.26880200 0.41942600 -1.99977100 H -2.35364100 2.60705000 -0.44772700 488 H -2.77643000 3.55649000 1.81190700 H -0.90412400 3.80414100 3.41959300 H 1.38476600 3.10765800 2.76456100 H 1.79360800 2.15239500 0.50501000 C 4.95960000 -1.34377300 1.86206800 N 5.48579500 -1.66890600 2.83780300 Table H.9 Cartesian coordinates for compound 8b (S0) X Y Z C 4.73875000 -1.43517200 -2.28175300 C 3.38197200 -1.38595600 -2.20740100 C 5.52825800 -1.16648200 -1.13207700 C 4.89818700 -0.84098300 0.10352900 C 3.46806700 -0.81021400 0.15356700 C 2.71431400 -1.07249600 -0.99159800 N 2.82636300 -0.53873000 1.34344500 P 1.19429900 -0.26707600 1.62376900 C 0.46802500 -0.78507500 0.08743500 C 1.28127800 -1.08275700 -0.96023500 O 0.72306200 -0.83867900 2.90352000 C -1.00025200 -0.83686400 -0.02966900 C -1.62391200 -0.44697000 -1.22465400 C -2.99823200 -0.51720400 -1.36605500 C -3.75856500 -0.97670300 -0.29450200 C -3.17249900 -1.35437600 0.90940100 C -1.79530200 -1.28061700 1.03743300 C 6.93874800 -1.20886600 -1.19054100 C 7.70360500 -0.93801400 -0.08387800 C 7.08360100 -0.60394000 1.13390600 C 5.71441900 -0.55539600 1.22335200 O 0.99085600 1.34769100 1.71720600 C 1.31463000 2.22192600 0.69138100 C 2.61937600 2.67679300 0.55161500 C 2.91370800 3.59419300 -0.45074100 C 1.91267800 4.05532500 -1.29860400 C 0.60843900 3.59844800 -1.14026800 C 0.30371900 2.67802300 -0.14450700 H 5.23436700 -1.68014500 -3.21556100 H 2.77696700 -1.59276600 -3.08513700 H 3.39266400 -0.53046800 2.17965800 H 0.80212900 -1.39806300 -1.88588600 H -1.02764600 -0.06191800 -2.04459000 H -3.78334000 -1.72121100 1.72629800 H -1.32611200 -1.58310200 1.96642000 H 7.41089600 -1.46035000 -2.13569300 H 8.78636300 -0.97521000 -0.14619100 H 7.68849900 -0.37899400 2.00599700 H 5.27910500 -0.27678600 2.17798600 H 3.38946500 2.32001400 1.22640100 489 H 3.93202400 3.95204200 -0.56362900 H 2.14713300 4.77447100 -2.07657400 H -0.17993300 3.96130500 -1.79202800 H -0.70952700 2.31856400 -0.00040700 H -3.47689300 -0.22392500 -2.29326100 S -5.51126100 -1.06128500 -0.46401300 O -5.86831300 -1.08042600 -1.87223300 O -6.05471700 -2.02290700 0.47894400 C -6.06094100 0.61549800 0.16137000 F -7.37311100 0.70025800 0.03456800 F -5.72797100 0.75218700 1.43431100 F -5.48497600 1.57157500 -0.55096500 Table H.10 Cartesian coordinates for compound 8b (S1) X Y Z C 4.73844200 -1.02285500 -2.42829800 C 3.36401800 -1.07703900 -2.32342900 C 5.55623200 -0.85437600 -1.28427200 C 4.93497000 -0.73861300 -0.00284400 C 3.51337700 -0.81943100 0.08209700 C 2.70057100 -0.97416000 -1.09064600 N 2.88168400 -0.79074000 1.28519200 P 1.22420400 -0.57674800 1.61253900 C 0.44510400 -0.94839600 0.06136900 C 1.28084400 -1.06846400 -1.04902200 O 0.86234700 -1.27827200 2.86095900 C -0.99090700 -0.97457500 -0.00597500 C -1.66767200 -0.93470200 -1.25989600 C -3.03818400 -0.95575900 -1.34042300 C -3.80309900 -1.03354400 -0.16594400 C -3.17273700 -1.06855900 1.09006400 C -1.80064600 -1.04532000 1.16207100 C 6.95313700 -0.79117600 -1.39063100 C 7.74877000 -0.61487100 -0.26928100 C 7.14582500 -0.48997200 0.98447200 C 5.76768700 -0.54772800 1.11788800 O 1.05366300 1.02316900 1.86056100 C 1.27965200 1.99634700 0.89921400 C 2.54384500 2.55972700 0.78638300 C 2.75235800 3.57396400 -0.14166600 C 1.70608900 4.01656200 -0.94313500 C 0.44366600 3.44538400 -0.81305000 C 0.22315600 2.43053900 0.10969400 H 5.20777300 -1.11149700 -3.40266800 H 2.76684200 -1.21221700 -3.21937200 H 3.44798900 -0.84182200 2.12163100 H 0.81803400 -1.26903500 -2.00923700 H -1.10625700 -0.85762400 -2.18307000 490 H -3.76669200 -1.14335600 1.99392100 H -1.33318700 -1.11599600 2.13776300 H 7.40623300 -0.88194900 -2.37314600 H 8.82777500 -0.56966100 -0.36457400 H 7.75756600 -0.34227200 1.86803400 H 5.35329200 -0.42599000 2.11353400 H 3.34567000 2.21275300 1.42934500 H 3.73698600 4.02111300 -0.23238700 H 1.87184300 4.81037600 -1.66409600 H -0.37844700 3.79278700 -1.43034400 H -0.75552600 1.97868000 0.22866200 H -3.53153900 -0.92296700 -2.30552600 S -5.53234600 -1.01773500 -0.26719100 O -5.96871900 -1.41425300 -1.59939100 O -6.12238900 -1.59609300 0.93211900 C -5.97291700 0.79790800 -0.16381300 F -7.28769900 0.93689900 -0.24853400 F -5.55528300 1.30239700 0.98932300 F -5.40083500 1.46149300 -1.16050000 Table H.11 Cartesian coordinates for compound 8c (S0) X Y Z C 3.22839300 -1.50801600 -2.28489100 C 1.87212300 -1.43161200 -2.21931200 C 4.01564400 -1.24997300 -1.13149200 C 3.38348800 -0.90794400 0.09862200 C 1.95411300 -0.85146700 0.13955400 C 1.20256600 -1.10164900 -1.00917800 N 1.30932400 -0.56705300 1.32512600 P -0.31854500 -0.26317700 1.59329700 C -1.04683900 -0.75996300 0.05073500 C -0.23139700 -1.08069800 -0.98809400 O -0.81281300 -0.82908300 2.86726800 C -2.51545000 -0.76693000 -0.07818800 C -3.12096600 -0.38675600 -1.28509900 C -4.49518200 -0.41644300 -1.43429500 C -5.30257300 -0.81644700 -0.36410400 C -4.71442200 -1.17920900 0.85094000 C -3.33758300 -1.15164300 0.99047900 C 5.42560300 -1.31836000 -1.18042500 C 6.18816600 -1.05634600 -0.07010000 C 5.56629300 -0.70529500 1.14204800 C 4.19766200 -0.63184700 1.22228700 O -0.48469800 1.35611800 1.69366700 C -0.06631200 2.23123500 0.70419500 C 1.24445400 2.69069100 0.70081000 C 1.63880500 3.61019600 -0.26413000 C 0.72976400 4.06810200 -1.21178300 491 C -0.58189100 3.60574900 -1.19102500 C -0.98621700 2.68360100 -0.23280400 C -6.72022900 -0.84429600 -0.51153200 N -7.86860300 -0.86715600 -0.63361700 H 3.72490000 -1.76603000 -3.21475000 H 1.26888100 -1.62891300 -3.10050600 H 1.86963600 -0.57065000 2.16525700 H -0.70988700 -1.38585300 -1.91744200 H -2.50876400 -0.03941300 -2.11055200 H -4.94896400 -0.11741800 -2.37255800 H -5.33807600 -1.48671100 1.68281800 H -2.88932500 -1.44147500 1.93381800 H 5.89919500 -1.58243100 -2.12145400 H 7.27048200 -1.11329100 -0.12516100 H 6.16951300 -0.48675500 2.01697700 H 3.76093900 -0.34071200 2.17251400 H 1.94009300 2.33562800 1.45322000 H 2.66201600 3.97183200 -0.27012500 H 1.04124400 4.78851600 -1.96107300 H -1.29895100 3.96575700 -1.92198100 H -2.00778100 2.32065400 -0.19580800 Table H.12 Cartesian coordinates for compound 8c (S1) X Y Z C 3.33514800 -1.34259400 -2.26457200 C 1.96243200 -1.34810100 -2.20948500 C 4.11917700 -1.06775800 -1.11245100 C 3.45601000 -0.79605500 0.12390200 C 2.03374400 -0.83738200 0.16446100 C 1.25496000 -1.09225200 -1.01787800 N 1.36298400 -0.67871900 1.33844800 P -0.29629300 -0.40177400 1.58589900 C -1.03348600 -0.87292700 0.04278800 C -0.16058400 -1.13381000 -1.02219700 O -0.72198400 -0.99490700 2.87094000 C -2.46289900 -0.84506900 -0.07987300 C -3.10060000 -0.95791400 -1.34909300 C -4.46806600 -0.92614100 -1.47563600 C -5.29202100 -0.77946200 -0.34351700 C -4.68470900 -0.66514500 0.92333900 C -3.31676300 -0.69929200 1.04927800 C 5.51799200 -1.05039100 -1.17064700 C 6.27926300 -0.76831300 -0.04549000 C 5.63679000 -0.48720000 1.16289100 C 4.25508900 -0.49706100 1.24910900 O -0.43499600 1.21680700 1.70987700 C -0.15417400 2.11091600 0.68875500 C 1.13068300 2.62345400 0.56627700 C 1.39369400 3.56219900 -0.42520500 492 C 0.38059700 3.98129400 -1.28014700 C -0.90293300 3.46200600 -1.14054500 C -1.17756000 2.52227100 -0.15478000 C -6.69980900 -0.74478700 -0.47827100 N -7.85329100 -0.71482200 -0.59039400 H 3.83852200 -1.54950900 -3.20360300 H 1.39193700 -1.56406100 -3.10717300 H 1.89879700 -0.68444900 2.19610700 H -0.59848600 -1.40390300 -1.97686400 H -2.51012000 -1.04835600 -2.25277700 H -4.91994600 -1.00686500 -2.45879700 H -5.30397800 -0.55875200 1.80747000 H -2.88940000 -0.64070000 2.04409700 H 6.00368400 -1.26144300 -2.11879000 H 7.36189800 -0.76011800 -0.10467300 H 6.22154900 -0.25299200 2.04623400 H 3.80700400 -0.24777800 2.20595900 H 1.90736200 2.29521200 1.24868400 H 2.39511300 3.96854800 -0.52405100 H 0.58894400 4.71626600 -2.05075800 H -1.69920200 3.79098100 -1.80040200 H -2.17316000 2.11123300 -0.02813700 Table H.13 Cartesian coordinates for compound 8d (S0) X Y Z C 3.96658600 -1.62228000 -2.28954600 C 2.61589300 -1.49139300 -2.19730000 C 4.78780800 -1.37535800 -1.15774900 C 4.19583200 -0.98672300 0.07848900 C 2.77082100 -0.87660800 0.14881700 C 1.98567900 -1.11621400 -0.97938800 N 2.16315600 -0.54964500 1.34365200 P 0.55589300 -0.17100600 1.63707100 C -0.22434900 -0.67273000 0.12268600 C 0.55367200 -1.04105500 -0.92816500 O 0.06314400 -0.68190900 2.93448100 C -1.69610300 -0.62978100 0.02847100 C -2.31365600 -0.21371200 -1.15967200 C -3.69401300 -0.19730300 -1.27697400 C -4.46842100 -0.59100700 -0.19189300 C -3.88386700 -0.99695100 1.00158700 C -2.50181700 -1.01157200 1.11042500 C 6.19280100 -1.49973300 -1.23451700 C 6.98857100 -1.24625500 -0.14575000 C 6.40698700 -0.84655100 1.07137900 C 5.04422900 -0.71877100 1.17863800 O 0.46024400 1.45722300 1.69813000 C 0.91630100 2.28566500 0.68577000 C 2.24681000 2.68416100 0.66989800 493 C 2.68261600 3.55665600 -0.32038400 C 1.79498500 4.02875600 -1.28129000 C 0.46349100 3.62804200 -1.24829400 C 0.01770000 2.75316200 -0.26443600 H 4.43258700 -1.91538000 -3.22477200 H 1.98678800 -1.67957900 -3.06221500 H 2.74033300 -0.56487100 2.17220200 H 0.04252500 -1.34438700 -1.84067400 H -1.70705900 0.11885100 -1.99548900 H -4.50381500 -1.32062800 1.83043400 H -2.03891300 -1.33692000 2.03490500 H 6.63552900 -1.80026600 -2.17963700 H 8.06645200 -1.34661600 -0.22195500 H 7.03708900 -0.63298600 1.92842700 H 4.63952900 -0.38917000 2.13049200 H 2.92574600 2.31728300 1.43179900 H 3.72150800 3.87004000 -0.33630400 H 2.13891500 4.71194800 -2.05096800 H -0.23621600 3.99911000 -1.99047800 H -1.01902700 2.43708400 -0.21872100 H -4.16844000 0.11128900 -2.20190900 S -6.24336400 -0.55716900 -0.33035900 O -6.58686700 -0.61833800 -1.74964100 O -6.79035100 -1.55176400 0.58960200 C -6.69337200 1.05737900 0.27475200 H -6.37399500 1.15321000 1.31148500 H -6.22679700 1.81685100 -0.35099200 H -7.77987100 1.12182200 0.20457700 Table H.14 Cartesian coordinates for compound 8d (S1) X Y Z C 4.07929300 -1.39921200 -2.30775000 C 2.70727300 -1.37003800 -2.21310600 C 4.90283500 -1.14432900 -1.17971300 C 4.28109000 -0.85592900 0.07474400 C 2.86031400 -0.85963100 0.15554600 C 2.04059100 -1.09501500 -1.00392900 N 2.22702600 -0.68363100 1.34765700 P 0.58374000 -0.35339700 1.63765300 C -0.20967700 -0.81846200 0.12381300 C 0.62458800 -1.10059100 -0.96690900 O 0.17718800 -0.91542000 2.94284300 C -1.64340600 -0.75679900 0.04033600 C -2.31346900 -0.83946200 -1.21332700 C -3.68582600 -0.77385600 -1.30330900 C -4.45541100 -0.62786700 -0.14561700 C -3.83378200 -0.54771400 1.10643400 C -2.46116900 -0.61517400 1.19552500 494 C 6.29934100 -1.16340600 -1.27716500 C 7.09951900 -0.90249600 -0.17335400 C 6.49806500 -0.60712800 1.05217200 C 5.11875500 -0.58068400 1.17700100 O 0.50417300 1.27234800 1.74835600 C 0.79511300 2.14744800 0.71493900 C 2.08531000 2.64647000 0.59003500 C 2.36157800 3.56693500 -0.41490000 C 1.35664100 3.98148000 -1.28161100 C 0.06768400 3.47641100 -1.13979100 C -0.22029500 2.55552000 -0.14023200 H 4.54900600 -1.61993400 -3.26102800 H 2.10719400 -1.57338300 -3.09431100 H 2.78594900 -0.70073700 2.19020600 H 0.15240900 -1.36476700 -1.90676300 H -1.74839800 -0.93719900 -2.13227200 H -4.43478500 -0.46327300 2.00544100 H -2.00458900 -0.59261600 2.17881400 H 6.75253900 -1.38622800 -2.23855100 H 8.17987800 -0.92258000 -0.26270300 H 7.11271300 -0.39041600 1.91959300 H 4.70434400 -0.32303200 2.14672400 H 2.85611000 2.32210600 1.28116000 H 3.36721600 3.96224900 -0.51559100 H 1.57561300 4.70147700 -2.06332900 H -0.72197900 3.80185900 -1.80936100 H -1.22011100 2.15536000 -0.01213700 H -4.17446400 -0.84659600 -2.26915700 S -6.20778700 -0.50332800 -0.27156500 O -6.62821900 -1.13303300 -1.52489200 O -6.79911100 -0.94812900 0.99138100 C -6.53289400 1.24566500 -0.42239900 H -6.16093100 1.75662400 0.46467500 H -6.04775600 1.62258700 -1.32177100 H -7.61525400 1.35916700 -0.49908300 Table H.15 Cartesian coordinates for compound 8e (S0) X Y Z C 3.75052200 -1.60949100 -2.29428600 C 2.39947300 -1.48491300 -2.19599600 C 4.57549900 -1.35611000 -1.16680700 C 3.98694600 -0.96720100 0.07107400 C 2.56169200 -0.86199200 0.14698000 C 1.77282100 -1.10909200 -0.97666400 N 1.95759000 -0.53095900 1.34225000 P 0.34631700 -0.17499200 1.64759200 C -0.43632300 -0.66757800 0.13119300 C 0.34053800 -1.03676200 -0.92003600 O -0.12714900 -0.70992600 2.94290400 495 C -1.90834000 -0.61878900 0.03654800 C -2.52564500 -0.21707800 -1.15613800 C -3.90524700 -0.19561400 -1.27153800 C -4.69823500 -0.55947400 -0.18668400 C -4.10257900 -0.94118500 1.01001400 C -2.72049800 -0.96792100 1.12283500 C 5.98076000 -1.47463200 -1.24921400 C 6.78013400 -1.21603100 -0.16433500 C 6.20184500 -0.81728600 1.05469700 C 4.83900600 -0.69490400 1.16734900 O 0.23011000 1.45034900 1.73373800 C 0.60607300 2.29914500 0.70532500 C 1.93248700 2.69236600 0.58176300 C 2.28444100 3.58678000 -0.42257300 C 1.31865800 4.08652100 -1.28937500 C -0.00738900 3.69086100 -1.14812600 C -0.36970200 2.79346600 -0.15051600 H 4.21369900 -1.90245500 -3.23099700 H 1.76742300 -1.67805200 -3.05772600 H 2.53925900 -0.53615100 2.16778600 H -0.17255900 -1.33914300 -1.83176900 H -1.91905200 0.10851400 -1.99465500 H -4.36506100 0.12562800 -2.19974600 H -4.71639600 -1.21639500 1.86038600 H -2.26436900 -1.27040100 2.05847100 H 6.42072500 -1.77498900 -2.19571000 H 7.85811300 -1.31196100 -0.24493000 H 6.83447600 -0.60043600 1.90906800 H 4.43705000 -0.36671200 2.12084000 H 2.67436500 2.30549600 1.27151800 H 3.31986800 3.89623700 -0.52249600 H 1.59775600 4.78753200 -2.06922600 H -0.76806100 4.08335500 -1.81552200 H -1.40005400 2.48007300 -0.02114300 C -6.18732900 -0.57974600 -0.32989000 F -6.62433800 -1.74833300 -0.83771700 F -6.81444800 -0.41329200 0.84359400 F -6.62748100 0.38252100 -1.15704700 Table H.16 Cartesian coordinates for compound 8e (S1) X Y Z C 3.84892700 -1.43999300 -2.28621400 C 2.47822400 -1.40540800 -2.20172500 C 4.66799700 -1.16792000 -1.15648200 C 4.03778800 -0.85870100 0.08947500 C 2.61870400 -0.86700700 0.16356700 C 1.80258100 -1.10977400 -0.99998600 N 1.97945400 -0.69564400 1.35513800 P 0.33859800 -0.34656100 1.63333400 496 C -0.44741900 -0.79836500 0.11551600 C 0.38981700 -1.10357200 -0.97043100 O -0.08233100 -0.90319200 2.93730200 C -1.87939200 -0.69964100 0.01292300 C -2.53223800 -0.71345900 -1.24901300 C -3.90474600 -0.62566400 -1.35178400 C -4.69824100 -0.51260300 -0.20871000 C -4.08197200 -0.48948600 1.04745600 C -2.71147200 -0.58152700 1.15792700 C 6.06373600 -1.18964700 -1.24429000 C 6.85835000 -0.90981400 -0.13937200 C 6.24943300 -0.58992500 1.07615100 C 4.86954400 -0.56039600 1.19215900 O 0.27638800 1.28166400 1.74785800 C 0.55752200 2.15209400 0.70856800 C 1.85743900 2.61006300 0.53510600 C 2.12480400 3.52494500 -0.47734400 C 1.10128300 3.97577900 -1.30315700 C -0.19714600 3.51247200 -1.11260100 C -0.47601200 2.59658300 -0.10594200 H 4.32477500 -1.67632600 -3.23283900 H 1.88288700 -1.61912000 -3.08386800 H 2.53141000 -0.73643300 2.20144600 H -0.08386300 -1.37753400 -1.90720800 H -1.95315200 -0.76088400 -2.16344700 H -4.36807300 -0.62773600 -2.33269900 H -4.68432600 -0.40185700 1.94568900 H -2.26837200 -0.59043000 2.14767000 H 6.52313200 -1.42926300 -2.19881000 H 7.93925000 -0.93239400 -0.22188100 H 6.85901600 -0.35442800 1.94241900 H 4.44698000 -0.27590400 2.15090700 H 2.64361700 2.25751900 1.19420800 H 3.13832000 3.88742500 -0.61587500 H 1.31326100 4.69162300 -2.09065400 H -1.00149600 3.86642000 -1.74943300 H -1.48264500 2.22853600 0.05931100 C -6.18173000 -0.47704400 -0.31424500 F -6.74052100 -1.69688300 -0.14852000 F -6.74149800 0.31466100 0.61898000 F -6.60054000 -0.03344600 -1.51240400 Table H.17 Cartesian coordinates for compound 8f (S0) X Y Z C 3.28337400 -1.48620000 -2.34080100 C 1.92832000 -1.42638200 -2.22726100 C 4.10662100 -1.22178300 -1.21539400 C 3.51142800 -0.88939300 0.03599700 C 2.08404600 -0.84966700 0.12528100 497 C 1.29585800 -1.10720400 -0.99556300 N 1.47473900 -0.57186000 1.33286100 P -0.14654200 -0.27803800 1.64979600 C -0.92500200 -0.78517600 0.13633300 C -0.13996700 -1.10323600 -0.92501000 O -0.58870100 -0.83728700 2.94650200 C -2.39779300 -0.78109800 0.05973500 C -3.04840000 -0.37688500 -1.10923400 C -4.43313100 -0.39593400 -1.21977800 C -5.20771600 -0.81677100 -0.13791700 C -4.57247200 -1.20612000 1.04469100 C -3.19468500 -1.18580500 1.14311600 C 5.51529400 -1.27454100 -1.31125500 C 6.31203900 -1.00686200 -0.22679900 C 5.72660700 -0.66569100 1.00646900 C 4.36068800 -0.60765300 1.13239500 O -0.31874400 1.34398900 1.75327200 C 0.05390900 2.21696800 0.74610400 C 1.35536100 2.70081100 0.70105700 C 1.70486500 3.62095000 -0.28050300 C 0.76085700 4.05547000 -1.20471700 C -0.54042600 3.56778800 -1.14378400 C -0.89989600 2.64506300 -0.16843000 H 3.74994100 -1.73623900 -3.28837900 H 1.29798300 -1.62952900 -3.08812500 H 2.06304300 -0.56034800 2.15325800 H -0.64771400 -1.41186500 -1.83782400 H -2.46543400 -0.01357300 -1.95016800 H -4.89275100 -0.06723400 -2.14429600 H -5.18491500 -1.52778800 1.88057800 H -2.72205800 -1.49831800 2.06771900 H 5.95984000 -1.53195100 -2.26831400 H 7.39254300 -1.05211500 -0.31800900 H 6.35615700 -0.44312000 1.86176200 H 3.95253200 -0.32525100 2.09788200 H 2.07891100 2.36256700 1.43470800 H 2.72080500 4.00093800 -0.31844600 H 1.03739400 4.77629200 -1.96730600 H -1.28430400 3.90779900 -1.85745600 H -1.91131000 2.25874600 -0.10202900 O -6.55678200 -0.87206200 -0.13558600 C -7.24012800 -0.49104600 -1.31218900 H -7.04690600 0.55656400 -1.56517800 H -6.96364300 -1.12804500 -2.15869700 H -8.29926000 -0.61869400 -1.09740400 Table H.18 Cartesian coordinates for compound 8f (S1) X Y Z C 3.35589900 -1.75743400 -2.12240200 498 C 2.00324700 -1.78527700 -2.00823000 C 4.17978800 -1.23398500 -1.07463100 C 3.55341300 -0.74128900 0.11500200 C 2.14714300 -0.82146600 0.23543600 C 1.32697600 -1.31131400 -0.84286200 N 1.53299200 -0.49011300 1.42111700 P -0.10696100 -0.21810600 1.70507600 C -0.89472400 -0.89305000 0.27886600 C -0.06603200 -1.35840400 -0.77455400 O -0.48381900 -0.63019200 3.07786600 C -2.32251300 -0.82192200 0.16662200 C -2.98782800 -1.01810400 -1.07454800 C -4.36220200 -0.95568000 -1.19045200 C -5.15045100 -0.68290800 -0.06457600 C -4.52036900 -0.47670800 1.17686900 C -3.15588900 -0.54825200 1.29058100 C 5.57030900 -1.19156100 -1.19013700 C 6.36508800 -0.67431400 -0.17378600 C 5.76010000 -0.17255200 0.98372500 C 4.38801400 -0.19901400 1.12912300 O -0.30251000 1.40837500 1.63725700 C -0.05533800 2.17215100 0.51225400 C 1.22527100 2.65813100 0.27882500 C 1.45376700 3.47070500 -0.82570600 C 0.41038400 3.79641800 -1.68530000 C -0.86861100 3.30884000 -1.43568000 C -1.10764700 2.49329700 -0.33641200 H 3.83604200 -2.13005200 -3.02247400 H 1.39699200 -2.17875400 -2.81905600 H 2.10565100 -0.46700900 2.25390300 H -0.55643600 -1.81983700 -1.62614500 H -2.41198500 -1.19445900 -1.97525200 H -4.81562600 -1.11095700 -2.16246100 H -5.14150400 -0.27485300 2.04322100 H -2.70610700 -0.41951800 2.26936100 H 6.02984400 -1.57209300 -2.09827400 H 7.44434200 -0.65083500 -0.28157300 H 6.37158300 0.25212000 1.77387600 H 3.95815400 0.23661300 2.02587100 H 2.02749800 2.40180700 0.96234300 H 2.45321600 3.85095400 -1.01131500 H 0.59207900 4.43292900 -2.54528500 H -1.68862300 3.56476400 -2.09927300 H -2.09894200 2.10774700 -0.12399900 O -6.48860700 -0.59929300 -0.06657500 C -7.18044300 -0.79497400 -1.28655000 H -6.88962200 -0.04598800 -2.02935200 H -7.00170800 -1.79829100 -1.68475700 H -8.23599400 -0.68104400 -1.05054600 499 Table H.19 Cartesian coordinates for compund 7a X Y Z C 3.76708 -2.08152 -0.32091 C 2.38146 -2.27970 -0.44485 C 4.22851 -0.92525 0.37739 C 3.28718 -0.01785 0.90539 C 1.93519 -0.22670 0.75903 C 1.45915 -1.38660 0.07198 N 1.00850 0.64170 1.32283 P -0.60656 0.76571 0.91944 C -0.98370 -0.86503 0.29728 C 0.04869 -1.66772 -0.05219 O -1.40118 1.36471 2.01670 C -2.39045 -1.25766 0.10315 C -2.76358 -2.02205 -1.01119 C -4.07240 -2.43063 -1.18899 C -5.04634 -2.07011 -0.25193 C -4.69219 -1.29262 0.85450 C -3.37959 -0.88841 1.02540 C 4.71205 -2.99201 -0.85736 C 6.05536 -2.76960 -0.71177 C 6.51284 -1.62425 -0.02092 C 5.62459 -0.72537 0.51045 O -0.70506 1.60141 -0.47797 C -0.44234 2.96145 -0.55929 C 0.64750 3.36593 -1.31860 C 0.90540 4.72378 -1.46661 C 0.08310 5.66448 -0.85534 C -1.00345 5.24233 -0.09644 C -1.27608 3.88742 0.05502 C -6.39808 -2.48644 -0.43090 N -7.49269 -2.82553 -0.57569 H 2.02133 -3.16555 -0.96156 H 3.64149 0.86279 1.43459 H 1.36509 1.34812 1.95108 H -0.19162 -2.65080 -0.45386 H -2.02405 -2.27787 -1.76223 H -4.34829 -3.01725 -2.05808 H -5.44661 -1.00922 1.57977 H -3.11291 -0.28667 1.88638 H 4.35190 -3.86990 -1.38633 H 6.77353 -3.47049 -1.12479 H 7.57998 -1.45807 0.08918 H 5.98246 0.15241 1.04080 H 1.27362 2.61602 -1.79030 H 1.75342 5.04506 -2.06308 H 0.28657 6.72392 -0.97273 500 H -1.65045 5.97152 0.38086 H -2.11705 3.54289 0.64500 Table H.20 Cartesian coordinates for compund 7b X Y Z C 4.00277 -2.51575 -0.32109 C 2.60051 -2.50152 -0.41789 C 4.64924 -1.43132 0.34491 C 3.86766 -0.38169 0.86954 C 2.49695 -0.38484 0.75167 C 1.83549 -1.46951 0.09610 N 1.72651 0.62452 1.31544 P 0.14035 0.98634 0.94161 C -0.49386 -0.57584 0.35470 C 0.39545 -1.53278 0.00219 O -0.52803 1.71594 2.04406 C -1.94942 -0.74774 0.19154 C -2.46037 -1.44582 -0.90980 C -3.82308 -1.64863 -1.05296 C -4.70261 -1.14753 -0.09821 C -4.21280 -0.43616 0.99201 C -2.84884 -0.23441 1.13484 C 4.78731 -3.56960 -0.85342 C 6.15154 -3.55294 -0.73424 C 6.79211 -2.47877 -0.07546 C 6.06184 -1.44487 0.45078 O 0.14263 1.81223 -0.46606 C 0.62974 3.10750 -0.56554 C 1.76644 3.31554 -1.33541 C 2.24982 4.60870 -1.49742 C 1.60374 5.68008 -0.88966 C 0.46744 5.45428 -0.11975 C -0.02930 4.16639 0.04630 H 2.09902 -3.33091 -0.90988 H 4.36110 0.44475 1.37405 H 2.20080 1.27642 1.92446 H -0.00171 -2.47252 -0.37840 H -1.78593 -1.81402 -1.67558 H -4.20174 -2.19240 -1.91127 H -4.89543 -0.04648 1.73908 H -2.47404 0.31683 1.98942 H 4.28760 -4.39176 -1.35800 H 6.74586 -4.36317 -1.14405 H 7.87404 -2.47610 0.01383 H 6.55972 -0.62247 0.95647 H 2.25334 2.46638 -1.80319 H 3.13554 4.77663 -2.10196 H 1.98306 6.68871 -1.01775 H -0.04254 6.28630 0.35549 H -0.91088 3.97354 0.64594 C -6.17834 -1.31857 -0.27662 F -6.82390 -1.39472 0.89756 F -6.47910 -2.42850 -0.96893 501 F -6.72501 -0.28757 -0.94839 Table H.21 Cartesian coordinates for compund 7c X Y Z C 3.81772 -1.79224 -0.30419 C 2.45737 -2.12615 -0.42859 C 4.16236 -0.58660 0.37747 C 3.13438 0.22982 0.89212 C 1.80998 -0.11451 0.74867 C 1.45014 -1.32258 0.07431 N 0.80201 0.66385 1.30351 P -0.81985 0.62193 0.90548 C -1.03638 -1.03688 0.28284 C 0.07152 -1.73847 -0.05108 O -1.66064 1.14696 2.00708 C -2.40194 -1.54937 0.06701 C -2.69627 -2.34243 -1.04917 C -3.96677 -2.86323 -1.23732 C -4.99727 -2.60630 -0.33037 C -4.70487 -1.80447 0.77291 C -3.43608 -1.27821 0.97096 C 4.84923 -2.61285 -0.82514 C 6.16439 -2.25825 -0.68066 C 6.50603 -1.06350 -0.00707 C 5.53178 -0.24846 0.50877 O -1.00480 1.45451 -0.48862 C -0.87685 2.83293 -0.55497 C 0.16528 3.35138 -1.31262 C 0.29001 4.72944 -1.44525 C -0.61676 5.57917 -0.82043 C -1.65379 5.04437 -0.06306 C -1.79306 3.66777 0.07314 H 2.18748 -3.04939 -0.93490 H 3.39782 1.14783 1.41086 H 1.08887 1.41041 1.92086 H -0.07319 -2.74107 -0.45057 H -1.92724 -2.53446 -1.79122 H -4.16577 -3.47263 -2.11512 H -5.48517 -1.58695 1.49749 H -3.23925 -0.66144 1.84085 H 4.57860 -3.52934 -1.34204 H 6.94857 -2.89198 -1.08220 H 7.55147 -0.79176 0.10194 H 5.80012 0.66831 1.02614 H 0.85953 2.67133 -1.79482 H 1.10071 5.13807 -2.04026 H -0.51728 6.65470 -0.92546 H -2.36615 5.70165 0.42563 H -2.59264 3.23602 0.66324 C -6.37940 -3.14334 -0.55765 H -6.95968 -2.47080 -1.19899 502 H -6.35595 -4.11834 -1.05047 H -6.92820 -3.25000 0.38074 Table H.22 Cartesian coordinates for compund 7d X Y Z C 3.74075 -2.24608 -0.31603 C 2.34191 -2.36980 -0.39278 C 4.28755 -1.09827 0.33198 C 3.41297 -0.12544 0.85843 C 2.04778 -0.26436 0.75998 C 1.48544 -1.41439 0.12380 N 1.18862 0.67028 1.32466 P -0.42983 0.87188 0.96326 C -0.92114 -0.75039 0.40282 C 0.05617 -1.61982 0.05481 O -1.14768 1.55591 2.06462 C -2.35434 -1.04978 0.24341 C -2.80655 -1.81359 -0.83563 C -4.14691 -2.14433 -0.98598 C -5.07837 -1.70099 -0.04599 C -4.64412 -0.92038 1.02931 C -3.30870 -0.59674 1.16902 C 4.61775 -3.22241 -0.85133 C 5.97573 -3.07185 -0.75207 C 6.51749 -1.93496 -0.11061 C 5.69596 -0.97295 0.41796 O -0.51958 1.67848 -0.45546 C -0.18180 3.01659 -0.57963 C 0.90223 3.33846 -1.38606 C 1.23401 4.67446 -1.57870 C 0.49094 5.67716 -0.96459 C -0.59022 5.33846 -0.15754 C -0.93613 4.00626 0.03899 H 1.91831 -3.24918 -0.87117 H 3.82897 0.75041 1.34915 H 1.60526 1.37775 1.91366 H -0.25137 -2.59875 -0.31007 H -2.10257 -2.13879 -1.59532 H -4.45181 -2.73081 -1.84434 H -5.37833 -0.57778 1.75097 H -2.99303 0.00758 2.01209 H 4.19418 -4.09410 -1.34251 H 6.64048 -3.82417 -1.16436 H 7.59510 -1.82555 -0.03665 H 6.11724 -0.10101 0.91027 H 1.46643 2.54120 -1.85833 H 2.07770 4.92997 -2.21211 H 0.75171 6.71956 -1.11666 H -1.17570 6.11614 0.32281 H -1.77314 3.72656 0.66753 O -6.40189 -1.96224 -0.09479 C -6.88669 -2.75287 -1.16104 503 H -7.95950 -2.84285 -1.00229 H -6.70424 -2.27474 -2.12890 H -6.43581 -3.75061 -1.15556 504 3.2 Dimerization The geometries for 8a-f and their dimeric complexes were fully optimized without symmetry constraint by using the functional M06-2X29 (accounting for the contributions of H-bond/ dispersion forces) and TZVP basis set30 as implemented in Gaussian 09. The PCM solvation model was used to account for the effects of the chloroform environment. All of the optimized structures were confirmed by frequency calculations to be minima using the same level of theory. The solution-phase optimized geometries were used in all the energy calculations. Single point calculations were computed at a higher level using the minimally diffuse-augmented ma-def2-TZVP (ma-TZVP) basis set31 (obtained from https://comp.chem.umn.edu/basissets/basis.cgi). The interaction energy (ΔEint) is defined as the gas-phase electronic energy difference between dimer and its isolated monomers (The enantiomers have exactly the same electronic energies), and the basis set superposition error (BSSE) were corrected by the counterpoise correction (CP) method,32 as implemented in Gaussian 09. All the reported dipole moments were obtained at the M06- 2X/ma-def2-TZVP level in gas phase. The distribution of electrostatic potential, V(r), on the molecular surfaces of 8 were computed at the M06-2X/TZVP level in gas phase. The V(r) was evaluated on the 0.001 e/Bohr3 contour of ρ(r) to generate the VS(r). The most negative and most positive VS(r) values (i.e., VS,min and VS,max, respectively) for electrostatic potential surface energies were calculated. The QTAIM analyses33 were based on the optimized geometries of dimers in CHCl3. The estimated energies (EHB) of hydrogen bonding interactions (for X−H•••O type in neutral system, X = C, N, O) were calculated using the empirical formula [EHB=1/2V(r)] reported by Espinosa et al., 34 where V(r) denotes the local potential electron energy density at the (3, −1) bond critical points (BCPs). Of 505 note, while it is clear that the estimated EHB have important role in energetic aspect of the dimer complex, they are not the total interaction energy (Table H.23). The quantitative molecular surface analysis, NCI plot and QTAIM analysis were performed by using the Multiwfn program.35 Energy decomposition calculations were undertaken on these optimized dimeric complexes using SAPT0.36 Based on a rigorous perturbation expansion of the intermolecular interactions, SAPT0 energies can be decomposed into a sum of four physically meaningful contributions; i.e., electrostatic (Eele), dispersion (Edis), induction (Eind), and exchange repulsion (Eexc). The first three components are attractive whereas the last is repulsive (Table H.25). All of the SAPT0 calculations have been performed using the Psi4 open-source quantum chemistry package,37 employing the density fitting procedure. Considering the molecular system size, the jun-cc-pVDZ basis-set (truncated Dunning-style basis set) was adopted for all the calculations since it provides the best trade- off between computational cost and accuracy.38 Figure H.16 The representative QTAIM analysis graphs for 8b•8b complex showing the (3, −1) bond critical points (BCPs) (red dots) and bond paths (blue dotted lines). 506 Table H.23 Double hydrogen bond lengths d (in Å), topological analysis values (in a.u.) of the density of all electrons ρ(r), Laplacian of electron density 2ρ(r) and local potential electron energy density V(r) at the (3, −1) bond critical points (BCPs) as well as the estimated energies EHB (in kcal mol –1) of these bonds among the optimized dimeric complexes, calculated at PCM(CHCl3)-M06-2X/TZVP level of theory. d ρ(r) 2ρ(r) V(r) EHB 8a 1.86; 1.86 0.0302; 0.0302 0.1157; 0.1156 −0.0281; −0.0280 −8.9; −8.8 8b 1.85; 1.86 0.0305; 0.0302 0.1144; 0.1170 −0.0285; −0.0279 −8.9; −8.8 8c 1.86; 1.86 0.0305; 0.0305 0.1156; 0.1156 −0.0283; −0.0283 −8.9; −8.9 8d 1.86; 1.85 0.0305; 0.0308 0.1145; 0.1159 −0.0285; −0.0286 −8.9; −9.1 8e 1.86; 1.85 0.0301; 0.0306 0.1137; 0.1171 −0.0277; −0.0286 −8.7; −9.0 8f 1.84; 1.86 0.0314; 0.0290 0.1187; 0.1133 −0.0299; −0.0271 −9.4; −8.5 Figure H.17 The calculated electrostatic potential surface minima absolute value (|Vs,min|) and maxima absolute value (|Vs,max|) of 8. 507 Table H.24 The interaction energies ΔE aint (in gas phase, all in a.u.), electronic energies for 8 and their dimeric complexes and BSSE energies (EBSSE) for the intermolecular interactions calculated at M06-2X/ma-def2-TZVP//PCM(CHCl3)-M06-2X/TZVP level of theory Emonomer Edimer EBSSE ΔEint 8a −1656.496751 −3313.041598 0.001113037 −0.046982963 8b −2357.697214 −4715.442129 0.001108823 −0.046592177 8c −1564.253165 −3128.553662 0.001090228 −0.046241772 8d −2059.937954 −4119.923383 0.00110601 −0.04636899 8e −1809.097417 −3618.241641 0.001043752 −0.045763248 8f −1586.530518 −3173.107187 0.00096453 −0.04518647 a ΔEint = Edimer − 2 Emonomer + EBSSE. Table H.25 Eele, Eexc, Eind and Edis, in the SAPT0 approach correspond to electrostatic exchange, induction and dispersion energy terms and total SAPT0 energy (ESAPT), respectively. All values are in kJ mol–1 Eele Eexc Eind Edis ESAPT 8a −176.4 143.8 −64.0 −73.6 −170.2 8b −166.4 138.5 −61.6 −66.7 −156.3 8c −165.3 141.6 −63.1 −68.0 −154.8 8d −164.5 137.4 −60.8 −66.9 −154.8 8e −163.3 139.5 −62.4 −66.6 −152.8 8f −162.7 144.8 −65.1 −69.3 −152.3 508 509 Figure H.18 The plots of molecular dipole moments (in Debye) for 8 and their respective dimer with the vectors originating from the center of mass. 510 Table H.26. Cartesian coordinates for compund 8a X Y Z P -0.06729 -1.26801 -1.30942 O 0.04071 0.03486 -2.29522 O 0.37326 -2.45608 -2.08912 N -1.66192 -1.35598 -0.79442 C 0.77801 -0.80799 0.19344 C 0.04930 -0.39275 1.25290 C -1.38734 -0.32079 1.35347 C -2.21483 -0.79972 0.34467 C -3.64042 -0.74494 0.48793 C -4.17980 -0.21533 1.68895 C -3.31175 0.26289 2.70998 C -1.96664 0.21059 2.54032 C -4.53031 -1.17965 -0.52432 C -5.88668 -1.11523 -0.34258 C -6.42121 -0.60803 0.85802 C -5.58423 -0.16573 1.84686 C 2.25553 -0.79859 0.20146 C 2.93731 0.23159 0.85557 C 4.32397 0.24367 0.89335 C 5.05671 -0.77144 0.25873 C 4.38040 -1.78528 -0.41033 C 2.99552 -1.79588 -0.44118 C -0.37704 1.28734 -1.86104 C 0.56146 2.16183 -1.33363 C 0.15114 3.42275 -0.92032 C -1.18285 3.79729 -1.03433 C -2.10896 2.91121 -1.57179 C -1.70950 1.64847 -1.99181 H -2.27877 -1.85343 -1.42505 H 0.58851 -0.09133 2.14827 H -3.74394 0.66599 3.61748 H -1.29831 0.57316 3.31264 H -4.15874 -1.56039 -1.46767 H -6.55160 -1.45112 -1.12824 H -7.49485 -0.56442 0.99241 H -5.98462 0.23525 2.77088 H 2.39128 1.04045 1.32403 H 2.48153 -2.59432 -0.96068 H 1.59617 1.84834 -1.26035 H 0.87741 4.11474 -0.51197 H -1.49917 4.78066 -0.71027 H -3.14757 3.20181 -1.66914 511 H -2.41563 0.94803 -2.42041 C 6.48854 -0.76555 0.29339 N 7.63615 -0.76751 0.31957 C 4.99950 1.31182 1.57128 N 5.53116 2.17046 2.11665 H 4.94310 -2.56740 -0.90252 Table H.27. Cartesian coordinates for compund 8a•8a X Y Z P 1.90604 -0.50927 0.28823 O 2.14538 -0.36271 -1.31994 O 1.30666 0.78854 0.74063 N 0.94770 -1.85024 0.53426 C 3.46091 -1.01286 0.99139 C 3.62819 -2.31092 1.33514 C 2.66970 -3.37543 1.22620 C 1.36740 -3.13848 0.79829 C 0.44462 -4.22575 0.64934 C 0.87736 -5.53104 0.99535 C 2.20303 -5.74108 1.47065 C 3.06377 -4.69977 1.57139 C -0.86300 -4.05174 0.13408 C -1.70455 -5.12350 -0.01092 C -1.28226 -6.41539 0.35530 C -0.02017 -6.61137 0.84717 C 4.55690 -0.02761 1.06906 C 5.87216 -0.40844 0.78195 C 6.91386 0.49795 0.85931 C 6.66430 1.82290 1.20587 C 5.34774 2.22166 1.47458 C 4.30638 1.30429 1.40853 C 2.44242 -1.49474 -2.07112 C 3.76675 -1.78475 -2.35747 C 4.05908 -2.91637 -3.10845 C 3.03573 -3.74204 -3.55574 C 1.71267 -3.43015 -3.26449 C 1.40597 -2.29791 -2.52262 H 4.59337 -2.59754 1.74740 H 2.50958 -6.74483 1.73637 H 4.07824 -4.85586 1.91908 H -1.21614 -3.07252 -0.16600 H -2.69609 -4.98348 -0.42171 512 H -1.95937 -7.25171 0.23761 H 0.31660 -7.60376 1.12252 H 6.07613 -1.42542 0.47066 H 3.29619 1.62611 1.62741 H 4.54292 -1.11949 -1.99903 H 5.08928 -3.15140 -3.34445 H 3.26873 -4.62563 -4.13553 H 0.91283 -4.06982 -3.61484 H 0.38407 -2.02557 -2.28402 C -7.75450 -2.76046 -1.28954 N -8.63693 -3.49291 -1.34061 C 7.74730 2.75882 1.27266 N 8.62960 3.49152 1.32249 C -5.05963 -3.58857 -1.82108 N -4.79681 -4.67632 -2.07713 H -7.93492 -0.19380 -0.65486 H -0.02237 -1.68990 0.24884 H 7.92716 0.19297 0.63471 C 5.05341 3.58538 1.81147 N 4.79082 4.67277 2.06928 P -1.91382 0.50661 -0.29632 O -2.15559 0.36226 1.31163 O -1.31448 -0.79207 -0.74630 N -0.95444 1.84676 -0.54289 C -3.46739 1.01004 -1.00249 C -3.63370 2.30792 -1.34743 C -2.67506 3.37220 -1.23769 C -1.37334 3.13503 -0.80814 C -0.45032 4.22204 -0.65881 C -0.88226 5.52731 -1.00588 C -2.20734 5.73758 -1.48273 C -3.06830 4.69650 -1.58397 C 0.85670 4.04784 -0.14208 C 1.69846 5.11940 0.00326 C 1.27698 6.41126 -0.36400 C 0.01547 6.60743 -0.85727 C -4.56355 0.02507 -1.08151 C -5.87934 0.40667 -0.79788 C -6.92120 -0.49941 -0.87673 C -6.67133 -1.82484 -1.22125 C -5.35428 -2.22438 -1.48637 C -4.31274 -1.30731 -1.41890 C -2.45305 1.49537 2.06101 C -3.77759 1.78614 2.34559 C -4.07038 2.91879 3.09483 C -3.04725 3.74471 3.54219 513 C -1.72398 3.43204 3.25274 C -1.41684 2.29879 2.51263 H 0.01533 1.68625 -0.25668 H -4.59810 2.59456 -1.76148 H -2.51327 6.74131 -1.74924 H -4.08233 4.85275 -1.93289 H 1.20924 3.06866 0.15881 H 2.68953 4.97924 0.41511 H 1.95424 7.24741 -0.24600 H -0.32069 7.59979 -1.13345 H -6.08375 1.42406 -0.48823 H -3.30217 -1.62976 -1.63504 H -4.55359 1.12066 1.98718 H -5.10076 3.15440 3.32947 H -3.28058 4.62906 4.12066 H -0.92432 4.07190 3.60317 H -0.39475 2.02586 2.27549 Table H.28. Cartesian coordinates for compund 8b X Y Z S 5.61567 0.37629 0.07635 P -1.24911 0.13035 1.77483 O -1.39075 1.75998 1.68533 O -0.74411 -0.20093 3.13403 O 6.18686 0.45726 1.41966 O 5.97790 1.32825 -0.97330 N -2.77131 -0.50598 1.45944 C -0.34080 -0.35107 0.31669 C -1.02404 -0.81521 -0.75230 C -2.44367 -1.04598 -0.85464 C -3.28853 -0.90261 0.23984 C -4.68917 -1.18673 0.11631 C -5.18381 -1.61649 -1.14283 C -4.29852 -1.75536 -2.24760 C -2.97824 -1.47938 -2.10059 C -5.60127 -1.03897 1.18946 C -6.93231 -1.31962 1.02565 C -7.41984 -1.75753 -0.22129 C -6.56258 -1.89960 -1.27894 C 1.12215 -0.14404 0.28104 C 1.72638 0.33877 -0.88721 C 3.09726 0.50483 -0.95742 514 C 3.85790 0.19577 0.16403 C 3.28933 -0.26129 1.34509 C 1.91526 -0.42322 1.40014 C 6.15973 -1.29851 -0.57959 C -1.85599 2.36194 0.52246 C -0.93322 2.86766 -0.38160 C -1.38994 3.48541 -1.53828 C -2.75440 3.59116 -1.78390 C -3.66555 3.08830 -0.86284 C -3.22060 2.47268 0.30065 H -3.36924 -0.57216 2.27423 H -0.45032 -1.07410 -1.63912 H -4.69722 -2.08624 -3.19873 H -2.29524 -1.58619 -2.93529 H -5.26870 -0.69503 2.16026 H -7.61452 -1.20012 1.85776 H -8.47369 -1.97706 -0.33953 H -6.92700 -2.23139 -2.24426 H 1.11475 0.60551 -1.74015 H 3.56650 0.88428 -1.85657 H 3.90766 -0.48525 2.20535 H 1.45502 -0.78110 2.31207 H 0.12491 2.77365 -0.16795 H -0.67636 3.88652 -2.24753 H -3.10709 4.07119 -2.68802 H -4.72928 3.17587 -1.04604 H -3.91793 2.08424 1.03258 F 5.74680 -2.25718 0.23376 F 7.47841 -1.31545 -0.64851 F 5.65151 -1.49944 -1.78513 Table H.29. Cartesian coordinates for compund 8b•8b X Y Z S -8.59680 -0.69151 0.23307 P -1.72217 1.01303 0.12729 O -1.61704 1.03417 1.75720 O -1.60070 -0.42578 -0.27372 O -8.45504 -2.14314 0.26821 O -9.41169 0.05003 1.18960 N -0.51945 2.00375 -0.46573 C -3.20019 1.90610 -0.29803 C -3.08118 3.20063 -0.67082 515 C -1.86830 3.95303 -0.85052 C -0.61881 3.35155 -0.74464 C 0.57497 4.11644 -0.96265 C 0.44736 5.49160 -1.28378 C -0.84322 6.08298 -1.38953 C -1.95416 5.33510 -1.18107 C 1.87048 3.55612 -0.85117 C 2.98326 4.32463 -1.07153 C 2.85730 5.68686 -1.40280 C 1.61603 6.25449 -1.50246 C -4.51259 1.24861 -0.13579 C -5.58857 1.95953 0.40853 C -6.83777 1.37571 0.52427 C -6.99562 0.06268 0.10368 C -5.94329 -0.67849 -0.41525 C -4.69906 -0.08212 -0.52889 C -9.33062 -0.30223 -1.45320 C -1.43163 2.24383 2.41681 C -2.53410 2.90736 2.93084 C -2.34355 4.11450 3.59077 C -1.06638 4.64416 3.72480 C 0.02772 3.96008 3.20808 C -0.14706 2.74933 2.55251 H 0.40849 1.58299 -0.36697 H -3.99970 3.74114 -0.88939 H -0.91759 7.13352 -1.64035 H -2.93924 5.77908 -1.26487 H 2.00689 2.51454 -0.58715 H 3.96751 3.88086 -0.99181 H 3.74482 6.28155 -1.57791 H 1.50850 7.30308 -1.75339 H -5.43582 2.97173 0.76194 H -7.67544 1.91192 0.95209 H -6.10267 -1.70506 -0.72053 H -3.86466 -0.63930 -0.93435 H -3.51768 2.46794 2.81601 H -3.19570 4.64010 4.00256 H -0.92292 5.58767 4.23503 H 1.02411 4.36949 3.31484 H 0.68630 2.18935 2.14293 S 8.53361 0.57630 -0.79184 P 1.71743 -0.99221 0.08287 O 1.56776 -1.02097 -1.54304 O 1.61996 0.45015 0.47884 O 8.38563 2.02242 -0.91458 O 9.21707 -0.24100 -1.78870 516 N 0.52225 -1.96772 0.71584 C 3.19837 -1.89792 0.46867 C 3.08145 -3.17277 0.90492 C 1.87031 -3.90394 1.16299 C 0.62174 -3.30182 1.05147 C -0.57182 -4.05213 1.31635 C -0.44445 -5.41260 1.69486 C 0.84565 -6.00315 1.81171 C 1.95609 -5.27013 1.55438 C -1.86700 -3.49344 1.19263 C -2.97981 -4.24930 1.45272 C -2.85380 -5.59647 1.84089 C -1.61303 -6.16229 1.95583 C 4.50613 -1.27959 0.17065 C 5.52107 -2.04781 -0.41293 C 6.75509 -1.49262 -0.69960 C 6.96107 -0.15167 -0.40620 C 5.97220 0.64170 0.15760 C 4.74208 0.07365 0.44269 C 9.49028 0.30633 0.80318 C 1.37390 -2.23607 -2.19003 C 2.46752 -2.89319 -2.73074 C 2.26918 -4.10617 -3.37774 C 0.99363 -4.64811 -3.47154 C -0.09160 -3.97009 -2.92885 C 0.09054 -2.75325 -2.28652 H -0.40619 -1.55032 0.61238 H 4.00307 -3.71700 1.10005 H 0.91974 -7.04186 2.10776 H 2.94062 -5.71460 1.64215 H -2.00367 -2.46357 0.88605 H -3.96363 -3.80723 1.35958 H -3.74110 -6.18137 2.04736 H -1.50596 -7.19941 2.25072 H 5.32628 -3.08162 -0.67015 H 7.54095 -2.07196 -1.16759 H 6.16812 1.68722 0.35993 H 3.95604 0.67344 0.88291 H 3.45000 -2.44450 -2.64534 H 3.11386 -4.62665 -3.81092 H 0.84426 -5.59614 -3.97166 H -1.08698 -4.38851 -3.00624 H -0.73528 -2.19621 -1.85834 F 8.90195 0.95444 1.79704 F 10.71961 0.75600 0.64739 F 9.52395 -0.98701 1.09040 517 F -8.58444 -0.84828 -2.40183 F -9.36713 1.00995 -1.63403 F -10.55340 -0.79136 -1.51500 Table H.30. Cartesian coordinates for compund 8c X Y Z P -0.35441 -0.70530 1.51094 O -0.45461 0.85524 2.00311 O -0.88820 -1.55386 2.61019 N 1.26338 -1.00200 1.17314 C -1.08460 -0.74019 -0.11643 C -0.27001 -0.71580 -1.19348 C 1.17304 -0.72041 -1.20652 C 1.91358 -0.86830 -0.04058 C 3.34625 -0.90524 -0.09016 C 3.98219 -0.79551 -1.35449 C 3.20171 -0.64813 -2.53457 C 1.84744 -0.61264 -2.45492 C 4.15310 -1.02093 1.06821 C 5.51952 -1.05051 0.97376 C 6.14907 -0.95979 -0.28320 C 5.39446 -0.83247 -1.41803 C -2.55682 -0.68313 -0.24047 C -3.13999 0.08460 -1.25598 C -4.51265 0.13274 -1.40832 C -5.32718 -0.57949 -0.52655 C -4.76318 -1.33177 0.50295 C -3.38715 -1.37872 0.64484 C 0.01690 1.87891 1.19068 C -0.88371 2.56294 0.38782 C -0.42187 3.59740 -0.41533 C 0.92626 3.93773 -0.41310 C 1.81391 3.24882 0.40442 C 1.36261 2.21506 1.21594 H 1.81133 -1.28826 1.97537 H -0.73802 -0.70659 -2.17526 H 3.70720 -0.56501 -3.48876 H 1.24517 -0.50417 -3.34955 H 3.70858 -1.07965 2.05386 H 6.11882 -1.13698 1.87137 H 7.22983 -0.98544 -0.34621 H 5.86799 -0.75234 -2.38975 518 H -2.51090 0.66523 -1.91956 H -2.95137 -1.96916 1.44051 H -1.92926 2.27887 0.40256 H -1.11875 4.13919 -1.04287 H 1.28273 4.74299 -1.04294 H 2.86371 3.51484 0.41467 H 2.03956 1.67112 1.86331 C -6.75216 -0.52862 -0.67676 N -7.89370 -0.48711 -0.79954 H -5.40153 -1.87895 1.18451 H -4.95869 0.72727 -2.19521 Table H.31. Cartesian coordinates for compund 8c•8c X Y Z P -1.91537 -0.50274 0.20770 O -2.01241 -0.37529 -1.41794 O -1.37332 0.81255 0.68264 N -0.94498 -1.81607 0.54520 C -3.51149 -1.03924 0.77523 C -3.67059 -2.33184 1.13880 C -2.66849 -3.36367 1.17882 C -1.33855 -3.09537 0.87383 C -0.35581 -4.13949 0.93268 C -0.77340 -5.44099 1.30909 C -2.13999 -5.68879 1.62110 C -3.04656 -4.68311 1.55630 C 1.00740 -3.92170 0.61799 C 1.91139 -4.94888 0.68886 C 1.49964 -6.23939 1.07108 C 0.18580 -6.47633 1.37233 C -4.63815 -0.08468 0.71951 C -5.89213 -0.50773 0.26597 C -6.96372 0.36501 0.22287 C -6.79184 1.68946 0.62435 C -5.54380 2.12831 1.06501 C -4.47584 1.24954 1.10783 C -2.25561 -1.50744 -2.18523 C -3.55717 -1.79969 -2.56061 C -3.79551 -2.92653 -3.33641 C -2.74160 -3.74481 -3.72301 C -1.44236 -3.43114 -3.34162 C -1.18844 -2.30555 -2.56991 519 H 0.03318 -1.64608 0.29434 H -4.66481 -2.63748 1.45741 H -2.43756 -6.68911 1.90897 H -4.08795 -4.86658 1.79389 H 1.36130 -2.94441 0.31301 H 2.95151 -4.76438 0.45213 H 2.22451 -7.04159 1.12694 H -0.14225 -7.46629 1.66632 H -6.01879 -1.52749 -0.07657 H -3.50896 1.58919 1.45629 H -4.35815 -1.14009 -2.24913 H -4.80708 -3.16329 -3.64102 H -2.93255 -4.62366 -4.32509 H -0.61908 -4.06419 -3.64700 H -0.18639 -2.02951 -2.26140 P 1.91529 0.50277 -0.20779 O 2.01246 0.37526 1.41785 O 1.37321 -0.81251 -0.68274 N 0.94490 1.81611 -0.54525 C 3.51140 1.03927 -0.77532 C 3.67051 2.33188 -1.13883 C 2.66841 3.36372 -1.17882 C 1.33847 3.09542 -0.87386 C 0.35574 4.13954 -0.93267 C 0.77333 5.44105 -1.30903 C 2.13993 5.68886 -1.62102 C 3.04649 4.68317 -1.55626 C -1.00747 3.92174 -0.61799 C -1.91146 4.94892 -0.68882 C -1.49971 6.23945 -1.07099 C -0.18587 6.47639 -1.37223 C 4.63807 0.08472 -0.71959 C 5.89199 0.50774 -0.26586 C 6.96359 -0.36500 -0.22272 C 6.79176 -1.68942 -0.62434 C 5.54378 -2.12824 -1.06518 C 4.47581 -1.24947 -1.10803 C 2.25575 1.50734 2.18519 C 3.55742 1.79978 2.56000 C 3.79592 2.92654 3.33588 C 2.74204 3.74455 3.72312 C 1.44267 3.43069 3.34230 C 1.18860 2.30519 2.57051 H -0.03326 1.64613 -0.29440 H 4.66473 2.63753 -1.45743 H 2.43750 6.68919 -1.90885 520 H 4.08789 4.86665 -1.79384 H -1.36138 2.94444 -0.31305 H -2.95158 4.76441 -0.45210 H -2.22457 7.04165 -1.12682 H 0.14219 7.46636 -1.66618 H 6.01860 1.52746 0.07680 H 5.41908 -3.15644 -1.37858 H 3.50899 -1.58911 -1.45663 H 4.35839 1.14040 2.24801 H 4.80759 3.16344 3.64005 H 2.93310 4.62333 4.32526 H 0.61942 4.06352 3.64820 H 0.18645 2.02899 2.26248 C -7.89825 2.60185 0.57519 N -8.78405 3.33183 0.53442 C 7.89819 -2.60179 -0.57514 N 8.78398 -3.33177 -0.53433 H -5.41905 3.15654 1.37830 H 7.93036 -0.03292 0.13201 H -7.93054 0.03290 -0.13171 Table H.32. Cartesian coordinates for compund 8d X Y Z S -6.24291 -0.22705 -0.31014 P 0.56680 -0.49522 1.64602 O 0.52828 1.10620 1.99079 O 0.06016 -1.22155 2.84164 O -6.80348 -0.24546 1.05286 O -6.56150 0.90289 -1.20241 N 2.15960 -0.87364 1.27340 C -0.23427 -0.66612 0.05980 C 0.53138 -0.79272 -1.04587 C 1.97163 -0.85375 -1.11752 C 2.75861 -0.89180 0.02681 C 4.18642 -0.97012 -0.07513 C 4.77002 -1.03818 -1.36698 C 3.94264 -1.00995 -2.52382 C 2.59460 -0.91705 -2.39551 C 5.03815 -0.96026 1.05651 C 6.39813 -1.04101 0.91331 C 6.97556 -1.13065 -0.36883 C 6.17702 -1.12523 -1.48062 521 C -1.70805 -0.55699 -0.00999 C -2.30196 0.12978 -1.07579 C -3.67910 0.23125 -1.17327 C -4.46333 -0.34393 -0.18376 C -3.90381 -1.00813 0.89698 C -2.52394 -1.11183 0.98221 C -6.73128 -1.73582 -1.13070 C 0.96248 2.03510 1.05308 C 0.01930 2.67220 0.26066 C 0.44265 3.61583 -0.66593 C 1.79491 3.91190 -0.79626 C 2.72610 3.26980 0.01098 C 2.31397 2.32790 0.94558 H 2.73543 -1.09264 2.07747 H 0.02067 -0.87139 -2.00292 H 4.40767 -1.06372 -3.50048 H 1.95837 -0.89432 -3.27271 H 4.63249 -0.87431 2.05695 H 7.03315 -1.02993 1.79021 H 8.05178 -1.19657 -0.47039 H 6.61029 -1.18509 -2.47240 H -1.67806 0.60994 -1.81956 H -4.14077 0.77248 -1.98984 H -4.53605 -1.42943 1.66907 H -2.07596 -1.62912 1.82092 H -6.43483 -2.57860 -0.50883 H -6.24736 -1.76865 -2.10523 H -7.81543 -1.68983 -1.23470 H -1.02862 2.42453 0.38111 H -0.28812 4.12129 -1.28512 H 2.12270 4.64670 -1.52078 H 3.77976 3.50212 -0.08189 H 3.02580 1.82534 1.58875 Table H.33. Cartesian coordinates for compund 8d•8d X Y Z S -8.59831 0.75220 0.22915 P -1.71727 -0.98096 0.04956 O -1.71438 -1.01757 -1.58386 O -1.56196 0.46058 0.42849 O -8.40339 2.20174 0.10272 O -9.40770 0.00819 -0.74384 N -0.48167 -1.97023 0.57474 522 C -3.16878 -1.86503 0.57155 C -3.02943 -3.15364 0.95578 C -1.80859 -3.90608 1.08123 C -0.56653 -3.30972 0.89282 C 0.63787 -4.07014 1.06634 C 0.52742 -5.43866 1.42022 C -0.75582 -6.02713 1.60296 C -1.87643 -5.28152 1.44087 C 1.92622 -3.51097 0.88439 C 3.04962 -4.27457 1.06517 C 2.94075 -5.63105 1.42530 C 1.70646 -6.19708 1.59564 C -4.48797 -1.20806 0.45935 C -5.58792 -1.92279 -0.02706 C -6.83944 -1.33360 -0.10288 C -6.98155 -0.01427 0.29924 C -5.90365 0.72743 0.75763 C -4.65572 0.12997 0.83329 C -9.28415 0.43842 1.85657 C -1.62296 -2.23984 -2.23777 C -2.78408 -2.85924 -2.67198 C -2.69036 -4.08047 -3.32637 C -1.44914 -4.66890 -3.53434 C -0.29523 -4.02881 -3.09792 C -0.37354 -2.80400 -2.44979 H 0.43913 -1.55856 0.39856 H -3.93544 -3.69056 1.22869 H -0.81669 -7.07319 1.87555 H -2.85582 -5.72332 1.58353 H 2.04924 -2.47354 0.59841 H 4.02827 -3.83068 0.93283 H 3.83660 -6.22211 1.56728 H 1.61265 -7.24080 1.87150 H -5.45195 -2.94071 -0.37180 H -7.69270 -1.87046 -0.49891 H -6.04375 1.76508 1.03471 H -3.80304 0.69463 1.18772 H -8.63737 0.90180 2.59792 H -9.35439 -0.63749 1.99847 H -10.27129 0.89782 1.85709 H -3.73795 -2.37519 -2.50020 H -3.58996 -4.57129 -3.67548 H -1.38012 -5.62310 -4.04035 H 0.67361 -4.48297 -3.26265 H 0.50861 -2.27637 -2.10525 S 8.59956 -0.78680 -0.15702 523 P 1.73333 0.99377 -0.11678 O 1.69036 0.99521 1.51674 O 1.58386 -0.43844 -0.53123 O 8.38882 -2.23482 -0.03758 O 9.39939 -0.05283 0.83138 N 0.51524 1.99930 -0.65172 C 3.20131 1.88190 -0.58413 C 3.07731 3.17933 -0.94221 C 1.86260 3.94117 -1.07529 C 0.61389 3.34771 -0.92690 C -0.58255 4.12088 -1.09678 C -0.45825 5.49728 -1.41361 C 0.83139 6.08134 -1.56123 C 1.94463 5.32478 -1.39838 C -1.87689 3.56690 -0.94435 C -2.99254 4.34281 -1.12026 C -2.86990 5.70690 -1.44575 C -1.62966 6.26824 -1.58546 C 4.51299 1.21325 -0.45449 C 5.60462 1.90771 0.07726 C 6.84922 1.30660 0.17364 C 6.99183 -0.00477 -0.25328 C 5.92115 -0.72681 -0.75794 C 4.68079 -0.11714 -0.85525 C 9.31563 -0.47605 -1.77180 C 1.54017 2.19777 2.19645 C 2.66643 2.84753 2.67547 C 2.51030 4.04848 3.35542 C 1.24332 4.58596 3.54432 C 0.12527 3.91551 3.06212 C 0.26547 2.71075 2.38752 H -0.41061 1.58962 -0.50263 H 3.99179 3.71747 -1.18264 H 0.90348 7.13340 -1.80649 H 2.92884 5.76397 -1.51322 H -2.01110 2.52412 -0.68368 H -3.97573 3.90326 -1.00943 H -3.75972 6.30788 -1.58402 H -1.52489 7.31805 -1.83276 H 5.46726 2.91868 0.44135 H 7.69555 1.82722 0.60450 H 6.05976 -1.75938 -1.05436 H 3.83403 -0.66599 -1.24676 H 8.67865 -0.93397 -2.52492 H 9.39599 0.59951 -1.91102 H 10.29933 -0.94250 -1.75571 524 H 3.64162 2.40231 2.51874 H 3.38177 4.56335 3.73943 H 1.12675 5.52501 4.06952 H -0.86323 4.33142 3.21016 H -0.58639 2.15975 2.00469 Table H.34. Cartesian coordinates for compund 8e X Y Z P -0.29534 -0.66583 -1.57442 O -0.25070 0.90238 -2.05197 O 0.22224 -1.48955 -2.70023 N -1.89283 -1.00974 -1.18922 C 0.48779 -0.69901 0.02827 C -0.71690 1.90413 -1.20968 C -2.50843 -0.89189 0.04442 H -2.45763 -1.30839 -1.97511 C -0.29256 -0.70527 1.12998 C 1.96272 -0.60576 0.10461 C 0.19545 2.60093 -0.43146 C -2.07062 2.20572 -1.18053 C -1.73508 -0.73948 1.18802 C -3.93796 -0.94613 0.13540 H 0.20620 -0.69380 2.09646 C 2.56011 0.16629 1.10942 C 2.78072 -1.26707 -0.81385 C -0.26225 3.61294 0.40208 H 1.24655 2.34385 -0.48798 C -2.51759 3.21705 -0.33903 H -2.75676 1.65176 -1.80941 C -2.37429 -0.65193 2.45643 C -4.53864 -0.85589 1.41827 C -4.77598 -1.05637 -1.00106 C 3.93601 0.24944 1.21121 H 1.93908 0.72098 1.80212 C 4.16266 -1.18110 -0.71782 H 2.33556 -1.86099 -1.60169 C -1.61775 3.91809 0.45463 H 0.44367 4.16421 1.01099 H -3.57338 3.45611 -0.30743 C -3.72527 -0.70852 2.57569 H -1.74795 -0.54092 3.33396 C -5.94813 -0.90968 1.52164 525 C -6.13869 -1.10173 -0.86842 H -4.35803 -1.09549 -1.99912 C 4.73516 -0.42643 0.29416 H 4.38893 0.84979 1.99160 H 4.78511 -1.70350 -1.43242 H -1.97115 4.70560 1.10819 H -4.20309 -0.64035 3.54523 C -6.73319 -1.03300 0.40711 H -6.39430 -0.84514 2.50738 H -6.76274 -1.18269 -1.74954 H -7.81141 -1.07127 0.50056 C 6.22515 -0.32703 0.43441 F 6.88031 -0.89248 -0.58589 F 6.66625 -0.92462 1.55737 F 6.64057 0.94969 0.50642 Table H.35. Cartesian coordinates for compund 8e•8e X Y Z P -1.78816 -0.87952 -0.00718 O -1.92584 -0.95876 -1.63350 O -1.54531 0.56338 0.31758 N -0.55054 -1.90801 0.43154 C -3.22182 -1.68192 0.67048 C -1.90096 -2.20091 -2.25429 C -0.65838 -3.21856 0.84820 H 0.36993 -1.54183 0.17123 C -3.09361 -2.94157 1.14274 C -4.52796 -0.99219 0.59844 C -3.09799 -2.84120 -2.53274 C -0.67799 -2.76539 -2.58546 C -1.89537 -3.73658 1.21413 C 0.52138 -4.03089 0.93178 H -3.99143 -3.41848 1.52985 C -5.67741 -1.70863 0.24627 C -4.64412 0.37190 0.87645 C -3.06686 -4.08390 -3.15206 H -4.03020 -2.35623 -2.26920 C -0.66155 -4.01052 -3.19809 H 0.23230 -2.22377 -2.35399 C -1.97988 -5.07445 1.69141 C 0.39432 -5.36120 1.40567 C 1.79905 -3.56121 0.54233 526 C -6.91279 -1.08858 0.20257 H -5.59397 -2.75689 -0.01372 C -5.88189 0.99592 0.83043 H -3.76113 0.93888 1.14175 C -1.85166 -4.67164 -3.47886 H -3.99498 -4.59276 -3.37923 H 0.28626 -4.46548 -3.45580 C -0.88126 -5.86297 1.78819 H -2.95401 -5.45157 1.98010 C 1.54929 -6.17101 1.49001 C 2.89818 -4.37375 0.63629 H 1.93245 -2.55549 0.16281 C -7.01253 0.26649 0.49552 H -7.79674 -1.64913 -0.07556 H -5.96565 2.05079 1.05594 H -1.83110 -5.64238 -3.95691 H -0.95578 -6.87981 2.15226 C 2.77519 -5.69138 1.11582 H 1.44285 -7.18471 1.85782 H 3.86907 -3.99813 0.33964 H 3.65194 -6.32285 1.18496 O 1.54529 -0.47282 -0.79240 P 1.77738 0.91986 -0.28916 O 1.75263 0.81025 1.34202 N 0.60281 2.01661 -0.73475 C 3.28128 1.76563 -0.71596 C 1.70292 1.96721 2.10846 C 0.76475 3.36729 -0.96135 H -0.33948 1.64672 -0.58303 C 3.21609 3.07884 -1.02771 C 4.56258 1.03970 -0.58425 C 2.88193 2.48937 2.61663 C 0.47488 2.56148 2.35876 C 2.03806 3.90266 -1.12037 C -0.39375 4.20717 -1.06327 H 4.15481 3.58297 -1.24742 C 5.66545 1.66995 0.00350 C 4.69644 -0.27697 -1.02971 C 2.82813 3.64235 3.38904 H 3.81713 1.98375 2.40841 C 0.43706 3.71722 3.12689 H -0.42191 2.10853 1.95120 C 2.18182 5.29105 -1.39703 C -0.20827 5.58614 -1.33553 C -1.70947 3.71457 -0.88719 C 6.87539 1.01167 0.12167 527 H 5.56031 2.67636 0.39014 C 5.90970 -0.93949 -0.91054 H 3.84765 -0.77521 -1.48034 C 1.60937 4.25995 3.64011 H 3.74161 4.05669 3.79663 H -0.51454 4.19413 3.32422 C 1.10503 6.10851 -1.50184 H 3.18369 5.68487 -1.52249 C -1.34271 6.42239 -1.43779 C -2.78764 4.55322 -0.99405 H -1.89020 2.67100 -0.65985 C 6.99494 -0.29551 -0.33733 H 7.72348 1.50323 0.58274 H 6.01052 -1.95515 -1.26886 H 1.57303 5.16038 4.23948 H 1.22588 7.16382 -1.71119 C -2.60546 5.92080 -1.27359 H -1.19044 7.47420 -1.64945 H -3.78745 4.15900 -0.86388 H -3.46575 6.57296 -1.35560 C 8.32131 -0.98629 -0.19395 C -8.36764 0.91420 0.47175 F 8.28253 -2.25576 -0.61293 F 8.73544 -1.00216 1.08231 F 9.28242 -0.36648 -0.89674 F -8.29235 2.24990 0.47904 F -9.10730 0.55732 1.53402 F -9.06852 0.56009 -0.61551 Table H.36. Cartesian coordinates for compund 8f X Y Z P -0.26940 -0.71877 1.45205 O -0.35916 0.83047 1.98780 O -0.83098 -1.58669 2.52326 N 1.35212 -1.03143 1.14550 C -0.96705 -0.69813 -0.18939 C 0.13426 1.87046 1.21184 C 2.03323 -0.88020 -0.05032 H 1.87742 -1.33997 1.95388 C -0.12539 -0.66316 -1.24429 C -2.43475 -0.59317 -0.33383 C -0.74792 2.59204 0.42100 528 C 1.48415 2.18752 1.26177 C 1.31999 -0.69098 -1.22606 C 3.46570 -0.93993 -0.06934 H -0.56977 -0.61503 -2.23563 C -2.98760 0.20656 -1.34512 C -3.30757 -1.26834 0.51787 C -0.26308 3.64537 -0.34304 H -1.79679 2.32005 0.41335 C 1.95855 3.24066 0.48947 H 2.14608 1.61317 1.89830 C 2.02325 -0.56136 -2.45520 C 4.13123 -0.80942 -1.31674 C 4.24644 -1.10233 1.10186 C -4.35310 0.30025 -1.51322 H -2.33421 0.77793 -1.99435 C -4.68640 -1.17871 0.36077 H -2.91008 -1.88855 1.31172 C 1.08919 3.96786 -0.31463 H -0.94513 4.21574 -0.96159 H 3.01171 3.49146 0.51912 C 3.37897 -0.61753 -2.50771 H 1.44297 -0.41719 -3.35941 C 5.54419 -0.86909 -1.35156 C 5.61395 -1.15314 1.03495 H 3.78129 -1.18115 2.07669 C -5.21480 -0.39403 -0.65983 H -4.77998 0.92272 -2.28978 H -5.32911 -1.72479 1.03706 H 1.46321 4.78800 -0.91451 H 3.90562 -0.51823 -3.44891 C 6.27246 -1.03930 -0.20542 H 6.03917 -0.77170 -2.31106 H 6.19180 -1.27626 1.94234 O -6.53917 -0.23603 -0.89646 H 7.35378 -1.08197 -0.24625 C -7.44871 -0.91044 -0.04154 H -7.33093 -0.58348 0.99476 H -8.44329 -0.64600 -0.39254 H -7.31805 -1.99394 -0.10309 Table H.37. Cartesian coordinates for compund 8f•8f X Y Z 529 P -1.87727 -0.68069 0.17148 O -1.98103 -0.61162 -1.45804 O -1.50782 0.70686 0.60703 N -0.74026 -1.84587 0.53838 C -3.39095 -1.40305 0.75905 C -2.08540 -1.78249 -2.19450 C -0.95502 -3.13845 0.96551 H 0.20124 -1.56967 0.24522 C -3.36759 -2.67436 1.21609 C -4.64297 -0.63213 0.60775 C -3.34204 -2.24345 -2.55451 C -0.92840 -2.44885 -2.57087 C -2.23241 -3.55678 1.31713 C 0.15798 -4.03886 1.06878 H -4.31300 -3.09374 1.55328 C -5.81639 -1.27348 0.18693 C -4.69986 0.73630 0.86191 C -3.44048 -3.40737 -3.30573 H -4.21791 -1.68415 -2.24801 C -1.04282 -3.61309 -3.31801 H 0.03185 -2.04233 -2.27379 C -2.42634 -4.88572 1.78604 C -0.07876 -5.35824 1.53134 C 1.47704 -3.66466 0.71447 C -7.00063 -0.58091 0.05234 H -5.78720 -2.32873 -0.05897 C -5.88817 1.44598 0.72771 H -3.80488 1.25493 1.18317 C -2.29413 -4.09425 -3.68511 H -4.41596 -3.77540 -3.59750 H -0.14829 -4.14564 -3.61504 C -1.39483 -5.76010 1.89195 H -3.43110 -5.18702 2.05896 C 1.00896 -6.25507 1.63042 C 2.50896 -4.55941 0.82342 H 1.69660 -2.66784 0.35142 C -7.04515 0.78778 0.32361 H -7.90704 -1.07073 -0.27872 H -5.89466 2.50472 0.94482 H -2.37469 -5.00255 -4.26829 H -1.55440 -6.76994 2.24839 C 2.27553 -5.86856 1.28525 H 0.81762 -7.26021 1.98771 H 3.51192 -4.25261 0.55502 O -8.25176 1.38434 0.15791 H 3.09912 -6.56655 1.36828 530 C -8.33895 2.77199 0.40320 H -7.67903 3.33435 -0.26349 H -9.37122 3.04863 0.20621 H -8.09188 3.00704 1.44226 O 1.41633 -0.62147 -0.76687 P 1.83250 0.72616 -0.25684 O 1.92694 0.56219 1.36857 N 0.73934 1.94851 -0.56176 C 3.37461 1.41953 -0.80087 C 2.06131 1.69004 2.16545 C 1.01695 3.27206 -0.83554 H -0.21903 1.67879 -0.32081 C 3.41037 2.72834 -1.13109 C 4.58217 0.56891 -0.75052 C 3.32940 2.09980 2.54636 C 0.92208 2.36797 2.57418 C 2.31559 3.66719 -1.13384 C -0.05108 4.23031 -0.83733 H 4.37195 3.13392 -1.43835 C 5.79213 1.08740 -0.26875 C 4.55868 -0.75917 -1.17042 C 3.45816 3.22070 3.35585 H 4.19021 1.53339 2.21153 C 1.06647 3.48818 3.38088 H -0.04872 2.00549 2.25485 C 2.57281 5.02733 -1.46077 C 0.24793 5.57818 -1.16178 C -1.38498 3.88475 -0.51009 C 6.93494 0.31648 -0.23204 H 5.82528 2.10639 0.09937 C 5.70451 -1.54638 -1.13737 H 3.63414 -1.18235 -1.54318 C 2.32997 3.91692 3.77086 H 4.44268 3.54834 3.66473 H 0.18603 4.02831 3.70516 C 1.58253 5.95435 -1.47826 H 3.59232 5.30883 -1.69797 C -0.79648 6.53029 -1.16379 C -2.37270 4.83427 -0.51933 H -1.64863 2.86871 -0.24170 C 6.89906 -1.00890 -0.66847 H 7.86985 0.70973 0.14553 H 5.64916 -2.56850 -1.48411 H 2.43399 4.79136 4.40023 H 1.79051 6.98741 -1.72745 C -2.07910 6.17066 -0.85116 531 H -0.55796 7.55674 -1.41735 H -3.38784 4.55224 -0.26999 O 8.06972 -1.68941 -0.59121 H -2.86938 6.91083 -0.85696 C 8.07363 -3.03908 -1.00557 H 9.08951 -3.39683 -0.86157 H 7.38820 -3.64032 -0.40134 H 7.80253 -3.13028 -2.06112 4. Measurements of Dimerization Constants Kdim Self-dimerization equilibria were studied by virtue of 1H NMR spectroscopic (additional 31P NMR analysis for 8b) dilution experiments in water-saturated CDCl3 (ca. 0.8% water in CHCl3). Nonlinear regression analysis has been performed to fit the following equation 39 by using the curve-fitting technique with OriginPro 8.0 program. The error of Kdim is the standard deviation of three measurements. 1+4Kdim[H]-√1+8Kdim[H] δobs = δm + (δd−δm) 4Kdim[H] where [H] is the total concentration Kdim is the dimerization constant δm is the free chemical shift of the monomer δd is the limiting bound chemical shift of the dimer δobs is the observable chemical shift; The chemical shifts at each concentration were recorded and fitted into the dimerization equation to determine the optimum solutions for the dimerization constant (Kdim), and the bound (δd) and free chemical shifts (δm). 532 Self-dimerization of 8b Figure H.19. Stacked partial 1H NMR spectra of compound 8b at different concentrations in water-saturated CDCl3 (298 K). Determination of the dimerization constant of 8b·8b, fitting result based on chemical shifts of phosphonamidate NH. Figure H.20. Stacked partial 31P NMR spectra of compound 8b at different concentrations in water-saturated CDCl3 (298 K). Determination of the dimerization constant of 8b·8b, fitting result based on chemical shifts of P atom. 533 Self-dimerization of 8c Figure H.21. Stacked partial 31P NMR spectra of compound 8c at different concentrations in water-saturated CDCl3 (298 K). Determination of the dimerization constant of 8c·8c, fitting result based on chemical shifts of phosphonamidate NH. Self-dimerization of 8d Figure H.22. Stacked partial 1H NMR spectra of compound 8d at different concentrations in water-saturated CDCl3 (298 K). Determination of the dimerization constant of 8d·8d, fitting result based on chemical shifts of phosphonamidate NH. 534 Self-dimerization of 8e Figure H.23. Stacked partial 1H NMR spectra of compound 8e at different concentrations in water-saturated CDCl3 (298 K). Determination of the dimerization constant of 8e·8e, fitting result based on chemical shifts of phosphonamidate NH. Self-dimerization of 8f Figure H.24. Stacked partial 1H NMR spectra of compound 8f at different concentrations in water-saturated CDCl3 (298 K). Determination of the dimerization constant of 8f·8f, fitting result based on chemical shifts of phosphonamidate NH. 535 6. Copies of NMR Spectra for New Compounds 1H NMR spectrum of 10. 13C{1H} NMR spectrum 10. 536 1H NMR spectrum of 11a. 13C{1H} NMR spectrum 11a. 537 1H NMR spectrum of 11b. 13C{1H} NMR spectrum 11b. 538 19F{1H} NMR spectrum 11b. 1H NMR spectrum of 11c. 539 13C{1H} NMR spectrum 11c. 1H NMR spectrum of 11d. 540 13C{1H} NMR spectrum 11d. 1H NMR spectrum of 11e. 541 13C{1H} NMR spectrum 11e. 19F{1H} NMR spectrum 11e. 542 1H NMR spectrum of 11f. 13C{1H} NMR spectrum of 11f. 543 1H NMR spectrum of 8a. 13C{1H} NMR spectrum of 8a. 544 31P NMR spectrum 8a. 1H NMR spectrum of 8b. 545 13C{1H} NMR spectrum of 8b. 31P NMR spectrum 8b. 546 19F{1H} NMR spectrum 8b. 1H NMR spectrum of 8c. 547 13C{1H} NMR spectrum of 8c. 31P NMR spectrum 8c. 548 1H NMR spectrum of 8d. 13C{1H} NMR spectrum of 8d. 549 31P NMR spectrum 8d. 1H NMR spectrum of 8e. 550 13C{1H} NMR spectrum of 8e. 31P NMR spectrum 8e. 551 19F{1H} NMR spectrum 8e. 1H NMR spectrum of 8f. 552 13C{1H} NMR spectrum of 8f. 31P NMR spectrum 8f 553 APPENDIX I PN-CONTAINING PYRENE DERIVATIVES: SYNTHESIS, STRUCTURE, AND PHOTOPHYSICAL PROPERTIES (WITH SUPPLEMENTARY INFORMATION) This Appendix includes previously published and co-authored material from Deng, C.-L., Bard, J.P., Zakharov, L.N., Johnson, D.W., Haley, M.M. “PN-Containing Pyrene Derivatives: Synthesis, Structure and Photophysical Properties.” Org. Lett. 2019, 21, 6427–6431 and the associated Supplementary Information document. The bulk of the writing and synthesis for this study was performed by Dr. Chun-Lin Deng, with assistance from Jeremy P. Bard. Editorial support was provided by Michael M. Haley and Darren W. Johnson. Introduction: Among various polycyclic aromatic hydrocarbons (PAHs), pyrene and its derivatives are of great interest because of their unique optical properties, outstanding chemical stability, good hole transporting ability, and their applications in organic electronic devices1 and chemosensors.2 When used as light-emitting materials, however, there are some drawbacks for the parent pyrene such as deep blue emission with a small Stokes shift and the formation of fluorescence quenching π-aggregates/excimers in condensed media.3 As a result, numerous efforts have been devoted for improving/altering the photophysical properties. The most common synthetic strategy for developing novel pyrene derivatives is to introduce various substituents at the 1/3/6/8-positions, 4/5/9/10-positions (the K-region), 554 and 2- or 2/7-positions on the pyrene core (Figure I.1a).4 Despite these efforts, the preparation of multisubstituted pyrenes at the non-K-region (1/2/3- and/or 6/7/8-positions) is still rather challenging. Figure I.1 (a) Numbering system for pyrene and its K-region and non-K-region. (b) Chemical structures of 1 and 2 in this work. The main group element-containing PAHs are strongly attractive since the incorporation of electron-donating/electron-accepting heteroatoms could readily tailor the electronic structures and also affect the intermolecular interactions due to their unique molecular geometries, which can be used to modulate the molecular solubility/morphology.5 These appealing characteristics make heteroatom-containing PAHs promising candidates for better-performing luminescent materials and organic electronics.6 Although there have been extensive studies on heterocycle-fused pyrenes on the K-region7 or heteroatom- functionalized pyrene derivatives at the “conventional” sites,4a,8 only a handful of non-K- region fused heterocycles such as sulfur-bridged pyrene-thienoacene,9 pyrene- benzo[b]phosphole and -benzo[b]silole,10 B,O-annelated pyrene derivative,11 and BN Lewis pair chelated pyrenes12 have been developed thus far. Nonetheless, their electronic structures and emission properties were altered only to a limited extent, suggesting that additional synthetic efforts remain to achieve a dramatic change in pyrene optoelectronic/redox properties within a general molecular framework. 555 In parallel with our efforts to devise novel fluorescent PN-heterocycles,13 we describe herein the preparation and photophysical properties of two types of non-K region fused PN-heterocyclic pyrene derivatives 1 and 2 (Figure I.1b) by a straightforward synthetic strategy. An important feature of this class of pyrene derivatives is that the optoelectronic/redox properties can be remarkably and rationally tuned by simple switching of the pendant substituents. Density functional theory (DFT) calculations14 revealed that the carbon atomic coefficients of the highest occupied molecular orbital (HOMO) for the PN-embedded core is dominant at the carbon atom connecting the −Ar group (CAr), while the carbon atom connecting the −R group (CR) has a larger contribution to the lowest unoccupied molecular orbital (LUMO) (see Supplementary Information section below). It is expected that introduction of an electron-donating group (EDG) at CAr and an electron-withdrawing group (EWG) at CR would readily destabilize and stabilize the HOMO and LUMO levels, respectively. The electronic perturbations and substituent effects on the parent core might trigger a bathochromic shift of λem as well as provide modifiable energy levels. Results and discussion The modular syntheses of pyrene derivatives 1 and 2 are shown in Scheme I.1. The key steps involve a PPh(OPh)2-mediated cyclization and a one-pot sequential Sonogashira cross-coupling/heteroannulation. The synthesis of PN-fused pyrene 1 commenced with the conversion of the hydroxyl group of 1-hydroxy-2-nitropyrene 3 to triflate 4 by treatment with trifluoromethanesulfonic anhydride. Sonogashira cross-coupling of 4 with 1-hexyne followed by subsequent reduction of the nitro group using zinc powder furnished amine 5a. Treatment of 5a with PPh(OPh)2 in boiling pyridine followed by in situ hydrolysis as 556 described previously13a gave the crude phosphinamidate after minimal purification. We found that the resultant PN-heterocycle can be exclusively monoiodinated at the 3-position of the pyrene using NIS to afford 6a. Finally, the Sonogashira cross-coupling/5-endo-dig cyclization sequences using the appropriate arylacetylene provided PN-heterocycles 1a and 1b in 87% and 63% yield over the two steps, respectively. Compounds 2a/2b with 3,5- bis(trifluoromethyl)phenyl were prepared in a similar manner. All the compounds are air- and thermally stable. In particular, 1b and 2a/2b have good solubilities in a wide variety of polar and nonpolar organic solvents. All the target structures were fully characterized by conventional techniques (1H, 13C, 19F, and 31P NMR and HRMS spectroscopy). Scheme I.1 Synthesis of Pyrene Derivatives 1 and 2. Single crystals of 1a suitable for X-ray diffraction were obtained by slow evaporation of hexanes into a CHCl3 solution. The phosphoryl group is a stereocenter and thus the 557 molecule crystallizes as a racemic mixture. The ORTEP diagram of one enantiomer with atom numbering and selected bond lengths is shown in Figure I.2a (CCDC 1936450). The newly formed pyrrole ring is nearly coplanar with the pyrene core whereas the six- membered PN-heterocycle is nonplanar, as the tetrahedral P atom is distorted ∼0.2 Å out of the mean plane along with a slightly twisted torsion angle (C1–C2–C3–C4 = 2.7(2)°). In the crystal lattice of 1a, the highly polarized P═O moiety forms two C–H hydrogen bonds with adjacent molecules. No distinct intermolecular π–π stacking interaction was observed, which can be attributed to the shielding effect of the bulky phenyl substituent on the phosphorus center and the propeller-like arrangement of the peripheral benzene ring on the pyrrole ring (where φ = 51.4°). Instead, multiple C–H···π interactions between the neighboring molecules arranged in an edge-to-face and face-to-face fashion with the distances from ∼2.81 to 2.87 Å can be identified (see Supplementary Information section below). The unique packing mode would efficiently prevent excimer formation to avoid fluorescence quenching and red-shifting. Based on the crystal structure, we also performed nucleus-independent chemical shift (NICS) calculations to investigate the influence of PN- heterocycle fusion on the aromaticity of the molecular system. The pyrrole ring on the periphery of 1a has relatively negative NICS(1) values of −8.01 and −8.92 and can be classified as aromatic (Figure I.2b). The PN heterocyclic ring shows small positive values (0.86 and 0.28), indicating that it is nonaromatic. The phenyl rings along the short and long-axis of the molecule exhibit qualitatively similar NICS values that are typical for pyrene. The results obtained from the NICS computations are in agreement with the structural parameters of the crystal structure. 558 Figure I.2 (a) X-ray crystallographic structure of 1a with the thermal ellipsoids drawn at 50% probability; all hydrogen atoms are omitted for clarity. Bond lengths in Å, and φ denotes the dihedral angle between the pyrrolyl and the appended phenyl substituent. (b) NICS(±1) indices (in ppm) of 1a′ (where the n-butyl group in 1a is replaced by a methyl group) determined at the GAIO-B3LYP/pcSseg-2 level of theory. The symbols +1/–1 denote the 1 Å points above/below the defined mean planes. The absorption spectra of 1 and 2 in CH2Cl2 solution are similar, as shown in Figure I.3. Compounds 1a/1b feature two strong absorption shoulders centered at ca. 430 and 410 nm, while broad and slightly red-shifted absorption bands with low-energy absorption (440– 450 nm) are observed for 2a/2b. Wide-range tunable emission color from blue to red (Figure I.3) with high quantum yields (Table I.1) was observed among these types of pyrene derivatives. The emission spectrum of 1a shows the presence of vibronic structure and the Stokes shift is small. These characteristics suggest that the structural displacement between the ground state (S0) and excited state is small due to the structural rigidity of 1a. 559 By contrast, the emission bands of 1b and 2 become structureless and increasingly red- shifted in the order of 2a → 1b → 2b. Notably, red-emissive 2b exhibits a large apparent Stokes shift (6806 cm–1) while maintaining a relatively good quantum yield. In all cases, no excimer-like or dual emission peaks were detected at higher concentration (up to 10–4 M–1). Also noteworthy is that the shape of the emission spectra for the colloidal suspensions of 1b and 2b (in THF/water mixtures) exhibits no change compared to their respective solution counterparts (Figures I.8 and I.10). Impressively, white-light emission could be achieved if appropriate ratios of 1a, 2a, and 2b were mixed in CH2Cl2 solution under a single excitation (Figure I.12). This observation demonstrates that there is no significant energy transfer among the three pyrene derivatives, which suggests the potential for preparation of multicolor emissive materials.15 560 Figure I.3 Electronic absorption (solid line) and emission spectra (dotted line) of 1 and 2 in CH2Cl2 at 298 K. Table I.1 Photophysical Data of 1 and 2 in CH2Cl2 at 298 K cmpd λ amax (nm) λem (nm) Φ c F Stokes Shift (cm –1) 1a 430 (4.58) 459 0.57 1469 1b 431 (4.50) 551 0.62 5053 2a 450 (4.51) 521 0.61 3028 2b 437b (4.62) 622 0.23 6806 a The longest absorption maximum wavelengths, molar absorption coefficients as log ε (M– 1 cm–1) given in parentheses. b A broad absorption band. c The relative fluorescence quantum yield. With increasing solvent polarity from cyclohexane to MeCN, the fluorescence spectra of triphenylamine-substituted 1b and 2b displayed a bathochromic shift of 61 and 87 nm, respectively (see Figures I.14, I.16 and Table I.2). Their positive solvatochromism is attributed to the distinctly separated HOMO–LUMO distributions in their electronic structures, as revealed by the DFT calculations. Lippert–Mataga plots of 2b show good linear correlation with the solvent polarity (Figure I.17). The dipole moment change (Δμ) between the S0 and the excited state is estimated to be 15.0 D. The time-dependent (TD-) 561 DFT calculated dipole moment of the first excited state (S1) near the Franck–Condon (FC) geometry of 2b is up to 23.7 D, which is significantly large compared to its S0 state (7.0 D). Both the DFT calculations and experimental results indicate that 2b is a typical push– pull type system with remarkable intramolecular charge transfer (ICT) character. In contrast, the photophysical parameters of 1a and 2a exhibit limited solvent effect, which are mainly from locally excited π → π* states of the parent core. As shown in Figure I.25, in the S1 state of 2b, the phenyl groups at the CAr- and CR-positions in the S0 state are oriented in a twisted fashion relative to the molecular plane (dihedral angles: 45.5°/44.2°), whereas their orientation becomes more coplanar in S1 (30.1°/25.6°). The C–C bond lengths connecting the central core and the phenyl groups at the CAr- and CR-positions are shortened by 0.02 and 0.03 Å, respectively. Meanwhile, the bond order indices for the relevant bonds within the peripheral and heterocyclic rings alternate in various degrees upon switching from S0 to S1 (Figure I.26), suggesting effective electron delocalization occurs among the pendant substituents and PN-heterocycle fused pyrene in the S1. Consequently, destabilized HOMO and lower LUMO energies were realized at the lowest excited state relative to S0 and lead to a smaller energy gap by ∼0.5 eV. Thus, the geometric relaxations caused by facile EWG/EDG rotations with respect to the central core are responsible for the observed large Stokes shift for 2b. The fluorescence quantum yields of 1b and 2b decrease with the increasing solvent polarity (Table I.3). Additionally, the calculated nonradiative decay rate constant (knr) for both compounds increases faster than the radiative term (kr) with increasing solvent polarity (Figures I.19 and I.21). In considering their small energy gaps16 and imperceptible increase of emission intensity under oxygen-free conditions (negligible intersystem crossing), the 562 diminished fluorescence could be ascribed to the free intramolecular rotation of the EWG/EDG that dissipates the excited state energy via nonradiative pathway. Nevertheless, the unrestrained intramolecular rotation could be suppressed effectively when the fluorophore is dispersed in an aggregated state, as compound 2b shows aggregation- induced emission (AIE) behavior (Figure I.11) with an increased fluorescence quantum yield (0.44) for its colloidal suspension. Thus, this type of pyrene derivatives with the facile ability to modify the Ar- and R-substituents could be a promising platform for expanding the scope of pyrene-based AIE luminogens.17 The electrochemical properties of 1 and 2 were investigated using cyclic voltammetry (Figure I.22 and Table I.4). Within the potential window of CH2Cl2, 1 exhibited two oxidation and one reduction waves, whereas 2 showed two oxidation and two reduction waves. The two fully reversible oxidation potentials for 1b and 2b are comparable and appear at less positive potential regions owing to the presence of the stronger electron- donating ability of the triphenylamine substituent. The introduction of the 3,5- bis(trifluoromethyl)phenyl group in 2 results in not only increased reversibility for the first reduction process but also a significantly positive shift of the reductive potentials. The calculated HOMO and LUMO energy levels from these potentials are mainly dependent on the appended CR/CAr substituents. Overall, the energy gaps between electrochemical oxidation and reduction are consistent with the HOMO–LUMO gaps obtained by the DFT calculations and the UV/vis results (Table I.4). 563 Conclusions In conclusion, we have prepared a novel type of fluorescent PN-embedded pyrene derivatives via a PPh(OPh)2-mediated cyclization and sequential Sonogashira cross- coupling/heteroannulation protocol. Both the experimental results and the DFT calculations have revealed that the electronic structures and electrochemical properties could be significantly tailored by appending the EDG/EWG at appropriate positions in the core structures. These appealing characteristics should make pyrene-based PN- heterocycles promising candidates for solution-processable organic electronics and intriguing fluorescent probes and sensors. Supplementary Information 1. Synthesis General. NMR spectra were obtained on a Varian Inova 500 MHz (1H: 500.11 MHz, 13C 125.76 MHz, 19F 470.53 MHz, 31P 202.46 MHz) or a Bruker Avance-III-HD 600 MHz (1H: 599.98 MHz, 13C: 150.87 MHz) spectrometer. Chemical shifts (δ) are expressed in ppm using residual non-deuterated solvent present in the bulk deuterated solvent (CDCl 13: H 7.26 ppm, 13C 77.16 ppm; DMSO-d6: 1H 2.50 ppm, 13C 39.52 ppm). 19F chemical shifts are reported against CFCl3 external standard (δ 0 ppm). 31P chemical shifts are reported against 85% H3PO4 (δ 0 ppm) as external reference. Mass spectra data were acquired on a Waters SYNAPT QToF in positive ion mode with a Shimadzu LC20AD HPLC front end. The solvents were MeCN:H2O:0.1% HCO2H at a flow rate of 0.05 mL min –1 with a 5 μL injection on a loop injection. Preparative SEC was performed using a JAI Recycling Preparative HPLC (Model LC-9101) with a JAIGEL-1H preparative column with CHCl3 as solvent. Analytical TLC was carried out on TLC plates (5  10 cm with 0.25 mm 564 thickness, silica gel 60 F254, Merck, Darmstadt, Germany) cut from the commercially available aluminium sheets. Solvents and reagents were used as purchased from suppliers, unless anhydrous conditions were employed, in which case, solvents were freshly distilled from sodium/benzophenone under N2 atmosphere (THF) or as purchased. 1- Hydroxypyrene (s1),18 2,3,5,6-tetrabromo-4-ethyl-4-nitro-2,5-cyclohexadien-1-one (s2),19 3,5-bis(trifluoromethyl)phenylethyne20 and phenyldiphenoxyphosphine [PPh(OPh)2] 21 were synthesized by their reported procedures. Scheme I.2 Synthesis of 1 and 2. 1-Hydroxy-2-nitropyrene (3). To a solution of 1-hydroxypyrene (s1, 123 mg, 0.5 mmol) in Et2O (50 mL) cooled to 5 °C was added reagent s2 (123 mg, 0.5 mmol) in small portions 565 over 5 min. The reaction mixture was stirred for 1 h at room temperature while following the reaction by TLC. The mixture was filtered, and the collected solid was dried under the vacuum to provide 3 (140 mg, 81%) as a brown-orange solid. Rf = 0.67 (hexane). 1H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 8.38–8.33 (m, 4H), 8.25 (d, J = 8.9 Hz, 1H), 8.21 (t, J = 7.7 Hz, 1H), 8.11 (d, J = 8.9 Hz, 1H). The obtained 1H NMR spectral data were in good agreement with those previously reported.22 2-Nitropyren-1-yl trifluoromethanesulfonate (4). To a solution of 3 (123 mg, 0.5 mmol) in CH2Cl2 (20 mL) was added Et3N (0.2 mL, 1.5 mmol) at room temperature. The mixture was cooled to 0 °C and then trifluoromethanesulfonic anhydride (92 μL, 0.55 mmol) was added dropwise over 2 min. After stirring for 12 h at rt, the reaction mixture was quenched with H2O (10 mL), then the layers were separated. The aqueous layer was extracted with CH2Cl2 (20 mL × 3) and the combined organic layer was washed with 3 N HCl and then dried over Na2SO4 and then filtered. The solvent was evaporated under reduced pressure and the crude material purified by flash column chromatography (4:1 hexane/CH2Cl2) to afford 4 (140 mg, 81%) as an amorphous yellow solid. Rf = 0.37 (4:1 hexane/CH2Cl2). 1H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 8.38–8.33 (m, 4H), 8.25 (d, J = 8.9 Hz, 1H), 8.21 (t, J = 7.7 Hz, 1H), 8.11 (d, J = 8.9 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 139.6, 133.1, 131.7, 131.6, 131.1, 130.8, 130.4, 128.8, 127.9, 127.5, 127.3, 126.7, 125.7, 123.3, 120.6, 120.2, 118.8 (q, J = 320.8 Hz). 19F{1H} NMR (471 MHz, CDCl3) δ −72.5. HRMS (ESI) m/z calcd for C17H9F3NO5S [M+H] + 396.0154, found 396.0145. 1-(Hex-1-ynyl)pyren-2-amine (5a). To an N2-degassed solution of 4 (116 mg, 0.34 mmol) and 1-hexyne (0.12 mL, 1 mmol) in 5:1 (v/v) THF/Et3N (30 mL) was added CuI (2 mg, 0.002 mmol) and Pd(PPh3)2Cl2 (21 mg, 0.03 mmol). The solution was stirred at 80 °C (oil 566 bath) under N2 for 12 h, then the reaction mixture was diluted with CH2Cl2 and filtered through a 4 cm pad of silica. The filtrate was concentrated under reduced pressure and the crude product purified by flash chromatography (hexanes/EtOAc/CH2Cl2, 20:1:1) over silica to give a brown oil. Rf = 0.47 (4:1 hexane/CH2Cl2). This oil was then dissolved in AcOH (10 mL), actived Zn powder (221 mg, 3.4 mmol) was added and the mixture stirred at r.t. for 1 h. H2O (20 mL) was added and the aqueous layer extracted with CH2Cl2 (20 mL × 2). The combined organic layer was washed with saturated NaHCO3 solution and dried over Na2SO4. Following evaporation of the solvent under reduced pressure, the crude residue was purified by flash column chromatography (hexane/EtOAc/CH2Cl2, 16:1:1) to afford 5a (84 mg, 83%) as a yellow solid. Rf = 0.24 (8:1 hexane/EtOAc). Mp 153−156 °C. 1H NMR (500 MHz, CDCl3) δ 8.41 (d, J = 9.1 Hz, 1H), 8.11 (d, J = 7.6 Hz, 1H), 8.08–8.07 (m, 2H), 7.95 (d, J = 8.9 Hz, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.81 (d, J = 8.9 Hz, 1H), 7.47 (s, 1H), 4.65 (s, 2H), 2.72 (t, J = 7.1 Hz, 2H), 1.81–1.76 (m, 2H), 1.66–1.61 (m, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 146.3, 132.9, 131.9, 130.1, 129.9, 128.5, 128.3, 126.4, 125.6, 125.5, 125.2, 124.7, 124.6, 110.4, 110.3, 102.0, 76.0, 31.4, 22.4, 20.0, 13.9. HRMS (ESI) m/z calcd for C20H22N [M+H] + 298.1596, found 298.1640. 1-((3,5-bis(trifluoromethyl)phenyl)ethynyl)pyren-2-amine (5b). To an N2-degassed solution of 4 (240 mg, 0.69 mmol) and 3,5-bis(trifluoromethyl)phenylethyne19 (310 mg, 1.04 mmol) in 5:1 (v/v) THF/Et3N (30 mL) was added CuI (13 mg, 0.07 mmol) and Pd(PPh3)2Cl2 (50 mg, 0.07 mmol). The solution was stirred at 80 °C (oil bath) under N2 for 12 h, then the reaction mixture was diluted with CH2Cl2 and filtered through a 4 cm pad of silica. The filtrate was concentrated under reduced pressure and the crude product purified by flash chromatography (hexanes/EtOAc, 30:1) over silica to give a brown oil. Rf = 0.31 567 (20:1 hexane/CH2Cl2). This oil was then dissolved in AcOH (10 mL), actived Zn powder (455 mg, 7 mmol) was added, and the mixture stirred at r.t. for 1 h. H2O (20 mL) was added and the aqueous layer extracted with CH2Cl2 (30 mL × 2). The combined organic layer was washed with saturated NaHCO3 solution and dried over Na2SO4. Following evaporation of the solvent under reduced pressure, the crude residue was purified by flash column chromatography (hexanes/EtOAc, 8:1) to afford 5b (227 mg, 72%) as a yellow solid. Rf = 0.24 (8:1 hexane/EtOAc). Mp 113−115 °C. 1H NMR (500 MHz, CDCl3) δ 8.41 (d, J = 9.0 Hz, 1H), 8.15 (t, J = 8.0 Hz, 2H), 8.11–8.08 (m, 3H), 7.99 (d, J = 8.9 Hz, 1H), 7.91–7.87 (m, 2H), 7.81 (d, J = 8.9 Hz, 1H), 7.45 (s, 1H), 4.71 (s, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 146.9, 133.5, 133.4, 132.3 (q, J = 33.7 Hz), 131.3 (q, J = 3.7 Hz), 130.0, 129.8, 129.5, 129.4, 126.4, 126.2, 126.0, 125.0, 124.6, 123.2 (q, J = 273.0 Hz), 121.6 (q, J = 3.8 Hz), 121.6, 118.8, 110.5, 101.6, 97.5, 89.0. 19F{1H} NMR (471 MHz, CDCl3) δ −63.0. HRMS (ESI) m/z calcd for C +26H14F6N [M+H] 454.1030, found 454.1023. Iodoheterocycle 6a. To a solution of aniline 5a (58 mg, 0.19 mmol) in dry pyridine (1 mL) was added PPh(OPh) 2 (115 mg, 0.39 mmol). The reaction flask was sealed and heated to 110 °C for 24 h. After cooling, toluene (20 mL) was added and the volatiles were removed in vacuo. The residue was dissolved in THF/H2O mixture (10 mL, v/v, 20:1). After heating at 60 °C (water bath) for 1 h, the THF layer was dried (Na2SO4), filtered and the solvent removed under reduced pressure. The crude residue was purified by flash chromatography (CH2Cl2/EtOAc, 2:1) over silica to give a brown oil. Rf = 0.21 (2:1 CH2Cl2/EtOAc). This oil was dissolved in AcOH (5 mL) and TFA (0.05 mL) added. NIS (47 mg, 0.2 mmol) was added and the mixture stirred for 1 h at r.t. The mixture was washed with saturated NaS2O3 (2 × 15 mL) and brine (15 mL) solutions, dried (MgSO4) and evaporated. The crude product 568 was purified by chromatography over silica (CH2Cl2/ EtOAc, 5:1) to give 6a (65 mg, 62%) as a yellow solid. Rf = 0.72 (2:1 CH2Cl2/EtOAc). Mp > 200 °C. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J = 9.4 Hz, 1H), 8.37 (d, J = 34.3 Hz, 1H), 8.28 (d, J = 9.2 Hz, 1H), 8.23–8.20 (m, 3H), 8.10 (d, J = 9.3 Hz, 1H), 7.99 (t, J = 7.6 Hz, 1H), 7.92–7.87 (m, 2H), 7.61–7.58 (m, 1H), 7.50–7.54 (m, 2H), 7.18 (s, 1H), 2.64–2.50 (m, 2H), 1.76–1.67 (m, 1H), 1.66–1.56 (m, 1H), 1.44–1.33 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 137.4 (d, J = 2.8 Hz), 134.2, 133.3 (d, J = 4.1 Hz), 132.8, 132.8, 132.7 (d, J = 2.8 Hz), 132.4, 131.8, 131.0, 130.2, 130.0, 129.9, 129.6, 129.5, 129.1, 128.8, 128.7, 126.8, 126.8, 125.9, 124.0, 121.3, 121.1, 113.8 (d, J = 11.8 Hz), 92.4 (d, J = 7.3 Hz), 32.0 (d, J = 4.5 Hz), 31.9 (d, J = 12.0 Hz), 22.6, 14.0. 31P{1H} NMR (201MHz, CDCl3) δ 13.5. HRMS (ESI) m/z calcd for C28H24INOP [M+H] + 548.0640, found 548.0629. Iodoheterocycle 6b. To a solution of aniline 5b (164 mg, 0.36 mmol) in dry pyridine (1 mL) was added PPh(OPh) 2 (213 mg, 0.72 mmol). The reaction flask was sealed and heated to 110 °C for 24 h. After cooling, toluene (20 mL) was added and the volatiles were removed in vacuo. The residue was dissolved in THF/H2O mixture (15 mL, v/v, 20:1). After heating at 60 °C (water bath) for 1 h, the THF layer was dried (Na2SO4), filtered, and the solvent was concentrated under reduced pressure. The resulting crude product was purified by flash chromatography (CH2Cl2/EtOAc, 15:1) over silica to give a brown oil. Rf = 0.51 (10:1 CH2Cl2/EtOAc). This oil was dissolved in AcOH (5 mL) and TFA (0.05 mL) added. NIS (96 mg, 0.43 mmol) was added and the mixture stirred for 1 h at r.t. The mixture was washed with saturated NaS 2O3 (2 ×15 mL) and brine (15 mL) solutions, dried (MgSO4) and evaporated. The crude product was purified by chromatography over silica (CH2Cl2/EtOAc, 40:1) to give 6b (205 mg, 81%) as a yellow solid. Rf = 0.83 (2:1 569 CH2Cl2/EtOAc). Mp > 200 °C. 1H NMR (600 MHz, THF-d8) δ 8.99 (d, J = 30.0 Hz, 1H), 8.78 (d, J = 9.4 Hz, 1H), 8.54 (s, 2H), 8.29–8.23 (m, 4H), 8.15–8.11 (m, 2H), 7.98 (t, J = 7.6 Hz, 1H), 7.90 (s, 1H), 7.85–7.81 (m, 2H), 7.45–7.37 (m, 3H). 13C{1H} NMR (151 MHz, THF-d8) δ 140.0 (d, J = 12.7 Hz), 138.8 (d, J = 2.9 Hz), 135.5 (d, J = 2.1 Hz), 135.4, 134.1, 133.2, 132.7, 132.6, 131.9 (d, J = 2.7 Hz), 131.7, 131.3 (q, J = 33.2 Hz), 131.3, 130.3, 130.1, 129.9, 129.6, 128.3 (br q), 128.0, 128.0, 127.2, 127.0, 126.8, 126.4, 125.8, 123.6, 123.5 (q, J = 273.3 Hz), 121.4, 120.9 (br q), 120.7, 113.4 (d, J = 10.7 Hz), 91.1 (d, J = 7.6 Hz). 19F{1H} NMR (471MHz, THF-d 31 18) δ −63.6. P{ H} NMR (243 MHz, THF-d8) δ 7.8. HRMS (ESI) m/z calcd for C32H18F6INOP [M+H] + 704.0075, found 704.0060. PN-Heterocycle 1a. To an N2-degassed solution of 6a (41 mg, 0.07 mmol) and phenylacetyl-ene (90 mg, 0.08 mmol) in 5:1 (v/v) THF/Et3N (6 mL) was added CuI (1.5 mg, 0.007 mmol) and Pd(PPh3)2Cl2 (14 mg, 0.007 mmol). The solution was stirred at r.t. for 6 h and monitored by TLC [new spot: Rf = 0.80 (2:1 CH2Cl2/EtOAc)]. After that, the mixture was heated at 80 °C (oil bath) under N2 for 2 h, then the reaction mixture was diluted with CH2Cl2 and filtered through a 4 cm pad of silica. The filtrate was concentrated under reduced pressure and the residue purified by flash column chromatography (hexanes/EtOAc, 6:1) to provide 1a (32 mg, 87%) as a yellow solid. Rf = 0.25 (hexanes/EtOAc, 4:1). Mp > 200 °C. 1H NMR (600 MHz, CDCl3) δ 8.66 (d, J = 9.2 Hz, 1H), 8.50 (d, J = 8.5 Hz, 1H), 8.48 (d, J = 35.5 Hz, 1H), 8.27–8.23 (m, 3H), 8.18 (d, J = 9.2 Hz, 1H), 8.01 (t, J = 7.6 Hz, 1H), 7.61 (dt, J = 6.9, 1.4 Hz, 2H), 7.44 (d, J = 2.6 Hz, 1H), 7.33–7.24 (m, 6H), 7.18–7.14 (m, 2H), 2.63–2.51 (m, 2H), 1.83–1.76 (m, 1H), 1.69– 1.62 (m, 1H), 1.45–1.35 (m, 2H), 0.90 (t, J = 7.4 Hz, 4H). 13C{1H} NMR (151 MHz, CDCl3) δ 144.9 (d, J = 1.8 Hz), 133.2, 132.8 (d, J = 3.7 Hz), 132.4, 132.1, 132.1, 132.0, 570 131.8, 131.7, 131.5, 131.3, 131.1, 130.6, 130.5, 129.7, 128.9, 128.6, 128.2, 128.0, 127.8, 127.7, 126.2, 125.9, 125.7, 125.6, 125.5, 125.5, 124.2 (d, J = 5.1 Hz), 123.7, 121.8, 121.7, 111.9 (d, J = 10.2 Hz), 107.8 (d, J = 5.8 Hz), 32.5 (d, J = 3.9 Hz), 32.1 (d, J = 12.6 Hz), 22.6, 14.0. 31P{1H} NMR (243 MHz, CDCl3) δ 14.8. HRMS (ESI) m/z calcd for C36H + 29NOP [M+H] 522.1987, found 522.1979. PN-Heterocycle 1b. A similar procedure was followed using N, N-diphenyl-4- ethynylaniline4 (22 mg, 0.08 mmol). Purification by column chromatography (silica gel, hexanes/EtOAc, 5:1) gave the crude product, which then further purified by preparative SEC to provide 1b (30 mg, 63%) as an amorphous orange powder. Rf = 0.34 (hexanes/EtOAc, 4:1). 1H NMR (500 MHz, CD2Cl2) δ 8.70 (d, J = 9.3 Hz, 1H), 8.55 (d, J = 8.9 Hz, 1H), 8.49 (d, J = 34.6 Hz, 1H), 8.29–8.25 (m, 3H), 8.20 (d, J = 9.3 Hz, 1H), 8.03 (t, J = 7.6 Hz, 1H), 7.56–7.53 (m, 2H), 7.49 (d, J = 2.6 Hz, 1H), 7.45–7.37 (m, 3H), 7.32– 7.28 (m, 6H), 7.09– 7.06 (m, 6H), 6.92–6.90 (m, 2H), 2.63–2.49 (m, 2H), 1.76–1.70 (m, 1H), 1.65–1.57 (m, 1H), 1.42–1.34 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 148.1, 147.6, 144.9 (d, J = 2.0 Hz), 133.2, 132.7 (d, J = 3.6 Hz), 132.5, 132.2, 132.1, 132.0, 131.6, 131.1, 130.6, 130.4, 129.6, 129.4, 128.8, 128.2, 128.1, 127.7, 126.1, 125.9 (d, J = 9.0 Hz), 125.6, 125.5, 125.4, 125.4, 124.6, 124.3 (d, J = 5.2 Hz), 123.6, 123.2, 122.7, 121.8, 121.7, 111.8 (d, J = 10.1 Hz), 107.4 (d, J = 5.7 Hz), 32.5 (d, J = 4.2 Hz), 32.0 (d, J = 12.7 Hz), 22.6, 14.0. 31P{1H} NMR (202 MHz, CDCl3) δ 14.0. HRMS (ESI) m/z calcd for C48H38N2OP [M+H] + 689.2722, found 689.2739. PN-Heterocycle 2a. To an N2-degassed solution of 6b (43 mg, 0.06 mmol) and phenylacetyl-ene (61 mg, 0.6 mmol) in 5:1 (v/v) THF/Et3N (6 mL) was added CuI (2 mg, 0.006 mmol) and Pd(PPh3)2Cl2 (10 mg, 0.006 mmol). The solution was stirred at room 571 temperature for 8 h and monitored by TLC [new spot: Rf = 0.85 (CH2Cl2/EtOAc, 2:1)]. After that, the solution was stirred at 65 °C (oil bath) under N2 for 2 h, then the reaction mixture was diluted with CH2Cl2 and filtered through a 4 cm pad of silica. The filtrate was concentrated under reduced pressure and the residue purified by flash column chromatography (hexanes/EtOAc, 6:1) to provide 2a (33 mg, 81%) as an orange-yellow oil. Rf = 0.34 (hexanes/EtOAc, 5:1). 1H NMR (600 MHz, CDCl3) δ 8.79 (d, J = 30.8 Hz, 1H), 8.69 (d, J = 9.2 Hz, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.33–8.30 (m, 3H), 8.25 (d, J = 9.2 Hz, 1H), 8.22 (s, 2H), 8.06 (t, J = 7.6 Hz, 1H), 7.78 (s, 1H), 7.58–7.57 (m, 2H), 7.50 (d, J = 2.8 Hz, 1H), 7.30–7.22 (m, 6H), 7.11–7.08 (m, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ 144.8 (d, J = 2.8 Hz), 139.7 (d, J = 13.3 Hz), 135.8 (d, J = 2.3 Hz), 133.2, 132.5 (d, J = 2.8 Hz), 132.0 (q, J = 33.2 Hz), 131.9, 131.8, 131.7, 131.6, 131.3, 131.0, 130.7, 130.5, 130.1, 128.9 (d, J = 4.4 Hz), 128.8, 128.2 (d, J = 14.3 Hz), 127.8, 127.2, 127.2, 127.0, 127.0, 126.6, 126.2, 125.8, 125.6, 124.1 (d, J = 5.5 Hz), 123.6, 123.3 (q, J = 273.3 Hz), 122.4, 121.8 (brq), 121.4, 111.0 (d, J = 8.9 Hz), 108.4 (d, J = 6.0 Hz). 19F{1H} NMR (471MHz, CDCl3) δ −62.8. 31P{1H} NMR (243 MHz, CDCl3) δ 11.8. HRMS (ESI) m/z calcd for C40H23F6NOP [M+H] + 678.1421, found 678.1426. PN-Heterocycle 2b. A similar procedure was followed using N,N-diphenyl-4- ethynylaniline (20 mg, 0.07 mmol). Purification by column chromatography (hexanes/EtOAc, 12:1) on silica gave the crude product, which then further purified by preparative SEC to provide 2b (34 mg, 67%) as an orange-red oil. Rf = 0.40 (hexanes/EtOAc, 5:1). 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J = 30.8 Hz, 1H), 8.63 (d, J = 9.3 Hz, 1H), 8.48 (d, J = 8.9 Hz, 1H), 8.31–8.27 (m, 3H), 8.22–8.20 (m, 3H), 8.05 (t, J = 7.6 Hz, 1H), 7.80 (s, 1H), 7.50–7.48 (m, 3H), 7.41–7.33 (m, 3H), 7.32–7.28 (m, 4H), 572 7.23–7.20 (m, 2H), 7.09–7.06 (m, 6H), 6.93–6.90 (m, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ 148.4, 147.5, 144.9 (d, J = 2.5 Hz), 139.7 (d, J = 13.3 Hz), 135.7 (d, J = 2.1 Hz), 133.2, 132.5 (d, J = 2.8 Hz), 132.3, 132.2, 132.1, 132.0 (q, J = 33.2 Hz), 131.8, 130.9, 130.9, 130.4, 130.0, 129.4, 128.8, 128.7, 128.3, 128.2, 127.0, 127.0, 126.8, 126.5, 126.2, 125.8, 125.6, 125.2, 124.7, 124.2 (d, J = 5.5 Hz), 123.6, 123.4, 123.3 (q, J = 273.3 Hz), 122.5, 121.8 (brq), 121.7, 121.4, 110.9 (d, J = 9.0 Hz), 108.0 (d, J = 6.0 Hz). 19F{1H} NMR (471MHz, CDCl3) δ −62.8. 31P{1H} NMR (202 MHz, CDCl3) δ 11.4. HRMS (ESI) m/z calcd for C52H32F N + 6 2OP [M+H] 845.2156, found 845.2175. 573 2. X-ray Structure Data and Molecular Packing Diffraction intensities for 1a were collected at 173 K on a Bruker Apex2 CCD diffractometer using CuK radiation,  = 1.54178 Å. Space group was determined based on systematic absences. Absorption corrections were applied by SADABS.23 Structure was solved by direct methods and Fourier techniques and refined on F2 using full matrix least- squares procedures. All non-H atoms were refined with anisotropic thermal parameters. All H atoms in the structure were found from the residual density map and refined without any restrictions with isotropic thermal parameters. All calculations were performed by the Bruker SHELXL-2014 package.24 CCDC 1936450 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre at www.ccdc.cam.ac.uk/data_request/cif. Crystallographic data for 1a: C36H28NOP, M = 521.56, 0.09 x 0.08 x 0.06 mm, T = 173(2) K, Monoclinic, space group P21/c, a = 8.6693(4) Å, b = 19.7886(8) Å, c = 15.5913(7) Å,  = 98.068(2), V = 2648.3(2) Å3, Z = 4, Dc = 1.308 Mg/m3, μ(Cu) = 1.150 mm–1, F(000) = 1096, 2θmax = 133.11°, 24252 reflections, 4670 independent reflections [Rint = 0.0572], R1 = 0.03681, wR2 = 0.0987 and GOF = 1.029 for 4670 reflections (464 parameters) with I>2(I), R1 = 0.0438, wR2 = 0.1045 and GOF = 1.029 for all reflections, max/min residual electron density +0.286/–0.381 eÅ–3. CCDC 1936450. 574 Figure I.4 ORTEP drawing of the structure of 1a (thermal ellipsoids drawn at 50% probability). Single crystal suitable for X-ray diffraction were obtained by diffusing n- hexanes into CHCl3 solution at room temperature. 575 Figure I.5 (a) Packing diagram of 1a as viewed along the b axis. (b) The multiple C−H···π and (c) C−H···O=P intermolecular interactions in the unit cell. Distances in Å. 576 3. Photophysical Properties UV/Vis data were obtained on an HP 8453 UV/Vis spectrometer. Fluorescence data were acquired with a Horiba Jobin-Yvon FluoroMax-4 fluorescence spectrophotometer. Dilute solutions in degassed spectral grade CHCl3 in a 1 cm quartz cell were used for measurements. Absorption coefficients taken from the slope of the Beer’s Law plot. Photoluminescence quantum yields were calculated by comparison with freshly prepared quinine sulfate in 0.5 M H2SO4 (ΦF = 0.55, λex = 366 nm, for emission maxima ~450 nm), fluorescein in 0.1 M NaOH (aq.) (ΦF = 0.91, λex = 470 nm, for emission maxima ~530 nm), Rhodamine 6G in EtOH (ΦF = 0.95, λex = 480 nm, for emission maxima ~550 nm) and Nile Red in dioxane (ΦF = 0.70, λex = 460 nm, for emission maxima ~600 nm) using an excitation slit width of 2 nm for all samples. To minimize the re-absorption effects, the absorbance in the 10 mm fluorescence cuvette was about 0.03~0.05 at their excitation wavelengths. The absolute photoluminescence quantum yield of colloidal sample of 2b (in THF/water, 2/98, v/v) was measured using the Hamamatsu absolute PL quantum yield measurement system, the error is within ± 1%. Fluorescence lifetimes were measured using time correlated single photon counting (TCSPC). Dilute solutions were prepared and placed in a 1 cm optical path quartz cuvette. A pulsed nanoLED was used to excite the samples at 344 nm at a 1 MHz repetition rate. The emission was detected via a longpass filter. For bi-exponential or tri-exponential decay histograms, the average fluorescence lifetime (τavg) is utilized and calculated based on the following equation:25 τavg = (Σα τ 2 i i / Σαiτi) 577 in which αi is the pre-exponential factor corresponding to the i th decay time constant, τi. The radiative rate constant kr and the non-radiative rate constant knr were estimated by using the equations kr = ΦF/F and knr = (1−ΦF)/F, where ΦF is the photoluminescence quantum yield. Solvent-dependent spectral shifts are interpreted in terms of the Lippert−Mataga plot,26 which describes the Stokes shift Δν (between the maxima of absorption and fluorescence emission, in cm–1) as a function of the dipole moment change (Δμ = μe – μ 25,26 g): 2∆𝑓 Δν = (∆μ)2 + Constant 4𝜋𝜀 30ℎ𝑐𝑎 (in SI units) where ε0 is the permittivity of vacuum, h is Planck’s constant, c is the velocity of light, Δf is the solvent polarity function, and a is the Onsager cavity radius. The Onsager cavity radius (a = 7.0 Å) estimated from the quantum chemical calculation by using DFT method at the B3LYP/6-311G(d,p) level. Thus, the dipole moment change (Δμ = μex − μg) obtained from the solvatochromic shift is calculated to be 15.0 D (Figure I.15). As the S0→S1 transitions in substituted pyrene derivatives are usually broad with an undefined vibrational pattern, the band maxima of the longest absorption and emission have been used to determine the apparent Stokes shift in this study. In the case of 1,4- dioxane, the “effective” dielectric constant ε is much higher as it adopts the boat conformation around dipolar species; while the protic solvent MeOH would interact with the strong hydrogen bond accepting P=O moiety in the molecule via hydrogen bonding, thus these two solvents were excluded in the plot. 578 Figure I.6 Absorption (solid lines) and fluorescence (dotted lines) spectra of 1 and 2 as well as pyrene in CH2Cl2 at 298 K. Inset: emission color under 365 nm UV light. 579 Figure I.7 Normalized fluorescence spectra (left) and relative fluorescence intensities (right) of 1a (10 μM) in pure THF and the corresponding colloidal sample at 298 K. Inset: the Tyndall phenomenon observed for the colloids. The colloidal suspension was prepared by dispersing compound 1a in THF/H2O mixture (2/98, v/v). The small red-shift and widening for the emission spectrum with diminished intensity were may be attributed to the increased solvent polarity enhanced by the water and the small tendency to form excitonic complexes. Figure I.8 Normalized fluorescence spectra (left) and relative fluorescence intensities (right) of 1b (10 μM) in pure THF and the corresponding colloidal sample at 298 K. Inset: the Tyndall phenomenon observed for the colloids. The colloidal suspension was prepared by dispersing compound 1b in THF/H2O mixture (2/98, v/v). The small red-shift for the emission maximum were found due to the increased solvent polarity, which is enhanced by the water. 580 Figure I.9 Normalized fluorescence spectra (left) and relative fluorescence intensities (right) of 2a (10 μM) in pure THF and the corresponding colloidal sample at 298 K. Inset: the Tyndall phenomenon observed for the colloids. The colloidal suspension was prepared by dispersing compound 2a in THF/H2O mixture (2/98, v/v). The small red-shift and widening for the emission spectrum accompanying diminished intensity may be attributed to the increased solvent polarity enhanced by water and the small tendency to form excitonic complexes. Figure I.10 (a) Fluorescence spectra of 2b (10 μM) in pure THF and the corresponding colloidal sample at 298 K. Inset: the Tyndall phenomenon observed for the colloids. The colloidal suspension was prepared by dispersing compound 2b in THF/H2O mixture (2/98, v/v). (b) Relative fluorescence intensities of 2b (10 μM) in THF/water mixtures with varying water content. Excitation wavelength: 430 nm. 581 Figure I.11 (a) Plots of maximum emission intensity and wavelength (λem) of 2b (10 μM) versus varying water fraction (fw) in the THF/water mixture. (b) Time-resolved fluorescence decay plots of 2b in pure THF (fw = 0%) and 98% water in THF solution (fw = 98%), λex = 344 nm. (c) Rate constants of radiative (kr, red) and non-radiative decay (knr, green) of 2b in pure THF (fw = 0%) and 98% water in THF solution (fw = 98%). The small red-shift for the emission maximum and diminished intensity in the first stage were due to the increased solvent polarity, which is enhanced by the water. When the water fraction is up to 60%, the hypsochromic-shift in the emission maximum and enhanced fluorescence intensity were observed. The absolute photoluminescence quantum yield of colloidal sample of 2b (fw = 98%) was determined to be 0.44. 582 The restricted intramolecular motion (RIR) of its substituents was realized upon aggregation due to the overcrowded environment within the non-K region of 2b. The blue- shifted emission can be associated with considerable geometrical restrictions in the aggregated state, which lead to smaller distortion of the excited state and hence smaller Stokes shift. Figure I.12 Emission spectrum excited at 430 nm (a) and its emission color coordinates in the CIE 1931 chromaticity diagram (b) of the solution mixture (1a/2a/2b, ~2/1/10, in a screened molar ratio, total concentration: 10 μM) in CH2Cl2 at 298 K. The pictures were taken under 365 nm UV light exposure. Figure I.13 Absorption (left) and fluorescence (right) spectra of 1a in various solvents. 583 Figure I.14 Absorption (left) and fluorescence (right) spectra of 1b in various solvents. Figure I.15 Absorption (left) and fluorescence (right) spectra of 2a in various solvents. Figure I.16 Absorption (left) and fluorescence (right) spectra of 2b in various solvents. 584 Table I.2 Photophysical data for compounds 1 and 2 585 aThe longest absorption maxima. b Not determined due to the limited solubility. c Relative quantum yields, errors within 5%. d Fitted with mono-exponential model. e Fitted with bi- exponential model and the amplitudes of two lifetimes given in parentheses. Table I.3 Lippert-Mataga Plot data for 2b Stokes Shift Solvent abs(nm) em(nm) Δf (cm–1) cyclohexane 434 558 0 5120 toluene 441 586 0.0131 5611 CHCl3 441 603 0.01482 6092 CH2Cl2 437 622 0.2171 6806 THF 437 620 0.21 6754 acetone 435 635 0.2843 7188 MeCN 434 645 0.3086 7240 Figure I.17 Plot of the Stokes shift (cm–1, Δv) versus the solvent polarity function (Δf) for 2b. 586 Figure I.18 Rate constants of radiative (kr, red) and non-radiative decay (knr, green) of 1a in various solvents. Figure I.19 Rate constants of radiative (kr, red) and non-radiative decay (knr, green) of 1b in various solvents. 587 Figure I.20 Rate constants of radiative (kr, red) and non-radiative decay (knr, green) of 2a in various solvents. Figure I.21 Rate constants of radiative (kr, red) and non-radiative decay (knr, green) of 2b in various solvents. The abrupt decrease of the quantum yield of 2b observed in highly polar solvents (MeCN, MeOH) could be related to the twisted intramolecular charge transfer (TICT)-like excited state, resulting in very small kr. 588 4. Electrochemistry All cyclic voltammetry (CV) experiments were conducted using a 3-electrode geometry using a Biologic SP-50 potentiostat. Electrolyte solutions (0.1 M) were prepared from anhydrous, deoxygenated CH2Cl2 and anhydrous Bu4NPF6. The working electrode was a glassy carbon electrode (3-mm diameter), with a Pt-coil counter electrode and an Ag wire pseudo reference. Sample concentrations were ca. 1 mM. The ferrocene/ferrocenium (Fc/Fc+) couple was used as an internal standard following each experiment. Potential values were re-referenced based on the redox potential of Fc/Fc+ being −4.8 eV vs the vacuum level.27 For reversible or quasi-reversible couples, Eox(red) = 1/2(Epc+Epa); for irreversible couples, value is estimated as the Epa (Epc) at peak current. 589 Figure I.22 Cyclic voltammograms of 1 and 2 (0.1 M Bu4NPF6 in CH2Cl2, potential vs Fc/Fc+, scanning rate ν = 50 mV s–1). Table I.4 Summary of electrochemical data of 1 and 2 E 1 E 2 E 1 E 2 E CV opt DFTred red ox ox LUMO EHOMO Eg Eg Eg cmpd (V)a (V)a (V) a (V) a (eV)b (eV)b (eV)c (eV)d (eV)e 1a −2.13 — 0.61 1.06 −2.67 −5.41 2.74 2.74 2.97 1b −2.18 — 0.46 0.71 −2.62 −5.26 2.64 2.60 2.82 2a −1.78 −2.16 0.69 1.08 −3.02 −5.49 2.47 2.52 2.79 2b −1.79 −2.18 0.46 0.70 −3.01 −5.26 2.25 2.35 2.58 a Potential vs Fc/Fc+. b E c CVHOMO/LUMO = −(Eox/red + 4.8 eV). Eg = EHOMO – E d opt LUMO. Eg = 1240/λ e onset. Determined by the DFT calculations (B3LYP/6‐311G**). 590 5. Theoretical Calculations The initial structures were generated from the X-ray crystallography data for 1a. Other similar structures are adjusted according to the structures in the single crystal. These initial structures were optimized using the functional B3LYP and 6-311G(d,p) basis set as implemented in Gaussian 09.28 In addition, all the optimized structures were confirmed by frequency analysis and the number of imaginary frequencies was zero. Initially, TD-DFT vertical excitation calculations were performed using the long-range-corrected CAM- B3LYP (which is reported are necessary to obtain a reliable energy ordering in the excited states of pyrene itself, it is composed of 19% HF exchange at short-range and 65% HF exchange at long-range)29 and B3LYP (20% HF exchange) theory with the unified 6- 311+G(d,p) basis set. We found that the former DFT method qualitatively reproduce the experimentally obtained absorption characteristics (possible vibrational progression on the PN-heterocyclic pyrene core may mix with the absorption band, like ca. 2320 cm–1 in 1, ca. 2220 cm–1 in 2, since the intensities for these two peaks are diminished as the ICT effect and structural/conformational flexibility increase), while the latter gave significantly red- shifted electronic transition energies with respect to the experimental values (Tables I.5- I.6). Nevertheless, all the methods assign the lowest energy absorption bands to the ground state (S0) → the first excited state (S1) electronic transitions with the largest oscillator strength, which are dominated by the transitions from HOMO to LUMO. The geometry optimization of S1 for 2b were carried out at TD-B3LYP/6-311G(d,p) level of theory. The PCM solvation model30 was used to account for the solvent effects of the CH2Cl2. Orbital composition analysis with Ros-Schuit (C-squared Population Analysis, SCPA) method and Mayer bond order analysis using Multiwfn software.31 591 Figure I.23 Atomic contributions to HOMO (left) and LUMO (right) electron densities for the parent core. The orange/blue circle diameter represents the atomic contribution, calculated at the B3LYP/6-311G(d,p) level of theory. Only functionalizable positions are shown. Figure I.24 Molecular orbital diagram for 1 and 2, calculated at the B3LYP/6-311G(d,p) level of theory. Table I.5 Selected wavelength, oscillator strength (f) and major configuration calculated at the PCM(CH2Cl2)-TD-CAM-B3LYP/6-311+G(d,p) level of theory 592 electronic λcal (nm) f Major configurations transitions 404 S1 ← S0 1.2408 HOMO→LUMO (97%) HOMO-1→LUMO (76%) 348 S2 ← S0 0.083 HOMO→LUMO+2 (8%), HOMO→LUMO+3 (6%) HOMO-2→LUMO (10%), 293 S3 ← S0 0.2946 HOMO→LUMO+1 (23%), 1a HOMO→LUMO+3 (41%) HOMO-2→LUMO (31%), HOMO→LUMO+1 (12%), 267 S6 ← S0 0.2078 HOMO→LUMO+3 (25%), HOMO→LUMO+4 (13%) ••• HOMO-1→LUMO (10%), 409 S1 ← S0 1.4206 HOMO→LUMO (86%) HOMO-2→LUMO (55%), 353 S2 ← S0 0.1745 HOMO-1→LUMO (24%) HOMO-2→LUMO (11%), 1b HOMO-1→LUMO (31%), 322 S3 ← S0 0.2814 HOMO-1→LUMO+2 (10%), HOMO→LUMO+2 (12%), HOMO→LUMO+3 (12%) ••• 428 S1 ← S0 1.2669 HOMO→LUMO (96%) 359 S2 ← S0 0.1585 HOMO-1→LUMO (82%) HOMO-2→LUMO (10%), 2a 307 S3 ← S0 0.3472 HOMO→LUMO+2 (52%) ••• HOMO-1→LUMO (18%), 433 S1 ← S0 1.3541 HOMO→LUMO (78%) HOMO-2→LUMO (54%), 367 S2 ← S0 0.3022 HOMO-1→LUMO (27%) HOMO-2→LUMO (19%), 2b 331 S3 ← S0 0.1888 HOMO-1→LUMO (28%), HOMO→LUMO+5 (13%) HOMO-1→LUMO (11%), 307 S4 ← S0 0.3803 HOMO→LUMO+2 (41%) ••• Table I.6 Selected wavelength, oscillator strength (f) and major configuration calculated at the PCM(CH2Cl2)-TD-B3LYP/6-311+G(d,p) level of theory 593 electronic λcal (nm) f Major configurations transitions 452 S1 ← S0 0.9763 HOMO→LUMO (97%) HOMO-1→LUMO (84%), 381 S2 ← S0 0.0913 HOMO→LUMO+3 (7%) 1a 351 S3 ← S0 0.0574 HOMO→LUMO+1 (93%) HOMO-2→LUMO (18%), 311 S7 ← S0 0.1868 HOMO→LUMO+3 (55%) ••• 495 S1 ← S0 0.6918 HOMO→LUMO (96%) 429 S2 ← S0 0.4885 HOMO-1→LUMO (95%) HOMO-2→LUMO (70%), 368 S3 ← S0 0.035 1b HOMO→LUMO+1 (13%) HOMO→LUMO+2 (79%), 350 S3 ← S0 0.4576 HOMO→LUMO+3 (10%) ••• 489 S1 ← S0 0.9142 HOMO→LUMO (98%) 401 S2 ← S0 0.1981 HOMO-1→LUMO (92%) 375 S3 ← S0 0.0157 HOMO→LUMO+1 (98%) HOMO-2→LUMO (12%), 363 S 2a 4 ← S0 0.2122 HOMO→LUMO+2 (83%) HOMO-2→LUMO (76%), 351 S5 ← S0 0.1329 HOMO→LUMO+2 (11%) ••• 546 S1 ← S0 0.4590 HOMO→LUMO (98%) 464 S2 ← S0 0.6173 HOMO-1→LUMO (97%) 397 S3 ← S0 0.0401 HOMO→LUMO+1 (87%) 2b 393 S4 ← S0 0.089 HOMO-2→LUMO (81%) 381 S5 ← S0 0.4755 HOMO→LUMO+2 (87%) ••• 594 Figure I.25 Selected bond lengths (Å) and dihedral angles (°) in the optimized S0 and S1 structures of 2b calculated by the DFT and TD-DFT methods at the PCM(DCM)- B3LYP/6-311G(d,p) levels of theory, respectively. Figure I.26 Selected Mayer bond indices in the optimized S0 and S1 structures of 2b calculated by the DFT and TD-DFT methods at the PCM(DCM)-B3LYP/6-311G(d,p) levels of theory, respectively. 595 Figure I.27 HOMO-LUMO energies and their differences (ΔE) in the optimized S0 and S1 structures of 2b calculated by the DFT and TD-DFT methods at the PCM(DCM)- B3LYP/6-311G(d,p) levels of theory, respectively. 596 Table I.7 Cartesian coordinates for compound 1a X Y Z P 1.07271 1.85190 -0.84132 O 1.75912 1.86337 -2.17463 N 0.29059 0.36049 -0.43130 C -0.30069 3.01724 -0.72302 C -1.58764 2.62532 -0.59726 C -2.04300 1.26294 -0.42146 C -1.09627 0.23466 -0.33634 C -1.41167 -1.10931 -0.07226 C -0.17112 -1.81462 0.00260 C 0.85022 -0.92824 -0.22115 C -2.76335 -1.49432 0.07082 C -3.76302 -0.48264 -0.04944 C -3.40905 0.89212 -0.29020 C -4.47584 1.84858 -0.39276 C -5.78125 1.49078 -0.26972 C -6.16574 0.13237 -0.02543 C -5.13875 -0.85136 0.08512 C -5.50169 -2.21016 0.33392 C -4.46487 -3.19010 0.45081 C -3.15396 -2.84482 0.32693 C -6.85992 -2.54893 0.45984 C -7.84953 -1.57994 0.34667 C -7.50791 -0.25136 0.10682 C 2.28843 -1.25341 -0.23423 C 3.15508 -0.84532 -1.26019 C 4.48665 -1.25318 -1.26134 C 4.97727 -2.07503 -0.24841 C 4.12459 -2.48812 0.77453 C 2.79445 -2.08078 0.78296 C 2.21831 2.18282 0.52987 C 3.51496 2.62105 0.24142 C 4.39171 2.93053 1.27905 C 3.97703 2.80604 2.60377 C 2.68327 2.37208 2.89511 C 1.80337 2.06258 1.86235 H -2.33609 3.40989 -0.60746 H -0.03005 -2.87038 0.17142 H -4.24196 2.88730 -0.58311 H -6.55961 2.24112 -0.35793 H -4.74443 -4.22075 0.64090 H -2.38378 -3.60172 0.41801 597 H -7.12812 -3.58283 0.64830 H -8.89227 -1.85896 0.44613 H -8.28255 0.50294 0.02015 H 2.78746 -0.21055 -2.05533 H 5.14078 -0.93120 -2.06379 H 4.49635 -3.12198 1.57161 H 2.14044 -2.39101 1.58924 H 3.83050 2.71005 -0.79073 H 5.39711 3.26605 1.05277 H 4.66070 3.04621 3.41000 H 2.36130 2.27359 3.92521 H 0.79965 1.72601 2.09595 C 0.09133 4.46599 -0.88476 H -0.78829 5.10750 -0.80849 H 0.80702 4.77492 -0.11639 H 0.56350 4.64550 -1.85531 H 6.01453 -2.38997 -0.25484 Table I.8 Cartesian coordinates for compound 1b X Y Z P 1.13732 1.90003 -0.45490 O 1.89705 2.13900 -1.72543 N 0.30622 0.38378 -0.36152 C -0.21800 3.06439 -0.19652 C -1.51655 2.69127 -0.17785 C -2.00654 1.33108 -0.24554 C -1.08499 0.27979 -0.31698 C -1.43536 -1.08146 -0.29555 C -0.21287 -1.82075 -0.32063 C 0.83343 -0.93595 -0.36839 C -2.79834 -1.44963 -0.25198 C -3.77288 -0.40715 -0.21913 C -3.38376 0.97900 -0.21055 C -4.42682 1.96566 -0.17102 C -5.74261 1.62560 -0.14355 C -6.16204 0.25578 -0.14793 C -5.15937 -0.75818 -0.18388 C -5.55750 -2.12994 -0.18348 C -4.54513 -3.14161 -0.21250 C -3.22432 -2.81367 -0.24296 C -6.92559 -2.45025 -0.15239 C -7.89117 -1.45124 -0.12087 598 C -7.51534 -0.11039 -0.11787 C 2.26314 -1.28399 -0.40810 C 3.16234 -0.74971 -1.34454 C 4.48426 -1.17155 -1.38822 C 4.95819 -2.15611 -0.50786 C 4.06113 -2.70122 0.42363 C 2.74451 -2.26731 0.47263 C 2.21309 1.94081 1.00945 C 3.51110 2.44692 0.88379 C 4.33409 2.53723 2.00469 C 3.86460 2.12392 3.25042 C 2.57018 1.61867 3.37910 C 1.74358 1.52913 2.26328 H -2.24750 3.48669 -0.08358 H -0.09961 -2.89312 -0.33686 H -4.16606 3.01543 -0.17230 H -6.50235 2.39939 -0.11955 H -4.85161 -4.18212 -0.21046 H -2.47324 -3.59458 -0.26591 H -7.22107 -3.49388 -0.15294 H -8.94192 -1.71675 -0.09760 H -8.27118 0.66714 -0.09176 H 2.83052 0.01205 -2.03753 H 5.15733 -0.73612 -2.11621 H 4.40031 -3.46336 1.11389 H 2.07422 -2.69703 1.20778 H 3.87033 2.75750 -0.08952 H 5.34006 2.92785 1.90437 H 4.50620 2.19436 4.12134 H 2.20648 1.29379 4.34692 H 0.73970 1.13375 2.36911 C 0.20888 4.50942 -0.10625 H -0.65961 5.15288 0.04484 H 0.90246 4.67091 0.72510 H 0.72001 4.83162 -1.01834 N 6.30406 -2.58818 -0.55843 C 6.96612 -2.72347 -1.81232 C 6.32670 -3.34993 -2.89054 C 8.26996 -2.23897 -1.98181 C 6.97692 -3.47747 -4.11449 H 5.32198 -3.73502 -2.76524 C 8.91959 -2.38576 -3.20408 H 8.76970 -1.74986 -1.15448 C 8.27717 -3.00058 -4.27839 H 6.46824 -3.96448 -4.93893 599 H 9.92836 -2.00530 -3.31953 H 8.78342 -3.10711 -5.23062 C 7.00755 -2.89381 0.64049 C 6.90728 -2.05549 1.75951 C 7.81823 -4.03475 0.71591 C 7.59636 -2.36115 2.92950 H 6.28944 -1.16733 1.70768 C 8.51752 -4.32352 1.88426 H 7.89856 -4.69062 -0.14240 C 8.40831 -3.49303 2.99913 H 7.50812 -1.70191 3.78586 H 9.14046 -5.21007 1.92569 H 8.94903 -3.72411 3.90941 Table I.9 Cartesian coordinates for compound 2a X Y Z P 1.08073 1.82858 -0.98826 O 1.68776 1.79759 -2.35873 N 0.30246 0.36193 -0.49900 C -0.28109 3.01164 -0.81857 C -1.57110 2.62595 -0.63430 C -2.02378 1.27660 -0.42288 C -1.07851 0.24491 -0.34939 C -1.38981 -1.08915 -0.03903 C -0.15048 -1.79966 0.00598 C 0.86569 -0.92612 -0.27880 C -2.73656 -1.46022 0.17098 C -3.73725 -0.44657 0.06143 C -3.38936 0.91726 -0.23495 C -4.45388 1.87479 -0.32930 C -5.75510 1.52755 -0.14142 C -6.13340 0.18152 0.16657 C -5.10714 -0.80321 0.26621 C -5.46431 -2.15029 0.57664 C -4.42771 -3.13180 0.67944 C -3.12176 -2.79941 0.48619 C -6.81641 -2.47670 0.77529 C -7.80657 -1.50646 0.67312 C -7.47054 -0.18966 0.37157 C 2.29725 2.18799 0.30888 C 3.57367 2.62497 -0.06057 C 4.50309 2.96126 0.92118 600 C 4.16142 2.86386 2.26871 C 2.88779 2.43116 2.64000 C 1.95459 2.09608 1.66397 H -2.31777 3.41114 -0.63516 H -0.00800 -2.85138 0.19693 H -4.22528 2.90496 -0.56681 H -6.53345 2.27814 -0.22586 H -4.70316 -4.15404 0.91518 H -2.35233 -3.55790 0.56747 H -7.08028 -3.50184 1.01131 H -8.84470 -1.77605 0.82922 H -8.24484 0.56575 0.29310 H 3.83279 2.69407 -1.10968 H 5.49231 3.29734 0.63334 H 4.88645 3.12503 3.03099 H 2.62290 2.35440 3.68796 H 0.96649 1.76119 1.95840 C 0.07467 4.44768 -0.94347 C 0.98778 4.90097 -1.90458 C -0.51184 5.39249 -0.08604 C 1.28695 6.25825 -2.01146 H 1.44201 4.19282 -2.58554 C -0.21108 6.74397 -0.20699 H -1.19675 5.06544 0.68492 C 0.69266 7.19117 -1.17019 H 0.92173 8.24347 -1.26544 C -0.81128 7.73880 0.74931 C 2.29295 6.69709 -3.04126 F 0.04039 8.03808 1.75994 F -1.10964 8.90766 0.14022 F -1.94650 7.28430 1.32025 F 2.24625 8.02509 -3.27401 F 3.55988 6.41110 -2.65453 F 2.10529 6.07640 -4.22701 C 2.30119 -1.25744 -0.33772 C 3.12835 -0.88549 -1.40889 C 2.84324 -2.05382 0.68548 C 4.45801 -1.29749 -1.44757 H 2.73175 -0.27804 -2.21143 C 4.17118 -2.46565 0.63933 H 2.21973 -2.33596 1.52555 C 4.98498 -2.08795 -0.42794 H 5.08167 -1.00372 -2.28428 H 4.57180 -3.07501 1.44146 H 6.02064 -2.40604 -0.46354 601 Table I.10 Cartesian coordinates for compound 2b X Y Z P 1.09355 1.82685 -0.83772 O 1.72796 1.90910 -2.19387 N 0.27307 0.34193 -0.50352 C -0.24458 3.02140 -0.58302 C -1.54667 2.65179 -0.46081 C -2.03421 1.29919 -0.39657 C -1.11392 0.24326 -0.40611 C -1.46244 -1.10945 -0.25623 C -0.24038 -1.85054 -0.25543 C 0.80335 -0.97646 -0.41360 C -2.82381 -1.46874 -0.14452 C -3.79936 -0.42523 -0.17553 C -3.41306 0.95516 -0.29390 C -4.45341 1.94310 -0.30900 C -5.76830 1.60745 -0.22054 C -6.18591 0.24309 -0.10381 C -5.18389 -0.77100 -0.07914 C -5.58067 -2.13731 0.04238 C -4.56824 -3.14865 0.07555 C -3.24845 -2.82640 -0.01076 C -6.94696 -2.45324 0.12822 C -7.91316 -1.45417 0.09859 C -7.53845 -0.11839 -0.01483 C 2.23175 -1.32739 -0.46238 C 3.10572 -0.87953 -1.46576 C 4.42728 -1.30210 -1.50523 C 4.92723 -2.20364 -0.55258 C 4.05407 -2.66411 0.44585 C 2.73831 -2.22805 0.48964 C 2.29439 2.03600 0.50637 C 3.58898 2.46598 0.19670 C 4.51073 2.68574 1.21805 C 4.14343 2.47824 2.54651 C 2.85202 2.05091 2.85833 C 1.92672 1.83218 1.84259 H -2.27562 3.45153 -0.40260 H -0.12652 -2.92028 -0.18005 H -4.19506 2.98917 -0.40388 H -6.52757 2.38168 -0.24093 602 H -4.87361 -4.18505 0.17076 H -2.49759 -3.60716 0.01508 H -7.24109 -3.49316 0.21909 H -8.96278 -1.71614 0.16543 H -8.29391 0.65954 -0.03556 H 2.75455 -0.18523 -2.21784 H 5.07942 -0.93272 -2.28657 H 4.41130 -3.36225 1.19214 H 2.08849 -2.59093 1.27732 H 3.86810 2.62073 -0.83808 H 5.51339 3.01792 0.97572 H 4.86173 2.65032 3.33988 H 2.56703 1.88844 3.89114 H 0.92523 1.50021 2.09145 N 6.27132 -2.63668 -0.59510 C 6.92331 -2.84707 -1.84406 C 6.27697 -3.53598 -2.87924 C 8.22641 -2.37511 -2.04978 C 6.91984 -3.73623 -4.09735 H 5.27273 -3.91204 -2.72572 C 8.86863 -2.59446 -3.26514 H 8.73150 -1.83794 -1.25621 C 8.21927 -3.27092 -4.29726 H 6.40594 -4.27092 -4.88832 H 9.87696 -2.22259 -3.40881 H 8.71945 -3.43418 -5.24464 C 6.99079 -2.87012 0.61253 C 6.93911 -1.94419 1.66312 C 7.76775 -4.02660 0.76044 C 7.64266 -2.18007 2.84073 H 6.34750 -1.04356 1.55264 C 8.48149 -4.24696 1.93508 H 7.80972 -4.74799 -0.04655 C 8.42018 -3.32920 2.98321 H 7.59323 -1.45410 3.64458 H 9.07817 -5.14679 2.03457 H 8.97235 -3.50627 3.89872 C 0.14546 4.45432 -0.57429 C 1.07345 4.97068 -1.49169 C -0.41659 5.32979 0.36499 C 1.40963 6.32107 -1.47147 H 1.52084 4.31364 -2.22608 C -0.07750 6.68050 0.37054 H -1.11049 4.94963 1.10392 C 0.83808 7.18944 -0.54544 603 H 1.10515 8.23658 -0.53350 C -0.66551 7.57543 1.42762 C 2.36117 6.85438 -2.50832 F -0.05528 7.40395 2.62525 F -0.55217 8.88285 1.11623 F -1.97891 7.32389 1.62840 F 2.97611 7.98634 -2.10358 F 3.32734 5.96264 -2.81731 F 1.72442 7.15128 -3.66702 Table I.11 Cartesian coordinates for the first excited state (S1) of compound 2b X Y Z P 0.60093 -0.68070 -0.52163 O -0.08151 -1.21096 -1.75320 N 0.48327 1.05772 -0.36509 C 2.36036 -0.94440 -0.40561 C 3.26878 0.11631 -0.42278 C 2.95183 1.48994 -0.41723 C 1.60297 1.89665 -0.36922 C 1.18059 3.22863 -0.24093 C -0.22076 3.19908 -0.11604 C -0.65760 1.87444 -0.20648 C 2.13341 4.30038 -0.24171 C 3.51152 3.94039 -0.34280 C 3.92607 2.56483 -0.43026 C 5.31915 2.30143 -0.52586 C 6.25755 3.29952 -0.53038 C 5.88237 4.67105 -0.44067 C 4.49174 4.98402 -0.34823 C 4.08964 6.35557 -0.25899 C 2.70381 6.66046 -0.16245 C 1.76213 5.65836 -0.15339 C 5.07997 7.36428 -0.26739 C 6.42728 7.04141 -0.35850 C 6.83159 5.71168 -0.44397 C -2.05189 1.48155 -0.18896 C -2.59029 0.38116 -0.89789 C -3.94220 0.11377 -0.88551 C -4.83806 0.91862 -0.14589 C -4.31099 2.01854 0.57233 C -2.96430 2.29137 0.53837 C -0.19792 -1.31093 0.99152 604 C -1.12138 -2.35756 0.89831 C -1.69584 -2.88772 2.05286 C -1.35418 -2.37409 3.30180 C -0.43304 -1.32915 3.39992 C 0.14767 -0.80260 2.25087 H 4.31616 -0.15511 -0.44323 H -0.87850 4.04823 -0.02250 H 5.66269 1.27821 -0.60443 H 7.31065 3.05066 -0.60687 H 2.39865 7.69896 -0.09653 H 0.71076 5.91352 -0.08068 H 4.77033 8.40169 -0.19984 H 7.17080 7.83089 -0.36287 H 7.88497 5.46347 -0.51558 H -1.93673 -0.25911 -1.47511 H -4.31912 -0.73725 -1.43648 H -4.97412 2.66015 1.13632 H -2.59356 3.13876 1.09993 H -1.38676 -2.75049 -0.07519 H -2.40710 -3.70191 1.97485 H -1.80102 -2.78726 4.19894 H -0.16564 -0.92888 4.37100 H 0.86896 0.00241 2.33575 N -6.19985 0.64166 -0.12473 C -6.83732 0.00557 -1.23232 C -6.59466 0.45446 -2.53696 C -7.72232 -1.05694 -1.01012 C -7.22562 -0.16706 -3.60873 H -5.92804 1.29142 -2.70316 C -8.35059 -1.66783 -2.08917 H -7.90303 -1.40409 -0.00057 C -8.10382 -1.22855 -3.39035 H -7.03959 0.18766 -4.61540 H -9.02727 -2.49557 -1.91352 H -8.59497 -1.70853 -4.22823 C -6.99765 0.98737 1.00813 C -6.56688 0.65221 2.29808 C -8.21984 1.64564 0.82554 C -7.35308 0.98534 3.39557 H -5.63189 0.12246 2.43186 C -8.99894 1.97107 1.93001 H -8.54531 1.90711 -0.17355 C -8.56926 1.64471 3.21685 H -7.01998 0.71733 4.39114 H -9.93991 2.48833 1.78537 605 H -9.18003 1.89977 4.07454 C 2.81072 -2.33314 -0.28620 C 2.05492 -3.42262 -0.77400 C 4.04310 -2.64576 0.33452 C 2.50277 -4.73114 -0.63941 H 1.12206 -3.23832 -1.28940 C 4.48640 -3.95643 0.44277 H 4.64766 -1.85483 0.75659 C 3.72532 -5.02371 -0.03706 H 4.07225 -6.04264 0.05629 C 5.77067 -4.24467 1.16847 C 1.68307 -5.84319 -1.23047 F 5.56351 -4.48383 2.48883 F 6.40105 -5.33684 0.67935 F 6.64776 -3.21827 1.10039 F 1.90363 -7.02795 -0.61707 F 0.35423 -5.60034 -1.15401 F 1.95969 -6.03592 -2.54533 606 6. Copies of NMR Spectra for New Compounds 1H NMR spectrum of 4 in CDCl3. 13C NMR spectrum of 4 in CDCl3. 607 19F NMR spectrum of 4 in CDCl3. 1H NMR spectrum of 5a in CDCl3. 608 13C NMR spectrum of 5a in CDCl3. 1H NMR spectrum of 5b in CDCl3. 609 13C NMR spectrum of 5b in CDCl3. 19F{1H} NMR spectrum of 5b in CDCl3. 610 1H NMR spectrum of 6a in CDCl3. 13C NMR spectrum of 6a in CDCl3. 611 31P{1H} NMR spectrum of 6a in CDCl3. 1H NMR spectrum of 6b in THF-d8. 612 13C NMR spectrum of 6b in THF-d8. 19F{1H} NMR spectrum of 6b in THF-d8. 613 31P{1H} NMR spectrum of 6b in THF-d8. 1H NMR spectrum of 1a in CDCl3. 614 13C{1H} NMR spectrum of 1a in CDCl3. 31P{1H} NMR spectrum of 1a in CDCl3. 615 1H NMR spectrum of 1b in CD2Cl2. 13C{1H} NMR spectrum of 1b in CDCl3. 616 31P{1H} NMR spectrum of 1b in CDCl3. 1H NMR spectrum of 2a in CDCl3. 617 13C{1H} NMR spectrum of 2a in CDCl3. 31P{1H} NMR spectrum of 2a in CDCl3. 618 19F{1H} NMR spectrum of 2a in CDCl3. 1H NMR spectrum of 2b in CDCl3. 619 13C{1H} NMR spectrum of 2b in CDCl3. 31P{1H} NMR spectrum of 2b in CDCl3. 620 19F{1H} NMR spectrum of 2b in CDCl3. 621 REFERENCES CITED Chapter 1 (1) Webber, M. 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