ANIONS AND ELECTRON-DEFICIENT AROMATIC RINGS by ORION BOYD BERRYMAN A DISSERTATION Presented to the Department of Chemistry and the Graduate School of the University of Oregon in partial fulfillment of the requirements for the degree of Doctor of Philosophy June 2008 11 University of Oregon Graduate School Confirmation of Approval and Acceptance of Dissertation prepared by: Orion Berryman Title: "Anions and Electron-Deficient Aromatic Rings" This dissertation has been accepted and approved in partial fulfillment of the requirements for the Doctor of Philosophy degree in the Department of Chemistry by: James Hutchison, Chairperson, Chemistry Darren Johnson, Advisor, Chemistry Michael Haley, Member, Chemistry Kenneth Doxsee, Member, Chemistry David Schmidt, Outside Member, Geological Sciences and Richard Linton, Vice President for Research and Graduate Studies/Dean of the Graduate School for the University of Oregon. June 14, 2008 Original approval signatures are on file with the Graduate School and the University of Oregon Libraries. © 2008 Orion Boyd Berryman 111 IV An Abstract of the Dissertation of Orion Boyd Berryman in the Department of Chemistry for the degree of to be taken Doctor ofPhilosophy June 2008 Title: ANIONS AND ELECTRON-DEFICIENT AROMATIC RINGS Approved: _ Darren W. Johnson More than two-thirds of all enzyme substrates and cofactors are anionic, emphasizing the essential role that anions play in biological processes. Moreover, anions can have detrimental effects on the environment by causing ground water contamination when anions such as perchlorate, phosphate and nitrate develop in intolerable levels. Owing to the prevalent nature of anions, traditional strategies employed to target anions-including hydrogen bonding, metal ion coordination and electrostatic interactions-have been extensively studied. An alternative approach to anion binding would complement the powerful array ofexisting techniques. Recently, in the supramo1ecu1ar chemistry community, new insight has been cast on how anions attractively interact with electron-deficient arenes, suggesting that aromatic rings are a viable anion binding strategy to balance existing methods. Chapter I provides a historical perspective of anions interacting with e1ectron- deficient arenes. This outlook has its origins in the late 1800s with the discovery of colored charge-transfer complexes between donor and acceptor molecules and continues with the progression of the field leading up to the recent supramolecular fascination. Chapter II represents our initial efforts at measuring anionlarene interactions in solution. In particular, sulfonamide based hydrogen bonding receptors were developed with pendant aromatic rings to test the strength of anionlarene interactions in solution. Complementary computational chemistry and crystallography were utilized to supplement the solution studies. Chapter III describes our quantum calculations and crystallographic efforts at using only electron-deficient arenes to bind halides. A Cambridge Structure Database survey supports our emphasis of understanding multiple anionlarene interactions. Chapter IV illustrates how tripodal anion receptors can be developed to bind anions using only electron-deficient aromatic rings. Furthermore, subtle changes in anion binding geometries are observed with isomeric receptors and corroborated with Density Functional Theory calculations. Chapter V is dedicated to the preparation of electron-deficient anion receptors that are conformationally stabilized by hydrogen bonds. Chapter VI is committed to using our knowledge of anion binding to study a series of ethynyl-pyridine sulfonamides capable ofhydrogen bonding to small molecules and anions. In conclusion, Chapter VII is a summary and future prospective for the field of anionlarene interactions. This dissertation includes previously published and co-authored material. v -------- - ------- Vi CURRICULUM VITAE NAME OF AUTHOR: Orion B. Berryman PLACE OF BIRTH: Homer, Alaska DATE OF BIRTH: August, 4th 1981 GRADUATE AND UNDERGRADUATE SCHOOLS ATTENDED: University of Oregon, Eugene, Oregon University ofNew Hampshire, Durham, New Hampshire DEGREES AWARDED: Doctor of Philosophy, 2008, University of Oregon Bachelor of Arts, Chemistry, Minor, Music, 2003, University of New Hampshire AREAS OF SPECIAL INTEREST: Supramolecular Chemisty Single Crystal X-ray Diffraction Organic Chemistry PROFESSIONAL EXPERIENCE: Research Assistant, Summer Internship, University ofNew Hampshire 2001-2003 Teaching Assistant, University of Oregon, 2003 Vll GRANTS, AWARDS AND HONORS: IGERT fellowship, University of Oregon, 2005-2008 Travel Grant, ISMSC, University of Pavia, Italy, 2007 Magna Cum Laude, University ofNew Hampshire, 1999-2003 PUBLICATIONS: Berryman, O. B.; Johnson, C. A.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. "Water and hydrogen halides serve the same structural role in a series of2+2 hydrogen-bonded dimers based on 2,6-bis(2-anilinoethynyl)pyridine sulfonamide receptors. " Angewandte Chemie International Edition, 2007, 46, 117-120. Berryman, O. B.; Bryantsev, V. S.; Stay, D. P.; Johnson, D. W.; Hay, B. P. "Structural criteria for the design ofanion receptors: the interaction ofhalides with electron- deficient arenes. " Journal ofthe American Chemical Society, 2007, 129,48-58 (highlighted in UO Press release - December 2006). Meisner, J. S.; Berryman, O. B.; Zakharov, L. N.; Johnson, D. W. "MethyI4-bromo-3,5- dinitrobenzoate. " Acta Crystallographica Section E, 2007,63,02466. Cangelosi, V. A.; Sather, A. C.; Zakharov, L. N.; Berryman, O. B.; Johnson, D. W. "Diastereoselectivity in the self-assembly ofAs2L2C!J macrocycles is directed by the As-n interaction. " Inorganic Chemistry, 2007, 46, 9278-9284. Rather Healey, E.; Vickaryous, W. J.; Berryamn, O. B.; Johnson, D. W. "In BOTTOM- UP NANOFABRICATION: Supramolecules, Self-Assemblies, and Organized Films;" Ariga, K., Nalwa, H 8., Eds.; American Scientific Publishers: Stevenson Ranch, 2007. Berryman, O. B.; Hof, F.; Hynes, M. 1.; Johnson, D. W. "Anion-n interaction augments halide binding in solution. " Chemical Communications, 2006, 506-508. Johnson, C. A.; Baker, B. A.; Berryman, O. B.; Zakharov, L.; O'Connor, M. J.; Hmey, M. M. "Synthesis and characterization ofpyridine- and thiophene-basedplatinacyclyne topologies. " Journal ofOrganometallic Chemistry, 2006, 691, 413-421. Vickaryous, W. J.; Hemey, E. R.; Berryman, O. B.; Johnson, D. W. "Synthesis and characterization oftwo isomeric, self-assembled arsenic-thiolate macrocycles. " Inorganic Chemistry, 2005. 44,9247-9252. V111 ACKNOWLEDGMENTS I must first express my sincere gratitude to my research advisor Darren W. Johnson for his continued direction and support throughout my doctoral tenure. My educational journey would have been wrought with difficulty without Dr. Johnson's continued zeal for chemistry. Additionally, I would like to thank my committee chair Prof. Jim Hutchison and members Profs Mike Haley, Ken Doxsee and David Schmidt for their insight and guidance. My doctoral research has profited from access to the VO single crystal X-ray diffractometer and I must express my sincere appreciation to the individuals that taught me the intricacies of single crystal X-ray diffraction. Namely, Darren W. Johnson, Elizabeth Rather-Healey and Lev N. Zakharov have been instrumental in this regard. The collaborative aspect of this dissertation has been possible through a number of excellent professional relationships that I would like to acknowledge. In particular, I would like to thank Dr. Benjamin P. Hay for an internship at the Northwest National Laboratory as well as a number of extended, yet insightful conversations. Additionally, Profs Fraser Hof and Michael J. Hynes have beneficially influenced my education. I have had the privilege of mentoring a number of beginning chemists but above all Aaron C. Sather has expressed excellence and hard work in the laboratory. I must acknowledge my coworkers for their continued entertainment and support. This investigation was sustained by funding from a National Science Foundation IGERT fellowship. IX This body of work is dedicated to a few special people that have touched my heart, mind and soul. I must express my sincere gratitude to my loving parents Jon Martin Berryman and Julia Rene Berryman who have chiseled and worked this rough stone throughout the years. My grandmother Betty L. Snow and Trumpet teacher Howard Hedges who showed me inspiration through music and the written word. Finally, my loving wife Erin Jane Berryman who's eternal patience wears away stone. --- -_._---------_._--------~~~~~~~--- x TABLE OF CONTENTS Chapter I. HISTORICAL PERSPECTIVE OF ANIONS INTERACTING WITH ELECTRON-DEFICIENT AROMATIC RINGS . Introduction . Nomenclature and Historical Perspective . Early Anion/arene Computations and Mass Spectrometry .. Renaissance of Anion/arene Computations .. A Flourish of Anion/arene Crystal Structures .. A Relative Dearth of Anion/Arene Solution Studies . Summary and Bridge to Chapter II . II. ANION-II INTERACTION AUGMENTS HALIDE BINDING IN SOLUTION . Introduction . Receptor Design . Receptor Synthesis, X-ray Diffraction and Electrostatic Potential Surface.. Solution Studies - Anion Binding .. Receptor pKa Measurement and Analysis . Anion-receptor Co-Crystal and Computational Analysis . Conclusion . Summary of Crystallographic Data . Bridge to Chapter III . III. STRUCTURAL CRITERIA FOR THE DESIGN OF ANION RECEPTORS: THE INTERACTION OF HALIDES WITH ELECTRON-DEFICIENT ARENES . Introduction . Background and Significance . Methods . Page 1 1 2 4 4 6 9 13 15 15 16 17 20 22 23 25 26 27 28 28 29 33 Xl Chapter Page General 33 Single Crystal Growth 33 X-ray Diffraction 34 Electronic Structure Calculations..... 34 Cambridge Structural Database Searches 35 Results and Discussion 36 TCB Crystal Structures 36 Electronic Structure Calculations of TCB 41 NBO Analysis 47 ~E(2) Analysis 47 Electronic Density Surfaces 47 Atomic Charge Analysis by NPA and ESP Methods 48 qCT Analysis 49 Electronic Structure Calculations for Other Arenes 49 NBO Analysis for Additional Arenes 52 Further Analysis of Single Crystal Structure Data 53 Surveys of the Cambridge Structural Database 54 Expanded CSD Survey 55 Structural Analysis of HalidelPyridine Complexes 57 Structural Analysis of Donor/Pert1uorobenzene Complexes 58 Summary and Conclusions 62 Supporting Information Available 67 Bridge to Chapter IV.... 67 IV. SOLUTION PHASE MEASUREMENT OF BOTH WEAK SIGMA AND C-H---X- HYDROGEN BONDING INTERACTIONS IN SYNTHETIC ANION RECEPTORS 69 Introduction to Electron-deficient Arene Containing Tripodal Receptors 69 Research Summary 71 Design and Synthesis of Tripodal Anion Receptors 72 Receptor Design 72 Receptor Synthesis 72 xu Chapter Page Solution Equilibria of Receptor/anion Complexes 73 1H NMR Titration Experiments 73 Solution Data for Tetra-n-butylammonium Bromide 75 Computational Studies 76 DFT Calculations of Model Compounds 76 DFT Calculations of Receptor/Br- complexes 77 Solution Studies with Chloride and Iodide 79 Concluding Remarks 79 Experimental Details 80 Bridge to Chapter V 81 V. INVESTIGATING THE USE OF INTRAMOLECULAR HYDROGEN BONDS TO STABILIZE RECEPTOR CONFORMATIONS; DESIGNING RECEPTORS FOR ANIONIARENE INTERACTIONS 83 Introduction... 83 Tripodal Receptor Design; Incorporating Hydrogen Bond Donors 85 Nitrogen Based Scaffolds for Anion Recognition 86 Synthesis ofNitrogen Based Anion Receptors 86 Solid State Behavior of Neutral Amine Based Receptors 87 Solid State Behavior of Protonated Amine Based Receptors 88 Phosphorus Based Receptors for Anion Recognition 90 Synthesis of Phosphorus Based Receptors 91 Solid State Behavior Tripodal Phosphine Oxide Based Receptors 92 Synthesis and Structure of Highly Electron-deficient Aromatic Rings 94 Conclusion 96 Bridge to Chapter VI 97 VI. A CONFORMATIONALLY DIVERSE SERIES OF MOLECULES; 2,6- BIS(ETHYNYL)PYRIDINE, BIPYRIDINE AND THIOPHENE; SCAFFOLDS FOR MODULAR RECEPTOR DESIGN 98 Introduction 98 2,6-bis(2-anilinoethynyl)pyridine Sulfonamides 100 Results and Discussion 111 X111 Chapter Page Ligand Design 111 Expanded Series of Sulfonamide Receptors 114 Synthesis of 2,6-bis(2-anilinoethynyl)pyridine Sulfonamides 114 Solid State Investigation of2,6~bis(2-anilinoethynyl)pyridine Sulfonamide Receptors . 117 Synthesis of Core Analogs 122 Solid State Investigation of Core Analog Sulfonamide Receptors .. , 123 Amide Functionalized Receptors 125 Synthesis of2,6-bis(2-anilinoethynyl)pyridine Amide Receptors 126 Solid State Investigations of2,6-bis(2-anilinoethynyl)pyridine Amide Receptors 127 Receptor Electronic Properties 130 Conclusion 133 Experimental Section 134 General 134 General Preparation of Sulfonamides 135 Sulfonamide 1 135 Sulfonamide 2 136 Arene 5 136 4-tert-butyl-2-(2-trimethylsilylethynyl)aniline 6 137 Sulfonamide 7a 138 Sulfonamide 7b 138 Sulfonamides 7d and 7e 139 Arene 8 140 Arene 9 140 Sulfonamide 10 141 Sulfonamide 11 142 Arene 12 142 Arene 13 143 Disulfide 14 144 Amide 16 144 General Crystallographic Data .. 145 (1-H20)2 145 (H1+-CI-) -(I-H20) 146 Chapter XIV Page Hl+-BF4- 146 Hl+-HS04- 146 (Z·HzO)z 146 (HZ+ ·C1-)z 147 (HZ+.Br-)z 147 Z no water 147 (7a-HzO)2 148 (7b-HzO)2 148 7d 148 10 148 11 149 13 149 H13+-CI- 149 14 149 VII. CONCLUDING REMARKS AND FUTURE PERSPECTIVES 150 Concluding Remarks 150 Future Perspectives 151 APPENDICES 155 A. SUPPORTING INFORMATION FOR CHAPTER II: ANION-II INTERACTION AUGMENTS HALIDE BINDING IN SOLUTION 155 B. SUPPORTING INFORMATION FOR CHAPTER III: STRUCTURAL CRITERIA FOR THE DESIGN OF ANION RECEPTORS: THE INTERACTION OF HALIDES WITH ELECTRON-DEFICIENT ARENES ... 183 C. SUPPORTING INFORMATION FOR CHAPTER IV: SOLUTION PHASE MEASUREMENT OF BOTH WEAK SIGMA AND C-H···X- HYDROGEN BONDING INTERACTIONS IN SYNTHETIC ANION RECEPTORS 198 D. SUPPORTING INFORMATION FOR CHAPTER V: INVESTIGATING THE USE OF INTRAMOLECULAR HYDROGEN BONDS TO STABILIZE RECEPTOR CONFORMATIONS; DESIGNING RECEPTORS FOR ANION/ARENE INTERACTIONS 247 xv Chapter Page E. SUPPORTING INFORMATION FOR CHAPTER VI: A CONFORMATIONALLY DIVERSE SERIES OF MOLECULES; 2,6- BIS(ETHYNYL)PYRIDINE, BIPYRIDINE AND THIOPHENE AS SCAFFOLDS FOR MODULAR RECEPTOR DESIGN 255 REFERENCES 265 XVi LIST OF FIGURES Figure Page CHAPTER I 1.1 General structure of Jackson-Meisenheimer complexes 3 1.2 The interaction of aromatic nitro compounds with electron donors (Y) . 4 1.3 MP2/aug-cc-pVDZ optimized geometries for cr interactions with 1,2,4,5-tetracyanobenzene 6 1.4 Single crystal X-ray structure from Reedijk and coworkers 7 1.5 Single crystal X-ray structure of ethylammonium substituted thiocyanuric acid 8 1.6 A portion of the tetracyanopyrazinelBr- single crystal X-ray structure 9 1.7 Single crystal X-ray structure of a neutral calyx[4]pyrrole anion receptor 11 1.8 X-ray structure of a tripodal receptor/Cl- complex 12 1.9 Single crystal X-ray structure of ruthenium permetallated cryptophane.... 13 CHAPTER II 2.1 ORETP representation of the single crystal X-ray structure of 1 19 2.2 Stick representation of the X-ray structure of receptor 1 and tetra-n- butylammonium bromide 23 2.3 HF geometry minimizations of 1 and 2 with chloride .. 24 CHAPTER III 3.1 Initial theoretical observation ofanion-n complexes 30 3.2 Electronic structure calculations have established that non-covalent anion-n complexes form between halide anions and these electron- deficient arenes 31 3.3 Solution and solid-state studies of these highly electron-deficient arenes yield data inconsistent with a non-covalent anion-n interaction 32 3.4 View down the b-axis of the KBr structure and the a-axis of the KI structure 37 3.5 Arrangement of four TCB molecules around the anion 38 3.6 The squares and circles show the locations ofhalide anions above tetracyanoarene pi-systems that have been observed in crystal structures... 40 3.7 MP2/aug-cc-pVDZ optimized geometries for Cl- complexes with TCB... 42 Figure 3.8 Electron density surfaces for Cl- complexes 1 - 4 . 3.9 MP2/aug-cc-pVDZ optimized geometries for complexes 5 - 13 . 3.10 The degree of displacement of a halide, X-, from the center of an arene . 3.11 Electron-deficient arenes and CSD refcodes .. 3.12 Histogram of doffset values for halide complexes .. 3.13 Histogram of doffset values for halide complexes with pyridine . 3.14 Locations of halide anions above the plane of pyridine fragments . 3.15 Histogram of the distribution of atom-centroid-carbon angles .. 3.16 Locations of electronegative atoms above the pentafluoroarene planes .. 3.17 When a halide is located above triazine, the most stable forms are a (j complex with F- .. 3.18 Views of a fragment of a Cl- receptor crystal structure .. XVll Page 48 50 54 56 57 57 58 60 61 62 65 CHAPTER IV 4.1 MP2/aug-cc-pVDZ optimized geometries for cr interactions with 1,2,4,5-tetracyanobenzene 70 4.2 Synthesis of tripodal anion receptors 1-3 73 4.3 IH NMR spectra from titrations of receptor 1 with NBu/Br- 76 4.4 B3LYP/DZVP optimizations starting from idealized atomic coordinates for anion-n geometries with Br- 77 4.5 Optimized geometries (B3LYP/DZVP) comparing the aryl CH hydrogen bonding model of 1 with the weak (j binding mode of 2 78 CHAPTER V 5.1 Computational studies (CAChe MM3) suggest that tripodal anion receptorlBr- complexes can form intramolecular hydrogen bonds 86 5.2 Stick and CPK crystal structure representations of the HCl salt ofTREN based trisamide receptor 1 90 5.3 Stick, CPK and nested representations of receptor 4 93 5.4 Synthesis and crystal structure of nitro-cyano-nitro functionalized benzoic acid 5 95 CHAPTER VI 6.1 Crystal structures of (1-HzO)z (left) and (2-HzO)z (right) 103 6.2 Space filling representations of the crystal structure of (H2-Cl)z 105 Figure 6.3 Wire frame representations of the crystal structures of (I·HzO)z (a), (Hl+.Cn·(I·HzO) (b), (H2+·Cnz(c), and (Hl+.Br-)z(d) .. 6.4 Macrocycles 4 and 4a '" . 6.5 Three-coordinate ligand design . 6.6 Four different representations ofthe 2+2 water dimer .. 6.7 Dimer of2 notably lacking assisting water molecules .. 6.8 Tetrasubstituted sulfonamide 7d . 6.9 Stick representations ofthe polymeric hydrogen bonding chain present in the solid state structure ofHl+·BF4- . 6.10 Stick representation of a portion ofthe HI+•HS04- crystal structure . 6.11 Stick representation of the single crystal X-ray structure of sulfonamide 10 . 6.12 Stick representation of the single crystal X-ray structure of sulfonamide 11 . 6.13 Stick representation of the single crystal X-ray structure ofarene 13 .. 6.14 Stick (left) and CPK (middle and right) representations of the H13+·CI- crystal structure . 6.15 Stick (left) and space filling (right) representations of the crystal structure of disulfide 14 . 6.16 Emission spectra of receptors 1,2 and 7a-b .. XV111 Page 109 112 113 117 119 119 120 121 124 125 128 129 130 132 CHAPTER VII 7.1 'Conformationally locked' bowl-shaped molecule with inward directed functionality 153 7.2 Example receptor exhibiting tethered electron-deficient aromatic ring and leaving group 154 XIX LIST OF TABLES Table Page CHAPTER II 2.1 Ka (M- I ) for receptors 1 and 2 with selected halides 20 CHAPTER III 3.1 Observed halide to arene distances (A) 39 3.2 Calculated properties of electron-deficient arenelhalide complexes 43 CHAPTER IV 4.1 Average Ka (M- I ) for receptors 1, 2 and 4 with halides 75 CHAPTER VI 6.1 Electronic absorption data for compounds 1,2,5, 7a-b and 9-14 131 xx LIST OF SCHEMES Scheme Page CHAPTER II 2.1 Synthesis of receptors 1 and 2 reagents and conditions 18 CHAPTER V 5.1. Synthesis ofTREN and TRPN based tripodal amide receptors 1 and 2.... 87 5.2. Synthesis ofphosphine and phosphine oxide tripodal amide receptors.... 92 CHAPTER VI 6.1. Synthesis of 2,6-(bis(2-anilinoethynyl)pyridine sulfonamides 102 6.2. Retrosynthetic breakdown of receptor scaffold 114 6.3. Synthesis of2,6-(bis(2-anilinoethynyl)pyridine sulfonamide receptors.... 116 6.4. Synthesis of core analogs 123 6.5. Synthesis of amide receptors 126 6.6. Synthesis of electron-deficient arene containing amide 16 127 CHAPTER VII 7.1. Synthesis of improved conformationally rigid sulfamide receptor 152 1CHAPTER I HISTORICAL PERSPECTIVE OF ANIONS INTERACTING WITH ELECTRON- DEFICIENT AROMATIC RINGS INTRODUCTION The underpinnings of this body of research focus on stabilizing anion complexes through the use of reversible non-covalent interactions. In particular, special attention has been afforded to the interactions exhibited between anions and electron-deficient aromatic rings, as well as the development of highly conjugated scaffolds for hydrogen bonding anion receptors. The 85 references found in Chapter I are quite impressive considering the nascent state of the field when we first started this project in 2004. While the interaction of anions with electron-deficient aromatic rings has recently garnered much attention, this by no means is a recent phenomenon. Chapter I of this dissertation begins with a succinct explanation of nomenclature and focuses on a historical perspective of anions interacting with electron-deficient aromatic rings. An introduction to recent (and not so recent) computational investigations concerning anions and electron-deficient aromatic rings as well as a structural survey of crystalline examples of this interaction is provided. Finally, the relatively few solution based observations ofanions interacting with electron-deficient aromatic rings are provided to introduce the research objectives of the current dissertation within the scope of the field. Chapters II-IV and VI include coauthored previously published work. NOMENCLATURE AND HISTORICAL PERSPECTIVE Anions are liberally defined as mono- or polyatomic ions bearing a negative charge. Because of the negative charge residing on the anion, an attraction to the 1t- system of aromatic rings (also known as arenes) or heterocycles has recently been thought to be counter-intuitive. Despite initial skepticism, a large number of computational studies and single crystal X-ray structures have definitively established the existence of this interaction when electron-deficient aromatic rings are employed. Due to the recent burgeoning examples and the lack of historical perspective of reversible anionlarene attractions, it is easy to assume that this is a modem discovery.I,2 However, it is important not to overlook the origins of attraction between anions and electron-deficient aromatic rings. A recent review by Hay, et al. also highlights this perspective.3 Initial reports from Jackson, et al. in the late l800s of highly colored complexes formed when electron-deficient picryl ethers were mixed with potassium alkoxides4, 5 eventually led to isolation of the covalent Jackson- Meisenheimer complexes, which are considered to be isolable intermediates on the nucleophilic aromatic substitution pathway (Figure 1.1).6 2 3R=Alkyl Figure 1.1 General structure of Jackson-Meisenheimer complexes formed when a picryl ether is mixed with potassium alkoxide. The isolation and characterization of Jackson-Meisenheimer complexes was initially complicated by a number of both reversible and non-reversible interactions between the anion (or nucleophile in this case) and the 1t -system. The various interaction types are characterized by the degree ofparticipation of the donor (anion) atom's electron pair,7 For instance, 1t-complexes (also known as donor-acceptor or charge-transfer complexes) can form as a result ofpartial transfer of electron density from an electron rich donor (or anion) through the LUMO orbital of an electron- deficient aromatic ring (Figure 1.2, 1).8 Additionally, a-complexes (Jackson- Meisenheimer complexes) arise as a result of the donor atom forming a covalent bond with an atom of the electron-deficient aromatic ring (Figure 1.2, 2). Other complicating interactions include proton transfer from the electron-deficient aromatic ring to the donor atom (Figure 1.2, 4 and 5), as well as substitution of aromatic substituents or complete transfer of an electron from the donor to the electron-deficient aromatic ring (Figure 1.2, 2). This variety of interactions has been well understood since at least 1968 with a number of reviews having been written on the subject.7,9-14 H3CO Y02NVN02 N02 3 CH2- 02Nl0(N02 Y N02 5 4 Figure 1.2 The interaction of aromatic nitro compounds with electron donors (y).7 EARLY ANION/ARENE COMPUTATIONS AND MASS SPECTROMETRY The assortment of possible anionlarene interactions suggests a continuum of possible attractions that depend on both the nucleophilicity of the anion and the degree ofelectron-deficiency of the aromatic ring. This multitude of binding geometries was later theoretically and experimentally established from molecular orbital calculations and binding affinities measured from gas-phase ion-molecule equilibrium measurements with pulsed electron high ion source pressure mass spectrometers. 15-26 Interestingly, gas phase techniques have resurfaced as a popular method to study anionlarene interactions.27,28 RENAISSANCE OF ANION/ARENE COMPUTATIONS The recent publication of higher level computations quantifying the interaction of anions with electron-deficient aromatic rings has regenerated interest in the 5supramolecular chemistry community.29-31 As a result, a renaissance in computational studies has emerged looking at a variety of anions. The most studied anions to date are the simple monoatomic ions,32-51 but recent studies have progressed to more complicated polyatomic anions with an assortment of geometries.29-31, 52-59 As for the electron-deficient aromatic ring, the most popular targets for study are fluorinated aromatic rings like hexafluorobenzene or heterocyclic rings such as triazine.29-33,36, 38- 48,50,51,53,55,57,59 However, the focus of these publications has been toward symmetric non-covalent interactions (Figure 1.3, A). Other forms of attractive interactions between anions and electron-deficient aromatic rings have been largely overlooked. In fact, in our introduction to this field of research we were also unaware of the alternative binding modes for anions and arenes. This misconception was propagated in our first generation of receptors60-it was not until our following crystallographic and computational study that we came to understand that there are a number of attractive interactions with electron-deficient aromatic rings. These include: a centered electrostatic interaction (A), an off-centered weak a interaction (B and C), and when available, aryl C-H hydrogen bonds (D, Figure 1.3). Our crystallographic and computational studies have helped refine the nature of possible interactions that were introduced in the early 1900s between anions and arenes and reminded the supramolecular community of their importance. 6A B c D Figure 1.3 MP2/aug-cc-pVDZ optimized geometries for cr interactions with 1,2,4,5- tetracyanobenzene include an unstable an ion-n complex (A), weak 0 complexes (D and C), and an aryl C-H hydrogen bond complex (D). A FLOURISH OF ANION/ARENE CRYSTAL STRUCTURES Recent computational interest has spurred the report of a number of illustrative crystal structures with anions positioned appropriately close to electron-deficient aromatic rings. This section of Chapter I focuses on relevant crystallographic examples of anions interacting with the n-systems of aromatic rings. Aryl C-H hydrogen bonds have generally been omitted; a number of excellent examples can be found in a review by Hay, et a/. J In addition to attractive anion/arene interactions the vast majority of these examples exhibit accompanying stabilizing forces in the solid state. For instance, in many cases the electronic character of an aromatic ring is perturbed by direct coordination of a metal cation. 58, 61-7J The anion is often present to balance charge or fill porous networks formed from metal organic frameworks. 7A representative example of a counter anion that interacts with the pyridine moieties of an octadentate copper(II) coordinated pyridine ligand is shown in Figure 1.4. In the solid state, two of the chlorides each exhibit four shOtt contacts with adjacent copper coordinated pyridine moieties. side view top view Figure 1.4 Single crystal X-ray structure from Reedijk and coworkers illustrating chloride/pyridine contacts in a copper (II) coordinated octadentate pyridine ligand. Hydrogen atoms and additional chloride counter anions have been omitted for clarity.67 Chlorides are represented as spheres and ligands represented as sticks. The next largest number of examples comes from crystal structures where both anion/arene interactions and ion pairing are employed to attract anions.36, 74, 75 One illustrative solid state example of tandem ion pairing and anion/arene interactions comes from the laboratories of Frontera and coworkers where cyanuric acid derivatives adorned with ammonium substituents were shown to crystallize with the halide counter 8anions cr, Br- and r- (Figure 1.5).36 The anions in this example are located slightly off-center from the aromatic ring centroid and are stabilized by hydrogen bonds with the positively charged ammonium substituent and contacts with the electron-deficient cyanuric acid derivatives. Figmoe 1.5 Single crystal X-ray structure of ethylammonium substituted thiocyanuric acid, illustrating both ion pairing and anionlarene interactions with chloride.36 Not surprisingly, a handful of examples utilize multiple interactions in addition to electron-deficient arenes to stabilize anion complexes, including hydrogen bonding, ion pairing and anionlarene interactions.44, 45, 76-78 The very nature of crystal structures makes isolating anionlarene interactions a difficult endeavor. Exceptionally rare are the examples that utilize only anion/arene interactions to position anions near electron- deficient aromatic rings. 79, 80 For example, Rosohka, et af. co-crystallized electron- deficient n:-systems with Br- and r. The solid state structures of electron-deficient arenes such as tetracyanopyrazine with Br- reveal multiple close contacts in the solid state depending on the ratio of starting materials (Figure 1.6). In addition to the recent 9solid state highlights of anionJarene interactions, numerous structures have been located from the Cambridge Structure Database and presented as evidence for anion/arene interactions. These examples are not presented here, but can be found within the references to this chapter. Through a survey of the Cambridge Structure Database, we have shown that in the absence of additional interactions, anions are preferentially located above the edge of electron-deficient aromatic rings. 61 Figure 1.6 A pOltion of the tetracyanopyrazinelBr- single crystal X-ray structure. Halides exhibit multiple off-center contacts in the solid state with the number of electron-deficient aromatic rings depending on the starting ratio. so A RELATIVE DEARTH OF ANION/ARENE SOLUTION STUDIES While there is a large body of research on covalent anion/arene (Jackson- Meisenheimer) complexes, we are interested in designing anion receptors that 10 incorporate electron-deficient aromatic rings to bind anions reversibly in solution. This section of Chapter I will focus on noncovalent or weakly covalent, reversible anionJarene interactions. Given the relatively weak nature of anionJarene interactions, only a handful of attempts have been made to measure these interactions in solution. Indeed, only two such examples existed at the outset of our research. Furthermore, at this point no designed receptors had been shown to exhibit anionlarene interactions in solution. In 1991, Schneider measured associations between sulfonate substituted aromatic rings and charge neutral aromatic rings in solution.81 These insightful measurements likely represent both n-stacking and anionJarene interactions that are occurring in solution and provide an early observance of anionJarene interactions. More recently, Rosokah, et al. utilized Uv-vis spectroscopy to measure association constants between halides and commercially available electron-deficient n-systems.80 Association constants of alkyl ammonium salts ofBr- and r with 1,2,4,5- tetracyanobenzene, 1,3,5-trinitrobenzene and tetracyanopyrazine were found to range from 0.8-9 M-1 in acetonitrile/dichloromethane solutions. Our initial study aimed to address the deficiency of designed receptors utilizing electron-deficient aromatic rings to bind anions. This receptor class is explained in detail in Chapter II. More recently, elegant receptor molecules illustrate or have been designed to illustrate anionJarene interactions. However, the large number of competing interactions in solution often requires the use of additional attractive forces to measure the relatively weak anionJarene interactions. Hydrogen bonds have been employed in receptors most often to assist in attracting anions to electron-deficient aromatic rings.60, 82-85 Ballester's 11 group in Spain has designed calix[4]pyrrole receptors that contain electron-deficient aromatic rings to assist in halide binding. An enhancement of anion binding is observed over a similar control receptor even when only modestly electron-deficient nitrobenzene substituents are attached to the receptor core. A single crystal X-ray structure illustrates the position of the chloride within the receptor cavity (Figure 1.7). Figure 1.7 Single crystal X-ray structure ofa neutral calix[4]pyrrole anion receptor hydrogen bonding to CI- and forming four Cl-/nitrobenzene contacts.8] Other supporting attractive interactions that have been employed include ion pairing and metal coordination.69 For instance, Ghosh and coworkers developed tripodal anion receptors containing electron-deficient aromatic rings built from tris(2- 12 ethylamino)amine. When protonated, these receptors bind halides in solution and X- ray crystal structures reveal close anion/arene contacts (Figure 1.8).75 Figure 1.8 X-ray crystal structure of a tripodal receptor/CI- complex. Receptor contains ion pairing and pendant electron-deficient aromatic rings to assist anion bincling.75 The tripodal receptor molecule is represented as sticks and the CI- as a sphere. Metal coordination has also been employed to assist anion binding in solution. Holman and coworkers were the first to highlight a fully ruthenium metallated cryptophane that binds anions within its cavity.86 '1-1 NMR spectroscopy unequivocally showed in solution the encapsulation of anions such as CF3S03-, SbF6- and PF6- in the metalated molecular container. CF3S03- or SbF6- are also contained within the cavity in the solid state and a representative crystal structure is shown in Figure 1.9. 13 Figm'e 1.9 Single crystal X-ray structure of a ruthenium permetallatecl cryptophane that encapsulates CF3S03- aided by six anion/arene interactions. Hydrogen atoms have been removed for clarity and the enclosed CF3S03- is represented as spheres.69 SUMMARY AND BRIDGE TO CHAPTER II Interactions between electron rich molecules or anions with electron-deficient aromatic rings have been recognized for over a century. These highly colored complexes were initially touted as intermediates to nucleophilic aromatic substitution reactions. More recently, the interactions of anions with electron-deficient aromatic rings have undergone much scrutiny leading to a better understanding of anion/arene interactions. A large number of computational studies have smfaced examining anion/arene interactions; these are supported by numerous single crystal X-ray structures and a handful of solution studies. Our contributions to this field will be presented in this dissel1ation with a particular focus toward the development of new binding motifs for anion receptors. 14 Chapter II focuses on our initial effort to probe anionJarene interactions, in which we designed and synthesized anion receptors to measure anionJarene interactions in solution. Based on the existing computational studies at the time, we felt it was necessary to incorporate an electron-deficient aromatic ring and a complementary hydrogen bond donor into our receptor design. This two-point recognition motif was compared to a control receptor lacking the electron-deficient aromatic ring. Complementary computational studies also supported our hypothesis that electron- deficient aromatic rings enhance halide binding in this system. 15 CHAPTER II ANION-rc INTERACTION AUGMENTS HALIDE BINDING IN SOLUTION INTRODUCTION This chapter was co-authored with Professors Fraser Hof, Michael J. Hynes and Darren W. Johnson. Professor Hof performed Hartree-Fock calculations that were used in the manuscript while Prof. Hynes assisted in calculating association constants for this system. Darren W. Johnson conceptualized the project and provided editorial assistance while Orion Berryman wrote this chapter and completed the CAChe computer modeling, synthesis, characterization, single crystal X-ray diffraction studies, literature searches, pKa measurements and titration experiments. This chapter includes work that was published in Chemical Communications (2006, 506-508, © 2006 The Royal Society of Chemistry). At the time of publication the authors of this work did not fully appreciate the distinction between different types ofanion/arene interactions. Therefore, the liberal use of the term "anion-rc" interaction should alert the reader to consider alternative binding modes. A detailed review of this concept is presented in Chapter III. 16 Molecular receptors designed to target anions utilize a variety of interactions to accomplish their goal. Some of the more common reversible bonds employed include hydrogen bonding, electrostatic interactions, hydrophobic effects, and coordination to a metal ion. I-4 A promising binding strategy to target anions that has recently garnered much attention in the literature is the anion-1t interaction. Currently, numerous computational studiesS-9 and single crystal X-ray structures6, 10-14 support the viability of using this noncovalent interaction as a design strategy to target anions. Several of these reports compare the anion-~ interaction to the familiar cation-~ interactionS, IS where a positively charged ion attractively interacts with an electron-rich aromatic ring. 16 The anion-1t interaction is similarly proposed to arise from a negatively charged species having a coulombic attraction to an area of low electron density in an electron- deficient aromatic ring. Despite the numerous solid state examples and theoretical treatments, surprisingly few solution phase examples recognize the anion-1t • • 13 mteractIOn. RECEPTOR DESIGN In an attempt to probe the efficacy of the anion-1t interaction to bind anions in solution, two receptor molecules were prepared (1 and 2, Scheme 2.1). Design of receptor 1 focused on a two point recognition motif utilizing both a hydrogen bond and an electron-deficient aromatic ring. 17 In contrast to 1, control receptor 2 lacked the electron-deficient aromatic substituent required for the anion-1t interaction. Any 17 enhanced association for anions that receptor 1 exhibits over receptor 2 should be a result of the favorable anion-x interaction present in the 1-anion complex. To the best of our knowledge, a receptor molecule designed to incorporate the anion-x interaction to bind anions in solution is unknown. Herein we report solution data illustrating the enhanced association for anions that designed receptor 1 shows over control receptor 2. RECEPTOR SYNTHESIS, X-RAY DIFFRACTION AND ELECTROSTATIC POTENTIAL SURFACE Receptor 1 was synthesized by converting o-iodoaniline to the correspondingp- toluenesulfonamidel8 3 followed by a palladium-mediated Ullmann coupling (Scheme 2.1).19,20 I H NMR spectroscopy and single crystal X-ray diffraction confirmed the structure ofreceptor 1 (see Appendix A). A similar procedure provides 2 in 87% yield starting from 2-aminobiphenyl. 18 u uU ~ SOI 2~ S02C1 ~ SO NH a I 2 b ~ I F+ ~ ceNHceNH2 89% 26% F la a l FI F U 1U~ S02C1 ~ SOa I 2 + ~~ceo 87% lala ~ II":: ~ a 2 Scheme 2.1 Reagents and conditions: (a) dry pyridine, rt, 4h. (b) C6BrFs, dry DMSO, Pd(PPh3)4, Cuo, 105°C, 5.5 h. Single crystals of 1 suitable for X-ray diffraction were grown by diffusing pentane into a chloroform solution ofthe receptor (see summary of crystallographic data). Receptor 1 crystallizes as a hydrogen bonded dimer in spacegroup P-l with two molecules of 1 per unit cell. It is interesting to note that one sulfonamide oxygen from each receptor molecule is located 3.1 A from the electron-deficient aromatic ring of an adjacent molecule?!' 22 In the crystalline state 1 is preorganized in the optimal conformation to interact with an anion through both a hydrogen bond and an anion-n interaction. 19 Electrostatic potential surfaces (EPS) of molecules have been used to illustrate areas of low electron density that can interact with electron-rich anions.?' 15 To highlight both the pre-organization of receptor 1 for binding anions and the predictive power that electrostatic potential surfaces have for the anion-n interaction, the crystal structure of 1 is shown alongside a minimized (CAChe 5.0, EHT) electrostatic potential surface plot of receptor 1 in the optimal conformation for complexing an anion (Figure 2.1).23 The center of the electron-deficient aromatic ring of receptor 1 (Figure 2.1) exhibits a surface of low electron density (white) that is optimal for interacting with an anion. Figure 2.1 (a) ORTEP representation of the single crystal X-ray structure of 1. Ellipsoids are at the 50% probabil ity .level with sulfur yellow, oxygen red, carbon gray, nitrogen blue, fluorine green and hydrogen light gray. (b) Calculated EPS plot of receptor 1, scaling areas of highest electron density (blue) to lowest (white). 20 SOLUTION STUDIES - ANION BINDING Following the synthesis of receptors 1 and 2, IH NMR spectroscopic titration experiments were performed for each receptor with the tetra-n-butylammonium salts of chloride, bromide and iodide. The downfield shift ofthe N-H resonances of 1 and 2 were monitored as aliquots from a stock solution of the corresponding salt in CDC!) were added to the receptors in CDC!). WinEQNMR24 was used to fit the raw data to a 1:1 association model (see Appendix A). Iterative calculations using WinEQNMR yielded the stability constants of the receptors with each anion25 (Table 2.1); each reported Ka for 1 represents the average of three titrations. Table 2.1 Ka (M-I) for receptors 1 and 2 with selected halides.a Receptor 1b Receptor 2b cr 30 ± 3 2(J(1), and Rl = 0.1570, wR2 = 0.2413, GooF = 1.030 for all 6901 data. CCDC #261862. 1-(n-BU4N-Cl): C3sH17BrFsN202.sS, M= 742.72, tric1inic, P-l, a = 10.863(4), b = 16.807(6), C = 21.000(7) A, a = 74.118(6t, P= 83.011(6)°, y = 89.974(6)°, V = 3658(2) A3, Z= 4, Jl(Mo-Ka) = 1.240 mm-I. Final residuals (498 parameters) Rl = 0.0916 for 4148 reflections with I> 2(J(1), and Rl = 0.1400, wR2 = 0.2477, GooF = 1.013 for all 6598 data. CCDC #286064. 27 BRIDGE TO CHAPTER III We were pleased with our initial success of designing a system to measure anion/arene interactions in solution. However, we were somewhat frustrated with the ambiguity that surfaced from incorporating two different interaction types into one receptor. We provided evidence supporting our statement that the differences in pKa values do not solely represent the drastically different Ka values measured for this system. Nevertheless, we felt the next logical step was to remove additional supporting interactions and focus directly on anion/arene interactions. Chapter III focuses on the interaction of anions with only electron-deficient aromatic rings and provides solid state and computational scrutiny that redirects the focus of anion/arene interactions from centered electrostatic interactions to off-center weakly covalent (J complexes. 28 CHAPTER III STRUCTURAL CRITERIA FOR THE DESIGN OF ANION RECEPTORS: THE INTERACTION OF HALIDES WITH ELECTRON-DEFICIENT ARENES INTRODUCTION This chapter was co-authored with Dr. Vyacheslav S. Bryantsev, David P. Stay, Prof. Darren W. Johnson and Chief Scientist Dr. Benjamin P. Hay. David Stay isolated single crystals ofthe structures presented in this study. Dr. Bryantsev completed all the quantum calculations found within. Dr. Hay aided with the literature and Cambridge Structure Database searches. Both Dr. Hay and Prof. Johnson assisted in conceiving this project and provided editorial assistance. Orion B. Berryman prepared the chapter, assisted in literature searches, solved the single crystal X-ray structure and assisted in the Cambridge Structure Database searches and data compilation. This chapter includes work that was published in Journal a/the American Chemical Society (2007, 129,48-58, © 2007 American Chemical Society) 29 BACKGROUND AND SIGNIFICANCE. Anion complexation by synthetic host molecules is an important theme in supramolecular chemistry.1One of the key challenges is the design of hosts that recognize specific anions. A variety of reversible and/or noncovalent interactions have been used to overcome these challenges, including hydrogen bonding, electrostatic interactions, hydrophobic effects and coordination to metal ions. A relatively new anion binding motif-the anion-n interaction-has attracted substantial attention in the recent literature. In this interaction, a negatively charged species is attracted to the center of a charge neutral electron-deficient aromatic ring as shown in Figure 3.1 ?-5 Although much of the evidence for the anion-n interaction has come from theoretical studies,2-13 there is mounting experimental support for an attractive interaction between anions and electron-deficient arenes from both X-ray structuresl4-16 and solution data. 14,17-19 Recently we,t8 along with others,11,12,19 have begun to investigate the utility of the anion-n interaction by deliberately incorporating electron-deficient arenes as binding sites within receptors designed to target anions. 30 Figure 3.1 Initial theoretical observation of anion-n complexes occurred in a study of the interaction between CI- and triazine.2 Anion-n complexes involving halides have been the most widely modeled and calculated structures have been reported for a variety of arenes (Figure 3.2).2-12 In these structures, the halide is located directly over the center of the arene ring. It has been established that this interaction is predominantly a non-covalent one, dominated by two components - (i) attraction between the negative charge of the anion and the electric field of the arene and (ii) anion-induced polarization. Despite the fact that calculations have found the strength of the anion-n interaction to be significant, typically ranging from 10 to 20 kcal mol-I, there are surprisingly few repolis of crystal structures that illustrate this interaction for free halides,12,14,15 and there are no examples of halide complexes with any of the unsubstituted arenes that have been studied in silica (Figure 3.2). ref 2,6,7, 9,10,11 ref 2,11 FylrF F¥F F ref 3,5,6,8-10 F F~F ~.,~F N F ref 5 X H'NAN,H XANAX I H ref 12, X= S, 0 31 r(NyCI ~ CIJlNJ FUF ref 7 ref 7,10 ~' 02NMN02 ref 4 ~ NcJlACN ref 9 Figure 3.2 Electronic structure calculations have established that non-covalent anion-n complexes form between halide anions and these electron-deficient arenes. Although theoretical studies have focused primarily on the non-covalent anion-n interaction, an experimental study on the solution behavior of halide complexes with highly electron-deficient arenes (Figure 3.3) suggests that a different binding motif may be operating in these systems. 14 Intense color changes were observed upon addition of halide salts to acetonitrile/dichloromethane solutions containing these arenes. Analysis of the visible spectral data revealed that the halide salts form classic electron donor-acceptor charge-transfer (CT) complexes with the organic n acceptors. This behavior is not consistent with a non-covalent anion-n interaction in which, by definition, there would be negligible CT. Moreover, crystal structures of alkylammonium halide salts with TCP and o-CA revealed the anions to be positioned over the periphery ofthe arene rings rather than over the center ofthe rings as anticipated for bonding arising primarily from electrostatic and polarization interactions. C'hO CI¥O CI o-CA CI¢OCI I I CI CI a p-CA NC'(YCN NC~CN TCB ~2 02N~N02 TNB NCXN~tCN NC N CN TCP 32 Figure 3.3 Solution and solid-state studies of these highly electron-deficient arenes yield data inconsistent with a non-covalent anion-n interaction. 14 This discrepancy between theory and experiment, coupled with the general paucity of structural data for anion-1t interactions with arenes such as those depicted in Figure 3.2 and 3.3, prompted us to undertake further investigations. To obtain additional structural information, alkali halide salts have been crystallized from solutions containing 1,2,4,5-tetracyanobenzene (TCB) and 18-crown-6. As described herein, the off-center geometries of the halide-arene complexes observed in these structures suggest an alternate interaction motif to the centered non-covalent anion-1t interaction widely promulgated in the literature. Electronic structure calculations on halide complexes with TCB and other electron-deficient arenes confirm the presence of alternate binding geometries in which the halide is positioned over the periphery of the ring and there is substantial CT from the halide donor to the 1t acceptor. Analysis of the Cambridge Structural Database reveals that when halides interact with electron- deficient 1t systems, they are more likely to reside over the periphery of the ring than 33 over the center, suggesting that the CT binding motif is more common than the non- covalent one. The results indicate that molecular design strategies for incorporating electron-deficient 1t systems within host architectures should consider the differing geometries attendant with CT versus non-covalent binding motifs. METHODS GENERAL. 1,2,4,5-tetracyanobenzene was obtained from TCI. Acetonitrile and dichloromethane were obtained from Aldrich and stored over 3 A molecular sieves. 18-crown-6 as well as the potassium and sodium salts were obtained from commercial suppliers without the need for further purification. SINGLE CRYSTAL GROWTH. Single crystals suitable for X-ray diffraction were grown by slow evaporation of acetonitrile/dichloromethane solutions at room temperature. TCB (0.030 g, 0.168 mmol), 18-crown-6 (0.100 g, 0.378 mmol) and KI or NaI (0.972 mmol) were added to acetonitrile (1 ml). The resulting suspension was sonicated and heated to reflux. The remaining dark red solution was evaporated at room temperature to yield dark purple crystals of the form [K(18-crown-6)(TCB)2tr or [Na(18-crown-6)(TCB)2tr-. The corresponding KBr structure, [K(18-crown- 6)(TCB)2tBr- was obtained in an analogous manner substituting KBr (0.116 g, 0.972 mmol) and a 9: 1 dichloromethane:acetonitrile solution as the solvent. Evaporation at room temperature resulted in orange single crystals of the KBr complex. 34 X-RAY DIFFRACTION. Single-crystal X-ray diffraction data for the [K(18-crown- 6)(TCB)2tBr-, [K(18-crown-6)(TCB)2tr and [Na(18-crown-6)(TCB)2tr compounds were collected on a Bruker-AXS SMART APEXlCCD diffractometer using MoKu radiation (A = 0.7107 A) at 152 K. Diffracted data have been corrected for Lorentz and polarization effects, and for absorption using SADABS.2o The structures were solved by direct methods and the structure solution and refinement was based on IFf All non- hydrogen atoms were refined with anisotropic displacement parameters whereas all hydrogen atoms were located and given isotropic Uvalues 1.2 times that of the atom to which they are bonded. All crystallographic calculations were conducted with SHELXTL.21 Crystallographic data (excluding structure factors) have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers 606748, 606749, and 606750. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: international code + (1223)336-033; email: deposit@chemcrys.cam.ac.uk). ELECTRONIC STRUCTURE CALCULATIONS. Electronic structure calculations were carried out with the NWChem program22 using second order Moller-Plesset perturbation theory (MP2).23 Geometries were optimized using the augmented correlation consistent double-I;: basis set (aug-cc-pVDZ)24 and frozen core approximation in the correlation treatment. Tight geometry optimization cutoffs were employed since standard optimization criteria may results in spurious negative frequencies. Frequency calculations were performed at the same level of theory to 35 characterize each stationary point as a minimum or a transition state. The electrostatic potential fit charges22 and NPA natural charges25 were calculated using HFlaug-cc- pVDZ electron densities. CAMBRIDGE STRUCTURAL DATABASE SEARCHES. The Cambridge Structural Database26 was searched for examples in which a halide anion was located within 4.0 A ofthe centroid of any six-membered ring in which all ring atoms were connected to exactly three other atoms. A total of 591 hits were obtained when the search was subject to the following general constraints: (i) R-factor less than 0.10, (ii) no disorder, and (iii) error free. Visual inspection revealed that the majority of the 1t-systems were either positively charged or bound to a positively charged atom. A much smaller subset of this data was retained after applying the additional constraints that either the molecule containing the 1t-system is charge-neutral or when the 1t-system occurred in a positively charged molecule, the positive charge is at least two bonds removed from the 1t-system. This yielded 30 examples most representative of the neutral electron- deficient arenes that have been studied theoretically.2-12 To examine the behavior when the 1t-system is in contact with a positive charge, we extracted a larger subset of the data, 138 fragments, in which the halide interacts with an arene ring containing a single nitrogen atom bound to a metal cation (Figures 3.13 and 3.14 in Results and Discussion). A second search was performed to investigate the assertion that there is a preference for neutral electronegative atoms to be located over the center of 36 perfluoroarenes.3 A hit was counted if (i) an electronegative atom F, Cl, Br, I, 0, S, or N was within 4.0 A of the centroid of any pentafluoroarene (ii) the contact was intramolecular or intermolecular, (iii) the R-factor was less than 0.05, (iv) there was no disorder, and (v) there was no error. This search yielded a total of 8077 fragments. A subset of this data, 1578 fragments, was obtained after applying the additional constraint that the electronegative atom must simultaneously contact all six carbon atoms of the arene, where each contact distance was less than the sum of van der Waals radii + 1.0 A(Figure 3.15, Results and Discussion)?? RESULTS AND DISCUSSION TCB CRYSTAL STRUCTURES. Further structural information for the anion-n interaction was obtained by growing single crystals in which TCB interacts with halide anions. TCB, 18-crown-6 and alkali halide salts were dissolved in acetonitrile (KBr) or 9: 1 dichloromethane:acetonitrile (KI, NaI) solvent and thoroughly mixed. The purpose of the 18-crown-6 was to enhance the solubility of the salts in organic solvent. Slow evaporation at room temperature yielded single crystals suitable for X-ray diffraction. Solutions of 18-crown-6 and TCB are colorless. As anticipated,14 addition of the alkali halide salts produced color changes consistent with the formation of CT complexes. When KBr was added, the solution became bright yellow yielding orange single crystals of [K(l8-crown-6)(TCB)2tBr-. When KI or NaI were added, the solution became red yielding dark purple single crystals of [K(l8-crown-6)(TCB)2tr- and [Na(l8-crown-6)(TCB)2tr-. 37 The KBr salt crystallizes in the space group P2 1/c whereas the KI and Nal salts - crystallize in the space group P 1. All three structures exhibit some common features. The alkali cations are encircled by the 18-crown-6 macrocycle. Two TCB ligands are coordinated to each cation via CN nitrogen atoms, with one above and one below the plane of the macrocycle yielding a total coordination number of 8. As illustrated in Figure 3.4, the crystals pack with alternating cation-bearing layers of 18-crown-6 and anion-bearing layers formed by interlaced axial TCB ligands. The structures differ in the orientation of the TCB groups. In the KBr salt, the planes of the two TCB ligands attached to each cation are roughly perpendicular to one another whereas in the Kl and Nal salts, they are roughly parallel to one another. FiglJloe 3.4 View down the b-axis of the KBr structure (top) and the a-axis of the Kl structure (bottom). The Nal structure (not shown) exhibits the same packing as the Kl structure. Atom color scheme: C, grey; H, white; N, blue; 0, red; K, turquoise; Br, magenta; 1, purple. 38 Despite the packing differences, the local environment about each halide anion is remarkably similar in all three crystals. As illustrated in Figure 3.5, four TCB molecules contact each anion. Distances for these contacts are given in Table 3.1. There are three distinct orientations: above the arene plane nearest to a carbon bearing a CN group (a and b), above the arene plane nearest to a carbon bearing a hydrogen atom (c), and nearly within the plane of the arene, contacting a C-H hydrogen atom (d). KBr a KI Figure 3.5 Arrangement of four TCB molecules around the anion is remarkably similar in all structures. The closest contact to each arene is indicated by a black bond. 39 Table 3.1 Observed halide to arene distances (A).a structure dcarbon dcentroid d p1ane KBr a 3.34 3.88 3.26 b 3.42 4.00 3.16 c 3.48 4.46 2.72 d 3.73 5.12 0.60 KI a 3.45 3.97 3.38 b 3.60 4.02 3.40 c 3.56 4.47 3.18 d 3.90 5.28 0.45 NaI a 3.46 3.99 3.43 b 3.57 4.03 3.35 c 3.53 4.39 3.05 d 3.90 5.29 0.33 aDistance between halide and nearest arene carbon atom (dcarbon), distance between halide and arene centroid (dcentroid), and distance between halide and mean plane of arene (dp1ane). bSee Figure 3.5 for structures. 40 Orientation d provides a clear example of an aryl C-H···anion hydrogen bond,2,28,29 whereas the nature of the interactions represented by the other orientations is not as obvious. In a - c the anions are located 2.7 to 3.4 A above the plane of the arene. The anions are not, however, located over the center of the arene as anticipated for the non-covalent anion-n interaction. This is clearly illustrated in Figure 3.6 which shows the halide positions above the TCB plane as well as those previously observed for halide complexes with the similar TCP arene. 14 In every case, the halide anion is positioned either over the periphery of the arene ring or outside the arene ring altogether. [] x= C-H, this work o X=N,ref14 Figure 3.6 The squares (TCB) and circles (TCP) show the locations of halide anions above tetracyanoarene n-systems that have been observed in crystal structures. 41 ELECTRONIC STRUCTURE CALCULATIONS OF TCB. Electronic structure calculations at the MP2/aug-cc-pVDZ level of theory were performed to evaluate the structure and interaction energies of 1:1 complexes formed between TCB and F-, cr, and Br- anions. Four geometries were evaluated for each halide. These include the non-covalent anion-n complex (1) a CT complex in which the halide is positioned above a C-H bond (2) a CT complex in which the halide is positioned above a C-CN bond (3) and a C-H hydrogen bond complex (4). Figure 3.7 illustrates these geometries for CI- and Table 3.2 summarizes the results obtained for all halides. Initial calculations focused on the non-covalent anion-n complex, 1. Somewhat to our surprise, 1 was not a minimum on this potential surface for any of the halides and could only be located by imposing C2v symmetry during the optimization. Prior theoretical studies have established that strongly nucleophilic anions, such as F-, always interact with electron-deficient arenes by engaging in nucleophilic attack on an arene carbon.2-8,lO Thus, the required imposition of symmetry constraints to compute anion-n complexes involving F- is well-established. However, this is the first instance where it has been necessary to impose symmetry constraints to obtain anion-n complexes for cr and Br-. 42 1 (centered, anion-n complex) 3 (off-center, CT complex) 2 (off-center, CT complex) 4 (aryl C-Hoooanion complex) Figure 3.7 MP2/aug-cc-pVDZ optimized geometries for cr complexes with TCB. Structure 1 is not a stable geometry for halide-TCB complexes, whereas two alternate geometries have been located for complexes in which the halide lies above the arene plane. In the global Cs symmetry minimum (2), the halide lies outside the perimeter of the aromatic ring above a C-H bond. This form is observed for F-, cr, and Br-. In the less stable C, symmetry minimum (3) the halide lies outside the perimeter of the aromatic ring above a C-CN bond. This form is observed for F- and cr, but is not a stationary point for Br-. Table 3.2 Calculated halide to arene distances (A),a electronic binding energies (LiE, kcal mor1),b natural bond order analysis of charge transfer interactions,C and charge transfer from the anion to the arene (qCT, e) derived from natural population analysis (NPA) or electrostatic potential fitting (ESP) for complexes ofF-, cr, and Br- with TCB (1 - 4), tricyanobenzene (5 - 8), triazine (9 - 11), and hexafluorobenzene (12 - 13). ~E Leading CT qCT qCT complex dcarbon dcentroid dp1ane (binding energy) interaction ~E(2) (NPA) (ESP) l(F)t 2.777 2.400 2.400 -33.93(2)d <1 0.008 0.221 2(F-) 1.500 2.427 1.676 -53.06 I4(Fl~1t*c=c >200 0.477 0.464 3(Fl 1.575 2.537 1.642 -47.24 - * >200 0.461 0.426I4(F )~1t c=c 4(F-) *2.590 4.073 0.000 -45.09 I4(F)~cr C-H >200 0.274 0.354 1(Cr)t 3.272 2.962 2.962 -28.34(I)d <1 0.009 0.180 2(Cr) 2.603 3.212 2.622 -29.80 I4(Cr)~1t*c=c 21.16 0.120 0.237 3(Cr) 2.673 3.206 2.677 -29.13 I4(Cr)~1t*c=c 14.20 0.116 0.244 4(Cr) 3.151 4.582 0.000 -27.00 I4(Cr)~cr*C-H 44.92 0.116 0.103 1(Br-)t 3.416 3.122 3.122 -27.70(1)d <1 0.009 0.178 2(Br-) 3.349 2.812 -28.68 - * 15.76 0.107 0.2242.788 I4(Br )~1t c=c 4(Br) 0.000 -25.33 * 37.68 0.0863.325 4.753 I4(Brl~cr C-H 0.097 .j:» w 5(F-)~ 2.841 2.475 2.475 -25.49(2)d <1 0.007 0.212 6(F) 1.500 2.474 1.607 -44.10 14(F-)~7t*c=c >200 0.477 0.484 7(F-) 1.791 2.672 1.811 -34.55 14(F-)~7t*c=c 120.0 0.281 0.343 8(F-) 2.527 3.992 0.000 -35.87 14(F-)~(}*C-H 153.6 0.175 0.197 5(Cl)~ 3.343 3.038 3.038 -21.52(2)d <1 0.007 0.168 6(Cr) 2.728 3.370 2.691 -22.72 14(Cl)~7t*c=c 14.35 0.086 0.205 7(Cl)~ 2.837 3.289 2.846 -21.85(l)d 14(Cn~7t*c=c 3.67 0.049 0.182 3.204 0.000 -21.63 * 36.72 0.078 0.0938(Cl) 4.638 14(Cl)~(} C-H 5(Br-) 3.490 3.198 3.198 -21.18 <1 0.007 0.159 6(Br-) 2.904 3.500 2.876 -21.91 14(Brl~7t*c=c 11.44 0.078 0.194 8(Br-) 3.377 4.808 0.000 -20.29 14(Brl~(}*C-H 31.07 0.072 0.092 9(Fl~ 2.845 2.179 2.179 -10.92(2)d <1 0.010 0.155 tOeFl 1.513 2.321 1.673 -26.34 14(F-)~7t*N=C >200 0.444 0.382 2.686 0.000 -18.54 * 54.13 0.075 0.080H(F-) 4.034 14(Fl~(} C-H 9(Cl) 3.397 3.146 3.146 -8.41 <1 0.007 0.110 W(Cl) 2.900 3.448 2.896 -8.68 14(Cl)~7t*N=C 9.60 0.043 0.110 H(Cl) 3.408 4.736 0.000 -10.50 14(Cn~(}*C-H 17.54 0.036 0.042 ~ ~ 9(Br) 3.553 3.313 3.313 -8.33 1o(Br-) 3.093 3.569 3.109 -8.27 11(Br-) 3.580 4.906 0.000 -9.83 12(P-Y:: 2.889 2.530 2.530 -19.18(2)d 13(F) 1.478 2.722 1.096 -26.01 12(Cr) 3.367 3.064 3.064 -16.03 12(Brj 3.511 3.223 3.223 -15.55 *I4(Br-)~1t N=C *I4(Br-)~(j' C-H *I4(P-)~1t c=c <1 0.006 0.093 7.30 0.035 0.097 15.22 0.033 0.041 <1 0.004 0.201 >200 0.501 0.593 <1 0.004 0.161 <1 0.004 0.148 aDistance between halide and nearest arene carbon atom (dcarbon), distance between halide and arene centroid (dcentroid), and distance between halide and mean plane of arene (dplane). bEecomplex) - E(halide) - E(arene) using absolute energies obtained at the MP2/aug-cc-pVDZ level of theory. cThe leading charge-transfer interaction between the filled halide donor lone pair and unfilled acceptor orbital with associated second- order perturbation energies (l1E(2), kcal morl). dComplex is not a minimum on this potential surface. The number of negative frequencies is given in parentheses. .;:.. U'1 46 In the case of F-, 2 and 3 are much more stable than 1, by 19 and 13 kcal mor l , respectively. The F-C distances of 1.50 and 1.58 A are only slightly longer than the average F-Carene bond length of 1.35 ± 0.02 A observed in the CSD. The carbon atom bonded to F- adopts an Sp3 geometry. Such geometries, which indicate a strongly covalent interaction, have been described previously in studies of nucleophilic substitution on aromatic rings and are denoted as Meisenheimer or 0" complexes.30,31 In the case ofcr and Br-, structures 2 and 3 are close in energy to transition state 1, but more stable by 0.8 to 1.5 kcal mor l . The X-C distances are much longer than the average X-Carene distances observed in the CSD: 2.60 and 2.67 A versus 1.73 ± 0.2 A for Cl; 2.79 A versus 1.90 A for Br. Although there is some distortion to the arene ring, the carbon atom nearest to the halide exhibits a geometry that is closer to that expected for Sp2 hybridization. As will be discussed below, these structures represent weakly covalent donor to n-acceptor complexes with smaller amounts of CT than observed for F-. Finally, geometry 4 confirms that halides also form stable complexes with TCB by hydrogen bonding to one of the C-H groups. Recent theoretical studies have established that arene C-H donor groups form moderate to strong hydrogen bonds with anions?8 The presence of electron-withdrawing substituents increases the acidity of arene C-H donors and, thus strengthens the interaction.29 The presence of four CN substituents in TCB yields quite acidic C-H groups, so much so that during the optimization of the F complex the TCB is actually deprotonated yielding a complex between HF and the TCB anion. Structure 4 contains the strongest arene C-H···Cr 47 bond yet calculated, with an electronic bonding energy of -27.0 kcal mor l compared to values of -16.0 kcal mor l for nitrobenzene and -8.6 kcal mor l for benzene?9 NBO Analysis. Insight into the nature of the bonding interactions in 1 - 4 was obtained by evaluating the extent of CT from the halide donor to the TCB acceptor. Natural Bond Order (NBO) methods25 can be used to estimate the extent of CT by removing the full set of off-diagonal matrix elements between two fragments of the NBO Fock matrix and recalculating the total energy to determine the associated variational energy change. The leading CT interaction between the filled halide lone pair (n) and unfilled antibonding acceptor orbital ( 0.7 A are closer to the arene perimeter and would indicate a CT complex. In structures calculated for cr CT complexes 2, 3, 6, 7, and 10, d ojfset ranges from 1.7 to 2.0 A; in crystal structures determined for 1,2,4,5-tetracyanoarenes (see Figure 3.6, interactions a and b), d ojfset ranges from 0.7 to 2.4 A. < dplane z~ 54 Figure 3.10 The degree of displacement of a halide, X-, from the center of an arene is given by doffset. This parameter is calculated from distances (dcentroid and dplane) that can be queried in a CSD search to provide do.ffset = (dcentrotl- d p1an/)1n SURVEYS OF THE CAMBRIDGE STRUCTURAL DATABASE Further evidence for CT interactions between halides and electron-deficient arenes is provided from a survey of the Cambridge Structural Database (CSD). A search for halide anions located within 4.0 A of the centroid of six-membered ring n systems yielded nearly 600 examples. In most of these cases, however, the n system was either positively charged or bonded directly to a positively charged atom. Retaining only charge-neutraln systems yielded the much smaller set of 19 structures shown in Figure 3.11. Within these structures there are 30 halide-arene complexes. Distances for these complexes were evaluated yielding the following ranges: dcentroid' 3.2 to 4.0 A; d p1ane , 3.0 to 3.9 A; do.!fset, 0.2 to 2.5 A. The frequency of d ojfset values is presented as a histogram in Figure 3.12. Few structures show the halide positioned near the center of the ring; rather, the distribution exhibits a maximum centered at d ojfset = 1.5 A,just outside the ring perimeter. In fact, 84% of the anions in the data set are 55 closer to the ring carbons (dojfset> 0.7 A) than to the centroid. Thus, available structural data indicate the CT motif to be more prevalent than the anion-1t motif. EXPANDED CSD SURVEY. To examine the behavior when the 1t system is in contact with a positive charge, a larger subset of the data was evaluated. There are 138 examples in which a halide interacts with an arene ring containing a single nitrogen atom bonded to a metal cation. These examples include ligands such as pyridine, bipyridine, 1,1O-phenanthroline, etc. Distances for these complexes were evaluated yielding the following ranges: dcentroid, 3.3 to 4.0 A; dplane, 2.6 to 3.9 A; dojfset, 0.3 to 2.7 A. A histogram of the dojfset values for these complexes is shown in Figure 3.13. As with charge-neutral arenes (Figure 3.12), the distribution shows a maximum above the ring perimeter and 84% of the anions observed are closer to a ring carbon than to the centroid. These data again suggest the CT motif to be the predominant mode of interaction. 56 R 0R O~NR2 RF*F o~ DOMeI~ R2N I ~ CNR~Ni(N'R WNi(N'H CN 0 0 BETMOD CEFGAV CYSTYM DUTREP CI NCxNrCN CI~:( NCX:::CCN CI:::"'" 0NC N CN NC ~ CN CI ref 14 ref 14 this work ~I Y OH TITYRN OMe Br~Bry R MAYFOI F F*,,::F F ~ F R LOHTIL, QACYOI, VAQZAP H I R2NryNXO02N~N 0 I H TASWALTAJPUP OH 0 O~NIlNJLNA NRI 2 R HIYDOIHAWHOC NINNIH o H'Nj~R SAN I I H XUBHAD Figure 3.11. Electron-deficient arenes and CSD refcodes for structures in which a halide is located:::; 4.0 A from the arene centroid. When more than one ring is present, the ring interacting with the halide is shown in bold. 57 3.02.51.0 1.5 2.0 doffse1' A 0.5 • tetracyanoarenes D others \- ,- ---,-a 0.0 5 4 Qj 3 n E ::J Z 2 Figure 3.12 Histogram of dqrfset values (see Figure 3.10) for halide complexes with structures shown in Figure 3.11. 8 6 '--Q) .0 4E ::J Z 2 a 0.0 0.5 1.0 1.5 2.0 2.5 3.0 dOffset' A Figure 3.13 Histogram of d ojfset values (see Figure 3.1 0) for halide complexes with pyridine fragments that are bound to a metal cation. STRUCTURAL ANALYSIS OF HALIDEIPYRIDINE COMPLEXES. Further insight into the nature ofthese interactions is obtained by locating the positions of the halides above the pyridine 1t systems. A plot of these positions, shown in Figure 3.14, reveals that there is a 58 preference for the halide to locate over the 2 or 6 carbon atom. This positional predilection is in accord with a previous CSD study35 of nitrogen heterocycles interacting with N03-, CI04-, BF4- and PF6- as well as being consistent with a CT bonding motif that is stabilized by the following resonance forms:36 M(n-1)+ +(~Il0-- o 00 M(n-1)+ II ON +1.& d\I----+-M Figure 3.14 Locations of halide anions above the plane of pyridine fragments that are bound to a metal cation. The pyridine metal complex is drawn to scale and the circle represents a doffset value of3.0 A. STRUCTURAL ANALYSIS OF DONORIPERFLUOROBENZENE COMPLEXES. The histograms presented in Figures 3.12 and 3.13 lead to the conclusion that halide anions are more likely to interact with an electron-deficient 1t system through a CT motif rather than the 59 anion-n motif. This is contrary to two prior analyses of the CSD, which report evidence of a marked preference for charge-neutral atoms bearing lone pairs to position themselves over the center of pentafluoroarenes3 and trinitrobenzene derivatives.4 In these analyses, the database was searched for instances in which any electronegative atom F, CI, Br, I, 0, S, or N was in contact with all six carbon atoms of the arene, where each contact distance was defined as the sum ofvan der Waals radii + 1.0 A.27 Evidence in support of the anion-n interaction was provided by histograms of atom-centroid-carbon angles showing that data were concentrated at angles close to perpendicular to the ring, consistent with a preference for an electronegative atom to reside above the arene centroid. In an effort to resolve the inconsistency, this analysis was repeated for pentafluoroarenes. Figure 3.15 shows that it is possible to reproduce the previously reported histogram very closely? However, such data are misleading and give rise to false conclusions regarding the location of electron-rich atoms positioned above electron-deficient arenes. First, the atom-centroid-carbon angle is a poor indicator for the location of an atom above the arene plane. When the atom is off-center, the angle obtained depends on the choice of carbon atom. It is possible for two of the six angles to be near 900 , even when the atom lies well outside the ring perimeter. In addition, these angles are not a very sensitive measure ofthe degree of displacement. For example, if the atom is constrained to be 3.5 A above the arene plane and to lie within a perpendicular plane containing a pair ofpara carbon atoms, the atom-centroid- carbon angle involving one of these para carbon atoms varies with daffiet as follows 60 (angle, d ojfset): 90°, 0 A; 80°,0.62 A, 70°, 1.27 A; 60°,2.02 A. Although the atom- centroid-carbon angles are indeed distributed about 90°, the distribution is wide, ranging from 55 to 126°. Evaluation of dojfset values for the data in Figure 3.15 reveals that in 65% of the cases the atom is closer to the ring perimeter than to the centroid (> 0.7 A) and in 17% of the cases, the atom lies outside the ring perimeter (> 1.4 A). 600 05 400 -0 E :::J Z 200 o+-.,........,--r~---.--"up: o 30 60 90 120 150 180 Atom-centroid-carbon angle, 0 Figure 3.15 Histogram of the distribution of atom-centroid-carbon angles for electronegative atoms in contact with all six carbon atoms of pentafluoroarenes. All six angles for each hit are plotted. A second, and perhaps more serious, source of confusion stemming from this search is that constraining the electronegative atom to be in simultaneous contact with all six arene carbon atoms biases the search to select data that tend to lie over the arene. A much larger number of hits are obtained when the search criteria are altered such that the electronegative atom must be within 4 A ofthe pentafluoroarene centroid. These hits contain the subset of data used to generate Figure 3.15. Distances in these 61 structures were evaluated yielding the following ranges: dcentraid' 2.4 to 4.0 A; d p1ane, 1.8 to 4.0 A; daffier, 0 to 3.5 A. The distribution ofthe electronegative atoms over the pentafluoroarene plane is illustrated in Figure 3.16. When the atom lies well outside the ring perimeter, a preference to lie in between the ring substituents is apparent. However, for dajfset values ranging from 0 to 2 A, statistical analysis ofthe data (supporting information) shows that charge-neutral electronegative atoms within 4 A of a pentafluoroarene centroid are distributed randomly over the arene surface; in other words, these data establish the complete absence of any preferred location over this 1t system. Figure 3.16 Locations of electronegative atoms above the pentafluoroarene plane. The arene is drawn to scale and the outer perimeter represents a dajfset value of 3.0 A. 62 SUMMARY AND CONCLUSIONS In this study, we have used electronic structure calculations and crystal structure data to investigate how halides interact with electron-deficient n systems. When the halide lies above the plane of the n system, the resul ts establish that three distinctly different types of complex are possible: strongly covalent (J complexes (A), weakly covalent donor n-acceptor complexes (B), and non-covalent anion-n complexes (C). As shown in Figure 3.17, examples of all three types occur with triazine. These complexes are distinguished from one another by the extent of CT and the position of the halide above the n system. A B C Figure 3.17 When a halide is located above triazine, the most stable forms are a (J complex with F- (A), a donor rc-acceptor complex with cr (B), and an anion-rc complex with Br- (C). Strongly covalent (J complexes result from nucleophilic attack at a ring carbon. These complexes are characterized by a large amount of CT from the anion to the n system. As established in earlier theoretical studies2- 12 and as confirmed in this study, such complexes represent the only stable geometry that locates F- above the plane of an aromatic ring. For the complexes investigated here, most F-C bond distances are 63 short, near 1.5 A. The ring carbon under attack adopts a tetrahedral geometry and, as a result, the F- anion is located outside the ring perimeter. There is substantial experimental precedent for the formation of stable 0' complexes in studies of nucleophilic substitution reactions of electron-deficient aromatic rings.3D,31 Consistent with these experimental studies, calculations have established that 0' complexes also are formed between electron-deficient arenes and other strongly nucleophilic anions. Examples include CN- and CO/- interacting with C6F6,3 and CN-, NC- and CO/- interacting with triazine.5,6 Weakly covalent donor n-acceptor complexes may be formed with less nucleophilic halides. These complexes are characterized by a smaller, but definite, amount of CT from the anion to the n system. Geometries for such complexes are consistent with much less covalent character than in the 0' complexes, exhibiting elongated halide-carbon distances and near planar arene carbon atoms. Like 0' complexes, the halide is located outside the ring perimeter. Experimental evidence for donor n-acceptor complexes, both in solution and in the solid phase, was provided by a recent study.14 Further analysis of crystal structure data presented herein confirms that there is a marked preference for halides to lie either over or outside the perimeter of electron-deficient six-membered rings. Results from electronic structure calculations are fully consistent with this result. For example, for three out of the four arenes evaluated in this study calculations show that when cr is located above the n system, the donor n-acceptor motif yields the more stable cr complex. 64 Non-covalent anion-n complexes may also be formed with less nucleophilic halides. These complexes are characterized by CT values of:S 0.01 e and a geometry in which the halide is located directly above the arene centroid. Although prior theoretical studies have yielded numerous examples of such complexes in the gas phase,2-l2 crystal structure analysis reveals that there are relatively few clear examples of anion-n complexes for halides in the solid state. Indeed, the current study has established that when an arene becomes sufficiently electron-deficient, non-covalent anion-n complexes may no longer represent stable geometries for halides larger than F-. For example, the non-covalent anion-n complexes for cr with TCB and 1,3,5- tricyanobenzene are both found as transition states on the MP2/aug-cc-pVDZ potential surface. Additionally, one should not overlook the fact that electron-deficient arenes bearing C-H groups are potent hydrogen bond donors. As noted elsewhere, even in the absence of electron-withdrawing substituents, simple arenes form C-H hydrogen bonds with anions that can exceed 50% the strength of those formed by O-H and N-H groups?8 In electron-deficient arenes, aryl C-H groups become much stronger donor groups?9 As shown in Table 3.2, both tri- and tetracyanobenzene yield hydrogen- bonded complexes with CI- and Br- that are 88 to 95% as strong as corresponding donor n-acceptor complexes, with interaction energies ranging from -20 to -27 kcal morl. In the case of triazine, C-H hydrogen bonding yields the most stable complexes with CI- and Br-, 18 to 21 % more stable than the corresponding anion-n or donor n- acceptor forms. 65 The role of aryl C-H binding sites is nicely illustrated in a recent crystal structure. IS Although attention was drawn to the fact that this structure contains one of the few examples of an anion-n interaction, containing a cr anion positioned above the center of a melamine ring, no mention was made of the interactions with the other electron-deficient arenes lining the binding cavity. As illustrated in Figure 3.18, C-H groups of Cu(II)-coordinated pyridine rings form six hydrogen bonds with the cr guest. Because each of these aryl C-H groups offers a more powerful binding site than the melamine n system,J? it likely that the six C-H hydrogen bonds play the dominant role in determining the position of the anion within this cavity. FigUl'e 3.18 Views of a fragment of a cr receptor lS crystal structure showing six hydrogen- bonding interactions with aryl C-H groups ofCu(ll)-coordinated pyridine rings and one anion- 7l: interaction with a melamine ring. Interaction geometries are near ideal with all C-H···Cr angles 2: 1500 and cr to C distances ranging from 3.9 to 4.3 A. 66 This study has refined our understanding of how halides interact with arenes. Existence of four potential binding motifs establishes electron-deficient arenes to be versatile building blocks, augmenting the arsenal of conventional hydrogen bonding and electrostatic components that have been used widely in the construction of anion receptors. 1 The results indicate that molecular design strategies for incorporating electron-deficient arenes within anionophore architectures should consider the quite different geometries encountered for the various interactions. The optimal binding motif for a given arene-anion pair may not be immediately obvious, suggesting that new systems should be evaluated on a case-by-case basis. Knowledge of preferred binding motifs provides a basis for optimizing host architectures for specific anions. For example, in cases where substantial covalent character is anticipated, such as with strongly nucleophilic anions and/or highly electron-deficient arenes (Figure 3.3), optimal interaction with the 1t system will be achieved when the arene building block is oriented so that the anion is able to adopt a position outside the ring perimeter. Constraining host architecture so that the guest is only permitted to interact with the edges of the arene could lead to enhanced selectivity for such anions. The influence of arene orientation is expected to decrease as the extent of CT decreases. Comparison of interaction energies for various binding motifs for cr and Br- with cyanide-substituted arenes reveals that although the strongest bonding is attained when the halide is positioned outside the ring perimeter, substantial stabilization is retained when the anion is held over the ring centroid. The insensitivity 67 of interaction energy to anion position is most pronounced in the Br- complexes with triazine. Although the anion-x and donor x-acceptor complexes exhibit dojfset values of oand 1.75 A, respectively, these two orientations yield essentially the same interaction energy (Table 3.2). SUPPORTING INFORMATION AVAILABLE Crystallographic data for the complexes [K(l8-crown-6)(TCB)2tBr-, [K(l8-crown- 6)(TCB)2tr and [Na(18-crown-6)(TCB)2tr. The full citation for ref 22, Cartesian coordinates and energies (Hartrees) for the MP2/aug-cc-pVDZ optimized geometries for 1 - 13, and a statistical analysis showing that the data in Figure 3.16 is randomly distributed over the arene. This material is available in Appendix B. BRIDGE TO CHAPTER IV Through the crystallographic and computational investigation presented in chapter III we have refined the nature of the interactions between electron-deficient arenes and halides anions. The importance of considering multiple binding geometries for these systems is also highlighted. Specifically, new crystal structures containing 1,2,4,5- tetracyanobenzene and alkali halide salts as well as evaluation of structures found in the Cambridge Structure Database and MP2/aug-cc-pVDZ calculations of halide complexes with TCB, 1,3,5-tricyanobenzene, triazine, and hexafluorobenzene establish that multiple binding modes are present in these systems. Moreover, in most cases the preferred binding geometry is actually over the edge of the electron-deficient aromatic ring. 68 Chapter IV explores our efforts at designing, synthesizing and studying anion receptors that take into consideration the information that was acquired in the above investigation. Tripodal anion receptors with appended electron-deficient aromatic rings were designed to bind halide anions utilizing only electron-deficient aromatic rings while allowing enough space to access off-center binding geometries. The receptor scaffold was based off a 1,3,5-triethylbenzene core utilizing steric gearing to assist in preorganizing the electron-deficient aromatic rings in solution. 69 CHAPTER IV SOLUTION PHASE MEASUREMENT OF BOTH WEAK SIGMA AND C-H···X- HYDROGEN BONDING INTERACTIONS IJ'l" SYNTHETIC ANION RECEPTORS INTRODUCTION TO ELECTRON-DEFICIENT ARENE CONTAINING TRIPODAL ANION RECEPTORS This chapter was co-authored with Aaron C. Sather, Dr. Benjamin P. Hay, Jeffrey S. Meisner and Professor Darren W. Johnson. Aaron Sather and Jeffrey Meisner assisted in synthesis and titration experiments to determine association constants. Dr. Hay completed the quantum calculations within and provided editorial assistance. Prof. Johnson devised the project and provided editorial assistance. Orion Berryman wrote this chapter, performed literature searches, assisted in synthesis and titration experiments, calculated association constants, isolated and solved the single crystal X- ray structures. Electron-deficient arenes offer a variety of interaction motifs complementing traditional anion binding strategies. We have shown crystallographically and computationally that three distinct binding motifs are possible. [1,2] These binding motifs, illustrated for cr complexes with 1,2,4,5-tetracyanobenzene are (i) the centered noncovalent anion-n interaction (A), (ii) off-center or 'weak cr' interactions (B 70 and C), and (iii) C-H~"X- hydrogen bonds (when acidic hydrogenss are available, D) (Figure 4.1). Although much recent attention has focused on the anion-n interaction,[3] there is evidence to suggest that this is not the predominant binding mode for many highly electron-deficient arenes. [2J In prior work we found that strongly electron- deficient arenes, such as the tetracyano-substituted example, exhibit stable weak (J and H-bonded geometries B - D, whereas the anion-n motif (A) was not a stable form in the solid and gas phases. ABC 0 Figure 4.1 MP2/aug-cc-pVDZ optimized geometries for CI- interactions with 1,2,4,5- tetracyanobenzene include an unstable anion-1c complex (A), weak (J complexes (D and C), and an aryl H-bond complex (D).[I] Atom colors: carbon gray, hydrogen white, nitrogen blue, and chloride green. The majority of prior computational studies on anion-arene interactions have been representative of the molecules in the gas phase. When moving from in silico to solution other factors need to be considered;[4-6] therefore, solution phase association constants (Ka) must be measured to understand fully the selectivity that will emerge in binding anions with electron-deficient arenes. In one case Kas have been determined for model electron-deficient aromatic rings from UV-Vis titrations with halides. [7J 71 NMR spectroscopy can provide complementary structural information that is not obtainable with UV-Vis spectroscopy. A handful of examples use IH NMR spectroscopy to characterize anion interactions with electron-deficient aromatic rings in solution, but in many cases additional attractive interactions are present (such as 1t- stacking, ion pairing or hydrogen bonding). [8-11] RESEARCH SUMMARY We present experimental and theoretical results on a series of neutral tripodal receptors that utilize only electron-deficient arenes to bind halides in solution (Figure 4.2). These receptors employ steric gearing to preorganize electron-deficient arenes, and IH NMR spectroscopic titrations and DFT calculations confirm that receptors 1-3 bind anions in a 1:1 stoichiometry. These studies highlight three key aspects that had not been observed previously for anions interacting with electron-deficient aromatic rings in solution: (i) IH NMR spectroscopy provides sensitive data for determining both the magnitude of anion binding (Ka) and the structure (1t contacts versus hydrogen bonding), even in cases of weak binding, (ii) the first observation of receptors binding anions in solution using only electron-deficient aromatic rings with either weak (J or C- H···X- hydrogen bonding interactions,[12] and (iii) the first quantitative measurement of the relative stabilities for such interactions in solution. 72 DESIGN AND SYNTHESIS OF TRIPODAL ANION RECEPTORS RECEPTOR DESIGN. The cavity present in syn conformers of 2,4,6-trisubstituted- 1,3,5-triethylbenzene[13] derivatives provides access for monoatomic anions to interact with the electron-deficient dinitroarenes via the n-system or hydrogen bonding (Figure 4.2). Receptors 1-3 are structural isomers composed of three electron-deficient arenes differing only in the position of their nitro substituents, which allows for an understanding of the effect of substitution pattern on receptor function. A key feature of the design strategy is that receptor 2 cannot form hydrogen bonds to anions (due to the bulky nitro groups being positioned ortho to each acidic aryl hydrogen) allowing us to study only the interaction between the anion and the n-system. Receptor 4, lacking electron-deficient aromatic rings, was also prepared as a control. RECEPTOR SYNTHESIS. Receptors 1-4 were synthesized in good yields from CsF- Celite assisted esterification ofknown 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene 5 with the corresponding benzoic acids (Figure 4.2) (see Appendix C). [14] Colorless single crystals of 1 and 2 were grown from slowly evaporating DMSO solutions. 1 and 2 crystallize in space groups P-l and P2/n, respectively, with four independent molecules per unit cell. [15,16] Interestingly, in the solid state receptors 1 and 2 crystallize with one electron-deficient functional group anti with respect to the other aromatic rings (Figure 4.2). Nevertheless, receptors 1-4 exhibit time-averaged C3v symmetry in solution on the NMR timescale suggesting that the up, up, down conformation does not dominate. 73 R " 0 '" oAoBr~__: I ',r.", OH CsF-Celite ~ RAO~"': ,/,/ + O~R MeCN, reflux ~ .", 25-76% : ,-_5_B_r -u- I JR ( l I (I,, 432 Figure 4.2 Synthesis of tripodal anion receptors 1-3 (left) and ORTEP representation of the crystal structure of receptor 1 (right, 50% probability ellipsoids with hydrogens omitted, carbon depicted as gray, hydrogen white, nitrogen blue and oxygen red). SOLUTION EQUILIBRIA OF RECEPTOR/ANION COMPLEXES 1H NMR TITRATION EXPERIMENTS. A previous study of strongly electron- deficient aromatic rings illustrated that UV-Vis spectroscopy is a suitable method to determine association constants for weak attractive interactions between halides and electron-deficient aromatic rings,(7,J7) We chose to investigate the utility of 'H NMR spectroscopy to determine association constants between halides (CI-, Br- and nand electron-deficient arenes in benzene, in part for the structural information provided by this technique. It is necessary when performing titration experiments to obtain data 74 where there is maximal change in the binding isotherm. [18] For solubility reasons, it was challenging to find an organic solvent where subtle interactions could be measured and the anion concentration could reach a large excess of the receptor concentration. The low solubility ofNBl14+1 and NBl14+cr in C6D6 prompted us to perform titration experiments with tetra-n-heptylammonium halide salts (NHep/Cr, NHep/Br- and NHep4+1) at 27°C. All three electron-deficient receptors 1-3 turned pale yellow upon addition ofBr- (see Appendix C, Figure C.5, middle. The picture exemplifies 90 equivalents oftetra-n-butylammonium bromide, NBl14+Br-). Whereas 2 showed relatively little change in the IH NMR spectrum, significant changes occurred with receptors 1 and 3 when NHep4+Br- was titrated into C6D6 solution of receptors. Association constants determined for receptors 1 and 2 with NHep4+Br- in d6-benzene at 27°C wear 18-35 M-I, [19] while control receptor 4-distinctly lacking electron- deficient arenes--exhibited no measurable binding by NMR and no visible color change (Table 4.1). These results lend support to our hypothesis that electron-deficient aromatic rings are required to bind anions in this neutral system. 75 Table 4.1 Average Ka (M- I) for receptors 1, 2, and 4b with halides ccr cBr- cr 1 2 4 26 53 18 35 t-Bu ~ N ~ "': t-Bu 1 "': ~ NH2 H2N ~ 5 il TMSt-BUQ + n~ NH2 Br No/- Br 6 EXPANDED SERIES OF SULFONAMIDE RECEPTORS. Our initial publication of the hydrogen bonding capability of two sulfonamide receptors built from bis(ethynyl)pyridine cores reported the synthesis, solution behavior and solid state characteristics exhibited by these receptors. In the following section we expand this series of receptors with the synthesis of three more sulfonamide receptors. By simply changing the functional groups appended to the sulfonamide we observe drastic changes in the electronic absorption spectra. We also report, through a crystallographic study, the solid state behavior for the whole series of sulfonamides. Synthesis of 2,6-bis(2-anilinoethynyl)pyridine sulfonamides. Synthesis began with previously reported 2-iodo-4-f-butylaniline,9 available in 73% yield via 115 iodination of 4-t-butylaniline (Scheme 6.3). Pd-catalyzed cross-couplinglO of2-iodo-4- t-butylaniline with trimethylsilylacetylene (TMSA) afforded ethynylarene 6 in 86% yield. Dianiline 5 was obtained in 79% yield by desilylation of 6 with weak basell followed by two-fold cross-coupling to 2,6-dibromopyridine. Sulfonamide receptor analogs 1,2, 7a and 7b were obtained in good yield (89-95%, Scheme 6.3) by treatment of dianiline 5 with an excess ofthe respective phenylsulfonyl chloride in pyridine. 14 Incorporation of substituents ranging from electron donating (OMe) to electron withdrawing (N02) into the 4-position ofthe sulfonamide phenyl rings was proposed to investigate electronic properties of the ligands as well as effects on guest binding. Sulfonamide 7c was additionally considered to examine solid-state and solution effects of a different substitution pattern and increased electron deficiency of the peripheral phenyl rings. The initial attempt to produce a 3,5-bis(trifluoromethyl)- sulfonamide receptor (7c) resulted only in isolation of tetra- (7d, Figure 6.8) and trisubstituted (7e) compounds, the result of enhanced reactivity of the electron deficient bis(trifluoromethyl)sulfonyl chloride. Subsequent efforts to control substitution via stoichiometric treatment with sulfonyl chloride afforded only a mixture ofmono-, di-, and trisubstituted adducts, out of which the desired product (7c) was difficult to separate from monosubstituted byproduct. The fortuitous isolation of7d, which does not contain sulfonamide hydrogens, provides solution evidence for the importance of water in sulfonamide receptors 1,2, 7a and 7b. The 116 lack of any effect on the water resonance in the IH NMR spectrum of7d is in stark contrast to the IH NMR spectra observed for receptors 1,2, 7a and 7b, providing further evidence for a solution based hydrogen bonding phenomena. Scheme 6.3 Synthesis of 2,6-bis(2-anilinoethynyl)pyridine sulfomaide receptors. TMSt-Bu~~I""'" /./ NH2 6 1. K2C03, MeOH, THF 2. A)l..~Br N Br Pd(PPH3)4, Cui i-Pr2NH, THF, 45 ac, 79% t-Bu 1 /./ I""'" -< N 5 ~ t-Bu I""'" HN h I o=s=o¢ R h NH I02;]0 R 1 R= Me 95% 2 R = N02 93% 7a R= OMe93% 7b R = Br 89% t-Bu 1 °~-o-S-CI \- 8 5 1'-':::: -< N 7c R' = S02CeH3(CF3h, R" = R'" = H 7d R' = R" = R'" = S02CeH3(CF3h 58% 7e R' = R" = S02CeH3(CF3h, R'" = H 13% I ": -< t-Bu ¢- N ~ t-Bu I ""'" ""'" h wR' R' h 'N I I R" R" 117 Solid state investigation of 2,6-bis(2-anilinoethynyl)pyridine sulfonamide receptors. Neutral receptors 1,2, 7a and 7b all exhibit the same propensity to crystallize as hydrogen bonded 2+2 dimers with water in the solid state. The solid state structure is very similar throughout the series of receptors differing only in minor adjustments to the hydrogen bonding and n-stacking distances. Figure 6.6 illustrates the similarity between receptors 1,2, 7a and 7b in the solid state with four different representations of the single crystal X-ray structures. , ( .'1 , \-"''' 4." .. '"\ " . Ii 1 R=Me 7a R=OMe ., 7b R=Br Figure 6.6 Four different representations of the 2+2 water dimer formed when 1,2, 7a and 7b are crystallized in its neutral form. 118 In one isolated instance a polymorph of receptor 2 was isolated. Attempts were being made to isolate co-crystals of2 and tetra-n-butylammonium iodide with CHCb/pentane diffusion conditions. The Receptors in this structure form a dimeric pair and with each receptor exhibiting the same helical arrangement. A single sulfonamide functionality from each receptor is interlocked with the neighboring molecule while the second sulfonamide functionality hydrogen bonds to a separate dimeric pair in the solid state. The key driving forces for the solid state structure are the hydrogen bonds between the pyridine-N and sulfonamide hydrogens from the adjacent receptor as well as intermolecular n-stacking (Figure 6.7). This structure remains the only example of dimer formation in these receptors without assisting water molecules. Unfortunately, the poor crystal quality resulted in data unsuitable for publication and only worthy of understanding connectivity and spacial arrangement. 119 FigUl'e 6.7 Polymorph of2 dimer notably lacking assisting water molecules. Each molecule colored differently and non H-bonding hydrogens removed for c1ariLy. Figure 6.8 TeLra substiLuted receptor 7d exhibits no interactions with water molecules in the solid sLate. 120 We reported previously that sulfonamide receptors 1 and 2 form 2+2 dimers in the solid state with water, halides or both water and halides. We have also found that larger guest molecules eliminate the 2+2 dimer formed in the solid state. Single crystals ofHl+·BF4- are isolated by dissolving receptor 1 in ethyl acetate and adding aqueous HBF4 while stirring vigorously. Crystallization is induced by layering with hexane. The larger size of the BF4- anion forces the receptor arms to the opposite side of the pyridine N in order to maintain a strong pyridinium hydrogen bond with the BF4 anion. One receptor sulfonamide forms a head-to-tail intermolecular hydrogen bond with an adjacent receptor molecule while the other sulfonamide hydrogen bonds to the BF4 anion of a second receptor. This sequence of hydrogen bonds forms a polymeric hydrogen bonding chain in the solid state (Figure 6.9). Figure 6.9 Stick representation of the polymeric hydrogen bonding chain present in the solid state structure of J-Il+.BF4-. 121 The solid state structure of H rt-·HS04- also deviates from the 2+2 structure observed for smaller guests. Single crystals of Hl~·HS04- were grown from THF solutions of receptor mixed with H2S04. Crystallization is aided by difTusing pentane and the Hl+·HS04- salt crystallizes in the P-1 space group with two receptor molecules and three THF solvent molecules per unit cell. Similar to the Hl~·BF4- structure the counter anion forms a strong hydrogen bond with the pyridinium nitrogen resulting in a conformation that puts the receptor arms on the opposite side of the molecule. However, the Hl~ ·HS04- structure is complicated by additional solvents of crystallization. Each sulfonamide also hydrogen bonds to a different I-IS04 anion which in turn donates a hydrogen bond to a THF solvent molecule (Figure 6.10). Figure 6.10 Stick representation of a portion of the HI+.HS04- crystal structure highlighting some of the hydrogen bonds present in the solid state. ----------- 122 Synthesis of core analogs. As mentioned above, the synthetic route for key intermediate 5 allows facile modification to investigate other core arenes in place of pyridine. Examination of both bipyridine and pyrrole cores indicated the potential to target larger guest molecules, a direct result of the change in bonding angle ofthe functionalized phenylacetylene arms. Dihalo-analogs of both heterocycles are known; 16 however, 2,5-dibromopyrrole has been reported to decompose rapidly upon concentration.16b Due to the well established chemistry of2,5-functionalized thiophenes,17 a thiophene core was proposed as a simple substitute to model the pyrrole core and determine if further examination of pyrrole analogs was warranted, specifically via examination of the solid-state structure. Synthesis of both core analogs began with desilylation of 6 followed by two-fold Pd-catalyzed cross-coupling with commercially available 6,6' -dibromo-2,2' -bipyridyl or 2,5-dibromothiophene, which afforded compounds 8 and 9, respectively (Scheme 6.4). While compound 9 was readily purified and characterized, intermediate 8 proved problematic due to extremely poor solubility in common organic solvents « 0.1 mM) and was isolated only as a 5:1 mixture with mono-coupled byproduct. Independent treatment of dianilines 8 and 9 withp-toluenesulfonyl chloride in pyridine provided sulfonamide receptors 10 and 11 in moderate to good yield. 123 Scheme 6.4 Synthesis of core analogs. 1. KZC03, MeOH, THF 2.~ )=N ~--( Br Br Pd(PPH3)4, Cui i-PrzNH, THF 50°C TMSt-BUQ~ 1'-'::: h NHz 6 1. KZC03, MeOH, THF 2. n Br--<'s/--Br Pd(PPH3)4, Cui i-PrzNH, THF, 45°C 75% t-Bu t-Bu -...-:: ~ ~ 8 9 HzNNHz t-Bu HzN t-Bu 53% p-tolSOzCI 82% p-tolSOzCI(2 steps) pyridine pyridine t-Bu t-Bu t-Bu Solid state investigations of core analog sulfonamide receptors. X-ray diffraction structures of core analogs 10 and 11 are shown in Figures 6.11 and 6.12, respectively. Substitution of bipyridine and thiophene into the ligand backbone clearly increases the binding cavity size and will allow exploration of binding larger polyatomic ions and small molecules compared to pyridine-based system. Single crystals of receptor 10 are grown from slowly diffusing hexane into ethyl acetate solutions of receptor resulting in 124 crystals of the P-l space group with 1 molecule contained in the unit cell. In the solid- state, the bipyridine core of sulfonamide 10 is highly planar with anti N-atoms, a factor which results in rotation of a single sulfonamide arm away from the proposed binding cavity. Intermolecular n-stacking interactions are observed between receptors and each sulfonamide functionality hydrogen bonds in a head-to-tail fashion with different adjacent molecules forming an infinite hydrogen bonding chain in the solid state. Figure 6.11 Stick representation of the single crystal X-ray structure of sulfonamide 10 with expanded bipyridine core. Single crystals of receptor 11 are also isolated from diffusing hexane/ethyl acetate mixtures. Receptor 11 crystallizes with 2 molecules per unit cell in the P-l space group Conversely, sulfonamide 11 exhibits a solid-state conformation with both receptor 125 arms rotated away from the binding cavity due to its pm1icipation in multiple intermolecular hydrogen bonds with adjacent receptors. Figure 6.12 Stick representation of the single crystal X-ray structure of sulfonamide 11 with expanded thiophene core. Only one molecule is shown and hydrogen atoms are removed for clarity. AM/DE FUNCTIONAL/ZED RECEPTORS. The modular design of this receptor class facilitates the production of a number of receptor types. We have shown above that sulfonamide receptors based off of 2,6-bis(2-anilinoethynyl)pyridine cores express a diverse array of host/guest interactions both in the solid state and in solution. We have also illustrated that the size of the receptor binding pocket can be adjusted by substituting the pyridine core with alternative heterocycles. This next section highlights another key aspect to our modular design. In addition to adjusting the 126 receptor cavity we can also dictate the terminal substituents attached to the receptor core and subsequently control the properties of the host and its potential guest interactions. Synthesis of 2,6-bis(2-anilinoethynyl)pyridine amide receptors. Treatment of dianiline 5 with chloroacetyl chloride and Et3N in CH2Ch12 afforded diamide 12 in very good yield. Reaction of arene 12 with potassium thioacetate in DMF12 resulted in acetyl-protected receptor 13. Treatment of 13 with K2C03 in MeOH and THF under both air-free and ambient conditions afforded the intramolecular disulfide analog 14 in 77% yield instead of desired dithiol15 (Scheme 6.5). Scheme 6.5 Synthesis of amide receptors. I~ I-Bu 4- N ~ I-Bu I"" I"" "'" NH2 H2N ..<:' 5 I"" CICOCH2CI I-Bu 4- N/. ~ I-Bu Et3N. CH3CI2 1 "" I "" 89% "'" NH HN..<:' ~O O~ R R KSAc, DMFr- 12 R = CI K2C03 92% 1_13 R = SAc MaOHI 77% 15R=SH~ I"" A N~ &:-.. I-Bu ?'" """ I-Bu 1 "" 1 "" "'" NH HN "'" O~S-S~O 14 In an initiative to investigate possible anionlarene interactions in these systems amide receptor 16, containing electron-deficient 3,5-dinitrobenzene substituents, was synthesized. The synthesis of 16 was achieved in fair yield (51 %) utilizing biphasic 127 reaction conditions in one step from key intermediate 5 (Scheme 6.6). Unfortunately, amide 16 is rather insoluble common organic solvents. Several attempts to crystallize both the neutral and protonated forms of 16 met failure. Frequently receptor 16 was isolated as tiny hair-like needles unsuitable for X-ray diffraction studies. Scheme 6.6 Synthesis of electron-deficient arene containing amide 16. I} I"'"/0~ N ~t-Bu I"'" ~ "'" t-Bu OzN ~ NOz ~ NH HN. KZC03, HzO, EtOAc ~ 51% ~N¢o o~N~HzN I~ I~5 16 NOz NOz Solid state investigations of 2,6-bis(2-anilinoethynyl)pyridine amide receptors. Crystals of arene 13 suitable for single crystal X-ray diffraction were obtained from slow diffusion ofhexanes into a concentrated solution of 13 in EtOAc. Arene 13 crystallizes in the Pc space group and displays dimeric association with intermolecular hydrogen bonding between amide hydrogen and carbonyl oxygen ranging from 2.85-3.01 A (Figure 6.13). The dimeric pair consists of two molecules in an anti-relationship with amide arms rotated away from the desired binding cavity. Also noted in the crystal structure is a long C-H···N hydrogen bond between a solvent dichloromethane molecule and a pyridine nitrogen on the receptor (3.29 A). 128 Figure 6.13 Stick representation of the single crystal X-ray structure of at'ene 13. Non H- bonding hydrogens have been removed for clarity. We report that we can influence the receptor conformation in the solid state by protonating the pyridine nitrogen and using an appropriately sized counter anion. In an unrelated experiment attempting to target metal ions with Arene 13, yellow single crystals were isolated from pentane diffused into THF solutions of the reaction mixture. Close inspection of the single crystal data revealed that the compound isolated was H13+oCr- (Figure 6.14). H13+·Cr- crystallizes in the P-I space group with 2 receptor molecules and 4 THF molecules per unit cell. Remarkably, H13+"Cr- forms a helical twist conformation around the Cr- anion, Numerous hydrogen bonds serve to 129 stabilize the cr in the solid state. One strong pyridinium N···Cr hydrogen bond (3.00 A) and two amide N···Cl- hydrogen bonds (3.25 Aand 3.27 A) are observed in the solid state. This solid state example nicely illustrates how drastic conformational control can be achieved by simple changes in the protonation state of the receptor. stick and H·bond representation CPK representation, fronl CPK representation, back Figure 6.14 Stick (left) and CPK (middle and right) representations of the J-I13+·CI- crystal structure highlighting the hydrogen bonding interactions observed in the solid state and the helical conformation formed around the CI- anion. Again we illustrate that we can affect the conformation of the molecule. X-ray diffraction quality single crystals of 14 were grown from evaporating EtOAc/Hexane solutions. Arene 14 crystallizes in the P-1 space group with two molecules per unit cell. Unlike arene 13, inspection of the X-ray data of neutral arene 14 revealed that the disulfide bond enforces a pre-organization of the amide hydrogen, disulfide linkage, and pyridine-N into the desired conformation, although space-filling models indicate that location of the disulfide bond prevents sufficient space for guests (Figure 6.15). 130 side view top view Figure 6.15 Stick (left) and space filling (right) representations of the crystal structure of disulfide 14. Note that the disulfide linkage inhibits the formation of intermolecular hydrogen bonds between amide substituents. RECEPTOR ELECTRONIC PROPERTIES. Key elements of the electronic absorption spectra of the new sulfonamide and amide receptors are presented in Table 6.1. In general, the spectra of the pyridine-core receptors all contain a characteristic pattern of three peaks with minimal change upon substitution beyond dianiline 5, a factor which suggests that electron density is localized in the pyridylacetylene scaffold. The differential substitution of the terminal arene rings of sulfonamides 1,2, 7a and 7b is as expected: the strongest electron donating substituent (OMe, 7a) exhibited the lowest energy Arnax while the most hypsochromically shifted sulfonamide is N02- substituted 2. The small change in Amax (24 nm) between strong donor and acceptor further supports the notion of limited intramolecular charge transfer, likely the result of non-planarity, length of conjugation pathway, and localization of electron density in the n-rich scaffolding. Of note, protonation of the pyridine core by addition of a slight 131 excess of TFA to receptor solutions in CH2Clz resulted in a synonymous absorption redshift for all receptors, with disulfide 14 exhibiting the greatest change. Additionally, the solution color changed from colorless to bright yellow. Initial modeling studies suggest an enhanced intramolecular charge transfer model due to a significant increase in electron deficiency of the pyridinium core as the rationale for this occurrence. Table 6.1 Electronic absorption data for compounds 1, 2, 5, 7a-b, 9-14 in CH2Cb at 25°C Compound Amaxa (Ei "'elltott Aclltott (+TFA) 1 330 (27,600) 432 480 2 319 (23,000) 425 453 5 359 (22,500) 401 7a 343 (23,000) 385 478 7b 342 (19,900) 374 465 9 378 (37,000) 432 10 315 (46,100) 363 457 11 357 (37,200) 442 12 335 (27,600) 445 13 330 (21,600) 362 14 337 (17,500) 362 499 a Units: nrn. bUnits: M- I cm- I . The sulfonamide receptors all exhibited weak fluorescent emission ( 2(J(I), and RI = 0.0580, wR2 = 0.1222, and GOF = 1.028 for all 8480 data, max/min residual electron density +0.502/-0.682 e A-3. 146 (Hl+-Cr)-(l-H20): (C43H43N304S2)2-H20-HCI, Mr = 1514.32,0.20 x 0.08 x 0.02 mm, triclinic, P-l, a = 9.9702(13) A, b = 12.8868(17) A, c = 17.363(2) A, a = 111.314(2t, jJ=95.475(3)0,y= 103.737(2)°, V= 1977.7(4)A3,z= I,Pealed= 1.271 gmL-I,,u= 0.215 mm-I, 28max = 54.00°, T = 173(2) K, Rl = 0.0671 for 5583 reflections (559 parameters) with I> 2a(/), and Rl = 0.1074, wR2 = 0.1673, and GOF = 1.027 for all 8485 data, maximin residual electron density +0.842/-0.723 e A-3 Hl+-BF4-: C43H44BF~304S2,M= 817.74, triclinic, P-l, a = 11.6480(18) A, b = 13.432(2) A, c = 15.472(2) A, a = 105.643(2)0,jJ = 109.855(2)°, 'I = 98.858(3)°, V= 2110.4(6) A3, Z= 2, Absorption coefficient = 0.188 mm-I. Final residuals (700 parameters) Rl = 0.0439 for 9043 reflections with I> 2a(/), and Rl = 0.0519, wR2 = 0.1251, GooF = 1.022 for all 17842 data. Hl+-HS04-: (Cg6HggN60gS4)- (C4HgO)3-(HS04-)2, M = 413.36, triclinic, P-l, a = 14.727(4) A, b = 15.082(4) A, c = 21.992(6) A, a = 83.367(5)°, jJ = 89.980(5)°, 'I = 84.521(5)°, V= 4829(2) A3, Z= 2, Absorption coefficient = 0.212 mm-I. Final residuals (1231 parameters) Rl = 0.0939 for 21772 reflections with I> 2a(/), and Rl = 0.2385, wR2 = 0.2466, GooF = 0.979 for all 41939 data. (2-H20)2: (C4IH3gNs09S2b Mr = 1619.78,0.30 x 0.20 x 0.01 mm, triclinic, P-l, a = 10.1 068(15) A, b = 12/5999(19) A, c = 17.186(3) A, a = 110.709(3)°, jJ = 97.006(3)°, 'I = 100.306(3)°, V= 1972.9(5) A3, Z= I,Pealed = 1.363 g mL-I,,u = 0.198 mm-I, 28max = 54.00°, T = 173(2) K, Rl = 0.0642 for 4980 reflections (674 parameters) with I> 2a(/), 147 and R1 = 0.1233, wR2 = 0.1462, and GOF = 1.034 for all 8413 data, maxImin residual electron density +0.312/-0.432 e A"3. (H2+-Cn2: (C4IH3gC1NsOgS2)2, Mr = 1656.66,0.30 x 0.25 x 0.02 mm, triclinic, P-1, a = 9.8907(13) A, b = 12.9533(17) A, c = 17.012(2) A, (J. = 107.831(2)°, {J = 95.845(2t, Y= 103.618(2)°, V= 1980.5(4) A3, Z= 1, Pealed = 1.389 g mL-\,u = 0.262 mm-\ 20max = 54.00°, T= 173(2) K, R1 = 0.0572 for 6572 reflections (594 parameters) with 1> 2(J(1), and R1 = 0.0744, wR2 = 0.1594, and GOF = 1.045 for all 8472 data, maxImin residual electron density +0.564/-0.290 e A-3. (H2+-Br-)2: (C43&4BrN304S2)2, Mr = 1621.68,0.21 x 0.07 x 0.02 mm, triclinic, P-1, a = 9.632(16) A, b = 13.33(2) A, c = 17.47(3) A, (J. = 108.39(4t, {J = 94.56(5t, y = 106.51(4)°, V= 2005(6) A3, Z= 1, Pealed = 1.343 g mL-I,,u = 1.175 mm-I, 20max = 54.00°, T= 173(2) K, R1 = 0.0598 for 5748 reflections (599 parameters) with 1> 2(J(1), and R1 = 0.1021, wR2 = 0.1527, and GOF = 1.035 for all 8622 data, maxImin residual electron density +0.6801-0.371 e A-3. 2 no water: C340H30gCl136N40064SI6, M= 7767.42, orthorhombic, Pcba, a = 27.226(4), b = 20.765(3), c = 31.191(4) A, (J. = 90°,{J = 90°, y = 90°, V= 17634(4) A3, Z= 2, Absorption coefficient = 0.452 mm-I. Final residuals (1138 parameters) R1 = 0.1272 for 21121 reflections with 1> 2(J(1), and R1 = 0.1872, wR2 = 0.4228, GooF = 1.460 for all 99616 data. 148 (7a-H20)2: (C43H4S]\h07S2)2, M= 1559.88, triclinic, P-1, a = 9.8389(19) A, b = 13.094(3) A, c = 17.479(3) A, a = 68.463(3)°, P= 75.262(3t, J' = 80.671(3)°, V = 2019.7(7) A3, Z= 1, Absorption coefficient = 0.185 mm- I . Final residuals (680 parameters) R1 = 0.0498 for 9074 reflections with I> 2(J(1), and R1 = 0.0676, wR2 = 0.1351, GooF = 0.987 for all 17590 data. (7b-H20)2: C41H39Br2N30SS2, M= 755.38, triclinic, P-1, a = 10.0725(7) A, b = 12.7166(8) A, c = 17.3538(11) A, a = 111.3340(10)°, P= 96.3670(10t, J' = 101.7700(10)°, V= 1984.8(2) A3, Z= 1, Absorption coefficient = 2.195 mm- I . Final residuals (638 parameters) R1 = 0.0351 for 8599 reflections with I> 2(J(1), and R1 = 0.0430, wR2 = 0.0974, GooF = 1.052 for all 22389 data. 7d: C42.sH47.sF12N1.504S2, M= 934.55, monoclinic, C2/c, a = 9.986(3) A, b = 54.639(16) A, c = 31.711(10) A, a = 99.004(6)°, P= 90°, J' = 90°, V= 17090(9) A3, Z = 16, Absorption coefficient = 0.221 mm- I . Final residuals (977 parameters) R1 = 0.0839 for 20434 reflections with I> 2(J(1), and R1 = 0.2161, wR2 = 0.2269, GooF = 0.867 for all 98547 data. 10: C4SH2SN404S2, M= 788.86, triclinic, P-1, a = 7.960(3) A, b = 10.860(4) A, c = 12.852(4) A, a = 101.699(7)°, P= 97.680(7t, J' = 95.720(6)°, V= 1068.9(6) A3, Z= 1, Absorption coefficient = 1.226 mm- I . Final residuals (318 parameters) R1 = 0.0779 for 4783 reflections with I> 2(J(1), and R1 = 0.1359, wR2 = 0.2033, GooF = 1.219 for all 9270 data. 149 11: C4zH4ZNz04S3, M= 734.96, triclinic, P-1, a = 11.748(5) A, b = 12.750(5) A, c = 13.028(6) A, a = 97.514(9)°, P= 95.518(10)°, y = 94.730(8)°, V = 1916.8(15) A3, Z = 2, Absorption coefficient = 1.273 nun-I. Final residuals (466 parameters) R1 = 0.1271 for 6692 reflections with I> 2lJ(l), and R1 = 0.2568, wR2 = 0.3612, GooF = 1.079 for all 13924 data. 13: C7sHsoChN60SS4, M= 1392.59, monoclinic, Pc, a = 16.1430(15) A, b = 9.5995(9) A, c = 25.146(2) A, a = 90°, P= 103.677(2)°, y = 90°, V = 3786.2(6) A3, Z = 2, Absorption coefficient = 0.252 nun-I. Final residuals (884 parameters) R1 = 0.0799 for 13075 reflections with I> 2lJ(l), and R1 = 0.1 057, wR2 = 0.2317, GooF = 1.064 for all 27274 data. H13+-cr: (C37H39CIN304Sz)(C4H80)z, M = 278.17, triclinic, P-1, a = 12.050(4) A, b = 14.724(5) A, c = 14.751(5) A, a = 110.303(6)0,P = 110.984(6)°, y = 91.054(6)°, V= 2261.2(12) A3, Z = 2, Absorption coefficient = 0.225 mm- I . Final residuals (608 parameters) R1 = 0.0807 for 5298 reflections with I> 2lJ(l), andR1 = 0.1557, wR2 = 0.2477, GooF = 0.991 for all 10149 data. 14: C3sH37N303SZ, M= 611.80, triclinic, P-1, a = 9.5029(18) A, b = 12.881(2) A, c = 13.585(3) A, a = 79.321(3)°, P= 86.979(3)°, y = 88.986(3)°, V = 1631.8(5) A3, Z = 2, Absorption coefficient = 0.202 mm- I . Final residuals (467 parameters) R1 = 0.0484 for 7398 reflections with I> 2lJ(l), and R1 = 0.0552, wR2 = 0.1374, GooF = 1.047 for all 14264 data. 150 CHAPTER VII CONCLUDING REMARKS AND FUTURE PERSPECTIVES CONCLUDING REMARKS The new millennium has brought with it a rebirth of anionJarene chemistry. This dissertation has chronicled the early exploration of this field and reviewed the many paths that researchers have taken to understanding the interactions between anions and electron-deficient aromatic rings. Initial investigations in the Johnson laboratory have illustrated that it is possible to develop anion receptors capable of interacting with anions by way of electron-deficient aromatic rings. This initial research led to the detailed crystallographic and computational study of the preferred binding mode for halide anions interacting with electron-deficient aromatic rings. The importance of considering multiple binding modes in these systems was highlighted. The following tripodal anion receptors-bearing electron-deficient aromatic rings-showed that it is possible to develop anion receptors capable of attracting anions using only electron- deficient aromatic rings. Furthermore, very subtle changes in binding orientations can be observed by l H NMR in these systems. The development of intramolecular hydrogen bonding receptors and highly electron-deficient binding motifs were 151 presented in an effort to increase the strength of anion/arene interactions. Finally, in collaboration with the Haley lab (UO), a crystallographic expedition was presented higWighting a conformationally diverse series of conjugated receptor molecules that show a predilection to bind anions and small molecules. Despite the rich history of anion/arene interactions and the recent resurgence of interest in these attractive forces, there remain many complexities to be understood. FUTURE PERSPECTIVES In short, this dissertation has established the necessary foundation for critical evaluation of anion/arene interactions. One of the exciting prospects of anion/arene interacts is their potential to deviate from trends in traditional anion binding selectivities. In particular, by improving receptor design (conformationally rigid host molecules containing newly developed electron-deficient aromatic rings) it will be possible to evaluate selectivity trends for anions interacting with electron-deficient aromatic rings. Scheme 7.1 presents a representative example of improving our first generation receptor design by removing the conformational flexibility from the receptor. Initial progress has been made toward this receptor but clearly more synthetic work needs to be achieved before quantitative studies are undertaken. 152 Scheme 7.1 Synthesis of improved conformationally rigid sulfamide receptor will aid in understanding the selectivity of anionlarene interactions. I .JVVV F*FR= IF ~ F F R' =Soc Another exciting prospective receptor class is highlighted in chapter V. The phosphine and phosphine oxide based receptors need further evaluation to determine whether intramolecular hydrogen bonds are established in solution or the solid state. Additionally, conformationally locking these bowl shaped architectures will result in an exciting new class of molecules that enlist the function of inward directed functionality (Figure 7.1). 153 x=o CI8 R = protectln!=j qrOllP 1) NEt:} OMF 2) Deprolechon o R I - "3 0 - / ---( II \I:. . " (./ CINI~ o HN'lO (~ HO .. "'.., "OH X ~ 0 01 no atom FigUl'e 7.1 'Conformationally locked' bowl-shaped molecule with inward directed functionality. Molecular design is based off of the X-ray structure of 4 shown in Chapter V, Figure 5.3. Now that we have presented a keen understanding of binding modes available for anion/arene interactions we can begin to look into the role of solvent affects on anionlarene interactions. It has yet to be illustrated whether the energy of anion/arene interactions is solvent dependent and proof of this statement would surely interest current readers. Another hypothesis is that electron-deficient aromatic rings can be used to alter traditional reaction rates. For instance this hypothesis could be simply tested by adding the appropriate electron-deficient aromatic ring to a reaction involving a polar or anionic transition state. If the electron-deficient arene has a role in stabilizing the transition state then the corresponding reaction rate should be increased. Alternatively, this theory could be tested intramolecularly with the leaving group and the electron-deficient aromatic ring incorporated into the same receptor. The correct receptor design would position the 154 electron-deficient aromatic ring appropriately to stabilize the leaving group during the reaction. An example receptor design is provided in Figure 7.2. Figure 7.2 Example receptor exhibiting tethered electron-deficient aromatic ring and leaving group. The vast majority of solution, solid state and computational studies of anionlarene interactions have focused on monoatomic anions. Clearly, further studies must be done on larger biologically and environmentally relevant anions for the importance of this interaction to be fully understoocl. 155 APPENDIX A SUPPORTING INFORMATION FOR CHAPTER II: ANION-n INTERACTION AUGMENTS HALIDE BINDING IN SOLUTION EXPERIMENTAL GENERAL. Pyridine, d-chloroform and acetonitrile was dried over 3A molecular sieves. Tetra-n-butylammonium salts were dried under a vacuum at 50°C and stored in a desicator. All other materials were obtained from TCI-America, Sigma-Aldrich, Acros and Strem. Nuclear Magnetic Resonance IH NMR, BC NMR and 19F NMR spectra were recorded on a Varian INOVA 300 (299.935), 125 (125.751) and 282 (282.224) MHz spectrometer respectively. Chemical shifts (0) expressed as ppm downfield from tetramethylsilane using either the residual solvent peak as an internal standard (CDCh IH: 7.27 ppm) or using CDCh spiked with 1% trimethylsilane for the IH NMR spectra. For the BC NMR spectra the middle CDCh peak (Q 77.00 ppm) was used as the internal standard. For the 19F NMR spectra C6F6 (0 -164.9 ppm) was used as the internal standard Signal patterns are indicated as b, broad; s, singlet; d, doublet; t, triplet; m, multiplet. Coupling constants (J) are given in hertz. 156 Single-crystal X-ray diffraction data for compounds 1 and l'nBU4+·cr were collected on a Bruker-AXS SMART APEXlCCD diffractometer using MOka radiation (A = 0.7107 A) at 152 K. Diffracted data have been corrected for Lorentz and polarization effects, and for absorption using the SADABS v2.02 area-detector absorption correction program (Siemens Industrial Automation, Inc., © 1996). The structures were solved by direct methods and the structure solution and refinement was based on IFf. All non-hydrogen atoms were refined with anisotropic displacement parameters whereas hydrogen atoms were placed in calculated positions when possible and given isotropic Uvalues 1.2 times that of the atom to which they are bonded. Hydrogen atoms of the amino groups in 1 and l'nBU4+·cr were located via difference Fourier map inspection and refined with riding coordinates and isotropic thermal parameters based upon the corresponding N atoms [U(H) = 1.2Ueq (0)]. All crystallographic calculations were conducted with the SHELXTL v.6.1 program package (Bruker AXS Inc., © 2001). 2-p-toluenesulfonamide-2', 3', 4', 5', 6'-pentafluorobiphenyl (1). An oven dried 100 mL round bottom Schlenk flask was charged with N-(2-iodophenyl)-4- methylbenzenesulfonamide (3.68 g, 14.9 mmol), copper powder (4.77 g, 75.1 mmol) and tetrakistriphenylphosphine palladium (0) (0.860 g, 0.741 mmol). Dry dimethylsulfoxide (46 mL) was added via a syringe to the reaction mixture. The mixture was degassed purging with N2 (3 x) and then bromopentafluorobenzene (3.70 157 mL, 29.7 mmol) was added. The solution was again degassed and then was heated at 115-120oC for 5.5 h. under a N2 atmosphere. The reaction was cooled to room temperature and was diluted with DCM (50 mL) and water (50 mL). The resulting foamy mixture was then filtered through a glass frit containing celite and silica gel. The remaining celite/silica gel pad was washed with DCM (3 x 50 mL). The resulting pale green solution was transferred to a 150 mL separatory funnel and washed with water (3 x 100 mL) followed by brine (1 x 100 mL). The separated organic layer was dried over MgS04. Removal of the DCM in vacuo left a crude pale green solid that was later purified by flash column chromatography (silica gel, 3:1 hexanes: ethyl acetate) to yield a colorless product (1.64 g, 26.7% yield) that crystallized overnight upon standing in the column eluent. Structure was determined by single crystal X-ray diffraction. Single crystals suitable for data collection were grown by diffusing pentane into a chloroform solution of 1 at -30°C. IH NMR (300 MHz, CDC!]; 25°C): () 7.56 (d, J = 8.1 Hz, 1H, CH), 7.48 (t, J = 4.5 Hz, 1H, ArCH), 7.41 (d, J = 4.6 Hz, 2H, ArCH), 7.35 (t, J= 4.2 Hz, IH, ArCH), 7.17 (m, 3H, ArCH), 6.35 (b, IH, NH), 2.41 (s, 3H, CH3); 19F NMR (282 MHz, CDC!]; 25°C): () -191.51 (q, J= 16.2 Hz, 2F CF),- 205.54 (t, J= 22.2 Hz, IF, CF), -213.14 (m, 2F, CF). 13C NMR (125 MHz, CDC!]; 25°C): () 144.37, 144.45, 136.36, 134.57, 131.90, 131.04, 129.73, 127.39, 127.25, 127.04, 122.46,21.62,0.202. 158 N-biphenyl-2-yl-4-methyl-benzenesulfonamide (2). Similar to literature procedure,1 an oven dried 50 mL round bottom flask was charged with 2-aminobiphenyl (0.330 g, 2.00 mmol) and pyridine (7.5 mL). To this stirred solution p-toluenesulfonylchloride (0.570 g, 3.00 mmol) was added and stirred for 4 h. The resulting pale pink solution with white precipitate was concentrated down in vacuo and diluted with dichloromethane (50 mL) and water (50 mL). The organic layer was separated and washed with 3M HCI (3 x 50 mL) and 1M NaHC03 (3 x 50 mL). Removal ofthe organic layer in vacuo resulted in a pale pink solid that was later crystallized from an 8:1 mixture ofhexanes and dichloromethane. Crystallization yielded colorless crystals (0.56 g, 87%). The structure was determined by single crystal X-ray diffraction. Single crystals suitable for data collection were grown by diffusing pentane into a chloroform solution of2 at -30°C. IH NMR (300 MHz, CDC!); 25°C): 0 7.80 (d, J= 8.1 Hz,2H, ArCH), 7.72 (d, J = 8.1 Hz, 1H, ArCH), 7.48 (d, J= 8.7 Hz, 1H, ArCH), 7.35 (m, 4H, ArCH), 7.20 (d, J= 8.4 Hz, 2H, ArCH), 7.12 (m, 1H, ArCH), 6.86 (m, 2H, ArCH), 6.58 (b, 1H, NH), 2.41 (s, 3H, CH3). NMR TITRATION EXPERIMENTS GENERAL. IH NMR spectra were recorded on a Varian 300 or 500 MHz spectrometer. Each titration was performed with 8 to 14 measurements in CDC!) at room temperature. CDC!) was passed through activated alumina and dried over 3A molecular sieves. Aliquots from a stock solution oftetra-n-butylammonium salts (60- 159 200 mM) were added to the initial solution of receptor (9 - 25 mM). All additions were done through septa with a syringe to minimize evaporation. All proton signals were referenced to an internal TMS standard. The association constants Ka were calculated by the non-linear regression curve fitting program WinEQNMR Table A.I IH NMR Titration data for receptor I and TBACI trial 1 fromGuest Stock Additio Vol. Guest added n () ppm Iml) Total Vol. (ml) Rl Gl 0 6.2480 0 0.6 9.677E-03 O.OOOE+OO 1 6.3005 0.01 0.61 9.518E-03 1.039E-03 2 6.3483 0.02 0.62 9.365E-03 2.044E-03 3 6.3937 0.03 0.63 9.216E-03 3.017E-03 4 6.4360 0.04 0.64 9.072E-03 3.960E-03 5 6.5128 0.06 0.66 8.797E-03 5.760E-03 6 6.5816 0.08 0.68 8.538E-03 7.455E-03 7 6.6474 0.1 0.7 8.294E-03 9.052E-03 8 6.7038 0.12 0.72 8.064E-03 1.056E-02 9 6.7789 0.15 0.75 7.74'1 E-03 1.267E-02 10 6.8479 0.18 0.78 7.444E-03 1.462E-02 11 6.9067 0.21 0.81 7.168E-03 1.643E-02 12 6.9735 0.25 0.85 6.831 E-03 1.864E-02 13 7.0401 0.3 0.9 6.451E-03 2.112E-02 14 7.1055 0.35 0.95 6.112E-03 2.334E-02 initial vol. (G) 0.6 Guest Stock Receptor Stock (M) (M) 0.009676678 0.063363558 mol Receptor 9.67668E-06 TBACI MW Receptor 2 MW 277.92 413.365 Mol Guest 0.00012672 7 •• 0 7.6 K1 = 24.1 +/- 0.8 7.' 160 6 .• 6.4 6.0 0.0 6 .• 10.4 1.5.6 20.6 26.0 Measured Che.i~al shifes fat: e. 1: 1 coaplex [0075] Graph A.I Binding isotherm from receptor I titration with TBACI trial 1 Table A.2 lH NMR Titration data for receptor 1 and TBACI trial 2 161 from Guest Stock Additio Vol. Guest added n () ppm I'mI) Total Vol. (ml) IrRl Gl 0 6.2414 0 0.6 9.822E-03 O.OOOE+OO 1 6.2950 0.01 0.61 9.661E-03 9.874E-04 2 6.3465 0.02 0.62 9.505E-03 1.943E-03 3 6.3969 0.03 0.63 9.354E-03 2.868E-03 4 6.4392 0.04 0.64 9.208E-03 3.765E-03 5 6.5203 0.06 0.66 8.929E-03 5.476E-03 6 6.5929 0.08 0.68 8.666E-03 7.086E-03 7 6.6544 0.1 0.7 8.419E-03 8.605E-03 8 6.7396 0.13 0.73 8.073E-03 1.073E-02 9 6.8080 0.16 0.76 7.754E-03 1.268E-02 10 6.8934 0.2 0.8 7.366E-03 1.506E-02 11 6.9692 0.25 0.85 6.933E-03 1.772E-02 12 7.0955 0.35 0.95 6.203E-03 2.219E-02 initial vol. mol Guest I(R) Receptor Stock (M) Guest Stock (M) G) 0.6 0.009821828 0.060233161 0.000120466 mol Receptor 9.82183E-06 TBACI MW Receptor 2 MW 277.92 413.365 ·4.0 I & '" · ·::l -4_0 7.2 162 7.0 6." 6.6 6.2 0.0 "." '.6 14-4 19.2 24.0 lOH3[Conc:entration]/aol dm-3 Heasux:ed Cheaic:al shifts fO:t a 1: 1 c:oaple)( [0105] Graph A.2 Binding isotherm from receptor 1 titration with TBACI trial 2 Table A.3 IH NMR Titration data for receptor 1 + TBACI trial 3 from Guest Stock Addition oppm Vol. Guest added (ml Total Vol. (ml) R] G] o 6.2463 0 0.6 1.040E-02 O.OOOE+OO 1 6.3003 0.01 0.61 1.023E-02 1.051E-03 2 6.3488 0.02 0.62 1.007E-02 2.069E-03 3 6.3962 0.03 0.63 9.907E-03 3.054E-03 4 6.4799 0.05 0.65 9.602E-03 4.934E-03 5 6.5543 0.07 0.67 9.316E-03 6.701 E-03 6 6.6207 0.09 0.69 9.046E-03 8.366E-03 7 6.6811 0.11 0.71 8.791 E-03 9.937E-03 8 6.7608 0.14 0.74 8.434E-03 1.213E-02 9 6.8279 0.17 0.77 8.106E-03 1.416E-02 10 6.9045 0.21 0.81 7.706E-03 1.663E-02 11 6.9863 0.26 0.86 7.258E-03 1.939E-02 12 7.1104 0.36 0.96 6.502E-03 2.405E-02 initial vol. Receptor Stock Guest Stock mol Guest I'R) 'M) I'M) IIG) 0.6 0.010402429 0.064137162 0.000128274 mol Receptor 1.04024E-05 TBACI MW Receptor 2 MW 277.92 413.365 163 164 &24.0 1 ~ ~ : ---....:>.,""',...-----------<-~---~-----...--~--::::"'~==:~=-,--------=-='''-'------------=""'--~~=----- ::: -240 -------------------------------------- '.2 '.0 6." 6.6 6.4 6.2 0.0 6.2 10.4 15.6 2.0.8 Measured Chemical shifts for:: fL 1:1 coapleH [0113] Graph A.3 Binding isothenn from receptor 1 titration with TBACI trial 3 Table A.4 IH NMR Titration data for receptor 1 + TBABr trial 1 165 from Guest Stock Vol. Guest added Addition 8 ppm (ml) Total Vol. (ml) [R] [G] 0 6.358 0 0.6 2.035E-02 O.OOOE+OO 1 6.359 0.01 0.61 2.001 E-02 3.260E-03 2 6.453 0.03 0.63 1.938E-02 9.470E-03 3 6.53 0.05 0.65 1.878E-02 1.530E-02 4 6.593 0.07 0.67 1.822E-02 2.078E-02 5 6.67 0.1 0.7 1.744E-02 2.841E-02 6 6.736 0.13 0.73 1.672E-02 3.541E-02 7 6.785 0.16 0.76 1.606E-02 4.187E-02 8 6.847 0.2 0.8 1.526E-02 4.972E-02 9 6.91 0.25 0.85 1.436E-02 5.849E-02 10 7.019 0.35 0.95 1.285E-02 7.327E-02 11 7.086 0.45 1.05 1.163E-02 8.523E-02 initial vol. Guest Stock (G) Receptor Stock (M) (M) mol Guest 0.0003977 0.6 0.020345215 0.198867778 4 mol Receptor 2.03E-05 TBABrMW 322.375 Receptor MW 413.365 7.' 166 7.0 G." G.G G.O G.Z 0.0 I." 3.6 5.4 7.Z 9.0 lO"''''Z[Conc.ent.J:at.ion]/_ol d:a-3 KeasW:9d Cheaical shifts for a 1:1 coaplex (0056] Graph A.4 Binding isotherm from receptor 1 titration with TBABr trial 1 -16.0 Table A.5 lH NMR Titration data for receptor 1 + TBABr trial 2 from Guest Stock Addition 8 ppm Vol. Guest added (ml\ Total Vol. (m!) R] G] 0 6.284 0 0.6 0.01982719 0 1 6.315 0.01 0.61 0.019502154 0.001980689 2 6.327 0.02 0.62 0.019187603 0.003897485 3 6.346 0.04 0.64 0.018587991 0.007551377 4 6.365 0.06 0.66 0.018024718 0.01098382 5 6.389 0.09 0.69 0.017241035 0.015759394 6 6.409 0.12 0.72 0.016522658 0.020137004 7 6.431 0.16 0.76 0.015653045 0.025436216 8 6.45 0.21 0.81 0.014686807 0.031324228 9 6.477 0.31 0.91 0.013072872 0.041159151 initial vol. Receptor Stock IrR) IrM) Guest Stock (M) mol Guest 0.6 1.98E-02 0.120822024 0.000241644 mol Receptor 1.98E-05 TBABrMW Receptor MW 322.375 413.365 16.0 I'~~' 7.0 167 6 .• 6.6 6.' 6.2 6.0 0.0 l.0 lO"''''ZrConcentJ:ati.on]/aol dIll-3 '.0 '.0 '.0 H'eesuJ:ed Ch••icIIlL shift.s foz: I!Il L: l co.pl.x [0104] Graph A.5 Binding isotherm from receptor 1 titration with TBABr trial 2 Table A.6 IH NMR Titration data for receptor 1 + TBABr trial 3 from Guest Stock Addition 8 ppm Vol. Guest added (ml\ Total Vol. (ml) R Gl 0 6.297 0 0.6 2.032E-02 0 1 6.299 0.01 0.61 1.999E-02 0.001977638 2 6.366 0.02 0.62 1.967E-02 0.003891481 3 6.398 0.03 0.63 1.935E-02 0.005744567 4 6.452 0.05 0.65 1.876E-02 0.009279685 5 6.497 0.07 0.67 1.820E-02 0.012603751 6 6.557 0.1 0.7 1.742E-02 0.017233701 7 6.606 0.13 0.73 1.670E-02 0.021483106 8 6.659 0.17 0.77 1.583E-02 0.026633901 9 6.710 0.22 0.82 1.487E-02 0.032365731 10 6.793 0.32 0.92 1.325E-02 0.041960315 initial vol. Receptor Stock Guest Stock IR) 1M) 1M) mol Guest 0.6 2.03E-02 0.120635905 0.000241272 mol Receptor 2.03E-05 TBABrMW Receptor MW 322.375 413.365 168 ... 169 •• ? 6.6 6.5 6.4 •. 3 0.0 1.0 <.0 lO....2[Con~lIntr:at1on]/.ol da-3 3.0 4.0 5.0 Pleasul:Qd ChQllli~al shifes tor a. 1:.1 co~lll)( (01015) Graph A.6 Binding isotherm from receptor 1 titration with TBABr trial 3 Table A.7 IH NMR titration data for receptor 1 + TBAI trial 1 170 from Guest Stock Vol. Guest added Add. 8ppm 1m!) Total Vol. (m!) Rl Gl 0 6.295 0 0.6 0.01911143 O.OOOOE+OO 1 6.309 0.01 0.61 0.01879813 1.9872E-03 2 6.329 0.03 0.63 0.01820137 5.7724E-03 3 6.356 0.06 0.66 0.01737403 1.1020E-02 4 6.377 0.09 0.69 0.01661864 1.5811 E-02 5 6.392 0.12 0.72 0.01592619 2.0203E-02 6 6.405 0.15 0.75 0.01528915 2.4244E-02 7 6.42 0.19 0.79 0.01451501 2.9154E-02 8 6.435 0.24 0.84 0.01365102 3.4634E-02 9 6.445 0.28 0.88 0.01303052 3.8570E-02 10 6.457 0.35 0.93 0.01232996 4.5620E-02 initial vol. Guest Stock IG) Receptor Stock (M) 11M) mol Guest 0.6 0.019111439 0.121219915 0.00024244 mol Receptor 1.91114E-05 TBAI MW Receptor MW 369.37 413.365 6.5 171 6" 6.4 6.4 6.3 6.3 0.0 1.0 2.0 3.0 4.0 5.0 lO...... ZCConcentra.tion]/.ol da-3 Measured Ch&lILic:a.l lIhiftS' for a. 1: 1 coaplex [0067] Graph A.7 Binding isotherm from receptor 1 titration with TBAI trial 1 Table A.8 IH NMR titration data for receptor 1 + THAI trial 2 172 from Guest Stock Vol. Guest added Addition oppm (ml) Total Vol. (ml) [R] [G] 0 6.303 0 0.6 2.032E-02 O.OOOE+OO 1 6.318 0.01 0.61 1.999E-02 1.934E-03 2 6.336 0.03 0.63 1.935E-02 5.616E-03 3 6.361 0.06 0.66 1.847E-02 1.072E-02 4 6.378 0.09 0.69 1.767E-02 1.538E-02 5 6.393 0.12 0.72 1.693E-02 1.966E-02 6 6.404 0.15 0.75 1.626E-02 2.359E-02 7 6.417 0.19 0.79 1.543E-02 2.837E-02 8 6.431 0.24 0.84 1.452E-02 3.370E-02 9 6.442 0.28 0.88 1.386E-02 3.753E-02 initial vol. Guest Stock (G) Receptor Stock (M) (M) mol Guest 0.0002358 0.6 0.020321024 0.117944067 9 mol Receptor 1.22E-05 TBAI MW 369.37 Receptor MW 413.365 6.5 173 6.5 6.4 6.4 6.3 6.3 0.0 K1 =30 +/- 6 0." 1.6 '.4 3.2 4.0 lO·*Z[Concentration]/liol da-3 H'e8.suE:ed Chuicel shifts fo!: a l~l complex [0062] Graph A.8 Binding isotherm from receptor 1 titration with TBAI trial 2 Table A.9 IH NMR titration data for receptor 1 + TBAI trial 3 from Guest Stock Addition 8 ppm Vol. Guest added (m!' Total Vol. (ml) R] G] 0 6.293 0 0.6 0.019498506 O.OOOOE+OO 1 6.306 0.01 0.61 0.019178859 1.9675E-03 2 6.326 0.03 0.63 0.018570006 5.7150E-03 3 6.344 0.05 0.65 0.017998621 9.2319E-03 4 6.364 0.08 0.68 0.017204564 1.4119E-02 5 6.379 0.11 0.71 0.016477611 1.8594E-02 6 6.395 0.14 0.74 0.0158096 2.2706E-02 7 6.41 0.18 0.78 0.014998851 2.7696E-02 8 6.421 0.23 0.83 0.014095306 3.3257E-02 9 6.442 0.28 0.88 0.013294436 3.8187E-02 initial vol. Receptor Stock Guest Stock IrG) I(M) M) mol Guest 0.6 0.019498506 0.120015161 0.00024003 mol Receptor 1.94985E-05 TBAI MW Receptor MW 369.37 413.365 S.o -s.o 6.S 174 6. S 6" 6 .. 6.3 K1 = 27 +/- 6 lO**Z[ ConcentEac1on]J.ol d:a-3 ReaSUEed Ch.-.:i~a.l shift. COE: a. 1:1 COllple~ (0107] Graph A.9 Binding isotherm from receptor 1 titration with TBAI trial 3 175 pKa DETERMINATION GENERAL. The pKa measurements were made with an Orion model 230Aplus pH meter equipped with a Triode 9107BN pH electrode. The pH meter was calibrated with 1:1 stock solutions ofacetonitrile/water buffered at 7.00 and 10.00 pH. The electrode was allowed to soak in acetonitrile for 2 hours prior to any measurements. Initial receptor concentrations were made to 10-3 M in acetonitrile and 0.06 g tetra-n- butylammonium iodide was added as a supporting electrolyte. A stock solution of tetramethylammonium hydroxide in ethanol 0.05 M (to avoid precipitation) was prepared under nitrogen. Aliquots of the stock tetramethylammonium hydroxide were added to the receptor solution under nitrogen and the resulting potential was measured. Titration curves were prepared by plotting the potential vs the total amount of stock tetramethylammonium hydroxide added. The relative pKa was taken as the pH at the half-neutralization potential. Table A.10 pKa determination for receptor 1 trial 1 Addition Total Added pH RelmV 0 0 7.97 -99.6 1 50 8.51 -135.5 2 100 8.76 -150.7 3 150 8.89 -158.7 4 200 9 -165.8 5 250 9.09 -171.3 6 300 9.17 -176 7 350 9.24 -180.3 8 400 9.3 -183.9 9 450 9.36 -187.6 10 500 9.41 -190.8 11 750 9.66 -206.2 12 800 9.74 -210.7 13 850 9.84 -216.9 14 900 9.92 -221.6 15 950 10 -226.9 16 1000 10.09 -232.5 17 1050 10.18 -237.7 18 1100 10.45 -255.4 19 1150 10.8 -278.3 20 1200 13.45 -442.5 21 1250 13.85 -468.9 22 1300 14.26 -493.5 23 1400 14.47 -507.7 24 1600 14.98 -540.3 25 1900 15.36 -564.1 HNP = -380 mV = pH 13.3 176 177 20001500 I pKa determination of receptor 1 I 0 ,------------,--------.-------- 500 1000 -100 • ••• -200 •••••• §. 'iii -300 :;::; c .Sl 0 a.. -400 -500 •••• ••• • • • • • • • • -600 I Total Vol. added (J!L)L- _ Graph A.10 pKa titration of receptor 1 trial I Table A.11 pKa determination for receptor 1 trial 2 Addition Total Added pH RelmV 0 0 8.15 -101 1 30 9.39 -177.2 2 60 9.8 -202.6 3 90 10.19 -227.4 4 105 10.5 -246.5 5 115 10.88 -270.8 6 120 11.48 -308.6 7 125 13.52 -436.5 8 130 15.02 -532.3 9 140 17.46 -678 10 150 17.84 -711.3 11 165 18.18 -733.3 12 195 18.49 -753.7 13 245 18.67 -766.3 14 295 18.73 -769.8 15 345 18.72 -770.6 HNP =-505 mV =pH 14.2 pKa determination of receptor 1 0 . . 50 100 150 200 250 300 350 400 -100 -200 • • •• • -300 • V -400 r •-500 P • ~ -600 -700 • •• • • • •-800 -900 Total Vol. added (DL) Graph A.ll pKa titration of receptor 1 trial 2 178 Table A.12 pKa determination for receptor 2 trial 1 Addition Total Added pH RelmV 0 0 8.56 -127.4 1 30 10.83 -268.2 2 40 10.97 -278 3 50 11.09 -286.2 4 55 11.15 -290.4 5 65 11.25 -297.6 6 75 11.35 -304.4 7 85 11.45 -311.4 8 100 11.62 -322.2 9 110 11.76 -331.9 10 120 11.95 -344.3 11 125 12.07 -352 12 130 12.27 -364.8 13 135 12.61 -386.8 14 140 13.17 -422.5 15 145 13.95 -472.8 16 150 14.5 -508.2 17 155 15.25 -556.6 18 160 16.36 -580.7 19 170 17.07 -666.8 20 180 17.6 -700 21 190 17.83 -720 22 200 17.93 -726 23 220 18.04 -736.8 24 250 18.22 -747.5 25 300 18.35 -755.8 26 350 18.39 -757.7 27 400 18.39 -757.7 HNP =-540 mV =pH 15.1 179 pKa determination of receptor 2 180 -160 100 200 300 400 500 -260 •.-. •• •• -360 '. •V •r -460 • ~ • P -560 • • -660 • • •• • -760 • • • • Total Vol. added (+L) Graph A.12 pKa titration of receptor 2 trial 1 Table A.13 pKa determination for receptor 2 trial 2 0 0 9.7 -201.8 1 20 10.76 -266.9 2 40 11.06 -285.7 3 60 11.28 -299.7 4 80 11.47 -312.2 5 100 11.68 -325.9 6 120 11.95 -343.6 7 130 12.16 -359.4 8 140 12.57 -385.3 9 150 13.65 -452.4 10 155 14.57 -510.2 11 160 16.3 -624 12 165 16.81 -652 13 170 17.12 -670.2 14 175 17.4 687.5 15 185 17.75 710.1 16 195 17.96 -724.3 17 215 18.15 -736.2 18 245 18.29 -745.5 19 295 18.38 -751.5 20 345 18.42 -753.8 HNP = -550 mV = pH 14.7 181 pKa determination of receptor 2 -160 50 100 150 200 250 300 350 400 ~ -260 • • • • + -360 +. •V i -460 •+-560 - ., -660 •• • • -760 • • • Total Vol. added (OL) Graph A.13 pKa titration of receptor 2 trial 2 REFERENCE 182 1 Sakamoto, T.; Kondo, Y.; Iwashita, S.; Nagano, T.; Yamanaka, H. Chem. Pharm. Bull. 1988, 36, 1305-1308. 183 APPENDIXB SUPPORTING INFORMATION FOR CHAPTER III: STRUCTURAL CRITERIA FOR THE DESIGN OF ANION RECEPTORS: THE INTERACTION OF HALIDES WITH ELECTRON-DEFICIENT ARENES CARTESIAN COORDINATES AND ABSOLUTE ENERGIES FOR OPTIMIZED STRUCTURES 1-13 AT THE MP2/aug-cc-pVDZ LEVEL OF THEORY 1, TETRACYANO-FLUORIDE ANION. -699.3309466394 a.u. (-81.9; -62.4 em-I) C -0.70843 -1.21592 -0.21924 C -1.41053 0.00000 -0.20599 C -1.43917 -2.45539 -0.23382 H -2.50222 0.00000 -0.17584 N -2.05830 -3.47195 -0.27329 F 0.00000 0.00000 2.18602 C 0.70843 1.21592 -0.21924 C -0.70843 1.21592 -0.21924 C 0.70843 -1.21592 -0.21924 C 1.41053 0.00000 -0.20599 C 1.43917 2.45539 -0.23382 C -1.43917 2.45539 -0.23382 C 1.43917 -2.45539 -0.23382 H 2.50222 0.00000 -0.17584 N 2.05830 3.47195 -0.27329 N -2.05830 3.47195 -0.27329 N 2.05830 -3.47195 -0.27329 1, TETRACYANO-CHLORIDEANION. -1059.3766931185 a.u. (-26.9 em-I) C -0.70890 -1.21697 -0.46715 C -1.41134 0.00000 -0.45187 C -0.70890 1.21697 -0.46715 C 0.70890 1.21697 -0.46715 C 1.41134 0.00000 -0.45187 C 0.70890 -1.21697 -0.46715 C -1.43876 -2.45721 -0.48010 H -2.50276 0.00000 -0.41464 C -1.43876 2.45721 -0.48010 C 1.43876 2.45721 -0.48010 H 2.50276 0.00000 -0.41464 C 1.43876 -2.45721 -0.48010 N -2.05549 -3.47476 -0.52632 N 2.05549 -3.47476 -0.52632 N -2.05549 3.47476 -0.52632 N 2.05549 3.47476 -0.52632 Cl 0.00000 0.00000 2.50012 1, TETRACYANO-BROMIDEANION. -3172.2621916160 a.u. (-20.1 em-I) C -1.21729 0.70902 -0.91052 C 0.00000 1.41148 -0.89382 C -2.45759 1.43865 -0.92389 H 0.00000 2.50288 -0.85566 N -3.47552 2.05464 -0.97155 Br 0.00000 0.00000 2.21709 C 1.21729 -0.70902 -0.91052 C -1.21729 -0.70902 -0.91052 C 1.21729 0.70902 -0.91052 C 0.00000 -1.41148 -0.89382 C 2.45759 -1.43865 -0.92389 C -2.45759 -1.43865 -0.92389 C 2.45759 1.43865 -0.92389 H 0.00000 -2.50288 -0.85566 N 3.47552 -2.05464 -0.97155 N -3.47552 -2.05464 -0.97155 N 3.47552 2.05464 -0.97155 2, TETRACYANO-FLUORIDE ANION. -699.3614274043 a.u. C 0.86447 -0.09673 -1.20986 C 1.56067 -0.31110 0.00000 C 0.86447 -0.09673 1.20986 C -0.52385 0.17733 1.21626 C -1.32733 -0.06252 0.00000 C -0.52385 0.17733 -1.21626 C 1.60874 -0.07791 -2.44285 H 2.62957 -0.53206 0.00000 C 1.60874 -0.07791 2.44285 C -1.19632 0.58573 2.41005 H -2.27659 0.48946 0.00000 C -1.19632 0.58573 -2.41005 N 2.24413 -0.07006 -3.45191 N -1.78641 0.94176 -3.38481 N 2.24413 -0.07006 3.45191 184 N F -1.78641 -1.79054 0.94176 -1.49009 3.38481 0.00000 185 2, TETRACYANO-CHLORIDE ANION. -1059.3790281928 a.li. C 1.07877 0.03170 -1.21762 C 1.72198 0.33145 0.00000 C 1.07877 0.03170 1.21762 C -0.22974 -0.51386 1.21830 C -0.92672 -0.69328 0.00000 C -0.22974 -0.51386 -1.21830 C 1.77549 0.27039 -2.45508 H 2.72555 0.76308 0.00000 C 1.77549 0.27039 2.45508 C -0.87283 -0.84699 2.46018 H -1.91933 -1.14085 0.00000 C -0.87283 -0.84699 -2.46018 N 2.38100 0.46360 -3.46271 N -1.37731 -1.16688 -3.49063 N 2.38100 0.46360 3.46271 N -1.37731 -1.16688 3.49063 Cl -2.27641 1.53200 0.00000 2, TETRACYANO-BROMIDE ANION. -3172.2637577693 a.li. C -1.48027 0.15209 1.21812 C -2.02462 0.60588 0.00000 C -1.48027 0.15209 -1.21812 C -0.35328 -0.70793 -1.21890 C 0.26891 -1.06297 0.00000 C -0.35328 -0.70793 1.21890 C -2.09287 0.56087 2.45550 H -2.88409 1.28029 0.00000 C -2.09287 0.56087 -2.45550 C 0.18637 -1.19149 -2.46056 H 1.12851 -1.73207 0.00000 C 0.18637 -1.19149 2.46056 N -2.62961 0.90050 3.46330 N 0.59377 -1.62813 3.49117 N -2.62961 0.90050 -3.46330 N 0.59377 -1.62813 -3.49117 Br 2.23011 0.91913 0.00000 3, TETRACYANO-FLUORIDE ANION. -699.3521595236 a.li. C -0.61766 1.16203 0.13783 C -1.31440 -0.07872 -0.19364 C -0.65790 -1.31304 -0.13947 C 0.75411 -1.39791 0.03852 C 1.48363 -0.19228 0.05715 C 0.84104 1.05063 -0.00022 C -1.20788 2.34685 -0.51233 H -2.38726 -0.04285 -0.39871 C -1.43140 -2.51412 -0.33543 C 1.43150 -2.66047 0.09305 H 2.57736 -0.22313 0.07506 C 1.62980 2.24810 -0.08222 N N N N F -1.69281 2.29878 -2.08174 2.01140 -0.93297 3.27178 3.23092 -3.49960 -3.70044 1.50100 -1.08207 -0.16252 -0.49737 0.14318 1.64296 186 3, TETRACYANO-CHLORIDEANION. -1059.3779531793 a.u. C 0.24838 1.00415 0.55978 C 1.06596 -0.13649 0.73022 C 0.57533 -1.41156 0.41597 C -0.75761 -1.56628 -0.06607 C -1.59437 -0.44052 -0.17007 C -1.11157 0.83363 0.17949 C 0.70970 2.28475 1.03427 H 2.09924 -0.01025 1.05934 C 1.42341 -2.56347 0.57818 C -1.26799 -2.86732 -0.40738 H -2.62449 -0.55709 -0.51603 C -1.99499 1.96570 0.09413 N 1.03749 3.30327 1.55802 N -2.76639 2.87179 0.04616 N 2.11971 -3.51769 0.73205 N -1.70972 -3.93869 -0.68335 Cl 1.39006 1.51096 -1.80345 4, TETRACYANO-FLUORIDEANION. -699.3487321985 a.u. C 1.21282 0.00000 -1.09941 C 0.00000 0.00000 -1.81358 C -1.21282 0.00000 -1.09941 C -1.19026 0.00000 0.32990 C 0.00000 0.00000 1.10902 C 1.19026 0.00000 0.32990 C 2.45048 0.00000 -1.83834 H 0.00000 0.00000 -2.90677 C -2.45048 0.00000 -1.83834 C -2.47307 0.00000 1.00498 H 0.00000 0.00000 2.66098 C 2.47307 0.00000 1.00498 N 3.45935 0.00000 -2.47266 N 3.54811 0.00000 1.51728 N -3.45935 0.00000 -2.47266 N -3.54811 0.00000 1.51728 F 0.00000 0.00000 3.69945 4, TETRACYANO-CHLORIDEANION. -1059.3745631877 a.u. C 0.00000 -1.21706 -1.40589 C 0.00000 0.00000 -2.11354 C 0.00000 1.21706 -1.40589 C 0.00000 1.21208 0.01862 C 0.00000 0.00000 0.74016 C 0.00000 -1.21208 0.01862 C 0.00000 -2.45293 -2.14754 H 0.00000 0.00000 -3.20642 C 0.00000 2.45293 -2.14754 C 0.00000 2.48092 0.70701 H 0.00000 0.00000 1.86730 C 0.00000 -2.48092 0.70701 N 0.00000 -3.45420 -2.79229 N 0.00000 -3.57333 1.18052 N 0.00000 3.45420 -2.79229 N 0.00000 3.57333 1.18052 Cl 0.00000 0.00000 3.89116 4, TETRACYANO-BROMIDE ANION. -3172.2584167556 a.u. C 0.00000 -1.21743 -2.01870 C 0.00000 0.00000 -2.72576 C 0.00000 1.21743 -2.01870 C 0.00000 1.21322 -0.59442 C 0.00000 0.00000 0.12390 C 0.00000 -1.21322 -0.59442 C 0.00000 -2.45327 -2.76026 H 0.00000 0.00000 -3.81863 C 0.00000 2.45327 -2.76026 C 0.00000 2.48132 0.09459 H 0.00000 0.00000 1.24304 C 0.00000 -2.48132 0.09459 N 0.00000 -3.45419 -3.40548 N 0.00000 -3.57493 0.56554 N 0.00000 3.45419 -3.40548 N 0.00000 3.57493 0.56554 Br 0.00000 0.00000 3.44846 5, TRICYANO-FLUORIDEANION. -607.3049199007 a.u. (-65.3; -65.3 em'l) C -1.39585 -0.03206 0.25636 C -0.67858 -1.24028 0.25873 C -2.83959 -0.06522 0.26349 H -1.20256 -2.19795 0.22911 N -4.02808 -0.09225 0.29872 F -0.00000 0.00000 -2.21789 C 0.72568 -1.19281 0.25636 C 0.67016 1.22487 0.25636 C 1.41340 0.03247 0.25873 C -0.73482 1.20781 0.25873 C 1.47628 -2.42655 0.26349 C 1.36331 2.49177 0.26349 H 2.50476 0.05753 0.22911 H -1.30220 2.14042 0.22911 N 2.09393 -3.44230 0.29872 N 1.93415 3.53454 0.29872 5, TRICYANO-CHLORIDE ANION. -967.3532302847 a.u. (-14,0; -14.0 em'l) C -1.40820 0.13617 -0.53119 C -0.57908 1.27204 -0.52997 C -1.17819 2.58614 -0.53652 H -2.49461 0.24115 -0.49813 N -1.67188 3.66711 -0.57980 Cl 0.00000 0.00000 2.50722 C 0.58617 -1.28763 -0.53119 187 C 0.82203 1.15145 -0.53119 C -0.81207 -1.13752 -0.52997 C 1.39116 -0.13452 -0.52997 C -1.65057 -2.31341 -0.53652 C 2.82875 -0.27273 -0.53652 H 1.03846 -2.28097 -0.49813 H 1.45615 2.03982 -0.49813 N -2.33987 -3.28144 -0.57980 N 4.01175 -0.38566 -0.57980 5, TRICYANO-BROMIDE ANION. -3080.2392284262 a.u. C 0.97527 1.02520 -0.94149 C 1.35903 -0.32803 -0.94041 C 2.76286 -0.66687 -0.94781 H 1.72755 1.81599 -0.90894 N 3.91800 -0.94569 -0.99274 Br 0.00000 -0.00000 2.25694 C -1.37548 0.33201 -0.94149 C 0.40021 -1.35721 -0.94149 C -0.39543 1.34097 -0.94041 C -0.96360 -1.01294 -0.94041 C -0.80390 2.72615 -0.94781 C -1.95896 -2.05927 -0.94781 H -2.43647 0.58811 -0.90894 H 0.70892 -2.40410 -0.90894 N -1.14001 3.86593 -0.99274 N -2.77799 -2.92025 -0.99274 6, TRICYANO-FLUORIDE ANION. -607.3345811788 a.u. C 0.21537 0.47631 1.22244 C 0.02308 -0.90605 1.21822 C -0.14211 -1.61094 0.00000 C 0.02308 -0.90605 -1.21822 C 0.21537 0.47631 -1.22244 C 0.01050 1.28902 0.00000 C -0.33299 -3.03186 0.00000 C 0.51968 1.15738 2.44707 H 0.06173 -1.45683 2.16401 H 0.06173 -1.45683 -2.16401 C 0.51968 1.15738 -2.44707 H 0.58428 2.22657 0.00000 N 0.78920 1.73510 3.45536 N 0.78920 1.73510 -3.45536 N -0.49391 -4.21370 0.00000 F -1.39846 1.80349 0.00000 6, TRICYANO-CHLORIDEANION. -967.3551621007 a.u. C 1.20097 0.30555 0.52102 C 1.23840 -1.06860 0.22316 C 0.02470 -1.76524 0.05198 C -1.21189 -1.10704 0.21095 C -1.22056 0.26756 0.50897 C -0.02155 1.00524 0.61282 C 0.04835 -3.17628 -0.25164 188 189 C 2.44482 1.01038 0.72158 H 2.19490 -1.58678 0.11943 H -2.15059 -1.65495 0.09778 C -2.48784 0.93300 0.69702 H -0.03940 2.06779 0.84858 N 3.48381 1.54769 0.93647 N -3.54526 1.43742 0.90145 N 0.06782 -4.34203 -0.48930 CI -0.02678 2.13884 -1.86844 6, TRICYANO-BROMIDE ANION. -3080.2403988245 a.u. C 0.78572 0.31724 -1.21154 C 0.11898 1.55560 -1.22583 C -0.22796 2.15965 0.00000 C 0.11898 1.55560 1.22583 C 0.78572 0.31724 1.21154 C 1.07995 -0.34398 0.00000 C -0.91037 3.43182 0.00000 C 1.16223 -0.28860 -2.46658 H -0.13400 2.03771 -2.17323 H -0.13400 2.03771 2.17323 C 1.16223 -0.28860 2.46658 H 1.58973 -1.30633 0.00000 N 1.50950 -0.73266 -3.51381 N 1.50950 -0.73266 3.51381 N -1.46000 4.48712 0.00000 Br -1.16930 -2.18052 0.00000 7, TRICYANO-FLUORIDEANION. -607.3193609577 a.u. C -0.01112 -1.25677 -0.05443 C 1.21564 -0.51893 -0.18535 C 1.21409 0.88363 -0.07260 C 0.01291 1.62432 0.01929 C -1.20073 0.90365 -0.06775 C -1.22599 -0.49868 -0.18044 C 2.47098 1.59221 -0.09625 C -0.02347 -2.60868 -0.60503 H 2.15896 -1.06001 -0.29333 H 0.02210 2.71349 0.09745 C -2.44579 1.63298 -0.08635 H -2.17859 -1.02405 -0.28459 N -0.03375 -3.67719 -1.12864 N -3.46854 2.24366 -0.10557 N 3.50363 2.18585 -0.11962 F -0.01264 -1.85118 1.63476 7, TRICYANO-CHLORIDE ANION. -967.3537734340 a.u. (-14.64 em-I) C -0.00703 -0.98129 -0.66243 C 1.22223 -0.30335 -0.53519 C 1.21477 1.06337 -0.20483 C 0.00620 1.76737 -0.02485 C -1.20902 1.07470 -0.20285 C -1.22965 -0.29188 -0.53403 C 2.46695 1.76901 -0.05691 C -0.01393 -2.36635 -1.07495 H 2.16218 -0.84943 -0.63336 H 0.01134 2.82689 0.24124 C -2.45444 1.79181 -0.05298 H -2.17491 -0.82884 -0.63184 N -0.02037 -3.45542 -1.55248 N -3.47302 2.39749 0.05091 N 3.49100 2.36570 0.04517 CI 0.00783 -1.86801 2.03245 8, TRICYANO-FLUORIDEANION. -607.3214706194 a.u. C 0.00000 1.19185 -0.28526 C 0.00000 1.22166 1.12901 C 0.00000 0.00000 1.82998 C 0.00000 -1.22166 1.12901 C 0.00000 -1.19185 -0.28526 C 0.00000 0.00000 -1.05401 C 0.00000 0.00000 3.27486 C 0.00000 2.48125 -0.95429 H 0.00000 2.17123 1.67255 H 0.00000 -2.17123 1.67255 C 0.00000 -2.48125 -0.95429 H 0.00000 0.00000 -2.33954 N 0.00000 3.57621 -1.41841 N 0.00000 -3.57621 -1.41841 N 0.00000 0.00000 4.46455 F 0.00000 0.00000 -3.58119 8, TRICYANO-CHLORIDEANION. -967.3534364159 a.u. C -1.19919 -0.10068 -0.00619 C -1.23842 -1.51264 -0.00043 C -0.02449 -2.22743 0.00258 C 1.20994 -1.54865 -0.00007 C 1.21222 -0.13614 -0.00583 C 0.01730 0.61492 -0.00900 C -0.04574 -3.67245 0.00846 C -2.46959 0.59535 -0.00911 H -2.19463 -2.04253 0.00164 H 2.15015 -2.10642 0.00229 C 2.50252 0.52227 -0.00836 H 0.03370 1.73441 -0.01367 N -3.56446 1.05912 -0.01104 N 3.61049 0.95381 -0.00996 N -0.06322 -4.86173 0.01330 CI 0.06341 3.81874 -0.02304 8, TRICYANO-BROMIDE ANION. -3080.2378127903 a.u. C 0.00000 1.20678 0.71727 C 0.00000 1.22461 2.12948 C 0.00000 0.00000 2.82596 C 0.00000 -1.22461 2.12948 C 0.00000 -1.20678 0.71727 C 0.00000 0.00000 -0.01356 C 0.00000 0.00000 4.27115 190 e 0.00000 2.48647 0.03913 H 0.00000 2.17289 2.67330 H 0.00000 -2.17289 2.67330 e 0.00000 -2.48647 0.03913 H 0.00000 0.00000 -1.12699 N 0.00000 3.58836 -0.40789 N 0.00000 -3.58836 -0.40789 N 0.00000 0.00000 5.46055 Br 0.00000 0.00000 -3.39060 191 9, TRIAZINE-FLUORIDE ANION. N -0.73730 1.17285 e -1.29628 -0.04879 N -0.64706 -1.22495 e 0.69039 -1.09822 N 1.38437 0.05210 e 0.60589 1.14701 H -2.38960 -0.08993 H 1.27268 -2.02449 H 1.11692 2.11442 F 0.00000 0.00000 9, TRIAZINE-CHLORIDE ANION. N 0.03528 -0.87282 e -1.10897 -0.82289 N -1.21647 -0.76717 e -0.03265 -0.71963 N 1.18193 -0.76282 e 1.14233 -0.81880 H -2.04183 -0.84183 H -0.06031 -0.65172 H 2.10284 -0.83430 el -0.00142 2.34738 9, TRIAZINE-BROMIDE ANION. e 0.91977 0.91977 N -0.35851 1.33797 H 1.69292 1.69292 Br 0.00000 -0.00000 e -1.25642 0.33666 e 0.33666 -1.25642 N -0.97947 -0.97947 N 1.33797 -0.35851 H -2.31257 0.61965 H 0.61965 -2.31257 -379.3048274267 a.u. (-49.2; -49.2 em-I) -0.50582 -0.48628 -0.50582 -0.48628 -0.50582 -0.48628 -0.47589 -0.47589 -0.47589 2.04619 -739.3554755842 a.u. -1.34829 -0.64359 0.69572 1.33188 0.75625 -0.58677 -1.21389 2.42296 -1.10928 -0.12913 -2852.2418712145 a.u. -1.44029 -1.45335 -1.42936 1.86619 -1.44029 -1.44029 -1.45335 -1.45335 -1.42936 -1.42936 10, TRIAZINE-FLUORIDE ANION. -379.3294080551 a.u. N -0.56710 0.00637 1.22263 e 0.34887 0.96210 1.12353 N 0.94562 1.45177 0.00000 e 0.34887 0.96210 -1.12353 N -0.56710 0.00637 -1.22263 e -0.77784 -0.69116 0.00000 H 0.62356 1.46865 2.06048 H H F 0.62356 -1.74251 0.18159 1.46865 -1.21787 -1.86062 -2.06048 0.00000 0.00000 192 10, TRIAZINE-CHLORIDE ANION. -739.3559045234 a.u. N -1.20372 -0.46387 -0.67832 C -1.11808 -1.34345 0.33042 N 0.01491 -1.79790 0.90554 C 1.13327 -1.33198 0.31130 N 1.19281 -0.45163 -0.69865 C -0.01134 0.01211 -1.09919 H -2.06041 -1.73599 0.72615 H 2.08614 -1.71490 0.69091 H -0.02182 0.77440 -1.87661 C1 -0.01176 2.51131 0.37488 10, TRIAZINE-BROMIDE ANION. N -0.71529 1.18983 C 0.37718 1.96523 N 1.00297 2.36479 C 0.37718 1.96523 N -0.71529 1.18983 C -1.17121 0.76780 H 0.80330 2.30986 H 0.80330 2.30986 H -2.01742 0.08122 Br 0.26485 -1.97202 -2852.2417747178 a.u. 1.19852 1.12631 0.00000 -1.12631 -1.19852 0.00000 2.07380 -2.07380 0.00000 0.00000 11, TRIAZINE-FLUORIDE ANION. -379.3169709605 a.u. N 0.00000 1.19305 0.08739 C 0.00000 1.12239 1.42738 N 0.00000 0.00000 2.17792 C 0.00000 -1.12239 1.42738 N 0.00000 -1.19305 0.08739 C 0.00000 0.00000 -0.57682 H 0.00000 2.07246 1.97453 H 0.00000 -2.07246 1.97453 H 0.00000 0.00000 -1.72876 F 0.00000 0.00000 -3.26239 11, TRIAZINE~CHLORIDE ANION. -739.3588083346 a.u. N -1.19828 -0.64494 -0.00231 C -1.10939 -1.98503 0.00339 N 0.02547 -2.71493 0.00620 C 1.14013 -1.95454 0.00264 N 1.19266 -0.61254 -0.00310 C -0.01149 0.01186 -0.00542 H -2.05112 -2.54394 0.00602 H 2.09666 -2.48773 0.00464 H -0.02650 1.11750 -0.01008 C1 -0.05818 3.41902 -0.01891 11, TRIAZINE-BROMIDE ANION. -2852.2442695895 a.u. N 0.00000 1.19585 1.48105 C 0.00000 1.12523 2.82241 N 0.00000 0.00000 3.56686 C 0.00000 -1.12523 2.82241 N 0.00000 -1.19585 1.48105 C 0.00000 0.00000 0.84328 H 0.00000 2.07432 3.36838 H 0.00000 -2.07432 3.36838 H 0.00000 0.00000 -0.25968 Br 0.00000 0.00000 -2.73633 12, HEXAFLUOROBENZENE-FLUORIDE ANION. -925.5378550230 a.u. C 1.28241 -0.54910 -0.24677 F 2.52890 -1.08048 -0.21607 F 0.00000 -0.00000 2.28285 C -0.16567 1.38514 -0.24677 C -1.11674 -0.83605 -0.24677 C -1.28241 0.54910 -0.24677 C 0.16567 -1.38514 -0.24677 C 1.11674 0.83605 -0.24677 F -0.32873 2.73033 -0.21607 F -2.20017 -1.64985 -0.21607 F -2.52890 1.08048 -0.21607 F 0.32873 -2.73033 -0.21607 F 2.20017 1.64985 -0.21607 12, HEXAFLUOROBENZENE-CHLORIDE ANION. -1285.5874924051 a.u. C 1.37919 -0.13728 0.51326 C 0.54481 -1.24789 0.55225 C -0.83485 -1.08098 0.54577 C -1.37995 0.19649 0.50021 C -0.54554 1.30709 0.46123 C 0.83413 1.14022 0.46771 F 2.70951 -0.29819 0.51952 F 1.07043 -2.47965 0.59619 F -1.63944 -2.15182 0.58333 F -2.71024 0.35742 0.49394 F -1.07116 2.53894 0.41723 F 1.63870 2.21105 0.43014 Cl 0.00194 -0.15680 -2.68269 12, HEXAFLUOROBENZENE-BROMIDE ANION. -3398.4732559122 a.u. C -0.98451 0.98451 0.89668 F -1.94078 1.94078 0.91219 Br -0.00000 0.00000 -2.32596 C -0.36036 -1.34487 0.89668 C 1.34487 0.36036 0.89668 C 0.98451 -0.98451 0.89668 C 0.36036 1.34487 0.89668 C -1.34487 -0.36036 0.89668 F -0.71038 -2.65116 0.91219 F 2.65116 0.71038 0.91219 F 1.94078 -1.94078 0.91219 F 0.71038 2.65116 0.91219 F -2.65116 -0.71038 0.91219 193 13, HEXAFLUOROBENZENE-FLUORIDE ANION. -925.5487386394 a.u. C -1.19506 -0.89963 -0.02044 C -0.00884 -1.64068 -0.00839 C 1.18547 -0.91267 -0.01653 C 1.19173 0.48241 -0.03564 C 0.00736 1.30458 -0.04889 C -1.18597 0.49543 -0.03970 F -2.39961 -1.55612 -0.01326 F -0.01640 -3.01520 0.01058 F 2.38272 -1.58233 -0.00540 F 2.40661 1.12867 -0.04269 F 0.01460 2.28120 -1.15811 F -2.39367 1.15496 -0.05068 F 0.01105 2.31134 1.03312 TETRACYANOBENZENE. -599.6087673856 a.u. C -0.71112 -1.22003 0.00000 C -1.41505 0.00000 0.00000 C -0.71112 1.22003 0.00000 C 0.71112 1.22003 0.00000 C 1.41505 0.00000 0.00000 C 0.71112 -1.22003 0.00000 C -1.43671 -2.46413 0.00000 H -2.50803 0.00000 0.00000 C -1.43671 2.46413 0.00000 C 1.43671 2.46413 0.00000 H 2.50803 0.00000 0.00000 C 1.43671 -2.46413 0.00000 N -2.04537 -3.48749 0.00000 N 2.04537 -3.48749 0.00000 N -2.04537 3.48749 0.00000 N 2.04537 3.48749 0.00000 TRICYANOBENZENE. -507.5961931348 a.u. C 1.32557 -0.45834 0.00000 C 0.26867 -1.39173 0.00000 C -1.05971 -0.91881 0.00000 C -1.33961 0.46319 0.00000 C -0.26585 1.37714 0.00000 C 1.07094 0.92854 0.00000 C -2.15138 -1.86529 0.00000 C 2.69108 -0.93050 0.00000 H 0.47576 -2.46453 0.00000 H -2.37223 0.82024 0.00000 C -0.53970 2.79579 0.00000 H 1.89646 1.64429 0.00000 N 3.81487 -1.31915 0.00000 N -0.76502 3.96335 0.00000 N -3.04986 -2.64420 0.00000 194 TRIAZINE. N 1.33837 C 0.92288 -279.6193158697 a.u. -0.35862 0.00000 0.92288 0.00000 195 N -0.35862 1.33837 0.00000 e -1.26067 0.33780 0.00000 N -0.97975 -0.97975 0.00000 e 0.33780 -1.26067 0.00000 H 1.69599 1.69599 0.00000 H -2.31676 0.62077 0.00000 H 0.62077 -2.31676 0.00000 HEXAFLUOROBENZENE. -825.8391823112 a.u. e -1.27087 -0.58793 0.00000 e -1.14460 0.80664 0.00000 e 0.12627 1.39457 0.00000 e 1.27087 0.58793 0.00000 e 1.14460 -0.80664 0.00000 e -0.12627 -1.39457 0.00000 F -2.49302 -1.15192 0.00000 F -2.24410 1.58306 0.00000 F 0.24892 2.73497 0.00000 F 2.49302 1.15192 0.00000 F 2.24410 -1.58306 0.00000 F -0.24892 -2.73497 0.00000 FLUORIDE ANION. -99.6681122581 a.u. CHLORIDE ANION. -459.7227643886 a.u. BROMIDE ANION. -2572.6092871756 a.u. SUPPORTING MATERIAL REFERENCES Full citation for NWChem software: Straatsma, T.P.; Apra, E.; Windus, T.L.; Bylaska, E.J.; de Jong, W.; Hirata, S.; Valiev, M.; Hackler, M. T.; Pollack, L.; Harrison, R J.; Dupuis, M.; Smith, D.M.A; Nieplocha, J.; Tipparaju V.; Krishnan, M.; Auer, A. A.; Brown, E.; Cisneros, G.; Fann, G. I.; Fruchtl, H.; Garza, J.; Hirao, K.; Kendall, R; Nichols, J.; Tsemekhman, K.; Wolinski, K.; Anchell, J.; Bernholdt, D.; Borowski, P.; Clark, T.; Clerc, D.; Dachsel, H.; Deegan, M.; Dyall, K.; Elwood, D.; Glendening, E.; Gutowski, M.; Hess, A.; Jaffe, J.; Johnson, B.; Ju, J.; Kobayashi, R; Kutteh, R; Lin, Z.; Littlefield, R; Long, X.; Meng, B.; Nakajima, T.; Niu, S.; Rosing, M.; Sandrone, G.; Stave, M.; Taylor, H.; Thomas, G.; van Lenthe, J.; Wong, A.; Zhang, Z.; 196 "NWChem, A Computational Chemistry Package for Parallel Computers, Version 4.6" (2004), Pacific Northwest National Laboratory, Richland, Washington 99352-0999, USA. STATISTICAL ANALYSIS OF THE POSITION OF ELECTRONEGATIVE ATOMS ABOVE THE PENTAFLUOROARENES. The experimental probability, expressed as a percent, of locating an atom at a given d(offset) value was determined by binning d(offset) values for the points shown in Figure 16 from 0.0 to 2.0 angstroms using a bin size of 0.05, dividing the number in each bin by the total number ofpoints, and multiplying the result by 100. The theoretical probablility, expressed as a percent, of finding an atom with a given d(offset) value for a randomly distributed set of atoms was determined by computing the area of a disc with an inner radius of r1 and an outer radius of r1 +0.05 angstroms, where r1 ranged from 0 to 1.95 angstroms, dividing this area by the total area of a circle of radius 2.00 angstroms, and multiplying by 100. A plot of the experimental probability (circles) and the theoretical probability (dashed line) versus the d(offset) value, presented below, shows that the experimental points track the theoretical line over the range of the data. 197 2.01.51.0 d A offset' 0.5 O--t=.----.--..-----.---.---.-----.----.-----.----r---r--r---,---,--.----.--.----.--......-t- 0.0 ~ 20~ :!:::::! :n(lj ..Q 0 ...... 1Q. Graph B.t Statistical analysis of the position of electronegative atoms above pentafluoroarenes. 198 APPENDIXC SUPPORTING INFORMATION FOR CHAPTER IV: SOLUTION PHASE MEASUREMENT OF BOTH WEAK SIGMA AND C-H···X- HYDROGEN BONDING INTERACTIONS IN SYNTHETIC ANION RECEPTORS EXPERIMENTAL GENERAL. d-chloroform and acetonitrile were dried over 3A molecular sieves. Tetra- n-alkylammonium salts were dried under a vacuum at 50°C (25°C for the NHep4+Cn and stored in a calcium carbonate filled dessiccator. All other materials were obtained from TCI-America, Sigma-Aldrich, Acros and Strem and used as received. All glassware was flame dried immediately prior to use. Nuclear Magnetic Resonance IH NMR and B C NMR spectra were recorded on a Varian INOVA 300 (299.935) and 125 (125.751) MHz spectrometer respectively. Chemical shifts (D) are expressed as ppm downfield from tetramethylsilane using either the residual solvent peak as an internal standard (CDC!) IH: 7.27 ppm, B C: 77.00 ppm), (C6D6 IH: 7.16 ppm, B C: 128.39 ppm) (d6-DMSO IH: 2.50 ppm, B C: 39.51 ppm) or using CDC!) spiked with 1% 199 trimethylsilane for the IH NMR spectra. Signal patterns are indicated as b, broad; s, singlet; d, doublet; t, triplet; m, multiplet. Coupling constants (.1) are given in hertz. 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene (5).1 To a mixture of paraformaldehyde (16.7 g, 556.3 mmol) and triethylbenzene 2 (10.0 mL, 53.1 mmol) in 100 mL ofHBr/AcOH (30 wt %) zinc bromide (19.7 g, 87.5 mmol) was slowly added at room temperature. The mixture was heated to 90 °C for 16.5 h, during which time white crystals formed. The reaction was cooled to room temperature, and the white solid was filtered off. The white crystals were washed with water (3 x 100 ml), and dried under vacuum overnight to give 22.79 g (51.7 mmol, 97%) of 5 as a white solid. Mp 169-170 °C; IH NMR (0.1 M in CDC!), 300 MHz) 0 4.58 (s, 6H), 2.94 (q, J = 7.7 Hz, 6H), 1.34 (t, J = 7.7 Hz, 9H); l3C NMR (CDC!), 300 MHz) 0 145.0, 132.6, 28.5,22.7, 15.6. 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1).2 1,3,5- tris(bromomethyl)-2,4,6-triethylbenzene (5) (0.441 g, 1.00 mmol) was added to a stirring suspension of2,4-dinitrobenzoic acid (1.06 g, 5.0 mmol), and CsF-Celite (1.13 g) in 150 ml of acetonitrile. The reaction mixture was heated at reflux for 16 h. After cooling to room temperature the lemon-yellow solution was evaporated under reduced pressure. The remaining yellow powder was dissolved in ethyl acetate and the solid CsF-Celite was filtered off. Evaporation of the remaining organic solvent produced an off-white solid that was dissolved in a minimal amount of dimethylsulfoxide. Water 200 was added slowly to precipitate out a white solid. The crude product was filtered off and washed with cold methanol to remove residual acid. The white solid was dried in air to yield pure product (0.5 g, 60%). mp 180-181 °C; 1H NMR (CDC!), 300 MHz) 0 8.825 (sd, 3H), 8.535 (dd, 3H), 7.899 (d, 3H), 5.544 (s, 6H), 2.871 (q,6H), 1.213 (t, 9H); lH NMR (0.005M in C6D6, 300 MHz) 0 7.81 (sd, 3H), 7.62 (dd, 3H), 6.76 (d, 3H), 5.47 (s, 6H), 2.94 (q, 6H), 1.08 (t, 9H); lH NMR (d6-DMSO 300 MHz) 08.81 (s, 3H), 8.64 (dd, 3H), 8.15 (d, 3H), 5.50 (s, 6H), 2.86 (q, 6H), 1.16 (t, 9H); l3C NMR (d6- DMSO, 300 MHz) 0 163.7, 148.9, 147.3, 147.1, 131.5, 131.3, 128.9, 128.6, 120.0, 63.0,22.3,16.1 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2).2 1,3,5- tris(bromomethyl)-2,4,6-triethylbenzene (5) (0.441 g, 1.00 mmol) was added to a stirring suspension of2,4-dinitrobenzoic acid (1.06 g, 5.0 mmol), and CsF-Celite (2.00 g) in 150 ml of acetonitrile. The reaction mixture was heated at reflux for 16 h. After cooling to room temperature the lemon-yellow solution was evaporated under reduced pressure. The remaining yellow powder was dissolved in ethyl acetate and the solid CsF-Celite was filtered off. Evaporation of the remaining organic solvent produced an off-white solid that was dissolved in a minimal amount of dimethylsulfoxide. Water was added slowly to precipitate out a white solid. The crude product was filtered off and washed with cold methanol. Residual 3,5-dinitrobenzoic acid is removed by dissolving the remaining solid in acetone (2 ml) and methanol (4 ml) followed by slow evaporation ofthe acetone. Pure (2) was isolated by filtering off the white solid and 201 washing with cold methanol (3 ml) yielding a white powder (0.5g, 60%). mp 201.5- 202.5 °C; IH NMR (CDCh, 300 MHz) () 9.23 (t, 3H), 9.15 (sd, 6H), 5.62 (s, 6H), 2.97 (q, 6H), 1.23 (t, 9H); IH NMR (DMSO-d6, 300 MHz) () 9.03 (t, 3H), 8.86 (sd, 6H), 5.68 (s, 6H), 3.00 (q, 6H), 1.32 (t, 9H); B C NMR (d6-DMSO, 300 MHz) () 162.6, 148.3, 147.5, 132.5, 129.5, 128.8, 122.6,62.6,22.5, 16.3 1,3,5-tris(3,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (3).1 1,3,5- tris(bromomethyl)-2,4,6-triethylbenzene (5) (0.441 g, 1.00 rnrnol) was added to a stirring suspension of3,4-dinitrobenzoic acid (1.06 g, 5.0 mmol), and CsF-Celite (1.13 g) in 150 ml of acetonitrile. The reaction mixture was heated at reflux for 16 h. After cooling to room temperature the lemon-yellow solution was evaporated under reduced pressure. The remaining yellow powder was dissolved in ethyl acetate and the solid CsF-Celite was filtered off. Evaporation of the remaining organic solvent produced an off-white solid that was dissolved in a minimal amount of dimethylsulfoxide. Water was added slowly to precipitate out a white solid. The crude product was filtered off and washed with cold methanol to remove residual acid. Pure product was obtained by flash column chromatography with 2:1 hexanes:ethyl acetate as the eluent (20%). mp 230°C (decomp); IH NMR (CDCh, 300 MHz) () 8.55 (sd, 3H), 8.44 (dd, 3H), 7.99 (d, 3H) 5.61 (s, 6H), 2.91 (q, 6H), 1.27 (t, 9H); IH NMR (d6_DMSO, 300 MHz) () 8.57 (sd, 3H), 8.42 (dd, 3H), 8.33 (d, 3H) 5.56 (s, 6H), 2.92 (q, 6H), 1.18 (t, 9H); IH NMR (0.001 Min C6D6, 300 MHz) () 7.93 (sd, 3H), 7.42 (d, 3H), 6.61 (dd, 3H), 5.43 (s, 6H), 2.88 (q, 6H), 1.08 (t, 9H). 202 1,3,5-tris(benzoatomethyl)-2,4,6-triethylbenzene (4).2 1,3,5-tris(bromomethyl)- 2,4,6-triethylbenzene (5) (0.661 g, 1.5 mmol) was added to a stirring suspension of benzoic acid (0.916 g, 7.5 mmol), and CsF-Celite (3.00 g) in 200 ml of acetonitrile. The reaction mixture was heated at reflux for 20 h. After cooling to room temperature the creamy white suspension was filtered and evaporated under reduced pressure. The remaining yellow oil was refluxed with water (200 ml) and the yellow solid was filtered off. The crude product was recrystallized from a minimal amount of acetone (0.605g, 73.7%). mp 139-140 °C; IH NMR (d6-DMSO, 300 MHz) 0 7.93 (d, 6H), 7.65 (t, 3H), 7.50 (t, 6H) 5.48 (s, 6H), 2.84 (q, 6H), 1.18 (t, 9H); 13C NMR (d6-DMSO, 300 MHz) 0 166.8, 147.9, 133.3, 131.1, 131.0, 130.3, 128.9,61.8,23.6, 16.9 203 NMR SPECTROSCOPIC TITRATIONS GENERAL. IH NMR spectra were recorded on a Varian 300,500 or 600 MHz spectrometer. Each titration was performed with 9 to 17 measurements in C6D6 at room temperature or 27 DC in a water bath. C6D6 was dried over 3A molecular sieves. Anion stock solutions were prepared by diluting with a known amount of receptor stock solution such that a constant receptor concentration is maintained throughout the titration. Aliquots from a stock solution of tetra-n-alkylammonium salts (ca. 200 or 500 mM) were added to the initial solution of receptor (1-5 mM). All additions were done through septa with Hamilton gas tight syringes to minimize evaporation. All proton signals were referenced to the residual solvent peak C6H6 (7.16 ppm). The association constants (Ka) were calculated by non-linear regression curve fitting software? The reported association constants were calculated from the proton on the receptor that exhibits the largest change throughout the titration and are presented as an average of two or three measurements. Table C.1 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium bromide trial I. Addnion X" equi. (M) I Vol X" added/aliquot (~L) I Total Vol In tube(~L) I [X"] (moVL) I [R] (molfL) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) peak 4 (ppm) 0 0.000 0 700 0 0.002051425 7.814 7.273 8.784 5.478 1 0.692 5 705 0.001418724 0.002051425 7.822 7.311 6.814 5.486 2 2.046 10 715 0.004198645 0.002051425 7.629 7.34 6.853 5.492 3 3.363 10 725 0.006897934 0.002051425 7.832 7.354 8.874 5.494 4 5.890 20 745 0.012082958 0.002051425 7.836 7.378 6.905 5.499 5 8.285 20 765 0.016996869 0.002051425 7.839 7.394 8.933 5.502 8 11.652 30 795 0.02390416 0.002051425 7.843 7.417 8.967 5.506 7 14.775 30 825 0.030309103 0.002051425 7.848 7.437 6.998 5.51 8 19.503 50 875 0.040008016 0.002051425 9 23.719 50 925 0.048658387 0.002051425 7.854 7.486 7.071 5.518 10 27.504 50 975 0.05842156 0.002051425 7.857 7.504 7.098 5.52 11 30.919 50 1025 0.063427342 0.002051425 7.86 7.518 7.12 5.522 12 38.838 100 1125 0.075570686 0.002051425 7.864 7.543 7.155 5.524 13 41.791 100 1225 0.085731462 0.002051425 14 45.997 100 1325 0.094358527 0.002051425 7.869 7.577 7.204 5.527 15 52.753 200 1525 0.108218403 0.002051425 7.874 7.599 7.237 5.529 18 59.057 250 1775 0.121151033 0.002051425 7.878 7.819 7.264 5.53 "NMRTit_HG EI -- - --- - 7.26 • K = 1.82e+l " bound = 7.463 • • • "55 of Residuals = 5.99349476397e-3 R Factor = 6.405 % • Min % bound = 7 % •Max % bound = 72% • 6.81 1.4e-3 Cone. of guest 1.2e-l Command: 5 H = HELP Graph C.1 Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium bromide trial 1. 204 Table C.2 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium bromide trial 2. Addition X· equiv. (M) I Vol. X- eddedialiquot(uL) I Totel Vol. in I1Jbe(vL) I [Xl (moIlL) I [R](moIIL) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) peak 4 (ppm) 0 0.000 0 700 0 0.002051425 7.814 7.273 8.764 5.478 1 0.892 5 705 0.001418724 0.002051425 7.822 7.312 8.815 5.486 2 2.048 10 715 0.004196645 0.002051425 7.828 7.339 8.852 5.491 3 3.383 10 725 0.006897934 0.002051425 7.831 7.353 6.873 5.494 4 5.890 20 745 0.012082958 0.002051425 7.836 7.378 8.905 5.498 5 8.285 20 765 0.018996889 0.002051425 7.839 7.394 8.933 5.502 8 11.652 30 795 0.02390416 0.002051425 7.843 7.419 8.971 5.506 7 14.775 30 825 0.030309103 0.002051425 7.846 7.439 7.001 5.51 8 19.503 50 875 0.040008016 0.002051425 7.851 7.487 7.042 5.515 9 23.719 50 925 0.048658397 0.002051425 7.854 7.487 7.072 5.518 10 27.504 50 975 0.05642'58 0.002051425 7.857 7.505 7.098 5.52 11 30.919 50 1025 0.063427342 0.002051425 7.86 7.518 7.12 5.522 12 36.838 100 1125 0.075570698 0.002051425 7.864 7.544 7.158 5.524 13 41.791 100 1225 0.085731462 0.002051425 14 45.997 100 1325 0.094358527 0.002051425 7.87 7.578 7.205 5.527 15 52.753 200 1525 0.108218403 0.002051425 7.874 7.6 7.238 5.529 16 59.057 250 1775 0.121151033 0.002051425 7.877 7.619 7.264 5.53 -_.- ., NMRTit HG - .. - El- _. . ---." .. ... - 7.26 • K = 1.7ge+l " bound = 7.467 • • • "SS of ResiduaLs = 5.96139952541:1e-3 R Factor = 6.13132 % • Min % bound = 7 % I•Max % bound = 71 % • 6.82 I· 1 .4e-3 Conc. of 9uest 1.2e-l Ii I Command: S - H = HELP , Graph C.2 Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium bromide trial 2. 205 Table C.3 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium bromide trial 3. Addmon x- equiv. (M) I Vol. x· added/aliquot (~L) I Total Vol. in tUbe(PL) IIXl (mollL) I [RJ(molfL) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) peak 4 (ppm) 0 0.000 0 700 0 0.002051425 7.614 7.273 6.764 5.476 1 0.692 5 705 0.001416724 0.002051425 7.623 7.304 6.616 5.466 2 2.046 10 715 0.004196645 0.002051425 7.626 7.336 6.65 5.491 3 3.363 10 725 0.006697934 0.002051425 7.631 7.351 6.67 5.494 4 5.690 20 745 0.012062956 0.002051425 7.635 7.373 6.9 5.496 5 6.265 20 765 0.016996669 0.002051425 7.636 7.39 6.926 5.501 6 11.652 30 795 0.02390416 0.002051425 7.643 7.415 6.965 5.506 7 14.775 30 625 0.030309103 0.002051425 7.646 7.436 6.997 5.51 6 19.503 50 675 0.040006016 0.002051425 7.65 7.464 7.036 5.514 9 23.719 50 925 0.046658397 0.002051425 7.654 7.465 7.069 5.517 10 27.504 50 975 0.05842158 0.002051425 7.657 7.503 7.096 5.52 11 30.919 50 1025 0.063427342 0.002051425 7.659 7.517 7.116 5.522 12 36.636 100 1125 0.075570696 0.002051425 7.664 7.542 7.154 5.524 13 41.791 100 1225 0.065731462 0.002051425 14 45.997 100 1325 0.094358527 0.002051425 7.669 7.576 7.204 5.527 15 52.753 200 1525 0.106216403 0.002051425 7.673 7.599 7.236 5.529 16 59.057 250 1775 0.121151033 0.002051425 7.677 7.619 7.264 5.53 . . NMRTit_HG . EI.. . .• . 7.26 • K = 1.67e+l il bound = 7.484 • • • il • 88 of Residuals = 5.89373754337e-3 R Factor = 5.890 % •Min %bound = 7 % Max %bound 69 % •= • 6.82 1 .4e-3 Cone. of guest 1.2e-l Command: 8 H = HELP Graph C.3 Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium bromide trial 3. 206 Table C.4 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium bromide trial 1. 207 Addition X equiv. (M) I Vol. X added/aliquot (~L) I Total Vol. in tUbe(pL) I [Xl (mol/L) I [R] (mol/L) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) 0 0.000 0 700 0 0.001956908 8.59 8.371 5.476 1 0.716 5 705 0.001400971 0.001956908 8.593 8.375 5.482 2 2.118 10 715 0.004144131 0.001956908 8.595 8.376 8.484 3 3.481 10 725 0.006811617 0.001956908 8.597 8.378 5.487 4 6.097 20 745 0.011931759 0.001956908 8.597 8.378 5.489 5 8.577 20 765 0.016784181 0.001956908 8.599 8.379 5.491 6 12.062 30 795 0.023605039 0.001956908 7 15.294 30 825 0.029929834 0.001956908 8.599 8.38 5.496 8 20.189 50 875 0.03950738 0.001956908 8.6 8.381 5.499 9 24.554 50 925 0.048049517 0.001956908 8.601 8.382 5.502 10 28.471 50 975 0.055715537 0.001956908 11 32.006 50 1025 0.062633652 0.001956908 8.602 8.383 5.505 12 38.134 100 1125 0.074625052 0.001956908 8.602 8.383 5.507 13 43.261 100 1225 0.084658672 0.001956908 8.602 8.384 5.509 14 47.615 100 1325 0.093177784 0.001956908 8.602 8.384 5.51 15 54.609 200 1525 0.106884226 0.001956908 8.602 8.385 5.511 16 61.135 250 1775 0.119635025 0.001956908 8.602 8.386 5.513 -- -- NMRfit_HG §l -" -_. - - - -- - 5.51 • •K = 3.34e+l •() bound = 5.520 • • • () •55 of ResiduaLs = 4.81808601762e-5 R Factor = 6.387 % Min % bound = 14 % • Max % bound = 83 % • 5.48 l.4e-3 Cone. of guest 1.2e-l Command: 5 - H = HELP Graph C.4 Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium bromide trial 1. 208 Table C.S 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium bromide trial 2. Addition o 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 X equiv. (M) I Vol.)\ added/aliquot (~L) I Total Vol. in tUbe(pL) I [Xl (mol/L) I [R] (mol/L) I 0.000 0 700 0 0.001956908 0.716 5 705 0.001400971 0.001956908 2.118 10 715 0.004144131 0.001956908 3.481 10 725 0.006811617 0.001956908 6.097 20 745 0.011931759 0.001956908 8.577 20 765 0.016784181 0.001956908 12.062 30 795 0.023605039 0.001956908 15.294 30 825 0.029929834 0.001956908 20.189 50 875 0.03950738 0.001956908 24.554 50 925 0.048049517 0.001956908 28.471 50 975 0.055715537 0.001956908 32.006 50 1025 0.062633652 0.001956908 38.134 100 1125 0.074625052 0.001956908 43.261 100 1225 0.084658672 0.001956908 47.615 100 1325 0.093177784 0.001956908 54.609 200 1525 0.106864226 0.001956908 61.135 250 1775 0.119635025 0.001956908 peak 1 (ppm) 8.589 8.594 8.596 8.597 8.598 8.599 8.599 8.6 8.6 8.601 8.601 8.602 8.602 8.601 8.602 8.602 8.602 peak 2 (ppm) 8.371 8.376 8.377 8.378 8.379 8.379 8.38 8.381 8.381 8.382 8.382 8.383 8.383 8.383 8.384 8.385 8.385 peak 3 (ppm) 5.475 5.482 5.486 5.487 5.489 5.491 5.494 5.496 5.498 5.502 5.502 5.505 5.507 5.507 5.51 5.511 5.513 5.51 K = 3.81e+l ~ bound = 5.518 • • • I • • 88 of Residuals = 9.48415553915e-5 • • • I R Factor = 7.959 % Min %bound = 15 % Max %bound = 88 % • • 1.2e-lCone. of guest 5.48 =- -----J 1 .4e-3 Command: S H = HELP I Graph C.S Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium bromide trial 2. 209 Table C.6 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium bromide trial 3. Addition )(" equiv. (M) I Vol. X added/aliquot (~L) I Total Vol. in tube(~L) I [Xl (moI/L) I [R] (moUL) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) 0 0.000 0 650 0 0.001956908 8.59 8.372 5.476 1 0.771 5 655 0.001507915 0.001956908 8.594 8.376 5.482 2 2.277 10 665 0.00445572 0.001956908 8.596 8.377 5.485 3 3.739 10 675 0.007316182 0.001956908 8.598 8.378 5.488 4 6.536 20 695 0.012790159 0.001956908 8.598 8.379 5.491 5 9.177 20 715 0.0179579 0.001956908 8.598 8.379 5.491 6 12.872 30 745 0.025189269 0.001956908 8.6 8.38 5.495 7 16.281 30 775 0.031860791 0.001956908 8.6 8.38 5.496 8 21.412 50 825 0.041901767 0.001956908 8.601 8.382 5.5 9 25.957 50 875 0.050795203 0.001956908 8.601 8.362 5.502 10 30.010 50 925 0.058727187 0.001956908 8.601 8.382 5.503 11 33.648 50 975 0.065845634 0.001956908 8.601 8.382 5.504 12 39.908 100 1075 0.078095985 0.001956908 8.601 8.383 5.506 13 45.102 100 1175 0.088261169 0.001956908 8.601 8.383 5.509 14 49.482 100 1275 0.096831815 0.001956908 8.602 8.384 5.51 15 56.460 200 1475 0.110486742 0.001956908 8.602 8.385 5.512 16 62.907 250 1725 0.123102707 0.001956908 8.602 8.386 5.514 .- - -- - - NMRTit HG -.. - El 5.51 • K = 3.32e+l • •il bound = 5.520 • • • • • il 55 of Residuals = • 7.87039680290e-5 1 R Factor = 8.264 % • • •Min % bound = 14 % I:Max % bound = 87 % • 5.48 1.5e-3 Cone. of guest 1.2e-l I· Command: 5 H = HELP i Graph C.6 Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium bromide trial 3. 210 Table C.7 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- butylammonium bromide. x- Vol. x- peak peak peak peak equiv. added/aliquot 1 2 3 4 (M (I..IL) X-I (mol/L) R] (mol/L (ppm) (ppm ( m (ppm) 0 0.000 0 0 0.004952176 7.826 7.284 6.778 5.481 1 0.716 5 0.00413377 0.004952176 7.836 7.335 6.845 5.491 2 2.119 10 0.012199661 0.004952176 7.844 7.377 6.9 5.499 3 3.483 10 0.020007445 0.004952176 7.852 7.414 6.947 5.505 4 6.101 20 0.034896706 0.004952176 7.865 7.472 7.023 5.516 5 8.582 20 0.048890372 0.004952176 7.877 7.523 7.092 5.524 6 12.070 30 0.068370764 0.004952176 7.889 7.583 7.16 5.534 7 15.304 30 0.086238985 0.004952176 7.898 7.631 7.235 5.541 8 20.201 50 0.112945252 0.004952176 7.91 7.685 7.307 5.549 9 24.568 50 0.136414395 0.004952176 7.92 7.735 7.373 5.556 10 28.488 50 0.157201351 0.004952176 7.927 7.771 7.422 5.56 11 32.025 50 0.175741068 0.004952176 7.933 7.796 7.463 5.564 12 38.157 100 0.207394243 0.004952176 7.938 7.823 7.496 5.565 13 43.287 100 0.233420187 0.004952176 7.949 7.882 7.564 5.569 14 47.643 100 0.255196998 0.004952176 7.955 7.907 7.597 5.571 15 54.641 200 0.289581435 0.004952176 7.961 7.943 7.642 5.573 16 61.171 250 0.32101497 0.004952176 7.967 7.96 7.681 5.574 17 101.003 stock stock 0.500186116 0.004952176 7.989 8.106 7.843 5.568 Table C.8 1,3,5-tris(3,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (3) and tetra-n- butylammonium bromide. Vol [X-) added (~L) 0 0.0000 0 600 0.000000 0.001 7.928 7.399 6.609 5.432 1 6.6557 10 610 0.006656 0.001 7.991 7.567 6.867 5.466 2 19.3333 20 630 0.019333 0.001 8.031 7.671 7.047 5.492 3 36.9091 30 660 0.036909 0.001 8.064 7.776 7.211 5.515 4 62.9014 50 710 0.062901 0.001 8.094 7.890 7.397 5.546 5 105.2632 50 760 0.105263 0.001 8.115 7.961 7.512 5.564 6 112.5060 70 830 0.112506 0.001 8.132 8.019 7.610 5.579 7 144.0645 100 930 0.144065 0.001 8.145 8.069 7.697 5.590 8 169.4951 100 1030 0.169495 0.001 8.154 8.103 7.758 5.598 9 199.5593 150 1180 0.199559 0.001 8.162 8.136 7.818 5.606 10 222.8421 150 1330 0.222842 0.001 8.165 8.153 7.850 5.609 11 246.7843 200 1530 0.246784 0.001 8.169 8.169 7.886 5.612 12 331.4607 250 1780 0.331461 0.001 8.175 8.183 7.919 5.613 13 406.0000 stock stock 0.406000 0.001 8.184 8.265 8.073 5.627 211 212 Table C.9 1,3,5-tris(benzoatomethyl)-2,4,6-triethylbenzene (4) and tetra-n-butylammonium bromide. Vol [X-] added (~L) 0 0.0000 0 600 O.OOOE+OO 4.959E-03 5.522 6.981 7.058 8.083 0.8339 5 605 4.135E-03 4.959E-03 5.522 6.982 7.059 8.079 2 2.4611 10 615 1.220E-02 4.959E-03 5.521 6.983 7.060 8.079 3 4.0362 10 625 2.001E-02 4.959E-03 5.520 6.983 7.061 8.077 4 7.0399 20 645 3.491E-02 4.959E-03 5.518 6.984 7.063 8.075 5 9.8630 20 665 4.891E-02 4.959E-03 5.516 6.985 7.064 8.073 6 13.7929 30 695 6.839E-02 4.959E-03 5.514 6.987 7.067 8.071 7 17.3976 30 725 8.627E-02 4.959E-03 5.511 6.988 7.069 8.069 8 22.7852 50 775 1.130E-01 4.959E-03 5.508 6.990 7.073 8.066 9 27.5198 50 825 l.365E-01 4.959E-03 5.504 6.992 7.076 8.063 10 31.7133 50 875 1.573E-01 4.959E-03 5.501 6.994 7.077 8.060 11 35.4534 50 925 1.758E-01 4.959E-03 5.499 6.996 7.082 8.058 12 41.8390 100 1025 2.075E-01 4.959E-03 5.494 6.999 7.087 8.054 13 47.0894 100 1125 2.335E-01 4.959E-03 5.491 7.001 7.091 8.051 14 51.4826 100 1225 2.553E-01 4.959E-03 5.488 7.004 7.094 8.049 15 58.4192 200 1425 2.897E-01 4.959E-03 5.483 7.007 7.099 8.044 16 64.7605 250 1675 3.211E-01 4.959E-03 5.479 7.010 7.104 8.040 17 100.9059 stock stock 5.004E-01 4.959E-03 5.454 7.030 7.160 8.018 Table C.10 I,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium iodide trial 1. x- equiv. (mol) Vol IX-) added (~L) [R) (molfL) 2.744E- 0 0.0000 0 700 O.OOOE+OO 03 5.479 6.770 7.278 7.820 2.744E- 0.7752 5 705 2.127E-03 03 5.486 6.809 7.307 7.826 2.744E- 2 2.2931 10 715 6.291E-03 03 5.489 6.831 7.322 7.829 2.744E- 3 3.7691 10 725 1.034E-02 03 5.490 6.842 7.331 7.830 2.744E- 4 6.6023 20 745 1.811E-02 03 5.494 6.876 7.353 7.833 2.744E- 5 9.2873 20 765 2.548E-02 03 5.497 6.893 7.366 7.836 2.744E- 6 13.0615 30 795 3.584E-02 03 5.500 6.926 7.382 7.839 2.744E- 7 16.5612 30 825 4.544E-02 03 5.503 6.948 7.402 7.843 2.744E- 8 21.8608 50 875 5.998E-02 03 5.506 6.980 7.425 7.845 2.744E- 9 26.5875 50 925 7.295E-02 03 5.508 7.000 7.436 7.847 2.744E- 10 30.8294 50 975 8.459E-02 03 5.509 7.026 7.456 7.849 2.744E- 11 34.6574 50 1025 9.509E-02 03 5.511 7.044 7.469 7.851 2.744E- 12 41.2927 100 1125 1.133E-Ol 03 5.512 7.071 7.488 7.854 2.744E- 13 46.8446 100 1225 1.285E-Ol 03 5.513 7.097 7.506 7.856 2.744E- 14 51.5586 100 1325 1.415E-Ol 03 5.514 7.117 7.519 7.858 2.744E- 15 59.1318 200 1525 1.622E-Ol 03 5.515 7.160 7.540 7.862 213 ~'f~~~~~~~~~~~~ NMRTit_HG?"C,,",~~~~~~~~ El 7.15 214 K = 1.20e+l ~ bound = 7.356 • • • • 55 of Residuals = 3.58279095953e-3 • R Factor = 5.239 % Min % bound = 7 % Max % bound = 55 % • • • 1.3e-lCone. of guest 5.81 I!!:::: ----l 1.7e-3 Command: 5 H = HELP Graph C.7 Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium iodide trial 1. Table C.lt 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium iodide trial 2. x- equiv. (mol) Vol [X-) added (Ill) [X-] (mol/l) 0 0.0000 0 700 O.OOOE+OO 2,484E-03 5,479 6.772 7.279 7.820 1 0.7123 5 705 1.769E-03 2,484E-03 5,486 6.810 7.307 7.826 2 2.1071 10 715 5.234E-03 2,484E-03 5,489 6.834 7.325 7.829 3 3,4633 10 725 8.603E-03 2,484E-03 5,491 6.849 7.335 7.830 4 6.0667 20 745 1.507E-02 2,484E-03 5,495 6.877 7.353 7.834 5 8.5339 20 765 2.120E-02 2,484E-03 5,497 6.898 7.368 7.836 6 12.0019 30 795 2.981E-02 2,484E-03 5.501 6.930 7.389 7.839 7 15.2177 30 825 3.780E-02 2,484E-03 5.503 6.956 7.407 7.842 8 20.0874 50 875 4.990E-02 2,484E-03 5.507 6.991 7,424 7.845 9 24,4306 50 925 6.069E-02 2.484E-03 5.509 7.014 7,448 7.848 10 28.3284 50 975 7.037E-02 2,484E-03 5.511 7.040 7.466 7.850 11 31.8459 50 1025 7.911E-02 2,484E-03 5.512 7.056 7,475 7.851 12 37.9429 100 1125 9,425E-02 2,484E-03 5.513 7.093 7.502 7.854 13 43.0445 100 1225 1.069E-Ol 2,484E-03 5.514 7.160 7.510 7.856 14 47.3760 100 1325 1.177E-Ol 2,484E-03 5.515 7.160 7.522 7.860 15 54.3348 200 1525 1.350E-Ol 2,484E-03 5.516 7.160 7.549 7.862 16 60.8281 250 1775 1.511E-Ol 2,484E-03 5.516 7.184 7.557 7.864 215 __.. - NMRTit HG -- EI - - - -- - 7.18 • • K = 1.01e+l <) bound = 7.460 • • • • <) 88 of Residuals = 4.84715262428e-3 R Factor = 6.378 % •Min % bound = 6 % Max % bound = 60 % • • 6.81 1.8e-3 Cone. of guest 1.5e-l Command: 8 - H = HELP Graph e.8 Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium iodide trial 2. Table C.12 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium iodide trial 1. x- equiv. (mol) Vol [X-] added (Ill) [X-] (moljLl 0 0.0000 0 700 O.OOOE+OO 2.484E-03 5.479 6.772 7.279 7.820 0.7123 5 705 1.769E-03 2.484E-03 5.486 6.810 7.307 7.826 2 2.1071 10 715 5.234E-03 2.484E-03 5.489 6.834 7.325 7.829 3 3.4633 10 725 8.603E-03 2.484E-03 5.491 6.849 7.335 7.830 4 6.0667 20 745 1.507E-02 2.484E-03 5.495 6.877 7.353 7.834 5 8.5339 20 765 2.120E-02 2.484E-03 5.497 6.898 7.368 7.836 6 12.0019 30 795 2.981E-02 2.484E-03 5.501 6.930 7.389 7.839 7 15.2177 30 825 3.780E-02 2.484E-03 5.503 6.956 7.407 7.842 8 20.0874 50 875 4.990E-02 2.484E-03 5.507 6.991 7.424 7.845 9 24.4306 50 925 6.069E-02 2.484E-03 5.509 7.014 7.448 7.848 10 28.3284 50 975 7.037E-02 2.484E-03 5.511 7.040 7.466 7.850 11 31.8459 50 1025 7.911E-02 2.484E-03 5.512 7.056 7.475 7.851 12 37.9429 100 1125 9.425E-02 2.484E-03 5.513 7.093 7.502 7.854 13 43.0445 100 1225 1.069E-01 2.484E-03 5.514 7.160 7.510 7.856 14 47.3760 100 1325 1.177E-01 2.484E-03 5.515 7.160 7.522 7.860 15 54.3348 200 1525 1.350E-01 2.484E-03 5.516 7.160 7.549 7.862 16 60.8281 250 1775 1.511E-01 2.484E-03 5.516 7.184 7.557 7.864 216 217 - NMRTit_HG El 5.51 • K = 2.6ge+l () bound = 5.523 • • • • () • SS of ResiduaLs = 4.3877400457ge-5 R Factor = 6.371 % • Min % bound = 11 % •Max % bound = 80 % • 5.48 1.3e-3 Conc. of guest 1.le-l Command: S H = HELP Graph C.9 Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenzoatomethy1)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium iodide trial 1. Table C.13 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium iodide trial 2. [R] (mol/Ll 2.081E- 0 0.0000 0 700 O.OOOE+OO 03 5.479 8.375 8.590 2.081E- 0.6595 5 705 1.372E-03 03 5.484 8.377 8.594 2.081E- 2 1.9507 10 715 4.059E-03 03 5.486 8.378 8.596 2.081E- 3 3.2064 10 725 6.672E-03 03 5.488 8.380 8.597 2.081E- 4 5.6166 20 745 1.169E-02 03 5.490 8.382 8.598 2.081E- 5 7.9007 20 765 1.644E-02 03 5.492 8.382 8.600 2.081E- 6 11.1115 30 795 2.312E-02 03 5.495 8.383 8.600 2.081E- 7 14.0887 30 825 2.931E-02 03 5.497 8.384 8.600 2.081E- 8 18.5971 50 875 3.870E-02 03 5.500 8.386 8.600 2.081E- 9 22.6181 50 925 4.706E-02 03 5.502 8.386 8.603 2.081E- 10 26.2266 50 975 5.457E-02 03 5.504 8.388 8.604 2.081E- 11 29.4832 50 1025 6.135E-02 03 5.505 8.388 8.604 2.081E- 12 35.1278 100 1125 7.309E-02 03 5.507 8.390 8.605 2.081E- 13 39.8509 100 1225 8.292E-02 03 5.510 8.392 8.606 2.081E- 14 43.8610 100 1325 9.126E-02 03 5.510 8.392 8.606 2.081E- 15 50.3036 200 1525 1.047E-Ol 03 5.513 8.393 8.607 2.081E- 16 56.3151 250 1775 1.172E-Ol 03 5.515 8.396 8.607 218 219 NMRTit_HG - - 19- -- - 5.51 • K = 2.42e+l •() bound = 5.525 • • • • •() 88 of ResiduaLs = 4.47871315283e-5 R Factor = 5.451 % •Min % bound = 11 % •Max % bound = 78 % • 5.48 1.4e-3 Cone. of guest 1.2e-l Command: 8 H = HELP Graph C.lO Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium iodide trial 2. 220 Table C.14 1,3,5-tris(benzoatomethyl)-2,4,6-triethylbenzene (4) and tetra-n-heptylammonium iodide. Vol [X-] added [R] X- equiv. (mol) (flL) (moI{L) 3.076E- 0 0.0000 0 700 O.OOOE+OO 03 6.973 3.076E- 0.4478 5 705 1.377E-03 03 6.973 3.076E- 2 1.3247 10 715 4.074E-03 03 6.974 3.076E- 3 2.1774 10 725 6.697E-03 03 6.974 3.076E- 4 3.8140 20 745 1.173E-02 03 6.975 3.076E- 5 5.3652 20 765 1.650E-02 03 6.974 3.076E- 6 7.5455 30 795 2.321E-02 03 6.974 3.076E- 7 9.5672 30 825 2.942E-02 03 6.974 3.076E- 8 12.6287 50 875 3.884E-02 03 6.974 3.076E- 9 15.3593 50 925 4.724E-02 03 6.975 3.076E- 10 17.8098 50 975 5.477E-02 03 6.975 3.076E- 11 20.0212 50 1025 6.158E-02 03 6.975 3.076E- 12 23.8543 100 1125 7.336E-02 03 6.975 3.076E- 13 27.0616 100 1225 8.323E-02 03 6.976 3.076E- 14 29.7848 100 1325 9.160E-02 03 6.976 3.076E- 15 34.1597 200 1525 1.051E-Ol 03 6.977 3.076E- 16 38.2420 250 1775 1.176E-Ol 03 6.978 3.076E- 17 63.1437 stock stock 1.942E-Ol 03 6.938 221 Table C.1S 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium chloride triall. Addition X- equiv. (M) I VolX added/aliquot (~L) ITotal Vol. in tube(~L} I [Xl (moVL) I [RJ (moVL) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) peak 4 (ppm) 0 0.000 0 700 0 0.002028795 7.813 7.27 6.76 5.477 1 0.679 5 705 0.001378421 0.002028795 7.828 7.326 6.83 5.487 2 2.010 10 715 0.004077426 0.002028795 7.838 7.373 6.892 5.496 3 3.303 10 725 0.006701976 0.002028795 7.843 7.394 6.923 5.5 4 5.787 20 745 0.011739702 0.002028795 7.848 7.425 6.965 5.506 5 8.140 20 765 0.016514019 0.002028795 7.853 7.448 6.999 5.51 6 11.448 30 795 0.023225086 0.002028795 7.861 7.48 7.047 5.516 7 14.515 30 825 0.029448075 0.002028795 7.867 7.506 7.084 5.52 8 19.160 50 875 0.038871459 0.002028795 7.873 7.538 7.133 5.525 9 23.303 50 925 0.047276099 0.002028795 7.878 7.564 7.16 5.528 10 27.020 50 975 0.054818725 0.002028795 7.883 7.587 7.203 5.532 11 30.375 50 1025 0.061625484 0.002028795 7.885 7.604 7.228 5.534 12 36.191 100 1125 0.073423868 0.002028795 7.891 7.632 7.269 5.538 13 41.057 100 1225 0.083295984 0.002028795 7.895 7.653 7.299 5.54 14 45.188 100 1325 0.09167797 0.002028795 7.897 7.669 7.322 5.541 15 51.826 200 1525 0.105144111 0.002028795 7.903 7.696 7.36 5.544 18 58.019 250 1775 0.117709349 0.002028795 7.908 7.719 7.392 5.546 -- - - NMRTit_HG ;~- -- "B.- .. - - 7.39 • K = 2.57e+l , ~ bound = 7.558 • j • • • ~ I 55 of Residuals = 1.2770230881ge-2 R Factor = 6.146 ~ : • I Min ~ bound = 9 ~ • Max ~ bound = 79 ~ • 6.83 I 1 .4e-3 Cone. of guest 1.2e-l i I I Command: 5 H = HELP Graph C.lt Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium chloride triall. 222 Table C.16 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium chloride trial 2. Addition X· equiv. (M) I Vol. X" added/aliquot (~L) I Total Vol. in tube(pL) I [Xl (moVL) I [R] (moVL) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) peak 4 (ppm) 0 0.000 0 700 0 0.002028795 7.813 7.271 6.761 5.478 1 0.679 5 705 0.001378421 0.002028795 7.825 7.321 6.824 5.486 2 2.010 10 715 0.004077426 0.002028795 7.837 7.372 6.891 5.496 3 3.303 10 725 0.006701976 0.002028795 7.843 7.396 6.925 5.501 4 5.787 20 745 0.011739702 0.002028795 7.849 7.426 6.967 5.506 5 8.140 20 765 0.016514019 0.002028795 7.855 7.45 7.002 5.511 6 11.448 30 795 0.023225086 0.002028795 7.861 7.48 7.046 5.517 7 14.515 30 825 0.028448075 0.002028795 7.868 7.504 7.082 5.521 8 19.160 50 875 0.038871459 0.002028795 7.873 7.537 7.132 5.525 9 23.303 50 925 0.047276099 0.002028795 7.878 7.584 7.16 5.528 10 27.020 50 975 0.054818725 0.002028795 7.863 7.586 7202 5.532 11 30.375 50 1025 0.061625484 0.002028795 7.865 7.602 7.226 5.534 12 36.191 100 1125 0.073423868 0.002028795 7.89 7.631 7.267 5.538 13 41.057 100 1225 0.083295984 0.002028795 7.895 7.652 7298 5.54 14 45.188 100 1325 0.09167797 0.002028795 7.898 7.67 7.323 5.542 15 51.826 200 1525 0.105144111 0.002028795 7.903 7.695 7.36 5.544 16 58.019 250 1775 0.117709349 0.002028795 7.907 7.718 7.38 5.546 .• - - __ NMRTit HG '-- E3 7.39 • K = 2.56e+1 il bound = 7.557 • • • • il 88 of ResiduaLs = 1 .24266454950e-2 R Factor = 6.255 % • •Min % bound = 8 % Max % bound 79 % •= 6.82 1.4e-3 Conc. of guest 1.2e-1 Command: 8 - H = HELP Graph C.12 Binding isotherm for titration of 1,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium chloride trial 2. 223 Table C.17 1,3 ,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra-n- heptylammonium chloride trial 3. Add~ion )\ equiv (M) I Vol )\ added/aliquot (~L) I Tolal Vol In tubeM) I (Xl (moUL) I [R](moUl) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) peak 4 (ppm) 0 0.000 0 700 0 0.002028795 7.813 7.271 6.761 5.477 1 1.349 10 710 0.002737427 0.002028795 7.832 7.351 6.864 5.492 2 2.661 10 720 0.005398814 0.002028795 7.841 7.386 8.909 5.499 3 3.937 10 730 0.007987288 0.002028795 7.844 7.404 6.935 5.503 4 6.387 20 750 0.012957153 0.002028795 7.85 7.431 8.974 5.508 5 8.709 20 770 0.017868845 0.002028795 7.856 7.455 7.01 5.512 6 11.975 30 800 0.024294862 0.002028795 7.862 7.484 7.053 5.517 7 15.005 30 830 0.030441504 0.002028795 7.887 7.509 7.089 5.521 8 19.595 50 880 0.039754902 0.002028795 7.873 7.541 7.137 5.526 9 23.692 50 930 0.048066858 0.002028795 7.879 7.587 7.16 5.529 10 27.371 50 980 0.055530858 0.002028795 7.882 7.587 7.204 5.532 11 30.693 50 1030 0.062289813 0.002028795 7.885 7.601 7.228 5.534 12 38.455 100 1130 0.073958971 0.002028795 7.891 7.634 2.27 5.538 13 41279 100 1230 0.083747453 0.002028795 7.895 7.655 7.302 5.541 14 45.379 100 1330 0.092063983 0.002028795 7.898 7.672 7.325 5.542 15 51.970 200 1530 0.105435658 0.002028795 7.903 7.896 7.361 5.545 16 58.125 250 1780 0.117924652 0.002028795 7.908 7.719 7.393 5.546 _.- -- NMRTit_HG _.- -- E3 7.39 • K = 2.55e+l • ~ bound = 7.558 • • • •~ 88 of ResiduaLs = 1 .28035935505e-2 ; , R Factor = 5.137 % • Min % bound = 13 % • ; Max % bound = 79 % • 5.85 2.7e-3 Cone. of guest 1 .2e-l Command: 8 H = HELP Graph C.13 Binding isotherm for titration of 1,3 ,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (1) and tetra-n-heptylammonium chloride trial 3. 224 Table C.t8 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium chloride trial I. Addition o 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 X equiv. (M) I Vol. X- addedlaliquot (~L) I Total Vol. in tube(~L) I [Xl (mollL) I [R] (mo~L) I 0.000 0 700 0 0.002064736 0.714 5 705 0.001475157 0.002064738 2.113 10 715 0.004363577 0.002064738 3.474 10 725 0.007172317 0.002064738 6.085 20 745 0.012563589 0.002064738 8.559 20 765 0.017672964 0.002064738 12.038 30 795 0.02485501 0.002064738 15.263 30 825 0.031514726 0.002064738 20.148 50 875 0.041599438 0.002064738 24.504 50 925 0.050593911 0.002064738 28.413 50 975 0.058665874 0.002064738 31.941 50 1025 0.065950329 0.002064738 38.057 100 1125 0.078576717 0.002064738 43.173 100 1225 0.089141653 0.002064738 47.518 100 1325 0.098111883 0.002064738 54.498 200 1525 0.112523071 0.002064738 61.010 250 1775 0.12597013 0.002064738 peak 1 (ppm) 6.569 6.593 8.596 8.598 8.599 8.6 8.601 8.601 8.601 6.6 8.601 8.601 8.601 6.6 8.6 8.6 6.6 peak 2 (ppm) 8.37 8.373 8.376 8.377 8.378 8.378 8.38 8.379 8.38 8.381 8.381 8.382 8.382 8.382 8.382 8.383 8.383 peak 3 (ppm) 5.475 5.482 5.467 5.49 5.493 5.495 5.497 5.5 5.503 5.505 5.506 5.506 5.51 5.511 5.513 5.514 5.516 .. NMRTit_HG _. - - --§,__·w ---- - 5.52 • •K = 5.35e+1 il bound = 5.519 I • • • • • il 55 of ResiduaLs = • 8.35420360090e-5 R Factor = 7.121 % • Min %bound = 16 % • Max %bound = 94 % 5.48 I .5e-3 Cone. of 9uest 1.3e-1 : Command: 5 H = HELP , Graph C.t4 Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenwatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium chloride trial I. 225 Table C.19 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium chloride trial 2. Addition X equiv. (M) I Vol. X added/aliquot (~l) I Total Vol. in tube(~l) I [Xl (maUL) I [R) (mol/l) I peak 1 (ppm) peak 2 (ppm) peak 3 (ppm) 0 0.000 0 700 0 0.002064738 8.589 8.37 5.475 1 0.714 5 705 0.001475157 0.002064738 8.593 8.373 5.482 2 2.113 10 715 0.004363577 0.002064738 8.596 8.376 5.487 3 3.474 10 725 0.007172317 0.002064738 8.598 8.378 5.49 4 6.085 20 745 0.012563589 0.002064738 8.6 8.379 5.493 5 8.559 20 765 0.017672964 0.002064738 8.6 8.379 5.495 6 12.038 30 795 0.02485501 0.002064738 8.6 8.38 8.498 7 15.263 30 825 0.031514726 0.002064738 8.601 8.38 5.5 8 20.148 50 875 0.041599438 0.002064738 8.601 8.38 5.503 9 24.504 50 925 0.050593911 0.002064738 8.601 8.381 5.505 10 28.413 50 975 0.059665874 0.002064738 8.601 8.381 5.506 11 31.941 50 1025 0.065950329 0.002064738 8.601 8.381 5.508 12 38.057 100 1125 0.078576717 0.002064738 8.601 8.382 5.51 13 43.173 100 1225 0.089141653 0.002064738 8.601 8.382 5.511 14 47.518 100 1325 0.098111883 0.002064738 8.6 8.383 5.513 15 54.498 200 1525 0.112523071 0.002064738 8.601 8.383 5.514 16 61.010 250 1775 0.12597013 0.002064738 8.6 8.383 5.516 .- .. .. , ., .. .. .~ NMRTit HG _ .' .. .. ._~-- o • S~.. _._~-- -~ .. -- -- , _.,- -- _. .._-~ -- ... .' 5.52 • •K = 5.51e+l ~ ~ bound = 5.518 • • • • • ~ • 55 of ResiduaLs = 7.95061059762e-5 R Factor = 6.952 % • Min % bound = 16 % • Max % bound = 94 % 5.48 1.5e-3 Cone. of guest 1.3e-l I Command: 5 H = HELP - Graph C.1S Binding isotherm for titration of 1,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammonium chloride trial 2. 226 Table C.20 1,3 ,5-tris(3 ,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n- heptylammonium chloride trial 3. Addition o 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 X equiv. (M) I Vol. X added/aliquot (~L) I Total Vol. in tUbe(pL) I [Xl (moIlL) I [R] (moI/L) I 0.000 0 700 0 0.002064738 0.714 5 705 0.001475157 0.002064738 2.113 10 715 0.004363577 0.002064738 4.797 20 735 0.009904628 0.002064738 7.339 20 755 0.015152113 0.002064738 9.749 20 775 0.02012876 0.002064738 13.140 30 805 0.027130068 0.002064738 16.287 30 835 0.033628288 0.002064738 21.058 50 885 0.043479639 0.002064738 25.319 50 935 0.052277369 0.002064738 29.147 50 985 0.060181928 0.002064738 32.606 50 1035 0.067322762 0.002064738 38.609 100 1135 0.079716985 0.002064738 43.639 100 1235 0.090104046 0.002064738 47.916 100 1335 0.098934994 0.002064738 54.799 200 1535 0.113145052 0.002064738 61.233 250 1785 0.126429665 0.002064738 peak 1 (ppm) 8.59 8.593 8.597 8.599 8.6 8.6 8.601 8.601 8.601 8.601 8.601 8.602 8.602 8.6 8.6 8.6 8.6 peak 2 (ppm) 8.37 8.373 8.376 8.378 8.379 8.379 8.38 8.38 8.381 8.381 8.381 8.382 8.383 8.382 8.383 8.383 8.383 peak 3 (ppm) 5.475 5.482 5.488 5.492 5.494 5.496 8.498 5.5 5.503 5.505 5.507 5.508 5.51 5.511 5.513 5.514 5.516 NMRTit_HG. - ..~ - - :~ §I - -- - 5.52 • • -K = 5.0ge+l d bound = 5.519 • • • • •d • 55 of ResiduaLs = 8.93143878784e-5 •R Factor = 6.873 ~ Min ~ bound = 16 ~ • Max ~ bound = 93 ~ 5.48 1.5e-3 Cone. of 9uest 1.3e-l Command: 5 H = HELP - Graph C.16 Binding isotherm for titration of 1,3 ,5-tris(3 ,5-dinitrobenzoatomethyl)-2,4,6- triethylbenzene (2) and tetra-n-heptylammoniurn chloride trial 3. 227 Table C.211,3,5-tris(benzoatomethyl)-2,4,6-triethylbenzene (4) and tetra-n-heptylammonium chloride. 0 0.0000 0 700 O.OOOE+OO 5.521 6.955 8.080 1 1.5868 10 710 2.454E-03 5.521 6.956 8.080 2 4.6301 20 730 7.161E-03 5.520 6.956 8.079 3 8.8947 30 760 1.376E-02 5.519 6.957 8.078 4 15.3003 50 810 2.366E-02 5.517 6.956 8.076 5 20.9611 50 860 3.242E-02 5.516 6.957 8.079 6 25.9998 50 910 4.021E-02 5.514 6.957 8.074 7 34.5806 100 1010 5.348E-02 5.512 6.957 8.071 8 47.4873 200 1210 7.345E-02 5.509 6.957 8.068 9 58.6480 250 1460 9.071E-02 5.506 6.958 8.065 228 Table C.22 Ethyl-3,5-dinitrobenzoate and tetra-n-butylammonium bromide. Vol [X-] [R) added (~L) (mol/Ll 4.330E- 0 0.0000 0 700 O.OOOE+OO 03 3.979 8.429 8.609 4.330E- 1 0.8089 5 705 3.503E-03 03 3.979 8.431 8.609 4.330E- 2 2.3927 10 715 1.036E-02 03 3.981 8.431 8.61 4.330E- 3 3.9328 10 725 1.703E-02 03 3.982 8.432 8.611 4.330E- 4 6.8890 20 745 2.983E-02 03 3.985 8.436 8.611 4.330E- 5 11.0372 30 775 4.779E-02 03 3.988 8.439 8.612 4.330E- 6 16.0931 40 815 6.969E-02 03 3.991 8.443 8.613 4.330E- 7 21.7554 50 865 9.421E-02 03 3.995 8.448 8.613 4.330E- 8 26.7989 50 915 1.160E-01 03 3.997 8.452 8.614 4.330E- 9 35.3952 100 1015 1.533E-01 03 4.004 8.457 8.615 4.330E- 10 42.4495 100 1115 1.838E-01 03 4.007 8.461 8.615 4.330E- 11 55.5634 250 1365 2.406E-01 03 4.014 8.475 8.617 4.330E- 12 64.6172 250 1615 2.798E-01 03 4.030 8.488 8.618 4.330E- 13 76.3037 500 2115 3.304E-01 03 4.040 8.499 8.62 NMRTit_HG - 8 I 8.51 i K = 4.16e-l a bound = 8.950 • • a 55 of ResiduaLs = 1.27587627503e-4 • • R Factor = 7.512 % Min % bound = o % Max % bound = 16 % 8.43 3.5e-3 Cone. of 9uest 4.ge-1 Command: 5 H = HELP Graph C.17 Near linear relationship obtained when ethyl-3,5-benzoate is titrated with tetra-n- butylammonium bromide. 229 Ethyl-3,5-dinitrobenzoate and ethyl-2,4-dinitrobenzoate were synthesized as test molecules to understand the role that preorganization plays in this system. JH NMR titrations of the ethyl-3,5-dinitrobenzoate with NBu4+Br- and NHep4+r result in complex binding isotherms that do not fit well to a I: 1 binding model (see graph C.l7). Unfortunately, the ethyl-2,4-dinitrobenzoate was insoluble in C6D6 preventing comparative titrations for this compound. UV-VlS SPECTROSCOPIC INVESTIGATION OF COMI>LEX FORMATION Absorbancevs \MJveIength 0.6 0.5 0.4 B 1'l b ~ 03 02 0.1 1 0 1 250 300 350 400 450 \wvelergth(nm) 500 550 600 Graph C.I8 UV-Vis titration of I ,3,5-tris(3,5-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) and tetra-n-heptylammonium iodide. 230 Absorbancevs WNelength 0.6 0.5 0.4 550500300250 350 400 450 wavelength (nm) Graph C.19 UV-Vis titration of I,3,5-tris(2,4-dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and tetra·-n-heptylammonium iodide with receptor (1) absorbance blanked. SINGLE CRYSTAL X-RAY DIFFRACTION DATA GENERAL. Single-crystal X-ray diffraction data for compounds 1,3,5-tris(2,4- dinitrobenzoatomethyl)-2,4,6-triethylbenzene (1) and 1,3,5-tris(3,5- dinitrobenzoatomethyl)-2,4,6-triethylbenzene (2) were collected on a Bruker-AXS SMART APEX/CCD diffractometer using MOka radiation ('A = 0.7107 A) at 152 K. Diffracted data have been corrected for Lorentz and polarization effects, and for absorption using the SADABS v2.02 area-detector absorption correction program (Siemens Industrial Automation, Inc., © 1996).4 The structures were solved by direct 231 methods and the structure solution and refinement was based on 1F12 . Hydrogen atoms for 1 were found from the residual density map and refined with isotropic thermal parameters whereas hydrogen atoms for 2 were placed in calculated positions and given isotropic U values 1.2 times that of the atom to which they are bonded. All non- hydrogen atoms were refined with anisotropic displacement parameters. Twelve dimethylsulfoxide molecules per unit cell are highly disordered and were treated by SQUEEZE.5 The correction of the X-ray data by SQUEEZE, 618 electrons per unit cell, is close to the required value for twelve DMSO molecules in the unit cell, 504 electrons per unit cell. All crystallographic calculations were conducted with the SI-IELXTL v.6.1 program package (Bruker AXS Inc., © 200 1).6 Figure C.l Packing diagram of receptor 2 illustrating the porous channels formed in the sol id state 232 PACKING DESCRIPTION FOR RECEPTORS 1 AND 2. Receptor 1 crystallizes in a 'nested' type of close pack conformation with one receptor molecule filling the 'cavity' of an adjacent molecule. In the case of receptor 2 a similar self- complementarity is observed; however, the packing arrangement reveals large pores of ca. 12.5 x 19.8 A. DFT CALCULATIONS METHODS. DFT calculations were performed with the NWCHEM program.? DFT calculations were done using the B3LYP functional8 using the DZVP basis set with DGauss Al coulomb fitting.9 Optimized geometries and absolute energies for all structures are provided as supporting information. MODEL COMPOUNDS. Br anion Energy -2573.7777630 hartree METHYL 3,5-DINITROBENZOATE. Energy -869.2950500 hartree 22 C 0.127000 3.845490 -0.001007 0 -0.177994 2.428497 -0.003006 C 0.888977 1.607498 -0.002000 C 0.490982 0.159500 -0.004013 0 2.045990 1.984497 0.000992 C -0.847000 -0.245500 -0.012009 C -1.141998 -1.608490 -0.016006 C -0.147003 -2.582489 -0.014008 C 1.175980 -2.148483 -0.007004 233 C 1.511978 -0.797500 -0.003006 N 2.255981 -3.161484 -0.006012 N -2.558000 -2.037491 -0.022995 o -2.785004 -3.249496 -0.020996 o -3.418000 -1.153488 -0.029984 0 3.417984 -2.751495 -0.006012 0 1.918991 -4.348495 -0.004013 H 0.701981 4.106491 0.892990 H -0.841995 4.348495 0.000000 H 0.700989 4.109497 -0.892990 H -1.651000 0.482498 -0.014008 H -0.393997 -3.638489 -0.016998 H 2.551987 -0.483505 0.002000 WEAK-SIGMA COMPLEX OF Br ANION WITH METHYL 3,5-DINITROBENZOATE. Energy -3443.1041652 hartree 23 C 0.600555 2.932434 -3.087326 0 0.207886 1.833481 -2.248489 C 1.169632 1.357254 -1.430679 C 0.643890 0.343048 -0.472000 0 2.338348 1.707748 -1.493973 C -0.746872 0.147583 -0.294418 C -1.159653 -0.879425 0.576400 C -0.261459 -1.594070 1.357056 C 1.101181 -1.327408 1.207932 C 1.558441 -0.372238 0.286713 N 2.061081 -2.088745 1.990967 N -2.579758 -1.209198 0.664795 o -2.940704 -2.019165 1.535660 o -3.347717 -0.683533 -0.149002 0 3.270203 -1.863113 1.815109 0 1.630554 -2.934586 2.794708 234 H 0.937836 3.773422 -2.472748 H -0.297821 3.208008 -3.646347 H 1.404709 2.634995 -3.769119 H -1.466415 0.640732 -0.929779 H -0.608322 -2.350891 2.050690 H 2.621140 -0.187546 0.169678 Br -1.339569 2.592850 1.100967 METHYL 2,4-DINITROBENZOATE. Energy -869.2821988 hartree 22 C -1.509979 -3.984985 0.537003 0 -1.335983 -2.549988 0.668000 C -0.872986 -1.927994 -0.423981 C -0.716980 -0.439987 -0.188980 0 -0.679977 -2.439987 -1.505981 C -1.863983 0.359985 -0.248978 C -1.779984 1.747986 -0.162979 C -0.524979 2.338989 -0.016998 C 0.638000 1.579987 0.046997 C 0.522995 0.195007 -0.031982 N 1.765000 -0.599991 0.081009 N -0.423981 3.810989 0.074005 0 0.701004 4.297989 0.208008 0 -1.473984 4.454987 0.007004 0 1.645996 -1.802994 0.321000 0 2.836000 -0.005997 -0.051987 H -2.227982 -4.211000 -0.256989 H -1.883987 -4.317993 1.505997 H -0.548981 -4.454987 0.309006 H -2.835983 -0.112000 -0.372986 H -2.667984 2.370987 -0.206985 H 1.608002 2.049988 0.163010 C-H COMPLEX OF Br ANION WITH METHYL 2,4-DINITROBENZOATE. Energy -3443.0929338 hartree 23 C 0.652893 3.853363 0.387756 0 0.338455 2.474700 0.680405 C -0.445740 1.855209 -0.209457 C -0.524948 0.376282 0.075974 0 -0.965927 2.381378 -1.l74622 C 0.673019 -0.341431 0.128998 C 0.663559 -1.735382 0.214706 C -0.558624 -2.406357 0.249741 C -1.773514 -1.718582 0.210938 C -1.738266 -0.332321 0.133896 N -3.029984 0.373276 0.195496 N -0.589066 -3.875656 0.342697 0 -1.696381 -4.428696 0.407654 0 0.489716 -4.476013 0.349319 0 -3.049698 1.481491 0.737091 0 -4.024887 -0.202209 -0.262787 H 1.151230 3.925354 -0.582794 H 1.329086 4.167831 1.184921 H -0.259109 4.459213 0.382355 H 1.654053 0.153412 0.093475 H 1.609482 -2.268921 0.255447 H -2.718033 -2.249115 0.254578 Br 4.120026 0.158112 0.112625 235 236 RECEPTOR CALCULATIONS. COMPLEX OF Br ANION WITH 1 WITHOUT SYkJlvfETRY Energy -5646.2918730 hartree 91 C -0.403885 1.170990 -3.176590 C -1.121078 -0.035995 -3.039093 C -0.450516 -1.274994 -3.006622 C 0.950760 -1.304000 -3.168274 C 1.680603 -0.106995 -3.316010 C 0.997757 I,J26984 -3.327072 C 3.200531 -0.145004 -3.432602 C 3.701263 -0.252991 -4.888596 C -1.232956 -2.563995 -2.777756 C -1.733200 -3.214005 -4.085068 C -1.142761 2.503983 -3.144455 C -1.599731 2.981995 -4.538330 C 1.799377 2.408981 -3.400360 n~ 0 2.370941 2.695984 -2.076340 L C 2.024445 3.835983 -1.462830 C 2.585342 3.888992 -0.060516 '" 0, 0 J.288651 4.696991 -1.904449 C 1.696609 -2.617004 -3.078033 0 2.199570 -2.774002 -1.707626 C 1.927887 -3.914993 -J .053604 C 2.391815 -3.837997 0.381760 ,y- O 1319107 -4.867996 -1.499496 C -2.610138 0.012009 -2.777344 d 0 -2.757950 0.119980 -1.328278 Br-H distances = 2.832,3.043 C -3.984329 0.336990 -0.835114 Br-H distances = 2.909, 3.02l c -3.914597 0.398987 0.673737 Br-C distance =3.432 A 0 -4.983932 0.569992 -1.487061 C -4.204727 1625992 1.275452 Figure C.2 Ball and stick representations of receptor 10FT minima with Br·without symmetry C -4.035538 1,809982 2,646545 237 C -3.556976 0.750992 3.415710 C -3.242889 -0.481003 2.849945 C -3.468002 -0.651993 1.487700 C 2.073715 3.004990 0.893326 C 2.445175 3.105988 2.236984 C 3.340210 4.106995 2.614441 C 3.875839 5.001984 1.689453 C 3.495224 4.873993 0.359604 C 3.251724 -4.794998 0.947052 C 3.532837 -4.815002 2.306549 C 2.952316 -3.836990 3.112579 C 2.110565 -2.856003 2.588409 C 1.836000 -2.865997 1.218781 N -3.264145 -1.996994 0.928680 N -3.390564 0.934982 4.866257 N 4.130600 5.776993 -0.617218 N 3.751816 4.232986 4.027817 N 3.953003 -5.774994 0.097382 N 3.259216 -3.849000 4.556793 0 4.562057 5.124985 4.309677 0 3.263611 3.444992 4.838547 0 -3.074585 -0.048004 5.539368 0 -3.600723 2.064987 5.325226 0 4.183868 5.397995 -1.792252 0 4.598267 6.840988 -0.201508 0 -3.762268 -2.233002 -0.183151 0 -2.654739 -2.823990 1.607224 0 4.299408 -6.841003 0.614273 0 4.185287 -5.449997 -1.071121 0 4.033813 -4.722000 4.968826 0 2.724869 -2.994003 5.263580 H 3.631424 0.744980 -2.966812 H 3.596725 -0.979996 -2.849655 238 H 4.797760 -0.276000 -4.918854 H 3.331329 -1.164000 -5.376633 H 3.365341 0.596985 -5.495926 H -0.620956 -3.289993 -2.238388 H -2.081100 -2.375992 -2.115875 H -0.899048 -3.477997 -4.748062 H -2.291153 -4.132004 -3.863098 H -2.393707 -2.541000 -4.644852 H -2.010834 2.428986 -2.484528 H -0.517609 3.277985 -2.693115 H -2.270538 2.255981 -5.015717 H -2.131989 3.937988 -4.461151 H -0.744858 3.126984 -5.211365 H 2.661835 2.317993 -4.063187 H 1.214127 3.267990 -3.719391 H 2.579987 -2.636993 -3.718491 H 1.082596 -3.479996 -3.326508 H -3.132721 -0.888000 -3.103165 H -3.104202 0.862991 -3.246521 H -4.556961 2.446991 0.655579 H -4.258087 2.760986 3.120850 H -2.855759 -1.293000 3.452789 H 1.368317 2.217987 0.627136 H 2.025604 2.401993 2.953842 H 4.579407 5.766983 1.994812 H 4.198227 -5.561005 2.725494 H 1.665710 -2.080994 3.210464 H 1.171677 -2.093002 0.833328 Br 0.040649 0.237991 2.156693 239 240 C 5.600983 -5.095490 -2.017487 C 5.164978 -5.018494 -0.700485 N 4.382980 5.989487 0.273500 N 3.046982 4.944489 -4.334488 N 5.785980 -5.934494 0.273500 N 5.549988 -4.254500 -4.334488 0 6.396988 -5.113495 -4.612488 0 5.071976 -3.453491 -5.138489 0 3.366989 6.107483 -4.612488 0 2.591980 4.130493 -5.138489 0 5.765976 -5.600494 1.462494 0 6.315979 -6.962494 -0.157500 0 4.104980 5.804489 1.462494 0 5.009979 6.962494 -0.157500 C -1.263000 -0.674500 3.095505 0 -1.723007 -1.062500 1.755493 C -2.531998 -0.225510 1.092500 C -2.841003 -0.752502 -0.290482 0 -2.921997 0.858490 1.481506 C -1.815002 -0.768494 -1.237488 C -2.071000 -1.115494 -2.565491 C -3.374008 -1.447495 -2.936493 C -4.421997 -1.446487 -2.017487 C -4.137009 -1.1 06491 -0.700485 N -5.240997 -1.187500 0.273500 N -3.668000 -1.822495 -4.334488 0 -4.835007 -2.126495 -4.612488 0 -2.735000 -1.809494 -5.138489 0 -4.942000 -1.336502 1.462494 0 -6.397003 -1.131500 -0.157500 H 1.013992 -3.748489 2.518494 H -0.550995 -3.011490 2.591492 H 1.168000 -3.734497 5.052505 241 H -0.257004 -4.615494 4.469498 H -0.425995 -2.979492 5.138504 H 5.020981 -0.960495 2.591492 H 4.876984 0.763489 2.518494 H 4.930984 -0.868500 5.138504 H 6.262985 0.096497 4.469498 H 4.787979 0.889496 5.052505 H -0.962006 1.852493 2.518494 H 0.459000 2.839493 2.591492 H -1.027008 1.712494 5.052505 H -1.076996 3.386490 4.469498 H 0.423996 2.715485 5.138504 H 4.221985 -2.615494 3.742493 H 2.838989 -3.655502 3.393494 H 3.883987 2.297485 3.393494 H 2.290985 2.975494 3.742493 H 2.744980 1.792496 -0.975479 H 2.445984 2.500488 -3.279480 H 4.017990 6.415497 -2.316483 H 2.970978 -2.417496 -0.975479 H 3.733978 -2.511490 -3.279480 H 6.338989 -5.830490 -2.316483 H -1.584000 -1.492493 3.742493 H -1.794006 0.225494 3.393494 H -0.788010 -0.508500 -0.975479 H -1.251007 -1.121490 -3.279480 H -5.428009 -1.717500 -2.316483 Br 1.642990 -0.377502 -2.198486 242 COMPLEX OF Br ANION WITH 2 WITH C3 SYlvI,'vlETRY fJ'vfPOSED. Energy -5646.3163446 hartree 91 V ~ ~~ ~?? ""-II '":>C 0.053986 3.017532 -0.272873 jv__e~'1 ~0'a~ 1.394730 ~ ) \~;.~C 3.027679 -0.718460 .y::-~C::- C 2.457382 3.017654 0.202835 ~I . It> 1if""",c:P """'~ n ~ \\1 \\c 2.173721 3.009308 1.587021 (. <:::"c:P ~\\ ~ c 0.843307 2.999069 2.046967 It //.1 11 I~ <"" e. tIlC -0.212800 3.009247 1.108627 ill 1 C 0.534409 2.971786 3.540176 ciosesl eMbon = 3.305 A C 0.467941 4.380325 4.167831 C 3.905746 3.010284 -0.275085 Figure CA Ball and stick representation of C 4.469147 4.427353 -0.516251 receptor 2 DFT minima with Br- C -1.084427 3.010254 -1.288300 C -1.587723 4.426407 -1.638351 C 3.323441 2.883942 2.566849 0 3.803223 1.498856 2.551102 C 3.597931 0.732162 3.640381 C 3.879395 -0.712082 3.370468 0 3.235092 I. 154236 4.726578 C 1.669724 2.921875 -2.205475 0 1.430313 l.539032 -2.628800 C 2.483231 0.787048 -3.003983 C 2.123900 -0.659546 -3.128754 0 3.602280 1.222916 -3.227585 C 0.897324 -l.162613 -2.672500 C 0.639084 -2.527954 -2.807617 C 1.572540 -3.410828 -3.337891 C 2.787643 -2.883987 -3.772797 C 3.077759 -1.524307 -3.669006 C 4.094406 -I. 197632 2.072998 C 4.333237 -2.561768 1.897171 C 4.322617 -3.459885 2.957550 243 C 4.093338 -2.950211 4.234985 C 3.865921 -1.592422 4.454910 N 3.779602 -3.787125 -4.375031 N -0.662918 -3.056000 -2.366928 N 4.115021 -3.869995 5.382339 N 4.600830 -3.071716 0.541809 0 4.643448 -4.298370 0.387497 0 4.783203 -2.244705 -0.354630 0 -0.805832 -4.284515 -2.341629 0 -1.539200 -2.241058 -2.067490 0 3.941025 -3.390915 6.508484 0 4.322189 -5.067764 5.156631 0 4.836990 -3.292800 -4.782104 0 3.492844 -4.986984 -4.455292 C -1.636902 2.883469 1.612747 0 -1.870026 1.493561 2.016266 C -2.713730 0.741333 1.282745 C -2.627304 -0.708618 1.640533 0 -3.471207 1.179306 0.431427 C -1.614105 -1.210953 2.468796 C -1.587570 -2.579315 2.744675 C -2.505768 -3.465210 2.191772 C -3.495300 -2.938843 1.362427 C -3.564346 -1.576447 1.074768 N -4.503220 -3.845749 0.794128 N -0.550446 -3.107239 3.645966 0 -0.444534 -4.335922 3.742310 0 0.139175 -2.292282 4.263992 0 -5.389160 -3.352234 0.087600 0 -4.417145 -5.048004 1.068314 H 1.277725 2.377472 4.074936 H -0.410950 2.452591 3.717743 H 1.420929 4.913956 4.058289 244 H 0.240723 4.312759 5.239502 H -0.306183 4.999054 3.694397 H 4.537308 2.489166 0.447800 H 4.003937 2.427277 -1.194092 H 4.439362 5.035522 0.397491 H 5.510773 4.374069 -0.855896 H 3.892990 4.963928 -1.280823 H -1.922836 2.414612 -0.919266 H -0.767900 2.502594 -2.202026 H -1.967148 4.949203 -0.751587 H -2.402817 4.373260 -2.372070 H -0.789000 5.047470 -2.063217 H 4.183563 3.487976 2.271683 H 3.056610 3.148758 3.587494 H 2.684067 3.200012 -2.481384 H 0.977570 3.525742 -2.796082 H 0.154587 -0.513718 -2.226944 H 1.360046 -4.470612 -3.411987 H 4.036819 -1.138794 -3.999069 H 4.082962 -0.536331 1.216278 H 4.487167 -4.518265 2.795837 H 3.673691 -1.220291 5.454941 H -1.807983 3.475479 2.513947 H -2.385864 3.162476 0.875046 H -0.863342 -0.559311 2.896744 H -2.453278 -4.526962 2.400177 H -4.332932 -1.191100 0.413589 Br 1.125702 -1.092407 0.623932 245 R= Figure C.S Vials containing tripodal anion receptors and halides in benzene. 246 SUPPORTING REFERENCES 1. A. Vacca, C. Nativi, M. Cacciarini, R, Pergoli, S. Roelens, J. Am. Chem. Soc. 2004, 126, 16456-16465. 2. Synthetic Communications. 1998.28(11),2021-2026. 3. A. P. Bisson, C. A. Hunter, J. C. Morales and K. Young, Chem. Eur. J., 1998,4,845-851 4. G. M. Sheldrick, SADABS: Area Detector Absorption Correction; University of Gottingen: Gottingen, Germany, 2001. 5. P. Van der Sluis and A. L. Spek, Acta Crystallographica, Section A: Foundations of Crystallography, 1990, A46, 194-20I. 6. G. M. Sheldrick, SHELXTL: Program Library for Structure Solution and Molecular Graphics, 5.10; Bruker AXS: Madison, WI, 2000). 7. E. J. Bylaska, W. A. de Jong, K. Kowalski, T. P. Straatsma, M. Valiev, D. Wang, E. Apra, T. L. Windus, S. Hirata, M. T. Hackler, Y. Zhao, P.-D. Fan, R. J. Harrison, M. Dupuis, D. M. A. Smith, J. Nieplocha, V. Tipparaju, M. Krishnan, A. A. Auer, M. Nooijen, E. Brown, G. Cisneros, G. I. Fann, H. Fruchtl, J. Garza, K. Hirao, R. Kendall, J. A. Nichols, K. Tsemekhman, K. Wolinski, J. Anchell, D. Bemholdt, P. Borowski, T. Clark, D. Clerc, H. Dachsel, M. Deegan, K. Dyall, D. Elwood, E. Glendening, M. Gutowski, A. Hess, J. Jaffe, B. Johnson, J. Ju, R. Kobayashi, R. Kutteh, Z. Lin, R. Littlefield, X. Long, B. Meng, T. Nakajima, S. Niu, L. Pollack, M. Rosing, G. Sandrone, M. Stave, H. Taylor, G. Thomas, J. van Lenthe, A. Wong, and Z. Zhang, NWChem, A Computational Chemistry Package for Parallel Computers, Version 5.0, 2006, Pacific Northwest National Laboratory, Richland, Washington 99352-0999, USA. 8. (a) Becke, A. D. Phys. Rev. A 1988, 38, 3098. (b) Becke, A. D. In The Challenge ofd and f Electrons: Theory and Computation; Salahub, D. R.; Zemer, M. C., Eds.; ACS Symposium Series, No. 394, American Chemical Society: Washington D. C., 1989; p166. (c) Becke, A. D. Int. J. Quantum Chem. Symp. 1989,23,599. (d) Perdew, J. P. Phys. Rev. B 1986, 33, 8822. 9. Godbout, N.; Salahub, D. R.; Andzelm, J.; Wimmer, E. Can. J. Chem. 1992, 70,560. 247 APPENDIXD SUPPORTING INFORMATION FOR CHAPTER V: INVESTIGATING THE USE OF INTRAMOLECULAR HYDROGEN BONDS TO STABILIZE RECEPTOR CONFORMATIONS; DESIGNING RECEPTORS FOR ANIONIARENE INTERACTIONS EXPERIMENTAL GENERAL. All chemicals were obtained from TCI-America, Sigma-Aldrich, Acros and Strem. Nuclear Magnetic Resonance IH NMR and 13C NMR spectra were recorded on a Varian INOVA 300 (299.935) and 125 (125.751) MHz spectrometer respectively. Chemical shifts (0) expressed as ppm downfield from tetramethylsilane using either the residual solvent peak as an internal standard (CDC!) IH: 7.27 ppm) or using CDC!) spiked with 1% trimethylsilane for the IH NMR spectra. For the 13C NMR spectra the middle CDC!) peak (Q 77.00 ppm) was used as the internal standard. Signal patterns are indicated as b, broad; s, singlet; d, doublet; t, triplet; m, multiplet. Coupling constants (J) are given in hertz. 248 Synthesis ofTREN based tripodal amide receptor (JeHCl). 3,5-dinitrobenzoyl chloride (3.152 g, 13.67 mmol) is weighed out into a 100 ml oven dried round bottom flask. Dry dimethylformamide (10 ml) is added via syringe and the reaction is stirred at o°C. Tris(2-aminoethyl)amine (0.51 ml, 3.40 mmol) is added dropwise and warmed to room temperature overnight. The remaining solution is heated to 160°C for an additional 2 hours. Upon cooling the reaction mixture is poured over ice and the resulting oily solid is triturated with methanol to yield a tan powder in 80 % yield (1.94 g, 2.71 mmol) IH NMR (300 MHz, d6 - DMSO; 25°C): 0 9.68 (t, 3H), 9.01 (t, J= 3.0 Hz, 3H), 8.95 (d, J= 3.0 Hz, 6H), 3.63 (b). Synthesis ofTRPN based tripodal amide receptor (2-HCl): 3,5-dinitrobenzoyl chloride (2.460 g, 10.67 mmol) is weighed out into a 100 ml oven dried round bottom flask. Dry dimethylformamide (10 ml) is added via syringe and the reaction is stirred at o°C. Tris(3-aminopropyl)amine (0.52 ml, 2.62 mmol) is added dropwise and warmed to room temperature overnight. The reaction mixture is poured over ice and the resulting oily solid is sonicated repeatedly with water to yield a tan powder in 50 % yield (1.1244 g, 1.45 mmol) IH NMR NMR (300 MHz, d6 - DMSO; 25°C): 0 9.31 (t, 3H), 9.00 (d, J= 3.0 Hz, 6H), 8.91 (t, J= 3.0 Hz, 3H), 3.60 (m, 2H), 3.38 (m, 2H), 1.76 (m, 2H). 249 Synthesis ojphosphine based receptor (3). Weigh out tris(methylamine) phosphineoxide hydrobromide (0.208 g, 0.57 mmol) and K2C03 (00408 g, 2.95 mmol) into an oven dried round bottom flask (l00 ml) under a nitrogen atmosphere using standard schlenk techniques. A I: I mixture of ethyl acetate: water (50 ml) is added to the reaction flask. In a separate container 3,5-dinitrobenzoyl chloride (0.388 g, 1.68 rnrnol) is dissolve in ethyl acetate 4 ml. This solution is transferred dropwise while stirring the reaction mixture vigorously. The ethyl acetate layer is separated and the solvent removed under vacuum. The resulting product decomposes under an oxygen atmosphere. IH NMR (300 MHz, d6- DMSO; 25 DC): 0 9.58 (t, J= 6.3 Hz, 3H), 9.07 (d, J = 1.8 Hz, 6H), 8.96 (t, J = 2.1 Hz, 3H), 3.91 (b,6H). Synthesis ojphosphine oxide based receptor (4).Weigh out tris(methylarnine) phosphineoxide hydrobromide (0.107 g, 0.28 mmol) and K2C03 (0.250 g, 0.03 rnrnol) into a round bottom flask (l00 ml) and dissolve with 1: I ethyl acetate:water (20 ml). In separate container weigh out 3,5-dinitrobenzoyl chloride (0.238 g, 1.03 mmol) and dissolve in ethyl acetate (3 ml). Transfer this solution dropwise to the reaction mixture while stirring vigorously. After 2 hours the ethyl acetate layer separated and the solvent is removed under vacuum yielding a white powder that is sparingly soluble in ethyl acetate, acetonitrile and hot ethyl alcohol. IH NMR (300 MHz, d6 - DMSO; 25 DC): 0 9.64 (t, 3H), 9.03 (t, J = 1.8 Hz, 6H), 8.92 (t, 3H), 4.13 (b, 6H). 250 FUMING HN03. Fuming RN03 is prepared by distilling equal parts (v) ofRN03 and H2S04• The red distillate is collected at standard pressure at 80°C. CAUTION fuming HN03 is a strong oxidizer and should be handled with extreme caution. Highly electron-deficient aromatic rings have the potential to be explosive. Handle with care. Synthesis of4-chloro-3,5-dinitrobenzoic acid (7). Freshly distilled fuming nitric acid (4 ml) and concentrated sulfuric acid (20 ml) are cooled to 0 °c in a round bottom flask equipped with a magnetic stir bar. 4-chlorobenzoic acid (6) (5 g, 31.93 mmol) is transferred to the acid solution in 5 portions while stirring vigorously. The reaction mixture is warmed to room temperature and the heat is slowly increased to 90°C. The yellow solution is heated for 8 hours. The reaction mixture is then cooled to room temperature and poured over 50 ml of ice. The pale yellow/green solid is filtered and washed with copious amounts of distilled water and dried under vacuum. The crystalline product is obtained in 92 % yield (7.25 g, 29.40 mmol) MP 166.1-167.0 °c. IHNMR (300 MHz, CDC!); 25°C): 0 8.66 (s, 2H), 3.29 (b, 1H). 251 Synthesis of4-chloro-3,5-dinitrobenzoic acid ethyl ester (8). (procedure adapted from J. Org. Chern. Vol. 66 No.9 2001, 2985.) Thionyl chloride (30 ml) is added dropwise to dry ethanol (90 ml) at 0 DC. After solution has returned to 0 DC the 4- chloro-3,5-dinitrobenzoic acid (7) is added and the reaction mixture is heated to reflux. After 8 hours of refluxing the colorless solution is removed from heat and cooled to room temperature. The colorless crystals that formed upon cooling are collected and washed with cold ethanol. The ethanol wash is combined with the reaction solution and the solvent is removed under reduced pressure. Additional ester (8) is obtained by recrystallization of the reaction residue from hot ethanol (6.11 g, 92 %). MP 85.3-87.3 DC. IH NMR NMR (300 MHz, CDCh; 25 DC): 8 8.61 (s, 2H), 4.48 (q, J= XX Hz, 2B), 1.45 (t, J = X.X Hz, 3H). Synthesis of4-cyano-3,5-dinitrobenzoic acid ethyl ester (9). In dry conditions under nitrogen using proper schlenk technique a flame dried 3-neck round bottom flask (100 ml) is charged with 4-chloro-3,5-dinitrobenzoic acid ethyl ester (8) (6.11 g, 22.26 mmol) and copper cyanide (2.79 g, 31.17 mmol). Dry dimethylformamide (30 ml) is added via syringe and the yellow solution is heated to 150 DC for 4 hours. After cooling to room temperature the dark green solution is poured over ice (150 ml). The dark green/red precipitate is collected and washed with water until the wash is colorless. The dark precipitate is dissolved in a minimal amount of ethyl acetate and filtered through a plug of silica. The eluent is collected in three portions with most of the - ------ 252 product being collected with the first 200 ml. The eluent is removed under reduced pressure and the resulting orange solid is recrystallized from hot ethyl alcohol in 52 % yield (3.07 g, 11.57 mmol) and the remaining ethyl ester (9) is obtained by reducing the ethyl alcohol concentration and fractional crystallization. IH NMR NMR (300 MHz, CDC!); 25 DC): D9.07 (s, 2H), 4.55 (q, J= 7.2 Hz, 2H), 1.49 (t, J= 7.5 Hz, 3H). IH NMR NMR (300 MHz, d6 - DMSO; 25 DC): D8.92 (s, 2H), 4.45 (q, J= 6.9 Hz, 2H), 1.38 (t, J= 7.2 Hz, 3H). 13C NMR (125 MHz, d6 - DMSO; 25 DC): D161.75, 151.18, 135.12, 129.59, 110.51, 105.69,63.01, 13.90. Synthesis of4-cyano-3,5-dinitrobenzoic acid (5). A round bottom flask (250 ml) is charged with 4-cyano-3,5-dinitrobenzoic acid ethyl ester (9) (5.22 g, 19.69 rnrnol). Glacial acetic acid (100 ml) and concentrated HCI (30 ml) are added to the round bottom flask and the reaction is heated to 90 DC overnight under a nitrogen atmosphere. After 14 hours the reaction is cooled to room temperature. The acid (5) is extracted with diethyl ether (3 x 150 ml) and subsequently dried with Na2S04. The diethyl ether is removed under reduced pressure leaving a yellow solid. Alternatively the product can be collected as a yellow solid (4.43 g, 95%) after removing the acetic acid/HCI under reduced pressure. The acid is 96% pure by 1H NMR and can be purified by washing the yellow solid with dichloromethane. IH NMR NMR (300 MHz, d6 - DMSO; 25 DC): D8.89 (s, 2H), 3.50 (b, 1H). 253 X-RAY DIFFRACTION. Single-crystal X-ray diffraction data for compounds I-HCl, 4 and 5 were collected on a Bruker-AXS SMART APEXlCCD diffractometer using MOka radiation (A = 0.7107 A) at 152 K. Diffracted data have been corrected for Lorentz and polarization effects, and for absorption using the SADABS v2.02 area- detector absorption correction program (Siemens Industrial Automation, Inc., © 1996). The structures were solved by direct methods and the structure solution and refinement was based on IFf. Hydrogen were found from the residual density map when possible and refined with isotropic thermal parameters and otherwise placed in calculated positions and given isotropic U values 1.2 times that of the atom to which they are bonded. All non-hydrogen atoms were refined with anisotropic displacement parameters. All crystallographic calculations were conducted with the SHELXTL v.6.l program package (Bruker AXS Inc., © 2001). Crystal data for I-HCl: C27H2SClNIOOIS, M = 765.02, triclinic, P-l, a = 12.3142(13) A, b = 13.2582(15) A, c = 20.049(2) A, a = 92.948(2)°, P= 95.577(2)°, y = 92.771(2t, V = 3248.9(6) A3, Z= 4, .u(Mo-Ka) = 0.208 mm- l . Final residuals (1155 parameters) Rl = 0.0430 for 13528 reflections with I> 2a(!), and Rl = 0.0716, wR2 = 0.1238, GooF = 0.978 for all 25458 data. Crystal data for 4: CgHIN30s.3P0.3 (C2H60S), M= 953.83, Rhombohedral, R3, a = 26.969(4) A, b = 26.969(4) A, c = 4.7896(9) A, a:= 90.00°,p = 90.00°, y = 120.00°, V = 3016.8(8) A3, Z= 3, .u(Mo-Ka) = 0.315 mm- l . Final residuals (213 parameters) Rl = 254 0.0543 for 2974 reflections with I> 2a(!), and R1 = 0.1004, wR2 = 0.0864, GooF = 0.801 for all 9960 data. Crystal data for 5: CSH3N306 ·(C2H60S), M = 252.21, monoclinic, P(2) 11c, a = 9.9021(17) A, b = 5.9929(10) A, c = 22.218(4) A, a = 90.00°, fJ = 96.386(3)°, y = 90.00°, V= 1310.3(4) A3, Z= 4, Jl(Mo-Ka) = 0.287 mm- I . Final residuals (226 parameters) R1 = 0.0460 for 3029 reflections with I> 2a(!), and R1 = 0.0622, wR2 = 0.1062, GooF = 1.053 for all 10638 data. 255 APPENDIXE SUPPORTING INFORMATION FOR CHAPTER VI: A CONFORMATIONALLY DIVERSE SERIES OF MOLECULES; 2,6-BIS(ETHYNYL)PYRIDINE, BIPYRIDINE AND THIOPHENE AS SCAFFOLDS FOR MODULAR RECEPTOR DESIGN 15000 1-«lO1l 13000 12000 11000 11m) 9000 lIOOO ) / iI I , !, T l-{ ~ T T ~ 8 ~ ;~ '" l1XXI .--.-l~~j'______ __ LL-"~__ L ~ I 8.5 f 7.5 I I 6.5 I 5.5 iii I 4.5 3.5 II (ppm) j 2.5 i 1.5 I 0.5 IllOOO 17000 16000 15000 IlOOO 11000 11000 10000 256 I / r Ii T en 1" '" T TI3 ~ " ~ :;: ~" I ~JLi~J~, .~ ~~ c ----.iL--__ 9000 7000 6000 sooo 4000 1000 7.5 5.5 4.5 4 3.5 Ill""",) I 2.5 1.5 0.5 257 0.00480 mmol) were dissolved in seperate portions ofCDCh with 1 % TMS (1 mL) passed through basic alumina and dried with 3 Amolecular sieves. Aliquots (400 J.!L) from each solution were transfered to an NMR tube via syringe and thoroughly mixed. IH NMR spectra were recorded on a Varian 300 MHz spectrometer. Proton signals were referenced to the 1 % TMS included in the CDCh. IH NMR (300 MHz, CDCh): 07.81-7.73 (m, 10H), 7.52-7.44 (m, 12H), 7.38-7.33 (m, 8H), 7.18 (d, J= 9 Hz, 4H), 6.85 (d, J = 9 Hz, 6H), 7.18 (d, J = 6 Hz, 3H) 2.29 (s, 6H), 1.26 (s, 18H). [1-H20)-[7a-H20). i-H20 (3.650 mg, 0.00488 mmol) and 7a-H20 (3.740 ~""" mg, 0.00480 mmol) I' ..•., '1' I' ~ ~; ~ s 1.' , .., ., fl (pp"") 'I' ~ , " i .., 258 [Hl+eCne[H7a+eCn. The stock solutions from the preparation of [leH20]e[7aeH20] (above) were combined and protonated with HCI gas (see below, General salt preparation). IH NMR spectra were recorded on a Varian 300 MHz spectrometer. Proton signals were referenced to the 1 % TMS included in the CDCh. IH NMR (300 MHz, CDCh): () 9.49 (s, 2H), 9.44 (s, 2H), 8.30 (b, 2H), 8.18 (d, J= 9 Hz, 4H), 8.12 (d, J= 9 Hz, 4H), 7.71 (d, J = 6 Hz, 4H) 7.46 (m, 12H), 7.17 (d, J= 6 Hz, 4 H), 6.85 (d, J = 6 Hz, 4H), 3.73 (s, 6H), 2.27 (s, 6H), 1.25 (s, 36H). I, I, / // j-.f /-_1 () 2000 .- ,..,. 2"" llIOO lBOO " 1600 1..,. 1200 1000 BOO 600 I .., ')',1\, '1"1 I' 'I' ~ ~~ s ~ ~ ~ I ,I i 8.5 ].5 1 6.5 fit 5.5 5 4.5 II (ppm) , 3.S i 2,' I I.' I ,., ·200 259 General salt preparation. A 10 mM stock solution of sulfonamide receptor dissolved in CDCh with I % TMS that has been passed through basic alumina and stored over 3 Amolecular seives was prepared. With a 9 inch pipette and 10 ml pipet bulb HCI gas is passed through the sulfonamide solution 20 times. The resulting yellow solution is diluted to the original volume and an appropriate aliqout is removed for study. (Hl+-Cr)2. 10 mM stock solutions of (Hl+-C02 were prepared according to the General salt preparation (above). IH NMR (300 MHz, CDCh): 89.51 (b, 2H), 8.40 (b, IH), 8.13 (d, J = 6 Hz, 4H), 8.00-7.75 (b, 4H), 7.48-7.41 (m, 6H), 7.18 (d, J = 6 Hz, 3H) 2.29 (s, 6H), 1.26 (s, 18H). ~ I 3800 3600 3200 I , r j I I !, , , / / / J .. / / ~ T T'"I T T T T ~ ~ ~ ~ ~ 8~ ~ ~ ~2800 2800 2400 2200 2000 '''''' 1600 1400 1200 1000 !lOO I i JO 9.5 , 8.5 I ' '~5 I •. 5 Ii' 5~5 f1 (ppm) i '.5 800 I J 400I' 200)L- o , I I 3~5 2.5 1.5 260 (H7a+-Cr)2. 10 mM stock solutions of (H7a+-C02 were prepared according to the General salt preparation (above).lH NMR (300 MHz, CDCb): ~ 9.36 (b, 2H), 8.31 (t, IH), 8.17 (d, J = 9 Hz, 4H), 7.72 (d, J = 9 Hz, 4H), 7.40 (m, 6H), 6.86 (d, J = 9 Hz, 4H) 3.75 (s, 6H), 1.26 (s, 18H). M~~ tr~; ~~il2 '\\7 \1' \;; \1 I (" , I i r ./~} J ; , j .' } T err T T -( ~ ~~ '" ~ ~.; ~ 5000 T ~500 ~ooo ·3500 3000 2500 I ! T ~ 1500 1000 I 9.5 i itS I i 7.5 i 6.5 , I I I I 5.5 S -4.5 f1(ppm) . [ 3.5 i 2.5 i 15 Jl. I 0.5 500 261 Dilution experiment: (l.HzO)z (88.260 mg, 0.180 mmo1) was dissolved in CDCh (600 ).1.1) saturated with H20. CDCh saturated with H20 was prepared by mixing equal parts (v/v) CDCh and H20 for 30 minutes followed by separation of the two layers. Aliquots of CDCh saturated with H20 were added to the initial solution of receptor (197 mM) until the end point of the titration is reached (minimal change in chemical shift observed per per aliquot of CDCh). All additions were performed through septa with a Hamilton gas tight microsyringe at room temperature. 1H NMR spectra were recorded after each addition on a Varian 300 MHz spectrometer. Proton signals were referenced to the residual CHCh signal. The dimerization constant Kdim was calculated by plotting the change in the shift of the sulfonamide proton versus the total concentration and the resulting data was fit to a 1:1 dimerization with the non-linear regression curve fitting software WinEQNMR. -13.0 I~~ 7.a 7.7 0.0 0.0 a.a 13.2 17.6 22..0 lO··2:[Concentz:",tiQn),.... l da-3 PlCl8suted Chea1cal shifts ~or 8 1:1 D1.81: [JDO:!::!:] 262 vol file vol Vol prior Total vol [R] NH peak removed added to in NMR prior to (ml) addition tube after addition 0 JD022_0 0 0 0.6 1.967E-01 7.855 0 JD022_1 0.01 0.6 0.61 1.934E-01 7.855 0 JD022_2 0.02 0.61 0.63 1.873E-01 7.854 0 JD022_3 0.02 0.63 0.65 1.815E-01 7.856 0 JD022_4 0.03 0.65 0.68 1.735E-01 7.86 0 JD022_5 0.04 0.68 0.72 1.639E-01 7.847 0 JD022_6 0.05 0.72 0.77 1.532E-01 7.845 0 JD022_7 0.05 0.77 0.82 1.439E-01 7.834 0 JD022_8 0.075 0.82 0.895 1.318E-01 7.837 0 JD022_9 0.1 0.895 0.995 1.186E-01 7.832 0 JD022_10 0.15 0.995 1.145 1.031E-01 7.82 0 JD022_11 0.2 1.145 1.345 8.773E-02 7.797 0 .ID022_12 0.25 1.345 1.595 7.398E-02 7.777 0 .ID022_13 0.45 1.595 2.045 5.770E-02 7.761 1.25 JD022_14 0.5 0.795 1.295 3.542E-02 7.725 0 JD022_15 0.5 1.295 1.795 2.556E-02 7.708 0 JD022_16 0.7 1.795 2.495 1.839E-02 7.679 1.75 JD022_17 1 0.745 1.745 7.850E-03 7.621 0 JD022_18 1 1.745 2.745 4.990E-03 7.599 1 .ID022_19 1.3 1.745 3.045 2.860E-03 7.562 NOESYID experiment. (l-H20)2 (88.260 mg, 0.180 mmol) was dissolved in CDC!] (600 ~l) saturated with H20. CDC!] saturated with H20 was prepared by mixing equal parts (v/v) CDC!] and H20 for 30 minutes followed by separation of the two layers. IH NMR spectra were recorded on a Varian 500 MHz spectrometer. Proton signals were referenced to the residual CHC!] signal. NOE between the water and sulfonamide protons were observed by irradiating either the guest water protons (3.042 ppm) or the hydrogen bonding sulfonamide protons (7.570 ppm) and observing signal enhancement from the other protons. D8G-51111 pulse S~quellce: NOES,'lD So 1yent: CDC 13 re.p. 25.0 C I Z98.1 I( User: I-1S-87 It.lOVA-SOO "leart.s" Relal<. delay 1.00(1 51'1;; Pulse 99.0 degrees Hh'ing O.SOO sec ,\cq. t Ille z .341 iCC .... ldth '999.7 H.I: 61 repel 1t 10ns OBSERVE HI, 500.1042443 MHz DATA PROCESSING l1 Jll! broaden 1ng 1.5 l-fl; fT sile 131072 Total t i ... e 37 1111'1, 7 sec B Pulse SCJl"l'n-::e; :-i{J(SY 10 Sol'/cnt~ Ci:'C13 reRp. 25.0 C / 293.1 x lIser' I-1S-87 lIIOVA-!JOO "j(aru~" Rel.,X, de lily 2.000 sec P"I se g~. 0 degrc .. s Ml" 10 mM (for halide salts HX gas was passed through the EtOAc solution of receptor). Alternatively, 1 drop of concentrated HX is added and the resulting yellow solution is thoroughly mixed). Hexanes cooled to O°C were layered on top of receptor solutions and set aside. After 3 days colorless (neutral receptor complex) or yellow (protonated receptor complex) single crystals were harvested for X-ray diffraction studies. Refer to ciffiles for exact structural details. 265 REFERENCES CHAPTER I (1) P. Gamez, T. J. Mooibroek, S. J. Teat and J. Reedijk,Acc. Chern. Res., 2007,40,435-444. (2) B. L. Schottel, H. T. Chifotides and K. R. Dunbar, Chern. Soc. Rev., 2008, 37, 68-83. (3) B. P. Hay and V. S. Bryantsev, Chern. Cornrnun., 2008, in press. (4) C. L. Jackson and W. F. Boos,Arn. Chern. J., 1898,20,444-455. (5) C. L. Jackson and F. H. Gazzolo,Arn. Chern. J., 1900,23,376-396. (6) J. Meisenheimer,Justus LiebigsAnn. Chern., 1902,323,205-226. (7) E. Buncel, A. R. Norris and K. E. Russell, Quart. Rev. Chern. Soc., 1968,22, 123-146. (8) R. S. Mulliken,J. Arn. Chern. Soc., 1952,74,811-824. (9) G. A. Artamkina, M. P. Egorov and I. P. Beletskaya, Chern. Rev., 1982,82,427-459. (10) C. F. Bernasconi, Ace. Chern. Res., 1978,11, 147-152. (11) C. F. Bernasconi, Chirnia, 1980,34, 1-11. (12) M. J. Strauss, Chern. Rev., 1970,70,667-712. (13) M. J. Strauss, Ace. Chern. Res., 1974,7,181-188. (14) F. Terrier, Chern. Rev., 1982,82, 77-152. (15) S. Chowdhury, E. P. Grimsrud, T. Heinis and P. Kebarle, J. Arn. Chern. Soc., 1986, 108, 3630-3635. (16) S. Chowdhury, T. Heinis and P. Kebarle, J. Arn. Chern. Soc., 1986,108,4662-4663. (17) S. Chowdhury and P. Kebarle, J. Arn. Chern. Soc., 1986,108,5453-5459. 266 (18) S. Chowdhury, H. Kishi, G. W. Dillow and P. Kebarle, Can. J. Chem., 1989,67,603-610. (19) S. Chowdhury, G. Nicol and P. Kebarle, Chem. Phys. Lett., 1986,127, 130-132. (20) E. P. Grimsrud, S. Chowdhury and P. Kebarle, Int. J. Mass Spectrom. and Ion Processes, 1986,68,57-70. (21) T. Heinis, S. Chowdhury, S. L. Scott and P. Kebarle, J. Am. Chem. Soc., 1988, 110, 400- 407. (22) K. Hirao and P. Kebarle, Can. J. Chem., 1989,67, 1261-1267. (23) K. Hiraoka, S. Mizuse and S. Yamabe, J. Phys. Chem., 1987,91,5294-5297. (24) K. Hiraoka, S. Mizuse and S. Yamabe, J. Chem. Phys., 1987, 86, 4102-4105. (25) P. Kebarle and S. Chowdhury, Chem. Rev., 1987,87,513-534. (26) G. J. C. Paul and P. Kebarle, J. Am. Chem. Soc., 1991,113, 1148-1154. (27) B. Chiavarino, M. E. Crestoni, S. Fornarini, F. Lanucara, J. Lemaire and P. Maitre, Angew. Chem. Int. Ed, 2007, 46, 1995-1998. (28) H. Sun and S. G. DiMagno, Angew. Chem. Int. Ed., 2006, 45, 2720-2725. (29) I. Alkorta, I. Rozas and J. Elguero, J. Am. Chem. Soc., 2002,124,8593-8598. (30) M. Mascal, A. Armstrong and M. D. Bartberger, J. Am. Chem. Soc., 2002, 124, 6274-6276. (31) D. Quinonero, C. Garau, C. Rotger, A. Frontera, P. Ballester, A. Costa and P. M. Deya, Angew. Chem. Int. Ed, 2002, 41, 3389-3392. (32) C. F. Carolina, A.; Quinoner, D.; Ballester, P.; Costa, A.; Deya, P. M., Chem. Phys. Chem., 2003, 4, 1344-1348. (33) A. Clements and M. Lewis, J. Phys. Chem. A, 2006,110, 12705-12710. (34) D. Escudero, A. Frontera, D. Quinonero and P. M. Deya, Chem. Phys. Lett., 2008, 455, 325- 330. (35) C. Estarellas, D. Quinonero, A. Frontera, P. Ballester, J. Morey, A. Costa and P. M. Deya, J. Phys. Chem. A, 2008,112, 1622-1626. (36) A. Frontera, F. Saczewski, M. Gdaniec, E. Dziemidowicz-Borys, A. Kurland, P. M. Deya, D. Quinonero and C. Garau, Chem. Eur. J., 2005, 11, 6560-6567. 267 (37) C. Garau, A. Frontera, P. Ballester, D. Quinonero, A. Costa and P. M. Deya, Eur. J. Org. Chern., 2004, 179-183. (38) C. Garau, A. Frontera, D. Quinonero, P. Ballester, A. Costa and P. M. Deya, Chern. Phys. Lett., 2004, 399, 220-225. (39) C. Garau, A. Frontera, D. Quinonero, P. Ballester, A. Costa and P. M. Deya, J. Phys. Chern. A, 2004, 108,9423-9427. (40) C. Garau, A. Frontera, D. Quinonero, P. Ballester, A. Costa and P. M. Deya, Chern. Phys. Lett., 2004, 392, 85-89. (41) C. Garau, D. Quinonero, A. Frontera, P. Ballester, A. Costa and P. M. Deya, Org. Lett., 2003, 5,2227-2229. (42) C. Garau, D. Quinonero, A. Frontera, P. Ballester, A. Costa and P. M. Deya, J. Phys. Chern. A, 2005,109,9341-9345. (43) C. Garau, D. Quinonero, A. Frontera, A. Costa, P. Ballester and P. M. Deya, Chern. Phys. Lett., 2003, 370, 7-13. (44) A. Garcia-Raso, F. M. Alberti, J. J. Fiol, A. Tasada, M. Barcelo-Oliver, E. Molins, D. Escudero, A. Frontera, D. Quinonero and P. M. Deya, Eur. J. Org. Chern., 2007,5821-5825. (45) A. Garcia-Raso, F. M. Alberti, J. 1. Piol, A. Tasada, M. Barcelo-Oliver, E. Molins, D. Escudero, A. Frontera, D. Quinonero and P. M. Deya, Inorg. Chern., 2007, 46, 10724-10735. (46) J. M. Hermida-Ramon and C. M. Estevez, Chern. Eur. J., 2007,13,4743-4749. (47) M. Mascal, Angew. Chern. Int. Ed, 2006, 45, 2890-2893. (48) D. Quinonero, A. Frontera and M. Deya Pere, Chern. Phys. Chern, 2008, 9, 397-399. (49) D. Quinonero, A. Frontera, C. Garau, P. Ballester, A. Costa and P. M. Deya, Chern. Phys. Chern., 2006, 7,2487-2491. (50) D. Quinonero, C. Garau, A. Frontera, P. Ballester, A. Costa and P. M. Deya, Chern. Phys. Lett., 2002, 359, 486-492. (51) H. Schneider, K. M. Vogelhuber, F. Schinle and 1. M. Weber, J. Arn. Chern. Soc., 2007,129, 13022-13026. (52) D. Escudero, A. Frontera, D. Quinonero, A. Costa, P. Ballester and P. M. Deya, J. Chern. Theory Cornput., 2007, 3, 2098-2107. (53) C. Garau, D. Quinonero, A. Frontera, D. Escudero, P. Ballester, A. Costa and P. M. Deya, Chern. Phys. Lett., 2007,438, 104-108. 268 (54) M. R. Jackson, R. Beahm, S. Duvvuru, C. Narasimhan, J. Wu, H.-N. Wang, V. M. Philip, R. J. Hinde and E. E. Howell, J. Phys. Chern. B, 2007,111,8242-8249. (55) D. Kim, P. Tarakeshwar and K. S. Kim, J. Phys. Chern. A, 2004,108, 1250-1258. (56) D. Quinonero, A. Frontera, D. Escudero, P. Ballester, A. Costa and P. M. Deya, Chern. Phys. Chern., 2007, 8, 1182-1187. (57) D. Quinonero, C. Garau, A. Frontera, P. Ballester, A. Costa and P. M. Deya, J. Phys. Chern. A,2005,109,4632-4637. (58) B. L. Schottel, H. T. Chifotides, M. Shatruk, A. Chouai, L. M. Perez, J. Bacsa and K. R. Dunbar, J. Am. Chern. Soc., 2006,128,5895-5912. (59) M. Zaccheddu, C. Filippi and F. Buda, J. Phys. Chern. A, 2008,112, 1627-1632. (60) O. B. Berryman, F. Hof, M. J. Hynes and D. W. Johnson, Chern. Cornrnun., 2006, 506-508. (61) O. B. Berryman, V. S. Bryantsev, D. P. Stay, D. W. Johnson and B. P. Hay, J. Am. Chern. Soc., 2007, 129,48-58. (62) R. Ahuja and A. G. Samuelson, Cryst. Eng. Cornrn., 2003, 5, 395-399. (63) C. A. Black, L. R. Hanton and M. D. Spicer, Chern. Cornrnun., 2007, 3171-3173. (64) C. A. Black, L. R. Hanton and M. D. Spicer, Inorg. Chern., 2007, 46, 3669-3679. (65) C. S. Campos-Fernandez, B. L. Schottel, H. T. Chifotides, J. K. Bera, J. Bacsa, J. M. Koomen, D. H. Russell and K. R. Dunbar, J. Am. Chern. Soc., 2005, 127, 12909-12923. (66) H. Casellas, C. Massera, F. Buda, P. Gamez and J. Reedijk, New J. Chern., 2006, 30, 1561- 1566. (67) P. de Hoog, P. Gamez, I. Mutikainen, U. Turpeinen and J. Reedijk, Angew. Chern. Int. Ed., 2004,43,5815-5817. (68) S. Demeshko, S. Dechert and F. Meyer, J. Am. Chern. Soc., 2004,126,4508-4509. (69) R. M. Fairchild and K. T. Holman, J. Am. Chern. Soc., 2005,127, 16364-16365. (70) I. Y. A. Gural'skiy, P. V. Solntsev, H. Krautscheid and K. V. Domasevitch, Chern. Cornrnun., 2006, 4808-4810. (71) P. U. Maheswari, B. Modec, A. Pevec, B. Kozlevcar, C. Massera, P. Gamez and J. Reedijk, Inorg. chern., 2006, 45, 6637-6645. 269 (72) B. L. Schottel, J. Bacsa and K. R. Dunbar, Chern. Cornrnun., 2005, 46-47. (73) X.-P. Zhou, X. Zhang, S.-H. Lin and D. Li, Cryst. Growth Des., 2007, 7,485-487. (74) M. Albrecht, C. Wessel, M. de Groot, K. Rissanen and A. Luechow, J. Arn. Chern. Soc., 2008,130,4600-4601. (75) P. S. Lakshminarayanan, 1. Ravikumar, E. Suresh and P. Ghosh,Inorg. Chern., 2007, 46, 4769-4771. (76) T. Dorn, C. Janiak and K. Abu-Shandi, Cryst. Eng. Cornrn., 2005, 7, 633-641. (77) M. Mascal, 1. Yakovlev, E. B. Nikitin and J. C. Fettinger, Angew. Chern. Int. Ed., 2007, 46, 8782-8784. (78) T. J. Mooibroek, C. A. Black, P. Gamez and J. Reedijk, Cryst. Growth Des., 2008, 8, 1082- 1093. (79) B. Han, J. Lu and J. K. Kochi, Cryst. Growth Des., 2008, 8, 1327-1334. (80) Y. S. Rosokha, S. V. Lindeman, S. V. Rosokha and J. K. Kochi, Angew. Chern. Int. Ed., 2004, 43, 4650-4652. (81) H. 1. Schneider, Angew. Chern. Int. Ed., 1991, 1411, 1417-1436. (82) G. Bruno, G. Cafeo, F. H. Kohnke and F. Nicolo, Tetrahedron, 2007, 63, 10003-10010. (83) G. Gil-Ramirez, E. C. Escudero-Adan, J. Benet-Buchholz, P. Ballester, Angew. Chern. Int. Ed. 2008, in press. (84) H. Maeda, T. Morimoto, A. Osuka and H. Furuta, Chern. Asian J., 2006,1,832-844. (85) H. Maeda, A. Osuka and H. Furuta, J. Inclusion Phenorn. Macrocyclic Chern., 2004, 49, 33- 36. 270 CHAPTER II (1) P. D. Beer and P. A. Gale, Angew. Chern. Int. Ed, 2001, 40, 486. (2) A. P. Bisson, V. M. Lynch, M.-K. C. Monahan, and E. V. Anslyn, Angew. Chern. Int. Ed, 1997,36,2340. (3) J. L. Sessler, S. Camiolo, and P. A. Gale, Coord. Chern. Rev., 2003, 240, 17. (4) A. Bianchi, K. Bowman-James, E. Garcia-Espana, and Editors, 'Supramolecular Chemistry of Anions', Wiley-VCH, New York, 1997. (5) D. Quinonero, C. Garau, C. Rotger, A. Frontera, P. Ballester, A. Costa, and P. M. Deya, Angew. Chern. Int. Ed, 2002,41,3389. (6) A. Frontera, F. Saczewski, M. Gdaniec, E. Dziemidowicz-Borys, A. Kurland, P. M. Deya, D. Quinonero, and C. Garau, Chern. Eur. J., 2005, 11, 6560. (7) M. Mascal, A. Armstrong, and M. D. Bartberger, J. Arn. Chern. Soc., 2002,124,6274. (8) D. Kim, P. Tarakeshwar, and K. S. Kim, J. Phys. Chern. A, 2004,108, 1250. (9) C. Garau, A. Frontera, D. Quinonero, P. Ballester, A. Costa, and P. M. Deya, J. Phys. Chern. A, 2004,108,9423. (10) P. de Hoog, P. Gamez, W. L. Driessen, and J. Reedijk, Tetrahedron Lett., 2002, 43, 6783. (11) P. de Hoog, P. Gamez, I. Mutikainen, U. Turpeinen, and J. Reedijk, Angew. Chern. Int. Ed., 2004,43,5815. (12) S. Demeshko, S. Dechert, and F. Meyer, J. Arn. Chern. Soc., 2004,126,4508. (13) Y. S. Rosokha, S. V. Lindeman, S. V. Rosokha, and J. K. Kochi, Angew. Chern. Int. Ed., 2004, 43, 4650. (14) J. Pang, Y. Tao, S. Freiberg, X.-P. Yang, M. D'Iorio, and S. Wang, J. Mater. Chern., 2002, 12,206. (15) C. Garau, A. Frontera, D. Quinonero, P. Ballester, A. Costa, and P. M. Deya, Chern. Phys. Chern., 2003,4, 1344. (16) J. C. Ma and D. A. Dougherty, Chern. Rev., 1997,97, 1303. 271 (17) A hydrogen bonding interaction is included in our first receptor design to enhance the association of the receptor for anions. IH NMR and UV-Vis spectroscopic studies of simple electron deficient aromatics such as hexafluorobenzene, 1,3,5-trifluorobenzene, 1,3,5- tribromobenzene and 1,3,5-trichlorobenzene showed no measurable binding with the halides. This suggested that a single anion-n interaction using a halogenated aromatic would not be strong enough to drive binding in solution. (18) T. Sakamoto, Y. Kondo, S. Iwashita, T. Nagano, and H. Yamanaka, Chern. Pharrn. Bull., 1988,36, 1305. (19) N. Shimizu, T. Kitamura, K. Watanabe, T. Yamaguchi, H. Shigyo, and T. Ohta, Tet. Lett., 1993, 34, 3421. (20) M. G. Banwell, B. D. Kelly, O. J. Kokas, and D. W. Lupton, Org. Lett., 2003,5,2497. (21) The X-ray crystal structure of 1 is in agreement with recent theoretical studies regarding the attractive interaction between the lone pair of a heteroatom and an electron-deficient aromatic ring. (22) 1. Alkorta, 1. Rozas, and J. Elguero, J. Org. Chern., 1997,62,4687. (23) CAChe, version 5.0, Fujitsu America, Beaverton, USA, 2002. (24) M. J. Hynes, J. Chern. Soc., Dalton Trans., 1993, 311. (25) The dimerization constants for receptors 1 and 2 were measured by IH NMR titrations (see method described in: A. P. Bisson; C. A. Hunter; J. C. Morales; K. Young. Chern. Eur. J. 19984,845). Receptor 1 exhibits weak dimerization (Ka ~ 2 M-1) in CDCb, whereas receptor 2 shows no measurable dimerization. Attempts to correct anion binding constants for the dimerization of receptor 1 failed to produce an acceptable fit to the data. Presumably, the weak dimerization in receptor 1 plays a negligible role in the binding of anions (see ESI). (26) O. B. Berryman, D. W. Johnson, 2005, unpublished results. (27) D. Quinonero, C. Garau, A. Frontera, P. Ballester, A. Costa, and P. M. Deya, Chern. Phys. Lett., 2002, 359, 486. (28) M. H. Abraham, P. L. Grellier, D. V. Prior, P. P. Duce, J. J. Morris, and P. J. Taylor, J. Chern. Soc., Perkin Trans. 2, 1989,699. 272 (29) Reference 28 presents a scale of hydrogen bond acidities based on 10gK values. While the sulfonamide functionality is not specifically addressed, data for other acidic functionalities are presented with the equation log K = LbpKa + Db relating pKa and hydrogen bonding Ka, where Lband Db are constants specific for a given family of molecules. Estimates using the upper limit of these constants result in predicted Ka values for receptor 2 sufficient to be detected by IH NMR spectroscopy. CHAPTER III (1) (a) Supramolecular Chemistry ofAnions; Bianchi, A., Bowman-James, K., Garcia-Espafia, E., Eds.; Wiley-VHC, New York, 1997; (b) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97, 1609; (c) Gale, P. A. Coord. Chem. Rev. 2000, 199, 181; (d) Gale, P. A. Coord. Chem. Rev. 2001,213, 79; (d) Beer, P. D.; Gale, P. A. Angew. Chem. Int. Ed. 2001,40,486; (e) Fitzmaurice, R. J.; Kyne, G. M.; Douheret, D.; Kilburn, J. D. J. Chem. Soc., Perkin Trans. 1 2002, 841; (f) Martinez-Mlifiez, R.; Sacenon, F. Chem. Rev. 2003, 103,4419; (g) Suksai, C.; Tuntulani, T. Chem. Soc. Rev. 2003, 32, 192; (h) Choi, K.; Hamilton, A. D. Coord. Chem. Rev. 2003, 240, 101; (i) Lambert, T. N.; Smith, B. D. Coord. Chem. Rev. 2003,240, 129; (j) Davis, A. P.; Joos, J.-B. Coord. Chem. Rev. 2003,240, 143; (k) Gale, P. A. Coord. Chem. Rev. 2003, 240, 191; (1) Fundamentals and Applications of Anion Separations; Moyer, B. A., Singh, R. P., Eds.; Kluwer AcademiclPlenum, New York, 2004: (m) Chupakhin, O. N.; Itsikson, N. A.; Morzherin, Y. Y.; Charushin, V. N. Heterocycles 2005, 66, 689; (n) Kubik, S.; Reyheller, C.; StOwe, S. J. Inc/. Phenom. Macro. Chem. 2005, 52, 137; (0) Schmidtchen, F. P. Top. Curro Chem. 2005,255, 1. (2) Mascal, M.; Armstrong, A.; Bartberger, M. D. J. Am. Chem. Soc. 2002, 124, 6274. (3) Quinofiero, D.; Garau, C.; Rotger, C.; Frontera, A.; Ballester, P.; Costa, A.; Deya, P. M. Angew. Chem. Int. Ed. 2002,41,3389. (4) Quinofiero, D.; Garau, c.; Frontera, A.; Ballester, P.; Costa, A.; Deya, P. M. Chem. Phys. Lett. 2002,359,486. (5) Alkorta, I.; Rozas, I.; Elguero, J. J. Am. Chem. Soc. 2002, 124, 8593. (6) Kim, D.; Tarakeshwar, P.; Kim. K. S. J. Phys. Chem. A. 2004, 108, 1250. (7) Garau, C.; Frontera, A.; Quinofiero, D.; Ballester, P.; Costa, A.; Deya, P. M. J. Phys. Chem. A 2004, 108,9423. (8) Garau, C.; Frontera, A.; Quinofiero, D.; Ballester, P.; Costa, A.; Deya, P. M. Chem. Phys. Lett. 2004,392, 85. (9) Garau, C.; Frontera, A.; Ballester, P.; Quinofiero, D.; Costa, A.; Deya, P. M. Eur. J. Org. Chem. 2005, 179. 273 (10) Quinofiero, D.; Garau, c.; Frontera, A; Ballester, P.; Costa, A; Deya, P. M. J. Phys. Chem. A 2005,109,4632. (11) Garau, c.; Quinofiero, D.; Frontera, A; Ballester, P.; Costa, A; Deya, P. M. J. Phys. Chem. A 2005, 109, 9341. (12) Frontera, A; Saczewski, F.; Gdaniec, M.; Dziemidowicz-Borys, E.; Kurland, A; Deya, P. M.; Quinofiero, D.; Garau, C. Chem. Eur. J. 2005, II, 6560. (13) Related charge-insulator complexes-in which an aromatic ring is sandwiched between an anion and a metal cation-lie outside the scope of the present study. For theoretical studies see: (a) Garau, c.; Quinofiero, D.; Frontera, A.; Ballester, P.; Costa, A.; Deya, P. M. New J. Chem. 2003, 2, 211. (b) Garau, C. Frontera, A; Quinofiero, D.; Ballester, P.; Costa, A; Deya, P. M. Chem. Phys. Lett. 2003, 382, 534. (c) Alkorta, 1.; Elguero, J. J. Phys. Chem. A 2003, 107,9428. For representative solid-state examples see: (d) Fairchild, R. M.; Holman, K. T. J. Am. Chem. Soc. 2005, 127, 16364. (e) Staffilani, M.; Hancock, K. S. B.; Steed, J, W.; Holman, K. T.; Atwood, J. L.; Juneja, R. K.; Burkhalter, R. S. J. Am. Chem. Soc. 1997, 119, 6324. (t) Holman, K. T.; Halihan, M. M.; Mitchell, A R.; Burkhalter, R. S.; Steed, J. W.; Jurisson, S. S.; Atwood, J. L. J. Am. Chem. Soc. 1996, 118,9567. (14) Rosokha, Y. S.; Lindeman, S. V.; Rosokha, S. V.; Kochi, J. K. Angew. Chem. IntI. Ed 2004, 43, 4650. (15) Demeshko, S.; Dechert, S.; Meyer, F. J. Am. Chem. Soc. 2004, 126,4508. (16) Single crystal X-ray structures also provide examples of anions interacting with charged 1t systems in which electron-deficient aromatic rings are coordinated to metal cations: (a) de Hoog, P.; Gamez, P. Mutikainen, 1.; Turpeinen, U.; Reedijk, J. Angew. Chem. Int. Ed 2004, 43,5815; (b) Schottel, B. L.; Bacsa, J.; Dunbar, K. R. Chem. Commun. 2005,46; (c) Shottel, B. L.; Chifotides, T. H.; Shatruk, M. Chouai, A.; Perez, L. M.; Gacsa, J.; Dunbar, K. R. J. Am. Chem. Soc. 2006, 128,5895. (17) NMR studies of N-confused porphyrins demonstrate an enhanced association with anions when C6Fs substituents are present: (a) Maeda, H.; Osuka, A.; Furuta, H. J. Inclusion Phenom. Macrocyclic Chem. 2004, 49, 33; (b) Maeda, H.; Furuta, H. J. Porphyrins Phthalocyanines 2004,8,67. For an example of an aryl sulfonate interacting with a neutral arene: (c) Schneider, H. J.; Werner, F.; Blatter, T. J. Phys. Org. Chem. 1993,6,590. (18) Berryman, O. B.; Hof, F.; Hynes, M. J.; Johnson, D. W. Chem. Commun. 2006,506. (19) Hoffman, R. W.; Hettche, F. New. J. Chem. 2003,27, 172. (20) Sheldrick, G. M. SADABS: Area Detector Absorption Correction, University of Gottingen: Gottingen, Germany, 2001. (21) Sheldrick, G. M. SHELXTL: Program Library for Structure Solution and Molecular Graphics, 5.10; Broker AXS: Madison, WI, 2000. 274 (22) NWChem, A Computational Chemistry Package for Parallel Computers, Version 4.6 (2004), Straatsma, T. P. et al. Computer Phys. Comm. 2000, 128,260-283. (23) Moller, C.; Plesset, M. S. Phys. Rev. 1934,46,618. (24) (a) Dunning, T. H., Jr. J. Chem. Phys. 1989, 90, 1007. (b) Kendall, R A; Dunning, T. H., Jr.; Harrison, R J. J. Chem. Phys. 1992,96,6796. (25) (a) NBO, Version 5.0, Glendening, E. D.; Badenhoop, J. K.; Reed, A E.; Carpenter, J. E.; Bohmann, J. A; Morales, C. M.; Weinhold, F. Theoretical Chemistry Institute, University of Wisconsin, Madison, WI, 2001; http://www.chem.wisc.edu/~nbo5.(b)AE.Reed.A E.; Curtiss, L. A; Weinhold, F. Chem. Rev. 1988,88,899. (c) Weinhold, F.; Landis, C. Valency and Bonding; Cambridge University Press: Cambridge UK, 2005. (26) (a) Cambridge Structural Database, Version 5.27, November 2005, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 l£Z, UK; (a) Allen, F. H.; Kennard, 0.; Taylor, RAce. Chem. Res. 1983, 16 146; (b) Allen, F. H.; Davies, J. E.; Galloy, J. J.; Johnson, 0.; Kennard, 0.; Macrae, C. F.; Mitchell, E. M.; Smith, J. M.; Watson, D. G. J. Chem. lrif. Comput. Sci. 1991, 31, 187. (c) Allen, F. H.; Kennard, O. Chemical Design Automation News 1993, 8, 31. (27) A previous histogram for electronegative atoms interacting with perfluoroarenes reported hits for compounds exhibiting a contact between the interacting heteroatom and an arene carbon if the distance was :S the sum of van der Waals radii.3 In fact, the actual criterion used in those studies was the sum of van der Waals radii + 1.0 A, which is the default option provided in the Quest Version 5 database searching program: C. Garau personal communication, February, 2006. (28) Bryantsev, V. S.; Hay, B. P. J. Am. Chem. Soc. 2005, 127, 8282. (29) Bryantsev, V. S.; Hay, B. P. Org. Lett. 2005, 7,5031. (30) Such complexes were first reported in: (a) Jackson, C. J.; Gazzolo F. H. J. Am. Chem. Soc. 1900, 23, 376. A structure was later isolated and characterized in: (b) Meisenheimer, J. Justus Liebigs Ann. Chem. 1902,323,205. (31) (a) Strauss, M. J. Chem. Rev. 1970, 70, 667; (b) Strauss, M. J. Ace. Chem. Res. 1974, 7, 181; (c) Bernasconi, C. F. Ace. Chem. Res. 1978,11, 147. (32) Besler, B. H.; Merz, K. M.; Kollman, P. A J. Comput. Chem. 1990, 11, 431. (33) Wiberg, K. B.; Rablen, P. R J. Compo Chem. 1993,14, 1504. (34) Table 1 of ref. 2 refers to a stable "attack" complex formed by cr and trifluorotriazine. This is the only reported instance where a donor n-acceptor complex was calculated for cr, Br- orr. (35) Ahuja, R; Samuelson, A. G. Crys. Eng. Commun. 2003, 5, 395. 275 (36) We do not observe a preference for the anion to be located over the para-position. Possible explanations include (i) electrostatic attraction between the anion and metal cation and (ii) the electropositive metal center inductively stabilizes anion binding at the ortho-positions more than at the para-position. (37) The C-H groups in Cu(II)-coordinated pyridine are more acidic than those in benzene. Thus, the strength for one of these interactions should exceed -8.6 kcal mOr1•28,29 With three electron donating amine substituents, the melamine n: system should form weaker complexes than triazine. Thus, the strength of this anion-n: interaction should be less than -8.4 kcal mor 1 (Table 3.2). CHAPTER IV (1) O. B. Berryman, V. S. Bryantsev, D. P. Stay, D. W. Johnson, B. P. Hay, J. Am. Chem. Soc. 2006, 129,48. (2) B. P. Hay, V. S. Bryantsev, Chem. Commun. 2008, in press. (3) For recent overviews see: (a) P. Gamez, T. J. Mooibroek, S. J. Teat, and J. Reedijk, Ace. Chem, Res., 2007, 40, 435; (b) B. L. Schottel, H. T. Chifotides, and K. R. Dunbar, Chem. Soc. Rev., 2008,37,68. (4) A. Bianchi, K. Bowman-James, E. Garcia-Espana, Editors, Supramolecular Chemistry of Anions, Wiley-VCH, New York, 1997. (5) J. L. Sessler, P. A. Gale, W.-S. Cho, Anion Receptor Chemistry, The Royal Society of Chemistry, Cambridge, UK, 2006. (6) J. L. Sessler, D. E. Gross, W.-S. Cho, V. M. Lynch, F. P. Schmidtchen, G. W. Bates, M. E. Light, P. A. Gale, J. Am. Chem. Soc. 2006, 128, 12281. (7) Y. S. L. Rosokha, S. V.; Rosokha, S. V.; Kochi, J. K.,Angew. Chem. 2004,116,4750; Angew. Chem. Int. Ed 2004, 43, 4650. (8) O. B. Berryman, F. Hof, M. J. Hynes, D. W. Johnson, Chem. Commun. 2006, 506. (9) R. M. Fairchild, K. T. Holman, J. Am. Chem. Soc. 2005, 127, 16364. (10) H. Maeda, A. Osuka, H. Furuta, J. Inc!. Phenom. Macrocycl. Chem. 2004,49,33. (11) H. J. Schneider, F. Werner, T. Blatter, J. Phys. Org. Chem. 1993,6,590. 276 (12) lH NMR spectroscopy has been used previously to demonstrate the importance of complementary C-H·"X- hydrogen bonding modes in receptors that bind anions using traditional H-bonds (a-e) or electrostatic attractions (f,g): a) C. -H. Lee, H.-K. Na, D.-W. Yoon, D.-H. Won, W.-S. Cho, V. M. Lynch, S. V. Shevchuk, J. L. Sessler,J. Am. Chem. Soc. 2003,125, 7301; b) J. Y. Kwon, Y. J. Jang, S. K. Kim, K.-H. Lee, J. S. Kim, J. Yoon, J. Org. Chem. 2004,69,5155; c) Q.-Y. Chen, C.-F. Chen, Tetrahedron Lett. 2004, 45, 6493; d) S. Ghosh, A. R. Choudhury, T. N. G. Row, U. Maitra, Org. Lett. 2005, 7, 1441; e) C. Fujimoto, Y. Kusunose, H. Maeda, J. Org. Chem. 2006, 71,2389; t) K. J. Wallace, W. J. Belcher, D. R. Turner, K. F. Syed, J. W. Steed, J. Am. Chem. Soc. 2003, 125,9699; g) I. E. D. Vega, P. A. Gale, M. E. Light, S. J. Loeb, Chem. Commun. 2005,4913. (13) G. Hennrich, E. V. Anslyn, Chem. Eur. J. 2002,8,2218. (14) J. C. Lee, Y. Choi, Synth. Commun. 1998,28,2021. (15) Crystal data for 1: C36H30N6018, M = 834.66, triclinic, P-1, a = 5.6949(12) A, b = 19.833(4) A, c = 33.883(7) A, a = 84.106(4)°, P= 85.278(5)°, y = 81.873(5)°, V= 3759.6(14) N, Z = 4, .u(Mo-Ka) = 0.121 mm'l. Final residuals (1321 parameters) R1 = 0.0566 for 16401 reflections with I> 20(1), and R1 = 0.1090, wR2 = 0.1446, GooF = 1.007 for all 23621 data. CCDC # 661394. (16) Crystal data for 2: (C36H30N6018)(C2~OS)3, M= 1069.04, monoclinic, n(1)/n, a = 28.272(12) A, b = 5.075(2) A, c = 37.126(15) A, P= 110.669(7)°, V= 4984(4) A3, Z = 4, .u(Mo-Ka) = 0.091 mm'l. Final residuals (544 parameters) R1 = 0.0857 for 8731 reflections with I> 20(1), and R1 = 0.1736, wR2 = 0.2640, GooF = 0.946 for all 33339 data. CCDC # 661395. (17) UV-Vis titrations for receptors 1 and 2 with NHep4+r at 21°C were performed to corroborate the lH NMR titrations herein. Regrettably, the charge transfer band that grows in throughout the titration appears as a shoulder on the residual NHep4+r band that increases throughout the titration. Thus UV-vis spectroscopy is impracticle for binding constant determination in this system. Nevertheless, binding isotherms were obtained and can be fit to 1: 1 binding models with the program DynaFit (P. Kuzmic, Anal. Biochem. 1996,237, 260.) resulting in association constants of 4.5 M'l for receptor 1 and 6.0 M'l for receptor 2. Receptors containing aromatic rings that are more electron-deficient and should exhibit charge transfer bands with anions that are further downfield are being synthesized to address this problem and will be reported in due course. (18) K. Hirose, J. Inc!. Phenom. Macrocyc!. Chem. 2001,39, 193. (19) Titrations of receptors 1 and 2 (~5 mM) with tetra-n-butylammonium bromide (NBu/Br-) were performed at room temperature resulting in lower association constants (averaging 4-6 M'\ These data indicate that counter cation and/or temperature plays a role in the anion binding ability of this system. Nevertheless, titrations of receptor 1 at these concentrations (~5 mM) with NBu4+Br- better illustrate the dramatic chemical shift changes for this receptor. 277 (20) Analogous titrations of 1 (2 mM) at 27°C with NHep4+halides also exhibit striking peak movement (up to 0.632 ppm for NHep/Ct, 0.500 ppm for NHep/Br- and 0.390 ppm for NHep4+0 throughout the experiment (Table 4.1 and Appendix C). (21) DFT calculations were performed with the NWCHEM program (a) using the B3LYP functional (b-e) with the DZVP basis set and DGauss Al coulomb fitting (f) (Optimized geometries and absolute energies for all structures are provided as Supporting Information). (a) Bylaska et al. NWChem, A Computational Chemistry Package for Parallel Computers, Version 5.0, 2006, Pacific Northwest National Laboratory, Richland, Washington 99352- 0999, USA; for a full author list see supporting information. (b) Becke, A. D. Phys. Rev. A 1988, 38, 3098. (c) Becke, A. D. In The Challenge of d and fElectrons: Theory and Computation; Salahub, D. R; Zerner, M. c., Eds.; ACS Symposium Series, No. 394, American Chemical Society: Washington D. c., 1989; p166. (d) Becke, A. D. Int. J. Quantum Chern. Symp.1989, 23, 599. (e) Perdew, J. P. Phys. Rev. B 1986, 33,8822. (f) N. Godbout, D. R. Salahub, J. Andzelm, E. Wimmer, Can. J. Chern. 1992, 70, 560. (22) (a) V. S. Bryantsev, B. P. Hay, J. Arn. Chern. Soc. 2005, 127, 8282. (b) V. S. Bryantsev, B. P. Hay, Org. Lett. 2005, 7, 5031. (23) An alternate conformation, 6.0 kcal/mol higher in energy, was located for 1-Br-, where the Br- forms a weak 0' complex (3.432 A) with one arene and bifurcated aryl H-bonds (2.832 A, 3.043 A, 2.909 Aand 3.021 A) with the other two (see Appendix C). It is possible that the H-bond complex and/or the weak 0' structure is responsible for the pale yellow or colors observed in solution when receptors 1 and 3 are mixed with Br- or r. (24) As a control, no color is observed when NHep/r is dissolved in C6D6 and heated to 27°C (25) NHep/r stock solutions were kept in a sonicator at 27°C to insure salt solubility CHAPTER V (1) P. A. Kollman and L. C. Allen, Chern. Rev., 1972,72,283-303. (2) G. C. Pimentel and A. L. McClellan, The Hydrogen Bond, 1960. (3) G. C. Pimentel and A. L. McClellan, Ann. Rev. Phys. Chern., 1971,22,347-385. (4) W. H. Rodebush, Chern. Rev., 1936,19,59-65. (5) P. A. Kollman, J. Arn. Chern. Soc., 1972,94, 1837-1842. (6) E. N. Lassettre, Chern. Rev., 1937,20,259-303. (7) A. S. N. Murthy and C. N. R Rao, J. Mol. Struct., 1970,6,253-282. (8) D. Ajami and J. Rebek, Jr., J. Arn. Chern. Soc., 2006, 128, 15038-15039. 278 (9) N. Branda, R. M. Grotzfeld, C. Valdes and J. Rebek, Jr., JAm. Chem. Soc., 1995,117,85- 88. (10) S. M. Butterfield and J. Rebek, Jr., Chem. Commun., 2007, 1605-1607. (11) R. J. Hooley, P. Restorp, T. Iwasawa and J. Rebek, Jr.,J. Am. Chern. Soc., 2007,129, 15639-15643. (12) T. Iwasawa, R. J. Hooley and 1. Rebek, Jr., Science, 2007, 317, 493-496. (13) L. R. MacGillivray and J. L. Atwood, Nature, 1997,389,469-472. (14) A W. Frank and D. J. Daigle, Phosphorus, Sulfur Relat. Elem., 1981,10,255-259. (15) R. Huang and B. J. Frost, Inorg. Chem., 2007, 46,10962-10964. CHAPTER VI (1) Ahn, C. M.; Shin, W.-S.; Woo, H. B.; Lee, S.; Lee, H.-W. Bioorg. Med. Chem. Lett. 2004, 14,3893-3896. (2) Baxter, P. N. W.; Dali-Youcef, R. J Org. Chem. 2005, 70,4935-4953. (3) Holmes, B. T.; Deb, P.; Pennington, W. T.; Hanks, T. W. J Polym. Res. 2006,2006, 133- 144. (4) Rajadurai, C.; Ivanova, A; Enkelmann, V.; Baumgarten, M. J Org. Chem. 2003,68,9907- 9915. (5) Yamaguchi, Y.; Kobayashi, S.; Wakamiya, T.; Matsubara, Y.; Yoshida, Z.-I.Angew. Chem. Int. Ed 2005, 44, 7040-7044. (6) Phelps, D.; Crihfield, A; Hartwell, J.; Hanks, T. W.; Pennington, W. T.; Bailey, R. D. Mol. Cryst. Liq. Cryst. 2000, 354, 1111. (7) Chen, J.; Korner, S.; Craig Stephen, L.; Rudkevich Dmitry, M.; Rebek, J., Jr. Nature 2002, 415,385-386. (8) Dalgamo, S. J.; Tucker, S. A; Bassil, D. B.; Atwood, J. L. Science 2005, 309, 2037-2039. (9) Hof, F.; Craig, S. L.; Nuckolls, c.; Rebek, J., Jr. Angew. Chem. Int. Ed 2002,41, 1488- 1508. 279 (10) Pluth, M. D.; Bergman, R. G.; Raymond, K. N. Science 2007,316,85-88. (11) Yoshizawa, M.; Tamura, M.; Fujita, M. Science 2006, 312, 1472. (12) Rhee, Y. M.; Sorin, E. J.; Jayachandran, G.; Lindahl, E.; Pande, V. S. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 6456-6461. (13) Dym, 0.; Mevarech, M.; Sussman, J. L. Science 1995,267, 1344-1346. (14) Richard, S. B.; Madem, D.; Garcin, E.; Zaccai, G. Biochemistry 2000,39,992-1000. (15) Sessler, J. L.; Gale, P. A; Cho, W.-S. Anion Receptor Chemistry, Royal Society of Chemistry, Cambridge, 2006. (16) Liu, K.; Cruzan, 1. D.; Saykally, R. J. Science 1996,271,929-933. (17) Friedman, 1.; Meharenna, Y. T.; Wilks, A; Poulos, T. L. J. BioI. Chem. 2007, 282, 1066- 1071. (18) Nagano, S.; Poulos, T. L. J. Bio!. Chem. 2005,280,31659-31663. (19) MacBeth, C. E.; Golombek, A P.; Young, V. G., Jr.; Yang, C.; Kuczera, K.; Hendrich, M. P.; Borovik, A S. Science 2000, 289, 938-941. (20) Hof, F.; Trembleau, L.; Ullrich, E. C.; Rebek, J., Jr. Angew. Chem. Int. Ed. 2003,42,3150- 3153. (21) MacGillivray, L. R.; Atwood, J. L. Nature 1997, 389, 469-472. (22) Yamanaka, M.; Shivanyuk, A.; Rebek, J., Jr. J, Am. Chem. Soc. 2004,126,2939-2943. (23) Atwood, J. L.; Barbour, L. J.; Jerga, A. Chem. Commun. 2001,2376-2377. (24) Biros, S. M.; Rebek, J., Jr. Chem. Soc. Rev. 2007, 36,93-104. (25) An understanding of the coordination preferences of anions is emerging, but the directionality is still less defined than for their cationic counterparts. For a detailed discussion, see: Kang, S. 0.; Hossain, M. A; Bowman-James, K. Coord. Chem. Rev. 2006, 250,3038. (26) Sanchez-Quesada, J.; Seel, C.; Prados, P.; de Mendoza, J.; Daleo1, I.; Giralt, E. J. Am. Chem. Soc. 1996,118,277-278. (27) Vilar, R. Angew. Chem. Int. Ed. 2003,42, 1460-1477. (28) Coles, S. J.; Frey, J. G.; Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Navakhun, K.; Thomas, G. L. Chem. Commun. 2003, 568-569. 280 (29) Gale, P. A; Navakhun, K.; Camiolo, S.; Light, M. E.; Hursthouse, M. B. J. Am. Chern. Soc. 2002,124,11228-11229. (30) Nielsen, K. A; Cho, W.-S.; Sarova, G. H.; Petersen, B. M.; Bond, A D.; Becher, J.; Jensen, F.; Guidi, D. M.; Sessler, J. L.; Jeppesen, J. O. Angew. Chern. Int. Ed. 2006, 45, 6848-6853. (31) For an example of water and halides occupying the same binding sites in a protein, see: Fiedler, T. J.; Davey, C. A.; Fenna, R. E. J. Bioi. Chern. 2000,275, 11964. (32) Wan, W. B.; Haley, M. M. J. Or. Chern. 2001, 66,3893-3901. (33) Crystal data for (1·H20)2: (C43145N305S2)2, A1r = 1495.88 , 0.31 x 0.18 x 0.15 mm, triclinic, P-l, a = 10.0377(17) A, b = 12.755(2) A, c = 17.357(3) A, a = 111.270(3)°, P= 96.113(3)°, Y= 102.966(3)°, V = 1974.4(6) N, Z = 1 (i.e., one dimer per unit cell), Pealed = 1.258 g mL-\ ,u = 0.183 mm-\ 2Bmax = 54.00°, T= 173(2) K, Rl = 0.0470 for 6966 reflections (662 parameters) with I> 2a(l), and Rl = 0.0580, wR2 = 0.1222, and GOF = 1.028 for all 8480 data, maximin residual electron density +0.502/-0.682 e A-3. (34) Crystal data for (2·H20)2: (C4IH39N509S2)2, A1r = 1619.78,0.30 x 0.20 x 0.01 mm, triclinic, P-l, a = 10.1068(15) A, b = 12/5999(19) A, c = 17.186(3) A, a = 110.709(3)°, P= 97.006(3)°, Y = 100.306(3)°, V= 1972.9(5) A3, Z = 1, Pealed = 1.363 g mL-\,u = 0.198 mm-\ 2Bmax = 54.00°, T= 173(2) K, Rl = 0.0642 for 4980 reflections (674 parameters) with I> 2a(l), and Rl = 0.1233, wR2 = 0.1462, and GOF = 1.034 for all 8413 data, maximin residual electron density +0.312/-0.432 e A-3. (35) The "staggered" conformation for sulfonamides refers to the conformation in which the lone pair of the nitrogen atom bisects the o-s-o angle (the lone pair is anti-periplanar to the S-C bond), see: Hirsch, A K. H.; Lauw, S.; Gersbach, P.; Schweizer, W. B.; Rohdich, F.; Eisenreich, W.; Bacher, A; Diederich, F. Chern. Med Chern. 2007,2,806. (36) Hynes, M. J. J. Chern. Soc. Dalton Transactions 1993,311-312. (37) Other potential guest molecules that did not co-crystallize with sulfonamide receptors include: hydrogen sulfide, methanol, ethanol, isopropanol, acetone, acetonitrile, dimethylsulfoxide, tetrahydrofuran, tetra-n-butylammonium halides and HS04-. (38) Crystal data for (H1+eBr")2: (C43144BrN304S2)2, A1r = 1621.68,0.21 x 0.07 x 0.02 mm, triclinic, P-l, a = 9.632(16) A, b = 13.33(2) A, c = 17.47(3) A, a = 108.39(4)°, P= 94.56(5)°, Y = 106.51(4)°, V= 2005(6) N, Z = 1, Pealed = 1.343 g mL-\,u = 1.175 mm-\ 2Bmax = 54.00°, T= 173(2) K, Rl = 0.0598 for 5748 reflections (599 parameters) with I> 2a(l), and Rl = 0.1021, wR2 = 0.1527, and GOF = 1.035 for all 8622 data, maximin residual electron density +0.680/-0.371 e A-3. 281 (39) Crystal data for (H2+·C02: (C41H3gCINsOgS2)2, U = 1656.66,0.30 x 0.25 x 0.02 mm, triclinic, P-l, a = 9.8907(13) A, b = 12.9533(17) A, c = 17.012(2) A, a = 107.831(2)°, P= 95.845(2)°, Y= 103.618(2)°, V= 1980.5(4) N, Z= 1, Pealed = 1.389 g mL"\,u = 0.262 mm"\ 2()max = 54.00°, T= 173(2) K, Rl = 0.0572 for 6572 reflections (594 parameters) with I> 2a(I), and Rl = 0.0744, wRl = 0.1594, and GOF = 1.045 for all 8472 data, maximin residual electron density +0.564/-0.290 e k 3• (40) The UV-Vis spectrum of HI+·BF4" is consistent with the yellow color of the protonated receptor in organic solutions. Upon protonation receptor I exhibits a new absorption peak with a A.max at 400 nm. The unique absorption characteristics of receptor HI+were used to study the host/guest interactions of this molecule in solution. Specifically, tetra-n- butylammonium halides were titrated into CH2Ch solutions ofHI+·BF4- while maintaining constant receptor concentrations. Evident changes in the UV-Vis spectra were observed upon addition of halide anions. In all cases the absorption bands at 240,290 and 330 nm were shown to increase in intensity throughout the titration while the intensity of the absorption band at 400 nm decreased, exemplifying isosbestic behavior. Unfortunately, at low concentrations equilibrium conditions were not observed precluding the determination of binding constants by UV-Vis spectrophotometric titrations. lH NMR spectroscopic titrations in CDCh were employed to examine the anion binding capability of receptor HI+ for tetra-n-butylammonium halides. The binding isotherms obtained from titrations of HI+·BF4- with halides exhibit a steep linear increase up to one equivalent of halide, with chloride affecting the steepest binding isotherm and iodide the shallowest. The second portion of the equilibrium exhibits a much smaller influence on the overall chemical shift of the complex. The second portion of the binding isotherm has made it difficult to determine association constants. Host guest equilibria will be reported in due course. (41) Subsequent iterations of this experiment resulted in the formation of precipitate suggesting that the first trial was supersaturated. The relatively low solubility of this complex in organic solvents has hindered further determination of association constants. (42) Crystal data for (HI+CO-(1-H20): (C43~3N304S2)2·H20·HCI,U = 1514.32, 0.20 x 0.08 x 0.02 mm, triclinic, P-l, a = 9.9702(13) A, b = 12.8868(17) A, c = 17.363(2) A, a = 111.314(2)0,p=95.475(3)0,y= 103.737(2)°, V= 1977.7(4)N,z= 1,Pealed= 1.271 gmL"\ ,u = 0.215 mm"\ 2()max = 54.00°, T= 173(2) K, R1 = 0.0671 for 5583 reflections (559 parameters) with I> 2a(I), and R1 = 0.1074, wR2 = 0.1673, and GOF = 1.027 for all 8485 data, maximin residual electron density +0.842/-0.723 e A"3.