Chemistry Theses and Dissertations

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https://hdl.handle.net/1794/2046

This collection contains some of the theses and dissertations produced by students in the University of Oregon Chemistry Graduate Program. Paper copies of these and other dissertations and theses are available through the UO Libraries.

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NEW METHODS FOR ELEMENTAL SULFUR ACTIVATION IN WATER: DEVELOPMENT OF HYDROPHOBIC SYSTEMS FOR SULFANE SULFUR UTILIZATION
(University of Oregon, 2025-02-24) Garcia, Arman; Pluth, Micha
Elemental sulfur (S8) is an underutilized source to study the role of sulfane sulfur, which primarily is a result of the low solubility of S8 in water (< 20 nM). However, a few examples in nature have demonstrated elemental sulfur can be stored within sulfur granules and hydrophobic pockets. To further understand the role and impact of S8 and sulfane sulfur related species this dissertation investigates new systems to increase the availability of S8 in water. The research presented in this dissertation is aimed to 1) develop systems to solubilize S8 in water, 2) investigate the thiol-activation of S8, and 3) further understand the rules to study S8 in water. Chapter I is a broad overview of reactive sulfur species and the role of sulfane sulfur in chemical biology. Chapter II is an initial investigation into applying surfactants to solubilize S8 in water and subsequent activity of the micelle/S8 system. Chapter III delves into applying cucurbit[n]urils (CB[n]) and develop a discreet host-guest system to solubilize, activate, and deliver S8. Chapter IV reports the development of ElliptiCB[n], a collaborative project that measures the ellipticity of solid state CB[n] hosts and host-guest complexes. This dissertation includes previously published and unpublished co-authored materials.
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MECHANISMS OF MEMBRANE TARGETING AND ACTIVATION OF PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASES (PIP5Ks)
(University of Oregon, 2025-02-24) Duewell, Benjamin; Hansen, Scott
The ability for cells to localize and activate peripheral membrane binding proteins is critical for signal transduction. Ubiquitously important in these signaling processes are phosphatidylinositol phosphate (PIP) lipids, which are dynamically phosphorylated by PIP lipid kinases on intracellular membranes. Functioning primarily at the plasma membrane, phosphatidylinositol-4-phosphate 5-kinases (PIP5K) catalyzes the phosphorylation of PI(4)P to generate most of the PI(4,5)P2 lipids found in eukaryotic plasma membrane. Recently, we determined that PIP5K displays a positive feedback loop based on membrane-mediated dimerization and cooperative binding to its product, PI(4,5)P2. In Chapter II of this dissertation, we examine how two motifs contribute to PI(4,5)P2 recognition to control membrane association and catalysis of PIP5K. Using a combination of single molecule TIRF microscopy and kinetic analysis of PI(4)P lipid phosphorylation, we map the sequence of steps that allow PIP5K to cooperatively engage PI(4,5)P2. We find that the specificity loop regulates the rate of PIP5K membrane association and helps orient the kinase to more effectively bind PI(4,5)P2 lipids. After correctly orienting on the membrane, PIP5K transitions to binding PI(4,5)P2 lipids near the active site through a motif previously referred to as the substrate or PIP binding motif (PIPBM). Our data reveals that the PIPBM has broad specificity for anionic lipids and serves a critical role in regulating membrane association in vitro and in vivo. The strength of the interaction between the PIPBM and various PIP lipids depends on both the membrane density and the extent phosphorylation on the inositol head group. Overall, our data supports a two-step membrane binding model where the specificity loop and PIPBM act in concert to help PIP5K orient and productively engage anionic lipids to drive the positive feedback during PI(4,5)P2 production. In Chapter III, we follow up on a recent study that showed PIP5K exist in a weak monomer-dimer equilibrium in solution but can shift to a dimeric state following membrane association. Dimerization potentiates PIP5K function, increasing lipid kinase activity 20-fold, providing a possible mechanism for the rapid PI(4,5)P2 generation seen during signaling events. In Chapter III we established a novel FÖrster Resonance Energy Transfer (FRET) biosensor to detect and quantify PIP5K dimerization on supported lipid bilayer technology using Total Internal Reflection Fluorescence Microscopy (TIRF-M). This FRET biosensor allows for the frequency and duration of PIP5K dimerization to be quantified with high resolution. We used this FRET biosensor to demonstrate that human PIP5K paralogs (α, β, and γ) are able to heterodimerize. Previous studies have shown that PIP4K enzymes inhibit PIP5K enzymes by an unknown mechanism. Here, we use the FRET biosensor to demonstrate the mechanism of inhibition is via blocking the dimer interface. The creation of this PIP5K dimerization FRET biosensor establishes a novel assay for examining how proteins and peptides modulate membrane-mediated dimerization of PIP5K, which will be critical for elucidating the mechanisms that control cellular PI(4,5)P2 lipid homeostasis in the future.
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Simulation of defects in molecular materials using ab initio methods
(University of Oregon, 2025-02-24) Gormley, Eoghan; Hendon, Christopher
Molecular materials such as metal-organic frameworks (MOFs) are emerging as an interesting class of materials for their wide range of applications as well as their customizability and tunability. Like other materials, the properties of molecular materials can be modified through the use of defects - however, the nature of these defects in these systems can be much more complex than in conventional materials. Because of this, modifying conventional computational methods is essential for understanding defects in these systems. This research addresses the limitations of traditional approaches by refining techniques for calculating chemical potentials and employing higher levels of theory, such as many- body perturbation theory (MBPT), to model the unique electronic structures of MOFs. These modifications attempt to account for the intricate chemical environments, large unit cells, and significant structural dynamics inherent to molecular materials. We propose that chemical potentials for defects should be calculated based on the reactions that form the defects, thereby incorporating the thermodynamics of covalent bond formation and cleavage, as opposed to referencing them to elemental phases and treating all atoms of a given species as thermodynamically equivalent. We also attempt to use MBPT to more accurately predict the electronic properties of these materials (thereby overcoming the underestimations of fundamental band gaps typical of simpler ab initio methods)which is essential to predict the stability of defects that these materials can host. Finally, a case study on Yttrium-based MOFs with HHTP linkers demonstrated the potential impact of defects and guest ions on conductivity, showcasing the practical implications of accurate defect modeling. Theoretical findings enhance the predictive power of computational methods for MOFs, informing material design and optimization for applications in catalysis, gas storage, and electronic devices. This dissertation includes previously published coauthored material.
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Fresh Quantitative Approaches for High-Throughput Characterization Using ChemFETs and Statistical Analysis
(University of Oregon, 2025-02-24) Banning, Douglas; Banning, Douglas
Anion receptors are an increasingly important area of focus in synthetic organic chemistry, especially in areas such as environmental pollution detection and remediation. Many organic anion receptors are hydrophobic, limiting their utility for direct evaluation of aqueous anion affinity. Electrochemical sensors such as chemically-sensitive field effect transistors (ChemFETs) can bridge this gap. Incorporation of anion receptors into the chemically sensitive membrane of a ChemFET can facilitate direct measurement of aqueous anion affinity of hydrophobic sensors. One key piece of information that this can elucidate is the relative affinities of anions with the host by direct comparison of detection limits for each anion. Relative ranking of anion detection limits can be compared to the Hofmeister series, especially useful for determining the placement of relatively unknown, reactive species into the Hofmeister series.Dodeca-n-butyl bambus[6]uril was used in the selective membrane of a ChemFET to produce the first reported placement of hydrosulfide in the Hofmeister series. The contribution of the binding pocket geometry on anion affinities was then explored by comparing anion detection limits of dodeca-n-butyl bambus[6]uril with dodecabenzyl bambus[6]uril. The utility of ChemFETs was then expanded to assess the anion affinity of metal organic frameworks (MOFs), to learn about the anion binding nature of a novel MOF. After studying the nature of host-guest interactions using electrochemical sensors, research efforts expanded to include a statistically-based analytical method for characterization of synthetic pathways. Design of experiments (DOE) is generally used to characterize processes, and quantify impacts of main and multi-factor interactions on desired outputs. In chemical applications, DOE can characterize syntheses, specifically the impacts of each factor (together or in isolation) on the resulting product. This information can then be used to provide optimization conditions to produce desired properties. Significantly, this evaluation technique can be applied to historical data in order to characterize reactions before running any new experiments. In this particular case, flat aluminum 13 (f-Al13) cluster was analyzed via DOE in an effort to optimize desired properties. This data was then used to provide optimization conditions for the factors of size (minimize) and polydispersity index (minimize). Two different sets of optimization conditions were used as a validation run to synthesize aluminum particles, demonstrating a drastic improvement in one of the two optimization conditions. Finally, other research efforts are examined and documented. These efforts include ChemFET characterization of anion receptors, synthetic challenges, and application of DOE to characterize and optimize reactions. Overall, this dissertation involves the coalescence of different areas of study in order to solve difficult problems.
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Investigation of Coffee Qualities through Electrostatic and Electrochemical Methods
(University of Oregon, 2025-02-24) Bumbaugh, Robin; Hendon, Christopher
This thesis presents groundbreaking research on using electrochemicalmethods in conjunction with % Total Dissolved Solids (%TDS) as a marker for brewed coffee qualities. The study emphasizes the necessity of brewing reproducible coffee for accurate measurements. It highlights the impact of adding water to coffee beans before grinding, which reduces electrostatic charge and results in a more uniform particle size distribution, enhancing consistent extraction during brewing. The research further examines the relationship between roast degree, measured by Agtron value, and %TDS, utilizing cyclic voltammetry (CV) as a novel technique for analyzing brewed coffee. A strong correlation is found between the integrated area of the observed reduction wave and %TDS, linked to hydrogen underpotential deposition (HUPD) on a platinum electrode. It is also found that coffee matrix molecules adsorb to the electrode surface, block reaction sites, and suppress the HUPD signal with multiple CV cycles. The study further explores the effects of varying brew parameters (grind size, water temperature, water amount, bean amount, and brew time) on CV characteristics, demonstrating linear correlations between %TDS, HUPD reduction wave area, and peak height, with shifts in brew parameters impacting these metrics. Additional CV characteristics, peak center and peak full-width-half-maximum both of which are known to relate to solution composition, are observed to shift with brew parameters but do not correlate to %TDS. The innovative use of CV for assessing coffee quality opens new avenues for electrochemistry techniques in food science, with potential applications in other acidic liquids such as wine and tea. Future research could leverage multifactor analysis for standard protocols in coffee scaling and flavor targeting, possibly incorporating electrochemical devices in brewing processes to allow consumers to adjust for individual flavor preferences. This dissertation includes previously published and unpublished co-authored material
Open Access
Disruption of Ribosome Biogenesis and Induction of Nucleolar Stress by Platinum(II)-based Chemotherapeutics
(University of Oregon, 2025-02-24) Yglesias, Matthew; DeRose, Victoria
Platinum(II) metal complexes—cisplatin, carboplatin, and oxaliplatin—represent a major class of antineoplastics agents used in a majority of cancer treatment regimens throughout the world. Despite their ubiquitous use, the precise mechanisms and targets responsible for cancer cell death are not fully understood. Overcoming these deficiencies will be necessary to address the limitation associated with current Pt-based chemotherapeutics in the clinical setting. Current literature has revealed, unlike cisplatin and carboplatin, oxaliplatin primarily kills cells through disruption of ribosome biogenesis. Ribosome biogenesis is intimately connected to the nucleolus, a phase-separated nuclear condensate, which also functions as a central hub for sensing and coordinating cellular stress response through nucleolar stress response.This work provides insight on the relationship between Pt(II) compounds and disruptions in ribosome biogenesis, and the impact on nucleolar structure. Chapter I summarizes the significance and current understanding of Pt-based chemotherapeutics in the context of ribosome biogenesis and the nucleolus. Chapter II identifies structural and chemical properties of Pt(II) compounds necessary for nucleolar stress induction through a novel immunofluorescence imaging approach for quantifying nucleolar stress. Chapter III applies this framework to a subset of monofunctional Pt(II) compounds which are also shown to induce nucleolar stress. Chapter IV examines spatiotemporal differences in nucleolar stress induced by Pt(II) compounds identified in previous studies—ruling out connections with intracellular accumulation and DNA binding. Chapter V discusses current progress on elucidating the molecular mechanisms for inhibition of rRNA synthesis by oxaliplatin by adapting a ChIP-based sequencing techniques to map the occupancy of RNA Polymerase I machinery along rDNA. Chapter VI provides a comprehensive review on the coordination metal ions with nucleic acids, highlighting recent examples of NMR and x-ray crystallography structures from the literature. This dissertation includes published and unpublished co-authored material.
Open Access
Understanding the Interplay Between Iron Adsorption, Surface Reconstruction, and Electrocatalytic Oxygen Evolution by Transition Metal (Hydr)oxides
(University of Oregon, 2025-02-24) Twight, Liam; Boettcher, Shannon
Renewable electricity-driven alkaline water electrolysis is poised to be a key technology for reducing the CO2 emissions from combustion of fossil fuels in industrial sectors like aviation and fertilizer manufacturing. One of the largest costs of operating water electrolyzers is that of the electricity needed to drive the liberation of hydrogen and oxygen gases. Therefore, improving electrolyzer efficiency – lowering the electrical power needed per kilogram of H2 generated – is essential to their widespread deployment. The anodic oxygen evolution reaction (OER) is a process with intrinsically slow kinetics that makes large contributions to electrolyzer inefficiency. The kinetics of OER can be hastened with the proper choice of catalyst the best of which are based on Ni and Co oxides or hydroxides with a minority component of incorporated Fe. Decades of research involving Ni/Co/Fe OER catalysts have been done, but there is still debate about the nature of the active sites in these materials. The complexity of these systems is to blame; the formation and maintenance of high OER activity sites depends on highly dynamic processes involving surface iron site dissolution-redeposition and catalyst structural change both of which are likely functions of the electrolyte pH, iron concentration in electrolyte, applied electrical bias, and catalyst chemical composition. This dissertation advances understanding of the nature of extremely high activity Fe active sites which form in-situ on nickel and cobalt hydroxide and lanthanum nickel oxide, three technologically promising catalysts. In Chapter I, I describe from a broad perspective the areas where high efficiency alkaline electrolyzers could serve to eliminate CO2 emissions and the role that OER catalysts will play in accomplishing this goal. In Chapter II, I report the results of fundamental investigations which reveal that Fe active sites are not of one, but two kinds: one that forms by surface adsorption of electrolyte Fe and another that substitutes for host metal atoms. In Chapter II, I describe the results of a deeper mechanistic investigation into the thermodynamic parameters that govern the activity of these surface Fe sites. Chapter III extends the methods used to understand Fe-sites on nickel hydroxides to an understudied perovskite oxide, lanthanum nickelate (LaNiO3). Together, these studies deepen our understanding of why Fe is a ubiquitous activator of OER catalysts and broaden the family of catalysts for which Fe activation is integral. As a result, new design principles for high performance alkaline electrolyzer anodes become evident. Catalysts should have a high density of sites for cooperative surface Fe site adsorption such that the activation energy and pre-exponential factors are optimized. Surface restructuring should be purposefully induced for those that need it for high OER activity to maximize active site formation. Where restructuring is required for high activity, surface chemical descriptors should be developed and utilized instead of bulk ones which may not directly connect to the relevant physical picture of catalysis. This dissertation contains previously published and un-published co-authored materials.
Open Access
Unique Mechanisms of Colloidal Stability Probed by Surface-Specific Vibrational Spectroscopy
(University of Oregon, 2024-12-19) Mapile, Ashley; Scatena, Lawrence
The stability of nanoparticles suspended in a solution, known as colloids, is crucial for their application in drug delivery systems, the solution processibility required for drop-casting films, and the long-term storage or transport of sensitive chemical materials. While current mechanisms for colloidal stability include implicit models of solvation – namely Derjaguin-Landau-Verwey-Overbeek (DLVO) and Flory-Huggins theories – these classical approaches neglect the role of specific solvent-surface interactions. Analyzing these surface-specific interactions in colloidal stability becomes increasingly relevant for nanosized particles, which have a highly accessible surface area compared to their bulk counterparts.This dissertation seeks to understand unconventional mechanisms of colloidal stability that are not explained by traditional theories alone, with oil-in-water emulsions and nanoparticles of metal-organic frameworks (nanoMOFs) as model materials. Leveraging the surface-specific spectroscopic technique, vibrational sum frequency scattering spectroscopy (VSFSS), this work provides a molecular-level understanding of the specific surface interactions that contribute to colloidal stability. In particular, emulsions can be stabilized by a steric layer of polymer alone, with colloidal behavior tunable by pH, electrolyte concentration, molecular weight, and temperature. These sterically-stabilized emulsions find applications in drug delivery systems that must withstand extreme physiological conditions. For bare nanoMOFs, an ordered solvation shell and solvent-metal surface binding contribute to unforeseen long-term stability in common solvents. Additionally, nanoMOFs coated with a polymeric binding agent – similar to those used in the paint industry – yield ultra-strong mixed-matrix membranes for gas separation technologies. Ultimately, this work bridges molecular interfacial chemistry with material properties, emphasizing the importance of understanding mechanisms of colloidal stability. This dissertation includes previously published co-authored material.
Open Access
Fourier Transform Based Analysis of Mass Spectra: Disentangling Mass Heterogeneity and Polydispersity
(University of Oregon, 2024-12-19) Swansiger, Andrew; Prell, James
Understanding the interactions of small molecules with biomolecules and their complexes is fundamental to the clinical interpretation of biological functions and pharmaceutical development. Conversely, these delicate interactions present a multiplexed problem requiring highly specific and sensitive analytical techniques to capture their subtle variances. Advances in soft ionization mass spectrometry (MS) methods such as electrospray ionization (ESI) and desorption electrospray ionization (DESI) have brought together solution phase separation techniques and sensitive gas phase analysis, reducing both sample concentration and purification requirements and enabling fast multiplexed analysis of data-rich biological samples. As the limitations on analyte size and complexity continue to be pushed back by instrumental and experimental innovations, MS deconvolution tools need to continually advance to keep pace with the increased mass heterogeneity and polydispersity of what we can successfully spray. Among current MS deconvolution algorithms, Fourier transform and Gábor transform (FT/GT) provide a consistent and invertible transform for quick recognition of several classes of periodic signal from polydisperse samples, requiring very few a priori assumptions about the sample while extracting the charge and mass information required by other algorithms for accurate modeling of congested mass spectra. The Prell group’s iFAMS software represents the state-of-the-art in Fourier deconvolution of mass spectra, enabling flexible selection of analyte signals from a spectrogram of m/z and frequency to filter out interferent ions. However, assignment of aperiodic mass shifts in data-rich spectra still proves challenging, as they do not produce unique frequency signals, requiring an understanding of previously unutilized aspects of FT/GT deconvolution for mass spectrometry. Additionally, although iFAMS results are highly reproducible, applications of iFAMS data analysis have remained mostly exploratory, as GT lacks a sufficiently high-throughput implementation for analysis of large data sets. In the first half of this dissertation, a new tool for mass spectrometry Fourier analysis is developed, utilizing the phase angle information from FT/GT for the characterization of small mass variants embedded in polydisperse mediums such as polymers and lipid membranes. The new method of FT/GT macromolecular mass defect (MMD) analysis achieved similar mass accuracy to mass-domain deconvolution methods and is robust to high instrument noise and low mass contaminants, enabling cross-validation of mass-domain deconvolution models. In a workflow complemented with liquid chromatography mass spectrometry, FT/GT MMD analysis enables characterization of polymer reaction intermediates. The second half of the dissertation extends the reproducibility of FT/GT analysis to protein quantitation of MS imaging data from biological tissue, developing a new workflow for batch deconvolution to process tens of thousands of spectra in a few hours. The distinct protein ion patterns generated by GT simplify characterization of brain tissue eluents, while expanding the range of isolatable proteoform signal available for imaging. This dissertation includes previously published and unpublished co-authored material.
Open Access
Substitution and Analysis of Additional Heteroatoms in 1,2λ5-Azaphosphinines
(University of Oregon, 2024-12-19) McNeill, John; Haley, Michael
Azaphosphinines are, simply put, six-membered heterocycles containing one nitrogen and one phosphorus atom. While garnering more attention in the last couple decades, they are still decidedly understudied. This lack of research is primarily due to the difficult and often intense reaction conditions required to synthesize them. This is especially true for the azaphosphinine moiety’s early iterations. In the Haley and Johnson groups we have found a facile synthetic pathway that allows us to circumvent these issues. In this dissertation I will discuss not only a history of the azaphosphinine functional group but also the results of my independent research. The main body of my Ph.D. work is concerned with the substitution of additional heteroatoms into our thoroughly studied azaphosphinines. These substitutions result in dramatic changes to both the supramolecular and photophysical properties of the heterocycles. While most of the work I will discuss is related to different orientations of pyrido-fused azaphosphinines, I also include a study on the thionation of the ubiquitous phosphoryl group. Chapter I is a holistic review of azaphosphinines. I begin by discussing the nomenclature and unusual electronic properties of these heterocycles before detailing a chronological progression of the literature concerning the three isomers and both valencies of the azaphosphinine functional group. In Chapter II I describe the synthesis and unexpected tautomerization effects observed in pyrido[2,3-e]-1,2λ5- azaphosphinines. Chapter III continues to explore the electronic effects of a pyrido fusion, but in this case, we are now considering the internal charge transfer present in pyrido[3,4-e]-1,2λ5-azaphosphinines. And lastly Chapter IV examines the thionating effect of Lawesson’s Reagent on our heterocycles and the dramatic impacts this transformation has on their photophysical properties. This dissertation includes previously published co-authored material.
Open Access
Towards an Understanding of S100A9 Activation of TLR4: Incorporating a Biochemical and Evolutionary Perspective.
(University of Oregon, 2024-12-19) Chisholm, Lauren; Harms, Michael
The central puzzle of my dissertation work is understanding how two molecules with very different physiochemical properties activate the same receptor, Toll-like receptor 4 (TLR4). TLR4 is an innate immune receptor that responds to both the bacterial glycosylated phospholipid LPS and small soluble host proteins. Despite decades of work, we have little mechanistic understanding of how soluble proteins activate this receptor. S100A9 is one such soluble protein, or Damage Associated Molecular Pattern (DAMP), that activates inflammatory pathways via Toll-like receptor 4 (TLR4). This activity plays important homeostatic roles in tissue repair, but can also contribute to inflammatory diseases. The mechanism of activation is unknown. Learning more about the mechanism of S100A9-induced inflammation can improve our understanding of many disease pathologies, as well as providing a promising new therapeutic target. In this dissertation I describe my work addressing this gap in the literature, using biochemical, biophysical, computational, and evolutionary methods. This dissertation includes previously published and unpublished co- authored material.
Open Access
Advancing the Chemical Understanding of Hydrogen Sulfide and Related Reactive Sulfur Species with Small Molecule Tools for Delivery and Sensing
(University of Oregon, 2024-12-19) Fosnacht, Kaylin; Pluth, Michael
Reactive sulfur species (RSS), such as thiols, polysulfides, hydrogen sulfide (H2S), and persulfides (RSSH), play essential roles in biological chemistry, including roles in redox homeostasis and small molecule signaling pathways. Previously known as a toxic gas, H2S was established as a gasotransmitter in the late 1990’s and is defined as a membrane permeable small molecule that is endogenously produced and involved in specific cell signaling pathways. For this reason, the association of H2S imbalances with various diseases, such as Parkinson’s disease, diabetes, and asthma, has been studied and changes in endogenous H2S are indicated as a potential disease biomarker. More recently, the importance of persulfides and other RSS in addition to H2S has become a major research focus due to their overlap in activity with H2S and newly discovered importance in biological processes. In particular, recent work has further clarified that many cellular signaling processes initially attributed to H2S are likely due to persulfides. Overall, understanding the RSS pool both fundamentally and also in biological systems is crucial. Carefully developed tools to both detect and deliver RSS are needed to further understand the rich chemistry of RSS within the body.Within this dissertation three main aims are addressed: (1) improved H2S sensing tools for longer duration studies, (2) donor molecules that release RSS, and (3) increasing fundamental understanding of persulfide reactivity. Chapter I is a comprehensive review of fluorescent probes of H2S and other RSS and includes discussion of the important advantages and limitations of each probe type. Chapter II features a cell-trappable H2S probe that provides a large, selective fluorescence turn-on to H2S and was used to sense H2S in live cells. Chapter III details a palette of thiol-activated H2S donors that also produce a fluorescent response in the blue to NIR emission wavelength range. Notably, the NIR donor was applied to live rats to image the fluorescence turn-on when subcutaneously delivered. Chapter IV describes the development of a small library of esterase-activated persulfide donors and kinetic analysis of persulfide release, donor side reactivity, and observed persulfide persistence. Chapter V is a combined computational and experimental analysis of persulfide reactivity with thiols where increasing steric bulk or electron withdrawal near the persulfide can shunt persulfide reactivity through the transpersulfidation pathway. Experimentally, we used a persulfide donor and persulfide trapping agent to monitor and measure transpersulfidation from a bulky penicillamine-based persulfide to a cysteine-based thiol, which is the first direct observation of transpersulfidation between low molecular weight species. This dissertation includes previously published co-authored material.
Embargo
Charge Transport Phenomena in Fe-Based High Surface Area Materials
(University of Oregon, 2024-08-07) McKenzie, Jacob; Brozek, Carl
While conductive metal-organic frameworks (MOFs) and open-framework metal chalcogenides (OFMCs) have received considerable attention in recent years, there are still fundamental questions that remain unanswered. With literature abound describing ion and solvent-dependent conductivity in mesoporous media and nonporous conductive polymers we expect such phenomena to be heightened and unique at the interfacial extremes that microporous materials and 2D Van Der Waals (vdw) materials possess. We utilize the unique properties of Fe-based materials to design model systems in TMA2FeGe4S10 (TMA: tetramethyl ammonium) and Fe(SCN)2(pyz)2 to explore the impact of solvent and electrochemically inert ions on charge transfer and transport. Taken together, this dissertation describes for the first time, critical solvent and ion interactions at interfacial extremes, which must be considered in the design of advanced energy storage technologies where solvent and ion presence is ubiquitous. These advanced energy storage technologies will prove critical in supporting renewable energy generation, to reduce and eventually eliminate CO2 emission.
Open Access
Fundamentals of Electrochemical Interfaces: Insights into Electrodes, Electrolytes, and Ion Transfer Kinetics
(University of Oregon, 2024-08-07) Zhao, Yang; Boettcher, Shannon
Electrochemistry is a field that lies at the crossroads of electricity and chemistry, focusing on the transformation between electrical and chemical potentials, typically occurring at the electrochemical interfaces - the dynamic region between electrode (electron conductors) and electrolyte (ionic conductors) where electrons are transferred, and ions/molecules are converted. The performance of modern electrochemical technologies for energy conversion and storage, which presents promising approaches for reducing pollutants and facilitating environmentally sustainable chemical processing, relies on a deeper and more profound comprehension of the electrochemical interfaces, specifically at atomic/molecular-scale and in relation to the fundamental steps of the interfacial reactions. However, even in a simple or elementary electrochemical system, the fundamental investigation is challenging, as the processes and the mechanisms that underlie them are complex. The presence of multiple phases contributes to the complexity, which is further amplified when taking into account the interaction of numerous factors influenced by varying potential bias which results in a potential gradient across the interface and the accompanying electric fields. This dissertation provides a comprehensive exploration of electrochemical interfaces, by delving into three fundamental aspects: electrodes, electrolytes, and ion transfer kinetics, each contributing significantly to our comprehensive understanding of electrochemical systems. We illustrate the underlying operational mechanism and design principles for porous carbon electrodes in redox-enhanced electrochemical capacitors. Additionally, we quantitatively assess how thermodynamics, kinetics, and interface layers control the apparent hydrogen evolution reaction activities in water-in-salt electrolytes. Furthermore, for the first time, we experimentally measured and determined the ion-transfer kinetic parameters using a model system of Ag electrodissolution and electrodeposition. Together, this dissertation provides key insights into the fundamental mechanisms that drive electrochemical systems, potentially contribute to the future innovations in energy technologies. This dissertation includes previously published co-authored materials.
Open Access
Understanding Interfacial Chemistry in Metal Based Soft Materials
(University of Oregon, 2024-08-07) LeRoy, Michael; Brozek, Carl
Soft materials are a class of materials including colloids, polymers, DNA, and proteins. Due to their organization on the mesoscopic length scales they exhibit a wide variety of properties such as self-assembly and response to external stimuli. This has led soft materials to be employed in a wide array of applications ranging from catalysis, electrochemistry, and membrane technologies. Ionic liquids and metal-organic framework are two distinct classes of hybrid organic-inorganic soft materials, that are well studied and used as filler materials for polymer membrane separation technologies. However, a current challenge is understanding how the interfacial chemistry between these filler materials and polymer impacts membrane structures and properties. In this dissertation, molecular chemistry is used to explore how mesoscopic properties give rise to those found in the bulk of ionic liquids and nanoscale metal-organic frameworks respectively.
Open Access
Structural and Electronic Coupling in Nanoscale Materials
(University of Oregon, 2024-08-07) McDowell, Benjamin; Nazin, George
As modern electronic devices continue to shrink in size, the limitations of Si as a transistor material become increasingly imminent. To overcome these limitations, it is necessary to explore alternative materials that can be used in electronic devices that surpass the miniaturization limit of Si-based devices. In this effort, it is important to develop an understanding of how materials behave when they are reduced in size and scale down to ultra-thin structures. Here, we explore how ultra-thin dielectric materials behave differently than their bulk counterparts, experiencing chemical interactions at interfaces that can result in unexpected structures and electronic properties. By using a combination of scanning tunneling microsocopy/spectroscopy and density functional theory, we study several manifestations of distinct structural and electronic properties arising in ultra-thin materials. We extend this physical picture to understand how the properties of these films affect adsorbed nanostructures, analogous to interactions occurring in a transistor setting.
Open Access
USING CIRCULAR DICHROISM AND FLUORESCENCE SPECTROSCOPY TO STUDY THE IMPACT OF 2-AMINOPURINE ON RNA FOLDING
(University of Oregon, 2024-08-07) Hoeher, Janson; Widom, Julia
RNA is an important biological molecule, with its function helping out with different processes in cells. How RNA functions is related to its structure, with different structured RNA behaving in different ways. Studying RNA structure is thus important to understand its function. One example of this are riboswitches, which help regulate gene expression. By binding a ligand, the riboswitch refolds, causing a change in gene expression. One method of studying RNA structure is by utilizing fluorescent base analogues of the native bases. To study the riboswitch, the fluorescent base analogue 2-aminopurine (2-AP) was substituted into six different locations in the L3 region of the preQ1 riboswitch. Using circular dichroism (CD) and fluorescence spectroscopy, along with fluorescence lifetimes, it was discovered that all modified locations were detrimental to the riboswitch’s ability to bind the ligand. In addition, fluorescence-detected circular dichroism (FDCD) was used to study short RNA molecules containing 2-AP, of up to three nucleotides in length. By comparing FDCD to CD, it was determined that in dinucleotides, the fluorescence came almost entirely from unstacked populations. Comparatively, while most of the fluorescence from the trinucleotide came from unstacked populations, some came from stacked populations. Through FDCD and CD, the amount of each construct in stacked and unstacked populations can be determined. This dissertation includes previously published co-authored material.
Open Access
QUANTITATIVE DETERMINATION OF GAS-PHASE THERMODYNAMIC BARRIERS OF PROTEINS FOR NATIVE ION MOBILITY-MASS SPECTROMETRY: APPLICATIONS AND IMPLEMENTATION OF AN IMPROVED IMPULSIVE COLLISION THEORY
(University of Oregon, 2024-08-07) Shepherd, Samantha; Prell, James
Ion mobility-mass spectrometry is a powerful tool for identifying and elucidating biomolecular structures and behaviors. This technique is able to retain even weak and non-covalent interactions permitting the study of native or native-like gas-phase biomolecular complexes including folded proteins, protein-protein complexes, and protein-ligand complexes. Historically, energetic and thermodynamic information has been limited to techniques on specialized instrumentation and/or computationally expensive strategies. This changed with the development of “proto-IonSPA” to allow rapid determination of thermochemical barriers for protein dissociation and unfolding on modern, commercially available instrumentation. In this work, reproducibility, repeatability, and applications of the use of thermochemical measurements on modern, commercially available instruments are assessed, inspired by a need to compare gas-phase dissociation and unfolding of proteins more broadly. This groundwork enables the development of an Improved Impulsive Collision Theory (IICT) in a Monte-Carlo python script, which in turn improves qualitative and quantitative understanding of activation in Collision Induced Unfolding and Dissociation. This program further enables the determination of gas-phase thermochemical barriers for the dissociation of proteins in modern commercially available mass spectrometers. Reasonable agreement is shown with literature standards and between different mass spectrometer designs and experimental parameters. This agreement is particularly noteworthy due to the drastic difference in timescales being compared (seconds in the literature to as low as microseconds in this work) This dissertation includes previously published co-authored material.
Open Access
INVESTIGATION OF PNICTOGEN-ASSISTED SELF-ASSEMBLY AND SELF- SORTING DESIGN PRINCIPLES TOWARDS PREORGANIZED MACROCYCLES
(University of Oregon, 2024-08-07) Mayhugh, Jacob; Johnson, Darren
Shape-persistent molecules have abundant chemical potential as organic functional materials. Access to these molecular cages and macrocycles, however, is nontrivial and often require long or low-yielding synthetic pathways that bottleneck their potential applications. To ameliorate this, dynamic covalent chemistry has shown to be promising in the formation of shape-persistent molecules as it marries the error-correction of self-assembly with thermodynamic control while giving the robustness of a covalent bond. The DWJ lab focuses on utilizing dynamic covalent reactions towards the facile preorganization of macrocyclic ensembles through the pnictogen-assisted self-assembly of oligothiols. This dissertation expands upon disulfide self-assembly design principles for a holistic understanding of the method’s boundaries.Chapter I introduces supramolecular concepts that are the cornerstone of this project. Specifically, self-assembly and dynamic covalent chemistry is introduced, with background information on the project’s beginnings provided as well. In Chapter II, the synthetic scope of disulfide self-assembly is explored. Following, Chapter III utilizes our newfound understanding to explore efficient pathways into material formation. iv Specifically, Perylene Diimide-containing macrocycles are generated in an efficient and high throughput dynamic pathway with implication on tailored organic materials. Chapter IV investigates the self-assembly of multicomponent oligothiol systems (self-sorting) towards the predictive assembly of three-dimensional architectures. Chapter V concludes the dissertation and provides potential future directions for this project. This dissertation includes co-authored and previously published results.
Open Access
THE DEVELOPMENT AND APPLICATION OF TRANSITION METAL–HYRDIDES IN CATALYSIS FOR ALKENE HYDROSILYLATION AND ISOMERIATION REACTIONS
(University of Oregon, 2024-08-07) Chang, Alison; Cook, Amanda
Metal-mediated alkene transformations is a rapidly developing field to obtain various organic precursors for pharmaceutical compounds, industrial chemicals, and consumer products. The pursuit of developing Earth-abundant catalysts is of great interest due to catalyst affordability in comparison to precious metal catalysts. Specifically, Ni catalysts serve as viable alternatives to previous metal catalysts due to the versatile reactivity of Ni. In addition to catalyst development, the catalyst mechanism is also just as important to inform future catalyst design. This often results in guided catalyst optimization and byproduct inhibition. The focal point of this thesis surrounds the development and investigation of Ni-catalyzed alkene hydrosilylation and alkene isomerization. Particularly, the formation of Ni–H intermediates to mediate these organic transformations. Reaction and catalyst optimization, substrate scope, and mechanism determination are reported for both alkene hydrosilylation and isomerization systems. Chapter I highlights the utility of Ni–H in these organic reactions, motivating our work described in Chapters II-VI. Chapter II reports on the reaction development and substrate scope of the homogeneous hydrosilylation (NHC)Ni (NHC = N-heterocyclic carbene) catalyst. Chapter III outlines the mechanistic investigation of the (NHC)Ni-catalyzed alkene hydrosilylation system described in Chapters II. Chapter IV is a continuation of the catalytic system developed in Chapter II and III and delves more deeply to explore the electronic structure of (NHC)Ni(alkene) catalysts. Modification of the NHC ligand gives rise to trends in catalytic ability. To obtain a deeper understanding of this system, ligand steric and electronic variation are tested to observe its influence on catalyst behavior. Chapter V illustrates the incorporation of the in situ hydrosilylation system developed in Chapter II into the remote hydrosilylation of a long chain alkene. This work also includes preliminary data on an in situ generated Ni-catalyzed alkene isomerization system in combination with a hydrosilylation system to install a silicon group distal to the initial reaction site. Chapter VI outlines the development, characterization, and investigation of a heterogeneous Ni alkene isomerization system. This chapter includes catalyst substrate scope, preliminary mechanistic data, and comparison to other Ni-catalyzed alkene isomerization systems. This dissertation includes previously published and unpublished coauthored material.