Theses and Dissertations
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Item Open Access Use of chemical ionization mass spectrometry for study of photochemical properties: ketone photolysis quantum yields(Colorado State University. Libraries, 2025) Berg, Tyson C., author; Farmer, Delphine K., advisor; Ravishankara, A. R., committee member; Sambur, Justin B., committee member; Jathar, Shantanu, committee memberMeasurements of organic radicals produced during organic trace gas photolysis are critical to our understanding of radical budgets throughout the troposphere. This dissertation demonstrates the utility of chemical ionization mass spectrometry for measurements of radical quantum yields in the photolysis of organic trace gases in the laboratory setting. Chapter 2 addresses the development of a coupled chemical ionization mass spectrometer with iodide reagent ions (I-CIMS) and wide band light source instrument design, which was used to measure the quantum yield for CH3C(O) from acetone photolysis, through measurement of CH3C(O)O2. Acetone is the most abundant oxygenated organic gas in the troposphere and its photolysis can account for up to 1/3 of radical production in the upper troposphere. The results from this chapter demonstrate that the I-CIMS can be used for acetone photolysis measurements under conditions of the troposphere. In Chapter 3, the I-CIMS measurements of the CH3C(O) quantum yield in acetone photolysis are expanded to temperatures (223 to 323 K) and pressures (150 to 850 mbar) reflecting the conditions of the troposphere. The measurements are used to parameterize the quantum yield of CH3C(O) for use in models of tropospheric radical production. The parameterization shows that acetone photolysis near the tropopause may be up to 1.4 times slower than previously expected. These are the only measurements of acetone photolysis under tropospheric conditions based on the detection of the dominant radical product, CH3C(O)O2. Chapter 4 explores a new, multiple-reagent ion system with Cl2- as the primary reagent ion (Cl2-CIMS). Cl2-CIMS provides higher sensitivity for small acyl peroxy radicals than achieved with I-CIMS. However, the higher background of Cl2-CIMS leads to higher limits of detection and the uncertainty on multiple reagent ion chemistries makes this system unsuitable for ambient measurements. Cl2-CIMS could be further improved through larger changes to the instrument design than those discussed here, and other novel reagent ion chemistries may be accessible using the multi-step ionization mechanism that produces Cl2-. Chemical ionization mass spectrometry is well-suited to fast, speciated measurements of radicals and is thus useful for measurements of complex photolysis mechanisms, like that of acetone in the troposphere. Further instrument development could improve CIMS sensitivities and limits of detection to organic radicals, expanding its utility to more photochemical systems and ambient measurements of radicals as well.Item Open Access Synthetic and spectroscopic investigations of electron spin relaxation(Colorado State University. Libraries, 2025) Moseley, Ian, author; Zadrozny, Joseph M., advisor; Finke, Rick, committee member; Prieto, Amy, committee member; Buchanan, Kristen, committee memberMolecular magnets (also referred to as single molecule magnets (SMMs)), are organometallic complexes which can retain their magnetization in the absence of an applied field. The loss of this magnetization due to environmental interactions is referred to as magnetic relaxation. Due to the small energy gap between electronic spin orientations, maintaining this magnetization typically requires the molecules be held at temperatures approaching absolute zero. This requirement is both costly and impractical for most of the envisioned applications, and as such considerable research efforts have been made to increase the operating temperatures of molecular magnets. This dissertation presents a series of investigations into the magnetic relaxation behavior of molecular magnets incorporating first-row transition metals coupled to adjacent spin centers through electron-electron interactions. Presented herein is a series of investigations which demonstrate a novel method for extending magnetic relaxation in spin-abundant environments, the synthesis and characterization of a low-coordinate iron species as a potential precursor to extended solids, the magnetic properties of a pair of iron-based coordination polymers, and an investigation into the design of electron paramagnetic resonance (EPR) imaging probes using spin forbidden transitions. This research serves as a starting point for future investigations into the control of magnetic relaxation phenomena through synthetic control of electron-electron interactions.Item Embargo Coherent vibrational dynamics in ethylene carbonate: insights from 2D infrared spectroscopy(Colorado State University. Libraries, 2025) Guerrieri, Luke Robert, author; Krummel, Amber T., advisor; Levinger, Nancy, committee member; Wilson, Jesse, committee member; Henry, Chuck, committee memberThe research presented in this dissertation explores the mechanisms of coherent vibrational relaxation in the cyclic carbonate ester, ethylene carbonate (EC). Coherent relaxation processes describe the redistribution of quantum superposition states, but relatively little is known about the molecular properties governing these processes for vibrational superpositions in chemical systems. EC, a highly coupled vibrational system with applications in organic battery electrolyte mixtures, serves as a model compound for studying coherent vibrational dynamics. The fundamental carbonyl stretch of EC couples to doubly excited states via Fermi resonance. An investigation of the carbonyl fundamental stretch using linear Fourier transform infrared spectroscopy (FTIR) and two-dimensional infrared spectroscopy (2DIR) reveals coherent relaxation mechanisms involving multiple vibrational degrees of freedom. Pump selective 2DIR experiments compare the relative intensities of coherent relaxation processes to different features in the 2DIR spectrum, finding a correlation between the spectral amplitude of coherent relaxation processes and Fermi resonance coupling strength. A follow up investigation uses 13C isotopic substitution to modify the Fermi resonance coupling strength in EC isotopologues. It is found that 13C substitution strengthens the Fermi resonance coupling in EC isotopologues; however, isotopic substitution is found to suppress the redistribution of quantum superpositions involving Fermi coupled vibrations. Analysis of vibrational lifetimes for the Fermi coupled states indicates that the relative strengths of coherent relaxation processes correlate with the strength of vibrational coupling to a manifold of experimental dark states. Those results suggest that coherent relaxation in EC is primarily driven by the delocalization of vibrational relaxation pathways, rather than the strength of direct coupling between Fermi coupled modes.Item Open Access Insight into alternative battery technologies using 3D configurations, protective coatings, and characterization of resistive properties(Colorado State University. Libraries, 2025) Windsor, Daniel S., author; Prieto, Amy L., advisor; Neilson, James R., committee member; Shores, Matthew P., committee member; Bandhauer, Todd M., committee memberThe omni presence of lithium-ion batteries (LIBs) have revolutionized the modern world due to this technology's implementation as an energy storage device in smart phones, wearable electronics, and electric vehicles. Lithium-ion batteries are well suited for these applications owing to the light weight of these systems and their ability to store a large amount of charge. For these reasons, LIBs are classified as energy dense systems, which describes the amount of energy a technology can store per unit mass. A battery metric where LIBs struggle in terms of performance is power density, or the amount of power a technology can produce per unit mass. These systems, also, require expensive feedstock materials that are geographically isolated which has profound impacts on economics and supply chain considerations for LIBs. Thus, if rechargeable batteries are to continue to advance, alternative battery configurations and chemistries must be studied. Chapter 1 describes the field of LIBs, in terms of the advantages and disadvantages of this technology. This discussion is followed by brief mentions of some of the champion materials found in the anodes, cathodes, and electrolytes currently implemented in LIBs. The discussion on the champion materials for LIBs also covers the drawbacks of each material, and ways in which future investigations can improve their performance. This is then followed by a section which highlights how alternative battery configurations and chemistries can address some of the inherent disadvantages of the LIBs system. This chapter concludes with a discussion on some important soft skills the author learned during the completion of this degree. Chapter 2 covers the development and advances made in the field of 3D batteries. This chapter begins with an introduction of the 3D battery field and includes a section which discusses the current advances made in the literature. This is then followed by a discussion on the computational advances made in the field of 3D batteries, where there is a critical need to develop digital twins of 3D batteries to better understand the chemo-mechanical dynamics of these complex systems. The following portion of this chapter covers the development of 3D batteries through the lens of critical performance metrics, being power density, energy density, and cyclability and scalability. For 3D batteries, this chapter identified that improvements in energy density is the area where further advances are most needed. Finally, this chapter discuss efforts being made in industry toward the commercialization of these 3D battery systems. Chapter 3 covers an investigation into the fundamental effect of a polymer protective coating, cyclized-polyacrylonitrile (cPAN), on the Na-ion (de)insertion chemistry of antimony-based anodes in sodium-ion batteries (NIBs). This investigation was able to determine that the cPAN coating had the most pronounced effect on the early cycle (cycles 1-10) Na-ion (de)insertion chemistry of the antimony-based anodes. The interfacial resistance was, also, diminished by the presence of the cPAN protective layer which implies that the cPAN helps to facilitate Na-ion transport at the electrode-electrolyte interface. Chapter 4 discusses a practical and beginners' approach to the learning electrochemical impedance spectroscopy (EIS) for rechargeable batteries. This chapter begins with a simple deconvolution of the EIS acronym, such that the reader has a deeper understanding of how each component of the acronym combines to create this technique. The chapter continues by discussing how to preform both qualitative and quantitative EIS analyses on rechargeable batteries, and finishes with a discussion on the EIS specifics of rechargeable battery systems. Chapter 5 covers the future areas in which the work presented in Chapter 3 can be extended. In particular this chapter discusses the critical need to quantify the SEI products of a cPAN coated antimony electrode, as early cycle numbers, and ways in which cPAN can be applied to high surface area substrates to ideally formulate a 3D sodium-ion battery.Item Embargo Core substitution of dihydrophenazine photoredox catalysts for organocatalyzed atom transfer radical polymerization(Colorado State University. Libraries, 2025) Puffer, Katherine, author; Miyake, Garret, advisor; Chen, Eugene, committee member; McNally, Andy, committee member; Peers, Graham, committee memberOrganocatalyzed atom transfer radical polymerization (O-ATRP) is a controlled radical polymerization method that uses organic photoredox catalysts (PCs) and visible light to produce polymers with well-defined structures. Organic PCs leverage an inherently sustainable resource, light, to drive chemical reactions under mild conditions and minimize dependency on rapidly depleting precious metals such as Ru and Ir, which are commonly used for catalysis. N,N-diaryl dihydrophenazine PCs in particular are notable for their success in mediating O-ATRP, producing polymers with low dispersities (Ð < 1.3). However, the non-unity initiator efficiency (I* < 100%) observed using dihydrophenazines in prior work shows their limited ability to achieve targeted molecular weights. This low I* has been attributed to a radical addition side reaction between the PC core and alkyl fragments generated during polymerization. In this work, core substitution (CS) is leveraged to modify PC structure as a route to block side reactivity and improve polymerization control. Exploration of alkyl CS revealed that the alkyl CS PC is the active catalyst during the majority of O-ATRP and can have improved catalytically relevant properties relative to the parent PC. Aryl and heteroatom CS PCs were also found to have improved PC properties, including longer excited state lifetimes and more highly reducing excited states. The new structure-property relationships revealed in this work were applied to improve polymerization outcomes and address current limitations of O-ATRP, such as expanding monomer scope and decreasing PC loadings. This work demonstrates the utility of CS as a versatile strategy to tune PC structure, properties, and performance while enhancing the ability of organic PCs to produce advanced polymeric materials.Item Open Access Applications of LC-QQQ for quantification of small molecules in biological media(Colorado State University. Libraries, 2025) Schwarz, Madeline Christine Roach, author; Reynolds, Melissa, advisor; Van Orden, Alan, committee member; Chung, Jean, committee member; VandeWoude, Sue, committee memberLiquid chromatography triple quadrupole mass spectrometry (LC-QQQ) is a popular instrumental technique with rising popularity in research and clinical laboratories. LC-QQQ allows for high analytical specificity due to specific biomarker detection, along with high analytical sensitivity due to the trace amounts of substances being accurately quantified. Due to these specific advantages, LC-QQQ is gaining popularity for clinical diagnoses to determine the extent of an infection or disease, leading to better informed treatment, or to determine the metabolic rate at which a drug moves through the body. Small molecules (<1000 Daltons) can be used as biomarkers for both clinical diagnosis and metabolomic studies and are detected at extremely low levels using LC-QQQ. This work endeavors to utilize LC-QQQ for two primary applications: first, for the detection of a biomarker for the purposes of diagnosing pulmonary fungal infections, second, for the detection of cannabinoids in plasma during their metabolism. Pulmonary fungal infections such as invasive pulmonary aspergillosis (IPA) have increased in incidence over the last decade due to the increased number of immunocompromised individuals. This increase is especially problematic when considering mortality rates associated with IPA are upwards of 70%. This mortality rate, in part, is due to the length of time it takes to diagnose a patient with IPA. When diagnosed early, mortality rates of IPA decrease by as much as 30%. Chapter 1 discusses current technologies employed in both medical and research laboratories to diagnose IIPA, including culture, imaging, polymerase chain reaction, peptide nucleic acid-fluorescence in situ hybridization, enzyme-linked immunosorbent assay, lateral flow assay, and liquid chromatography mass spectrometry. For each technique, Chapter 1 discusses both promising results and potential areas for improvement with each technique, paying special attention to liquid chromatography mass spectrometry as a potential diagnostic method. Due to the demonstrated need for diagnostic methods that decrease time-to-diagnosis for IPA, Chapter 2 discusses the development and implementation of a method for the quantification for low levels of glucosamine from Aspergillus species using LC-QQQ. The limit of detection in the final method used on samples of Aspergillus was calculated to be 0.020 ± 0.001, with a limit of quantification of 0.061 ± 0.004 ng/mL. The method described in Chapter 2 also has a high internal repeatability (R2 = 0.9996) and does not require a derivatization step for specificity. This allows for ease of translation to a clinical setting. The method was applied to several pathogenic species of Aspergillus, including Aspergillus fumigatus, which causes more than 90% of cases of IPA. Due to the reduced sample prep and run time, high analytical sensitivity, and high specificity the developed glucosamine detection method discussed in Chapter 2 was applied to samples of biological media relevant to clinical diagnosis of IPA in Chapter 3. Artificial sputum medium and artificial bronchioalveolar lavage fluid were used to determine the matrix effects of clinical samples on the developed method. The FDA's bioanalytical method development standards were applied, and it was determined that the artificial media cause extremely strong and inconsistent matrix effects. Separation methods were also tested to remove the glucosamine from the artificial media but were unsuccessful. These results show that the method requires further validation before it can be implemented on clinical samples. Chapter 4 delves into a method to detect CBD, Δ9-tetrahydrocannabinol, and their major metabolites using LC-QQQ. Cannabinoids and their metabolites are of major interest to the medical community due in part to their recent decriminalization. Chapter 4 details the LC-QQQ method developed, as well as the endeavors to account for matrix effects. Several protein precipitation methods were tested in an attempt to reduce sample preparation time and increase throughput. Unfortunately, the separation methods developed did not lead to quality control samples that met FDA standards, so more work is needed before the method can be applied to clinical samples. While the methods described are not fully realized for clinical sample testing, the research described provides valuable insights into a few areas. First, it is the first work to describe LC-QQQ detection of glucosamine derived from several fungal species. The work also provides insight for future method optimization work. Finally, this work demonstrates the effect that matrices can have on method development and some of the problem-solving steps that are required to bring a method from the research lab to a clinical setting.Item Open Access Extending the life of electrochemically deposited anodes in 3D sodium ion batteries with cPAN(Colorado State University. Libraries, 2025) Medina, Dylan, author; Prieto, Amy, advisor; Rappe, Anthony, committee member; Nazemi, Reza, committee memberHumanity constantly seeks to improve the simplicity of their lives, and as such develops technologies to assist with this endeavor. Almost all of these technologies rely on electricity. From large stationary objects to the small mobile devices we see everywhere, they must be charged. For some this means operation almost exclusively on a battery, for others they rely on constant power from the power grid, and most use a rechargeable battery charged from the power grid as a blend. But even power stations have limits for how much they can generate at a time and need to rely on power generated during low demand times to supplement higher demands, and such the power grid also relies on batteries. Chapter I discusses the basis of why energy storage is so important, the history of the modern lithium-ion battery, and where storage technology is heading to improve supplemental battery types. The basics of why sodium ion batteries are attractive as a supplement to lithium-ion batters is outlined. Finally, the geometries of 3D batteries are described, and a key feature leading to uneven distribution of material on 3D electrodes is highlighted. Chapter II focuses on developing a procedure to cyclize polyacrylonitrile (PAN) to act as a binder to keep material in electrical contact to the anode current collector after it fractures and separates. Simple equipment such as a dip coater and a tube furnace are used to evenly coat the substrate with the precursor, which is then annealed to form cPAN. Verification of the cyclization of PAN to form cPAN is done via Fourier Transform Infrared (FTIR) analysis, and sample thickness is measured using scanning electron microscopy (SEM). Once the procedure for the fabrication steps is verified, the actual anodes must be made. In chapter III, cyclic voltammetry is used to get the correct parameters for sample electrodeposition and the anodes are made. After samples were annealed with a layer of cPAN, SEM and energy-dispersive X-ray spectroscopy (EDS) are used to characterize the samples. There is a detailed discussion for the fabrication of a pouch half-cell, and some trends observed when they are evaluated as an electrode using battery cycler. Chapter IV attempts to get a realistic application by placing cPAN coated anodes in a full cell and placing them on a battery cycler. Every step along the way was characterized by measuring the internal resistance, which is noted as an indicator of how or why the cells may be acting abnormally. In conclusion, the overlap of each section is summarized and discussed. The hypothesis for why the cells do not cycle effectively is that the polymer is too thick. Future work will focus on repeating the coating of cPAN onto antimony anodes but with better control over thickness. Refinements to the process such as a thinner polymer layer, calendaring, and a better contact and compression system could provide insight and useful results in the future.Item Open Access FALCON: a new approach to processing fluxes of aerosols(Colorado State University. Libraries, 2025) Liedtke, Roman, author; Farmer, Delphine, advisor; Nielson, Jamie, committee member; L'Orange, Christian, committee memberThe removal processes for atmospheric aerosols impact the radiative balance of Earth and how nutrients and pollutants move. Dry deposition is poorly modeled globally and over many types of surfaces compared to wet deposition. Important surface types on Earth, like the ocean and cryosphere, can be better understood by generating larger datasets of dry deposition measurements over those surface types. Aerosol properties, such as size, influence deposition in addition to surface and meteorological properties. More size-dependent dry deposition measurements can help models improve their dry deposition estimates, especially if those measurements have smaller uncertainties. Dry deposition velocities can be calculated from vertical aerosol fluxes. Fluxes of aerosols are generally noisier than gas or energy fluxes but can still be found with the eddy covariance technique when fluxes are measured over a long period of time. Using the eddy covariance technique to find aerosol fluxes requires fast (10Hz) measurements using two adjacent instruments. Aerosol concentrations are collected by a portable optical particle spectrometer (POPS) and wind velocities are found with a sonic anemometer. We demonstrate one way of calculating vertical aerosol fluxes over various surfaces. EddyPro and custom scripts process anemometer and POPS data into long-term and continuous flux datasets. This document provides instructions on each step of processing data, starting from the raw files produced and ending at a point where fluxes and deposition velocities are calculated.Item Open Access 5-iodonaphthyl azide labeling of specific membrane proteins via energy transfer from donar chromophores(Colorado State University. Libraries, 1991) Meiklejohn, Bruce I., author; Barisas, B. George, advisorThe conditions required for activation of 5-iodonaphthyl-1-azide (INA) by energy transfer from donor chromophores have been examined and methods developed for identifying specific plasma membrane proteins proximal to known plasma membrane receptors. INA is hydrophobic and when inserted in the plasma membrane lipid bilayer, can be activated through energy transfer from the donor fluorochrome, eosin isothiocyanate (EITC). The energy transfer efficiency was greatly increased under anaerobic conditions; the triplet lifetime of EITC conjugated to BSA increased from 10 μ sec to approximately 1 msec in solutions treated with glucose oxidase and catalase for 120 min. To determine whether [125I]-INA would specifically label known membrane proteins, a μ-chain specific EITC-derivatized anti-murine IgM antibody was incubated with murine B-lymphocytes treated with 2. 6 x 10-5M [125I]-INA. When B-lymphocytes were irradiated with 40 mW per centimeter 514 nm light from an argon ion laser, the 66 kDa IgM heavy chain was derivatized with INA and identified on autoradiographs of SDSPAGE gels. In similar experiments, 2H3 rat basophilic leukemia cells were incubated with EITC-IgE which bound to the monomeric Fcε receptor. Four [125I]-INA derivatized plasma membrane proteins with molecular weights of 53, 38, 34, and 29 kDa were identified on autoradiographies of SDS-gels. When IgE was crosslinked with mouse anti-rat IgE three additional proteins with molecular weights of 60, 54, and 43 kDa, were labeled with the photoprobe. Under these conditions the receptor was known to be part of large molecular weight aggregates which contain non-receptor proteins. Collectively, these results suggest that INA may be useful in characterizing protein-protein interactions in the plasma membranes of intact cells under physiological conditions.Item Open Access Asymmetric conjugate additions to pyridine and quinoline(Colorado State University. Libraries, 1984) Wettlaufer, David G., author; Meyers, A. I., advisorExtensive studies have investigated the stereochemical and mechanistic aspects of NADH (nicotinamide adenine dinucleotide)mimics. With potential use in mind, chiral 4-methyl and 4-phenyl-1,4- d ihyd ropy rid ines were synthesized by alkylation of 3- oxazolinylpyridine. (This oxazoline and the oxazolinylquinoline below were derived from (1S,2S)-1-phenyl-2-amino-3-methoxypropanol). Addition of excess methyllithium gave the dihydropyridines, isolated as the methyl urethanes, in 85-90% de and 79-81% yield. This high stereoselectivity was found to be independent of temperature and concentration. The oxazoline was readily removed to the aldehyde in 60% yield fil quaternization with methyl fluorosulfonate followed by reduction and hydrolysis. Phenyllithium addition gave the addition products in 84% de and 94% yield. Chiral 4-methyl-1,4-dihydropyridines were also synthesized by alkylation of 3-imino pyridines with excess methyl cuprates. These imines were prepared from 3-pyridinecarboxaldehyde condensed with phenylalaninol, phenylalaninol methyl ether, (S)-ethylvalinate, and (S)-t-butylvalinate. The highest stereoselectivity was realized upon alkylation of the t-butylvalinate imine to give the dihydropyridines as the methyl urethanes in 56% de. Mild acid hydrolysis yielded N-carbomethoxy- 3-foDT\Yl-4-methyl-l,4~ihydropyridines in 82% yield.Item Embargo Cryo-electron microscopy of cloneable inorganic nanoparticles(Colorado State University. Libraries, 2024) Guilliams, Bradley Forrest, author; Ackerson, Christopher J., advisor; Sambur, Justin, committee member; Crans, Debbie, committee member; Stasevich, Tim, committee memberOur understanding of biology is best understood through direct, empirical measurements of biomacromolecules and biological systems. The functions of proteins are directly linked to both their structure and their intracellular organizations. Single particle cryo-electron microscopy has revolutionized modern structural biology by enabling the structural determination of proteins and protein-complexes in purified samples without the need to form large crystals as required by X-ray crystallography. With single particle cryo-EM, atomic and near-atomic resolution structures are now routine which offer insight into the functions of biomacromolecules. While these insights are invaluable, there is increasing momentum for integrative structural biology which aims to accomplish structural determination of biomacromolecules in their cellular, tissue, or organismal context. There remains a grand challenge in biological imaging where biological materials have low innate contrast. Cloneable contrast labels that impart contrast to discrete protein densities do not reliably exist for cryo-electron microscopy. In contrast, fluorescent proteins are reliable and routine for localizing fluorescent protein / protein of interest genetic fusions in visible-light microscopies. We have proposed and developed intracellularly synthesized inorganic nanoparticles called 'cloneable nanoparticles' as a solution to this grand challenge. Cloneable nanoparticles are inorganic nanoparticles, synthesized by a protein/peptide (or combination thereof) which controls and defines the properties of the inorganic nanoparticle. Here we have defined the cloneable nanoparticle paradigm and described the development of a cloneable selenium nanoparticle. Further, we show the application of the cloneable selenium nanoparticle as a cloneable contrast label for biological electron microscopy and correlative light-electron microscopy and detail progress towards adapting the cloneable selenium nanoparticle for use in cryo-electron tomography. With the aim to later expand cloneable nanoparticles to include a myriad of orthogonal cloneable contrast labels (analogous to different colored fluorophores), and to gain understanding about enzymatic nanoparticle synthesis, a single particle cryo-EM study is on-going. Lastly, we have shown the application of directed evolution for cloneable nanoparticles, suggesting that this is a viable path, alongside rational protein design, towards developing future cloneable nanoparticle cryo-electron microscopy labels.Item Open Access Does orientation matter? Controlling laccase orientation on planar gold electrodes(Colorado State University. Libraries, 2024) Perry, Collin, author; Ackerson, Christopher, advisor; Snow, Christopher, committee member; Dandy, David, committee member; Neale, Nathan, committee memberEnzyme electronics are becoming more common in modern life. Even though these technologies have been integrated into everyday life, the fundamental understanding of how an enzymes' orientation at the electrode surfaces affects the enzymes catalysis is still unknown. To understand this more we designed a library of laccase mutants, all with a single solvent exposed cysteine. These cysteine residues are used to bind to a gold electrode modified with a monolayer of sulfhydryl molecules capped with a maleimide binding group. Each mutants' single cysteine will bind to the maleimide group orienting each mutant differently at the electrode surface. The wild type enzyme (WT) and all the mutants, D113C, N264C, H470C all show activity toward a common substrate 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Although each mutant does show catalytic activity in solution, we were unable to obtain an electrochemical response from the laccase library using the maleimide capped electrodes for either ABTS or oxygen. Modification of the electrodes via the deposition gold clusters makes the electrode surface more topographically complex. The cluster modified electrodes bound with WT laccase displayed an electrochemical response for the reduction of oxygen to water. The increased topography from using gold clusters allows for electron transfer with laccase enzymes, while the planar electrodes modified with the laccase enzymes in which we achieved an electrochemical response.Item Embargo Data-driven strategies for organic structure-property and structure-reactivity relationships(Colorado State University. Libraries, 2024) Santhanalakkshmi Vejaykummar, Shree Sowndarya, author; Paton, Robert, advisor; Prasad, Ashok, committee member; Kim, Seonah, committee member; Nielsen, Aaron, committee memberThe prediction of molecular properties plays a pivotal role in various domains, from drug discovery to materials science. With the advent of machine learning (ML) techniques, particularly in the field of cheminformatics, the prediction of properties for small organic molecules has witnessed significant advancements. This document delves into the diverse machine-learning strategies employed for the accurate prediction of properties crucial for understanding molecular behavior. In Chapter 1, I offer insights into the evolution of data-driven modeling through Quantitative Structure-Property Relationships (QSPR), highlighting promising advancements in utilizing chemical features to construct predictive models for molecular properties. In Chapter 2, I delve into the primary stage of modeling, focusing on data collection for predictive tasks. I illustrate how the integration of automation and computational tools' advancement can construct modular workflows for FAIR (Findable, Accessible, Interoperable, and Reusable) chemistry. This approach aims to enhance the usability and reproducibility of scientific data. In Chapter 3, I emphasize leveraging computational tools to access high-level data for small organic molecules. I showcase the creation of a novel metric for assessing organic radical stability, utilizing a comprehensive chemical database of radicals. This involves employing straightforward physical organic descriptors, namely fractional spin, and buried volume, computed through systematic computational workflows. In Chapter 4, I explore the progression of graph-based models designed to forecast molecular properties, specifically Bond Dissociation Energy. Additionally, I conduct a thorough examination of two particular applications pertinent to pharmaceutical and atmospheric chemistry. I demonstrate that utilizing a minimal number of molecules from the relevant chemical space can notably enhance large-scale machine-learning models. Finally, in Chapter 5, I combine the developed tools from Chapters 3 and 4, to perform goal-directed molecular optimization in identifying novel radicals for aqueous redox flow batteries using graph neural networks (radical stability, redox potentials, and bond dissociation energy) and reinforcement learning. This de novo molecular optimization strategy has successfully identified 32 new radical candidates. By amalgamating insights from diverse studies, this dissertation endeavors to offer a comprehensive grasp of how machine-learning strategies are transforming the terrain of molecular property prediction.Item Open Access Establishing base-catalyzed halogen transfer as a general platform for C–H functionalization(Colorado State University. Libraries, 2024) Bone, Kendelyn I., author; Bandar, Jeffrey, advisor; Crans, Debbie, committee member; Henry, Chuck, committee member; Belisle, John, committee memberIn contrast to traditional multi-step routes, C–H functionalization offers a resource and time efficient route to desired products. Current methods for oxidative C–H functionalization are developed on three predominate reactivity platforms (1) hydrogen atom transfer, (2) single- electron transfer, and (3) C–H insertion. Despite their synthetic power, methods built on these platforms are restricted to similar bond conversions, substrates, and selectivities. Thus, there remains a strong demand for new mechanistic approaches to oxidative C–H functionalization that offer a departure from traditional reactivity. In efforts to address this need, new methods for oxidative coupling based on a base-catalyzed halogen transfer (X-transfer) reactivity platform are described herein. Chapter one provides an overview on the development of a X-transfer enabled direct C–H hydroxylation of mildly acidic N-heteroarenes and benzenes. Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development of reactions that complement and address the limitations of existing methods for the introduction of aromatic hydroxyl groups is an important goal. To this end, this chapter discusses the development of a protocol that employs an alkoxide base to catalyze X-transfer from sacrificial 2-halothiophene oxidants to aryl substrates, forming SNAr-active intermediates that undergo nucleophilic hydroxylation. Key to this process is the use of 2-phenylethanol as an inexpensive hydroxide surrogate that, after aromatic substitution and ii rapid elimination, provides the hydroxylated arene and styrene byproduct. Use of simple 2-halothiophenes allows for C–H hydroxylation of 6-membered N-heteroarenes and 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends the scope to electron-deficient benzene substrates. Mechanistic studies indicate that aromatic X-transfer is reversible, suggesting that the deprotonation, halogenation, and substitution steps operate in synergy, manifesting in unique selectivity trends that are not necessarily dependent on the most acidic aryl position. The utility of this method is further demonstrated through streamlined target molecule syntheses, examples of regioselectivity that contrast alternative C–H hydroxylation methods, and the scalable recycling of the thiophene oxidants. Chapter two describes the elaboration the X-transfer enabled C–H functionalization platform to encompass benzylic C(sp3)–H bonds. Thus, a benzylic C–H oxidative coupling reaction with alcohols that proceeds through a synergistic deprotonation, halogenation and substitution sequence is discussed. In contrast to existing radical-based pathways for C–H functionalization, this process is guided by C–H acidity trends. This gives rise to new synthetic capabilities, including the ability to functionalize diverse methyl(hetero)arenes, tolerance of oxidizable and nucleophilic functional groups, precision regioselectivity for polyalkylarenes and use of a double C–H etherification process to controllably oxidize methylarenes to benzaldehydes.Item Embargo Understanding structure property relationships in niobium–based oxides for high-rate anodes(Colorado State University. Libraries, 2024) Salzer, Luke David, author; Sambur, Justin, advisor; Dong, Yuyang, committee member; Henry, Chuck, committee member; Weinberger, Chris, committee memberWith the growing usage of portable electronic devices, electric vehicles, and grid level storage, a diverse set of energy storage devices is required for each application. Current commercial level lithium-ion batteries commonly utilize graphite as the anode material. While graphite possesses impressive energy storage, graphite struggles with high (dis)charge applications. One class of materials of interest to replace graphite are niobium-based oxides, some of which fall into a group of materials called Wadsley-Roth crystallographic shear compounds. Wadsley-Roth (W-R) compounds possess unit cells with nxm blocks of edge-shared octahedra, which boast high-rate capabilities, having higher volumetric capacities than graphite at various (dis)charge rates. While various (W-R) compositions of have been synthesized and their electrochemical properties explored, the origin of the excellent rate capabilities and capacities is unclear. Herein, niobium-based anodes for high-rate lithium-ion batteries are investigated to understand the structure-property relationships in W-R materials with different block sizes, levels of disorder, and composition. Additionally, a niobium oxide polymorph falls into a unique class of energy storage materials called pseudocapacitors, which possess high energy density while the charge storage mechanism mimics that of a capacitor. Sections of this work describe current and future investigations of pseudocapacitive niobium oxide to better understand the origin of this interesting material. Chapter 1 begins with a brief introduction, background, and motivation on the need for high-rate, high-capacity anode materials as an alternative for graphite, to address the growing need for high-power, high-energy density materials. Chapter II describes the synthesis of three structurally similar W-R compounds with different block sizes and investigates the electrochemical performance of each material. Chapters III and IV investigate methods to improve the electrochemical performances of W-R compositions through defects and dopants. Chapter V investigates the pseudocapacitive niobium oxide that also exhibits high-rate capabilities through a process called pseudocapacitance, in which the material possesses electrochemical characteristic similar to both batteries and capacitors. In the final chapter, Chapter VI, concludes the dissertation by describing further directions necessary to better understand the structure property relationships resulting in high-rate, high-capacity niobium-based oxide anodes.Item Open Access Synthesis of α,α-Difluorobenzylic structures via new base-promoted reductive and oxidative coupling reactions(Colorado State University. Libraries, 2024) Hooker, Leidy V., author; Bandar, Jeffrey S., advisor; Kennan, Alan, committee member; Finke, Richard, committee member; Reisfeld, Brad, committee memberα,α-Difluorobenzylic substructures have been a desired product in a variety of industries from pharmaceuticals to agrochemicals to electronic materials. This thesis highlights the traditional and fundamental challenges associated with accessing these valuable products from trifluoromethylarenes and difluoromethylarenes, respectively, with an emphasis on base-promoted strategies to facilitate these transformations. Both a general Lewis base-promoted reductive coupling strategy and a Brønsted base-promoted oxidative coupling strategy have been developed with the purpose of achieving more modular access to α,α-difluorobenzylic substructures. Chapter One describes the significance of defluorinative strategies on small molecule organofluorines and the background of defluorinative strategies on trifluoromethylarenes, specifically, including previous and current work by the Bandar Group. The monoselective defluorofunctionalization of trifluoromethylarenes has been a long-standing challenge within the chemistry community and in 2019 the Bandar Group began to expand this methodology to include Lewis-base promoted approaches to access value-added products. Chapter One is intended to be the foundation of this thesis and convey the importance of fluorinated small molecules in a variety of applications with a specific emphasis on defluorinative strategies to functionalize trifluoromethylarenes. Chapter Two describes the long-standing challenges for selective defluorofunctionalization of trifluoromethylarenes, specifically of electronically unactivated arenes. Insight gained from the Bandar Group's reported Lewis base-promoted strategy was used to pragmatically develop an approach for selective functionalization of electron-neutral trifluoromethylarenes. This chapter will provide background on the prevalence of trifluoromethylarenes, strategies that selectively functionalize unactivated systems, and my efforts to expand Lewis-base promoted functionalization to this class of arenes. Chapter Three describes the fundamental challenge of deprotonative strategies that result in unstable carbanions, particularly α,α-difluoromethylarenes and our approach to achieve their productive functionalization. Difluorobenzylic substructures are valuable in a variety fields such as pharmaceuticals, agrochemicals, and electronic materials. Our group's Halogen transfer platform provides an approach to rapidly capture unstable carbanions with base-stable halogen oxidants (2-halothiophenes) which was sequenced with substitution via in situ pronucleophiles. The scope is highly general and provides alternative selectivity to traditional nucleophilic fluorination or radical halogenation methods, while pronucleophiles can be aliphatic alcohols or aromatic alcohols and thiols to achieve value-added products.Item Embargo Analytical methods for evaluation of two classes of bioactive compounds(Colorado State University. Libraries, 2024) Haase, Allison Adelle, author; Crans, Debbie C., advisor; Jarosova, Romana, committee member; Menoni, Carmen, committee member; Peebles, Christie, committee memberAnalytical chemistry and techniques are the underlying support of most kinds of chemical research, as well as biological and environmental research in general, and is a broad field with many different methodologies and modalities. The major subdivisions of analytical chemistry stated in this dissertation are characterization, separation, identification, and quantification, though these fields can overlap. This dissertation focuses on two different research projects involving analytical chemistry, a project focusing on the characterization of novel compounds versus a project consisting of the separation, identification and quantification of compounds in a complex mixture. However, these different research projects are linked through their use of analytical chemistry and the fact that both research projects involve the study of bioactive compounds. Chapter 1 is an introductory chapter consisting of a discussion of the types of analytical chemistry mentioned in later chapters, as well as an overview of the projects that comprise the bulk of the dissertation. Chapter 2 details the studies used to characterize Vanadium complexes for potential use as anti-cancer agents, specifically focusing on the electrochemical evaluation of the complexes' redox properties using non-aqueous cyclic voltammetry. In addition, the hydrolytic stability of the complexes in both saline solution and DMSO was evaluated using ultraviolet-visible light spectroscopy. The potential relationship of these experimentally determined properties was compared to computed properties of the complexes calculated using the Chemicalize website. Vanadium complexes have been studied for various biological properties, as vanadium is a relativity non-toxic metal with various oxidation states. These complexes have been synthesized with a Schiff-base backbone and non-innocent catecholate ligands, which can provide a variety of redox activity on both the metal centers and the ligand. Some compounds in this class of complexes are effective against cancer cells, particularly those of dangerous brain cancers like glioblastoma, while not being overly toxic with long-term use due to the compound degrading into less harmful byproducts upon exposure to water. However, changing the catecholate ligand on these complexes significantly changes the stability and redox properties of the complexes. The potential source of the changes in hydrolytic stability and redox potentials were evaluated. Chapter 3 details the research involving the attempt to separate, identify, and quantify all 24 neutral hexoses from complex samples at very low concentrations using Gas chromatography–Mass spectrometry. It describes issues with separating enantiomers and intermolecular condensation forming rings and anomers, which further complicates separation when one does not use a chiral column. It delves into the scientific literature for possible separation methods without derivatization and why they were not used for this project. It then describes two derivatization methods for hexose separation. Chapter 4 is a concluding chapter that speaks of what was learned from these projects and the potential future directions of those projects.Item Embargo Cu-P-Se nanoparticles: understanding the reaction pathways for the colloidal synthesis of energy conversion and storage materials(Colorado State University. Libraries, 2024) Neisius, Nathan A., author; Prieto, Amy L., advisor; Finke, Richard, committee member; Herrera-Alonso, Margarita, committee member; Paton, Robert, committee memberNanotechnology has garnered considerable interest over the last 40 years, owing to the unique, desirable properties that can be targeted through established synthetic methods for tuning the size of materials at the nanoscale. As no one single material has properties suitable for a wide range of applications, property driven synthesis has been at the forefront of the nanoparticle (NP) field. Particularly, colloidal NP syntheses provide a large synthetic landscape to explore as a result of the vast synthetic tunability to target specific parameters such as, particle size, morphology, composition, and defects. Although significant efforts have been made toward deciphering the transformation processes of unary and binary NPs, traditionally the colloidal NP field has been driven by a top-down approach, driven by trial-and-error methods, limiting the design of desired, complex materials. Thus, to further progress nanoparticle technology, understanding the underlying transformation processes occurring throughout the formation of colloidal nanoparticles is essential to develop novel materials as well as control the structure/property relationships. The copious amounts of both organic and inorganic interactions, as well as the complexity of capturing the transformation from molecular to the solid-state regime, complicates the reaction landscape for more complex, ternary phases. The purpose of the work included and explained in this dissertation is to develop stoichiometric syntheses for both Cu-P-Se ternary phases, Cu3PSe4 and Cu7PSe6, and to then understand the reaction pathways for an improved retrosynthetic analysis and enable translation of the synthetic knowledge to other systems. Cu-P-Se ternary chalcogenide NPs are of particular interest, owing to the synthetic complexity of navigating a rich phase space with thermodynamically stable binary phases close in energy to the desired ternary phases, as well as applicable structural properties for thermoelectrics, photovoltaics, and battery applications. Therefore, to contribute to the progression of the nanoparticle field the general objectives of this study are, (1) analyzing the transformation of commonly employed precursors and solvents (2) capture the influence of precursor reactivity on ternary phase formation, and (3) perform careful characterization of speciation and final nanoparticles, all of which to establish a full scope of Cu-P-Se nanoparticle formation and the impact of individual synthetic parameters on chalcogenide-based precursors. In Chapter 1, the relevant literature for the following chapters is reported and reviewed to provide the essential background information. This chapter is divided into 6 subsections; (1) Need for renewable energy and how nanoparticles provide solutions, (2) State of nanoparticle synthesis field, current limitations, and progress towards developing a better understanding of nanoparticle reaction pathways, (3) Motivation for exploring the Cu-P-Se phase space, (4) Se reactivity in NP syntheses, (5) Cu3P – the required precursor for Cu-P-Se formation, (6) Dissertation overview, publications, and presentations. The first colloidal NP synthesis report on Cu3PSe4 was developed by a previous group member, Dr. Jennifer Lee, which demonstrated that the phase purity of Cu3PSe4 requires the use of Cu3P NPs and selenium powder (Se) in ODE as precursors. Alternate reaction precursors, and therefore pathways, were disproven throughout this study, leading to the working hypothesis that the interactions of Se and ODE were a necessary step to form active species that then react with Cu3P NPs. Although frequently employed in NP research, and heavily characterized, the implications of the Se/ODE solution on Cu3PSe4 phase formation are still misunderstood. Therefore, the studies presented in Chapter 2 are aimed at probing the Cu3PSe4 reaction landscape and the findings are separated into (1) ex situ reactions that are characterized with molecular and solid-state characterization techniques to determine the implications of the solution dynamics on Cu-P-Se NP phase formation, and (2) how different Se/ODE speciation can be isolated and subsequently favor the alternate, metastable Cu-P-Se phase, Cu7PSe6. A persistent limitation to the previous study is that ODE contaminates the final products, making the findings and analysis of Se/ODE rather difficult to interpret, thus requiring a simplified, cleaner reaction to produce phase pure Cu3PSe4. For that reason, Chapter 3 shifts the direction of the Cu3PSe4 synthesis towards a more stoichiometric, atom-economical reaction by eliminating ODE as the solvent. Rather, a long-chain, aliphatic solvent, octadecane (ODA) is employed that proves to be an operationally inert solvent under the standard synthetic conditions and produces cleaner, phase pure Cu3PSe4 NPs as determined by powder X-ray diffraction (PXRD) and transmission electron microscopy (TEM). If ODA was reacting with Se0 powder, the most favorable pathway, commonly cited in literature, is the formation of H2Se and oxidized ODA (alkene). Hence, molecular characterization techniques, nuclear magnetic resonance (NMR, 1H and 13C) and fast-Fourier infrared spectroscopy (FT-IR), were utilized to demonstrate the absence of oxidized ODA species, which is consistent with Se0 preferentially reacting with Cu3P, promoting a more direct reaction pathway. Eliminating the presence of alternate, competing reaction pathways in the ODE synthesis and establishing a near-stoichiometric reaction, allows us to capture the underlying transformation process of Cu3P to Cu3PSe4. From these systematic improvements, we hypothesize that Se0 powder is dispersed in ODA, which promotes a formal eight-electron transfer between Cu3P and 4 Se0. Extracting the synthetic information from the previous chapters to target the metastable Cu-P-Se phase, Cu7PSe6, provides the framework for Chapter 4. Previous methods to isolate Cu7PSe6 are based on traditional, solid-state techniques, where the elemental precursors are ground and subsequently heated to high temperatures (>1000K). Although a colloidal or solution-based synthesis has yet to produce phase-pure Cu7PSe6 particles, attempts explained in Chapter 2 provide a basis on the phase space complexity, where the products consisted of Cu7PSe6 but with thermodynamic byproducts, Cu-Se phases and Cu3PSe4 present. Therefore, an alternate Se precursor, diphenyl diselenide (Ph2Se2), is employed to form the metastable phase, which effectively avoids Cu3PSe4 formation. Importantly, an alternate route to form Cu3PSe4 is with analogous dialkyl diselenide precursor, dibenzyl diselenide, where a key finding is the presence of amorphous phosphorus (P) on Cu1-xSe binaries at low temperatures, which then efficiently reincorporates once the desired 300 ˚C reaction temperature is reached. Thus, in Chapter 4 we investigate why Cu7PSe6 is favored with Ph2Se2 as a precursor, which is predicated on the formation of byproduct species that effectively "trap" P. A proof of concept is explored to further demonstrate the dynamics of P in solution, where the Cu-P-Se phase space can be controllably toggled across by injecting P(5+) species. A drawback for the Cu-P-Se syntheses is the lack of compositional understanding of the pre-synthesized Cu3P NPs, thus further complicating the reaction stoichiometries. Chapter 5 first investigates the previously published synthesis by Liu et al., by thoroughly characterizing the final Cu3P nanoparticles under identical reaction conditions and exploring alternate reaction stoichiometries to reduce the presence of residue precursors. From such, it is determined that the particles substantially deviate from the stoichiometric Cu3P composition, with a Cu:P ratio around 1.5:1.0. Particular focus is also placed on monitoring the degradation of a green phosphorous source, triphenyl phosphite, P(OPh)3. Although triphenyl phosphite (TPOP) has been previously used for transition metal phosphide systems, a lack of systematic investigations leads to questions on the reduction of TPOP en route to forming Cu3P, a formal P(3+) to P(3-) event. Additionally, limited characterization of the final organic byproducts in the original synthesis, begs to question what, if any, byproducts could be contaminating the Cu3P NPs. Therefore, we develop and probe stoichiometric syntheses that isolate phase pure Cu3P NPs to avoid the original 30-fold excess of P. The transformation of hexadecylamine (reductant and ligand) and TPOP were characterized with 1H and 31P NMR to evaluate the role of each en route to forming Cu3P. As this is project is still developing, the necessary future directions are given to systematically approach this problem, with an emphasis on first-step experiments and essential characterization methods to completely grasp the decomposition mechanism of TPOP. Ultimately, this has implications when systematically applying TPOP to alternate transitional metal phosphide NP syntheses, as well as developing more precise Cu-P-Se syntheses. Finally, the work presented herein is summarized in Chapter 6 along with an outlook on the project as a whole. Specifically, future directions and preliminary insight into the underlying reaction pathways and mechanism of Cu3PSe4 formation are explored. Additionally, we explore preliminary data on an analogous material Ag-P-Se, which was plagued for years by the lack of a reproducible Ag-P precursor synthesis that limited our ability to extract the synthetic intuition from the Cu-P-Se system. However, recent literature findings on a potential Ag3P precursor provides promise on synthesizing Ag-P-Se phases in the future, which is critically analyzed to ensure that any bottlenecks in future syntheses are limited. Ultimately, the work provided in the following chapters is aimed at making strides to developing a more in depth understanding of precursor interactions between transition metals and main group elements, as well as properly monitoring such reactions to extract synthetic information to analogous systems. With the knowledge gained on the presented studies, we aspire to contribute to the NP field in order to continually improve NP synthesis and therefore nanomaterials. Finally, this work is supported by NSF Macromolecular, Supramolecular, and Nanochemistry (MSN #2109141).Item Open Access Mesoscopic revelations: studying the shape of AOT reverse micelles(Colorado State University. Libraries, 2024) Gale, Christopher D., author; Levinger, Nancy E., advisor; Krummel, Amber, committee member; Prieto, Amy, committee member; Buchanan, Kristen, committee memberAerosol-OT (AOT) reverse micelles are a quintessential model system for studying nanoconfinement, creating consistent reverse micelles with a repeatable and very small size (~1-10 nm) using just 3 components. These reverse micelles have been used for studying the behavior of water and solutes in nanoconfinement, modeling the behavior of key solutes and proteins in a system more analogous to in vivo work, synthesizing nanoparticles, and even as a vehicle for suspending proteins in a low-viscosity solvent for high quality NMR experiments. Despite their usefulness, AOT reverse micelle's shape is poorly understood, but important to understanding behavior within a reverse micelle. Interfacial properties have been found to be key to many aspects of behavior within AOT reverse micelles and distance from the interface as well as the actual amount of interface present are highly dependent on shape. Therefore, the study of shape is key to a better understanding of AOT reverse micelles and behavior in nanonconfinement. In this work, I develop a series of metrics for shape--- coordinate-pair eccentricity (CPE), convexity, and the curvature distribution--- and apply them to several simulations of AOT reverse micelles. The simulations were designed to test the impact of the force field on the shape and behavior of the reverse micelles, including the first parameterization of AOT into the OPLS force field. The system was extensively checked to ensure equilibration was achieved and the system was not biased by the starting configuration. To aid in the shape analysis, I have developed a model and a formal proof to predict how the CPE changes for an arbitrary shape as it grows to model the shape behavior of general core-shell structures. Additionally, I measured the dipole moment of AOT, the rotational anisotropy decay of water, and several radial distribution functions to provide experimental verification where possible and further explore the behavior of the AOT reverse micelle system. Several key findings emerge from this work. Most notably, I find that AOT reverse micelles are significantly aspherical and non-convex over every force field tested, providing robust evidence that AOT reverse micelles are aspherical at any given moment in time. This provides strong evidence in support of the idea that experimental observations of spherical particles are the result of ensemble averaging. I also observe that the shape at the AOT/oil interface is comparatively more spherical with a "Goldilock's" value of convexity, neither too high nor too low, compared to the water/AOT interface. My model predicts that the CPE should fall with the addition of a shell, here provided by the AOT surfactant layer, suggesting this is largely the result of geometry. There is great variation between simulations and metrics in their dynamics, but in general, the shape appears to change on the order of 10 ns. This provides a useful method of deducing which values may or may not be impacted by shape, based on the time scale. For instance, it can reasonably be said that shape likely has no impact on water dynamics based on the roughly four orders of magnitude difference in the time scales of each process, which is supported by my own findings. Across all metrics studied, there are noticeable differences between simulations, but none of the differences are consistent. I believe this observation has important implications for both the behavior and simulation of AOT reverse micelles. First, this implies that the forces and interactions giving rise to different aspects of the reverse micelle are complex and largely independent, and that there is a disconnect between molecular-level measurements like radial distribution functions and and mesoscopic-level measurements like shape. Second, this implies that any simulation parameterized on one measure has no guarantee that it reproduces any other aspect of the reverse micelle accurately.Item Open Access The development of new synthetic methods and techniques using strong Brønsted bases(Colorado State University. Libraries, 2024) Hoteling, Garrett A., author; Bandar, Jeffrey, advisor; Miyake, Garret, committee member; Menoni, Carmen, committee member; Peebles, Christie, committee memberBrønsted bases are indispensable tools in synthetic chemistry and, as such, deprotonation serves as a ubiquitous mode of molecular activation. By pushing the boundaries of what is possible within the acid-base reaction paradigm, unique synthetic methods and techniques can be developed. The work described in this thesis focuses on gaining a fundamental understanding of strong-base chemistry in efforts towards the development of new base-promoted synthetic methods. Herein, Brønsted bases have been investigated in two ways; 1) the design and application of benchtop-stable precatalyst salts for valuable organic superbases; and 2) the implementation of base-promoted halogen-transfer to develop benzylic oxidative coupling reactions with alkyl (hetero)arenes. This dissertation consists of five chapters. Chapters One and Three provide background and motivation for the work disclosed in this dissertation. Chapters Two, Four and Five represent project areas I have developed with Chapter Two adapted from published work and Chapters Four and Five as drafts of unpublished work. Below is a list of the chapters including a summary of the content for each. Chapter One describes the importance of organic superbases and their relevance to the synthetic community and the Bandar Group as a whole. Presented here will be the various classes of superbases and their unique properties that distinguish them from other classes of bases. Additionally, applications and known limitations to use of these bases will be discussed here. Chapter Two describes work along with Dr. Stephen J. Sujansky on the development of benchtop-stable organic superbase salts and the method for their facile in situ activation. Here, air-sensitive organic superbases form salts when mixed with carboxylic acids that are indefinitely stable on the benchtop. When combined with an epoxide additive, the carboxylate will react to open the epoxide and generate an alkoxide that can neutralize the superbase conjugate acid. This strategy is effective at promoting catalytic Michael-type additions and polymerizations as well as stoichiometric substitution and Pd-catalyzed cross-coupling reactions. This strain-release mechanism not only provides an accessible precatalyst for air-sensitive superbases but provides a new opportunity for controlling base concentration in situ. Chapter Two describes the development of the Bandar Group’s base-promoted halogen transfer research program. The history and importance of this mechanistic platform will be discussed as well as previous reports in the area by our group. In this chapter, the mechanism of base-promoted halogen-transfer is described, which enables the exchange of weakly acidic C–H bonds for C–X bonds that can be subsequently substituted with a pronucleophile in situ. This section will also provide the necessary background and motivation for Chapters Four and Five. Chapter Four describes the development of a new method for the synthesis of benzylic amines from alkyl (hetero)arenes. The development, optimization, and scope investigation of this reaction are described herein. The results of this work represent the first general approach for benzylic C–H amination, functioning on a broad scope of alkyl (hetero)arenes and amine coupling partners. Chapter Five describes the use of base-promoted halogen-transfer to enable alkyl (hetero)arene desaturation. With ethyl- and longer alkyl-substituted arenes, after benzylic halogenation, elimination takes place in the presence of excess base, a process that is competitive iv with the substitution protocol described in Chapter Two. Here, this reactivity has been exploited to develop a general desaturation technique for alkyl (hetero)arenes. Under desaturation conditions, an amine pronucleophile can be added, at which point β-addition followed by subsequent desaturation affords the β -aryl enamine, which is a diversifiable functional handle. This chapter describes the development of desaturation, cascade enamine formation, and the modification of enamine products.