Browsing by Author "Paton, Robert, committee member"
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Item Embargo Application and effects of metal-based therapeutics on cancer cell lines in tissue culture(Colorado State University. Libraries, 2024) Klugh, Kameron Leigh, author; Crans, Debbie, advisor; Paton, Robert, committee member; Menoni, Carmen, committee memberIn recent years, metal-based drugs have emerged as significant players in the field of therapeutics, leveraging the unique properties of metals to enhance medical treatments. These compounds, incorporating transition metals such as vanadium and platinum, have shown remarkable efficacy in treating various conditions, most notably cancer. The ability of such metals to form complex structures with organic molecules allows for precise targeting and modulation of biological pathways, leading to improved drug efficacy and reduced side effects. Thus, this approach has opened new avenues for designing advanced therapeutics such as vanadium(V) Schiff base catecholate complexes for the treatment of cancer. This thesis aims to explore the potential of non-innocent Schiff base vanadium(V) catecholate complexes as promising agents against glioblastoma, an aggressive form of brain cancer. Two catecholate ligands, 3,5-di-isopropyl catechol and 3,4,6-tri-isopropyl catechol, were synthesized and coordinated to both known and novel vanadium(V) Schiff base scaffolds. Upon testing on glioblastoma T98g cell lines, two of the new complexes, namely [VO(3-tBuHSHED)(TIPCAT)] and [VO(3,5-tBuHSHED)(TIPCAT)], showed remarkable antiproliferative activity. Parallelly, the manuscript delves into the therapeutic applications of platinum-based drugs and how the resistance of platinum-based chemotherapeutics remains a significant challenge. This area of the manuscript identifies the newly discovered role of long non-coding RNAs in platinum-resistance in gastrointestinal cancer treatment. The interaction of these drugs with cellular RNA, in addition to DNA, contributes to this resistance. This manuscript examines the speciation of cisplatin and oxaliplatin, their interactions with DNA and RNA, and the resulting physiological responses of long non-coding RNAs. It identifies aberrantly expressed lncRNAs in platinum-resistant gastrointestinal cancer cell lines, including those from oral cavity, esophageal, gastric, and colorectal cancers. Despite testing different cell lines, similar patterns of aberrant expression compared to normal cells suggest consistent changes in gene expression and cellular pathways. Understanding these changes may help develop new therapeutic strategies for gastrointestinal cancer patients. Together, the vanadium(V) complex investigations and the new insights into platinum-resistance underscore progress in the understanding of the molecular interactions of metal-based drugs, offering pathways to enhance their efficacy and overcome resistance in cancer therapy.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 Engineering and evolving helical proteins that improve in vivo stability and inhibit entry of Enfuvirtide-resistant HIV-1(Colorado State University. Libraries, 2019) Walker, Susanne N., author; Kennan, Alan, advisor; Yao, Tingting, committee member; McNally, Andrew, committee member; Paton, Robert, committee memberMethods for the stabilization of well-defined helical peptide drugs and basic research tools have received considerable attention in the last decade. Enfuvirtide is a 36-residue chemically synthesized helical peptide that targets the viral gp41 protein and inhibits viral membrane fusion. Enfuvirtide-resistant HIV, however, has been prolific, and this peptide therapy requires daily injection due to proteolytic degradation. In this dissertation I have developed a method for stabilizing helical peptide therapeutics termed helix-grafted display proteins. These consist of the HIV-1 gp41 C-peptide helix grafted onto Pleckstrin Homology domains. Some of these earlier protein biologics inhibit HIV-1 entry with modest and variable potencies (IC50 190 nM - >1 μM). After optimization of the scaffold and the helix, our designer peptide therapeutic potently inhibited HIV-1 entry in a live-virus assay (IC50 1.9-12.4 nM). Sequence optimization of solvent-exposed helical residues using yeast display as a screening method led to improved biologics with enhanced protein expression in Escherichia coli (E. coli, a common bio-expression host), with no appreciable change in viral membrane fusion suppression. Optimized proteins suppress the viral entry of a clinically-relevant double mutant of HIV-1 that is gp41 C-peptide sensitive and Enfuvirtide-resistant. Protein fusions engineered for serum-stability also potently inhibit HIV-1 entry.Item Open Access Investigating biosynthetic pathways of the Aspergillus genus through biomimetic total synthesis of secondary metabolites(Colorado State University. Libraries, 2022) Benson, Brooke, author; Williams, Robert M., advisor; Kennan, Alan J., advisor; Paton, Robert, committee member; Crans, Debbie, committee member; Crick, Dean, committee memberThe prenylated indole alkaloids are a class of secondary metabolites containing a unique bicyclo[2.2.2]diazaoctane core and a wide range of biological activity. This complex structure has prompted extensive investigation into the biochemical synthesis of these compounds. Currently, three disparate biochemical strategies are known to be used by producing fungi to construct the bicyclic core: (1) NADPH-dependent bifunctional reductase/Diels-Alderase-mediation in formation of the monooxopiperazines; (2) brevianamide assembly through cofactor-independent pinacolase resulting in spontaneous intramolecular Diels-Alder (IMDA) generation of the bicyclo[2.2.2]diazaoctane core; (3) Diels-Alderase mediated enantiodivergent generation of the dioxopiperazines via cytochrome P450 oxidation to achiral azadienes and successive enzyme-mediated stereoselective IMDA reaction. This work aimed to employ biomimetic total synthesis to aid in elucidation of the biosynthetic pathways in the Aspergillus genus, which utilizes the third strategy. This author reports the first total syntheses of 6-epi-Notoamides T10-12 and Notoamide T2, as well as an improved total synthesis of 6-epi-Notoamide T. Also reported are synthetic efforts towards 6-epi-Notoamide T9, Notoamide TI, and Citrinalin C.Item Open Access Oxidative quenching organic photocatalyst design, synthesis and application in dual nickel/photoredox-catalysis(Colorado State University. Libraries, 2023) Chrisman, Cameron Hayes, author; Miyake, Garret, advisor; Paton, Robert, committee member; Zadrozny, Joseph, committee member; Kipper, Matthew, committee memberThe work described in this dissertation focuses on the development of a new class of organic photocatalysts and the application of oxidative quenching photocatalysts in dual nickel/photoredox-catalysis. The design of new organic photocatalysts is crucial for eliminating the need to use rare/expensive ruthenium and iridium that have dominated the field of photoredox catalysis. Additionally, the majority of the catalysts describe here-in operate through an oxidative quenching mechanism that remains underexplored in the field of dual nickel/photoredox catalysis. The first detailed mechanistic study on oxidative quenching in this field is reported and applied in a broad range of couplings.Item Open Access Phosphorus ligand-coupling reactions for the functionalization of pyridine and other azines(Colorado State University. Libraries, 2021) Nottingham, Kyle G., author; McNally, Andrew, advisor; Paton, Robert, committee member; Henry, Chuck, committee member; Cohen, Robert, committee memberPyridines and related azines are ubiquitous in pharmaceuticals, agrochemicals, and materials. The discovery and development of new purpose-built molecules is contingent on our ability to modify these motifs. Described herein are the development of methods that selectively functionalize pyridine and diazine scaffolds through phosphorus ligand-coupling. Novel phosphine reagents were designed and leveraged to construct C–C, C–O, and C–N bonds on azines from their C–H precursors. Chapter one introduces the history of phosphorus ligand-coupling and defines the reactivity explored throughout this thesis. Both seminal and contemporary examples of phosphorus ligand-coupling reactions are also discussed to provide context for this work. Chapter two focuses on a method to incorporate fluoroalkyl groups onto azines and pharmaceuticals using phosphorus ligand-coupling. This method offers a complementary alternative to widely used radical addition approaches which often produce regiomeric product mixtures on azines. Chapter three presents the investigation of a phosphorus-mediated alkenylation reaction on pyridines and quinolines. Examination of the reaction of pyridylphosphines with alkyne acceptors uncovered divergent reaction pathways from alkenylphosphonium salts. Mechanistic studies provide an explanation for the origin of selectivity obtained in these reactions. Lastly, chapter four expands upon one of these reaction pathways and describes the development of a method for the direct conversion of pyridines into pyridones and aminopyridines.Item Open Access Reductive coupling reactions of organosilanes for the monoselective C–F functionalization of trifluoromethylarenes(Colorado State University. Libraries, 2022) Wright, Shawn E., author; Bandar, Jeffrey, advisor; Paton, Robert, committee member; Borch, Thomas, committee member; Herrera-Alonso, Margarita, committee memberThe mono-selective defluorofunctionalization of trifluoromethylarenes is an emerging strategy to access ⍺,⍺-difluorobenzylic derivatives, which are difficult to access in a divergent manner. Fluorine incorporation is a common strategy employed during the optimization of potential pharmaceuticals in the drug discovery process. Much effort has been spent over the past few decades in developing fluorination methodologies, and the result has been tremendous growth in aryl and alkyl fluorination and trifluoromethylation reactions. On the other hand, methods to install other fluoroalkyl motifs are less developed. Due to the abundant availability of trifluoromethylarenes, mono-selective defluorofunctionalization reactions would be an ideal route to access ⍺,⍺-difluorobenzylic derivatives, which are becoming increasing examined in drug discovery settings. Chapter one will provide the necessary background to understand the context of the work described throughout the following chapters. First, there will be an overview of the importance of fluorine for the development of pharmaceutical compounds. Then there will be a brief summary of the different strategies that have been developed to achieve the trifluoromethylation of arenes as well as the common routes to access ⍺,⍺-difluorobenzylic compounds. Finally, a thorough discussion of the challenges and reported solutions to achieve mono-selective defluorofunctionalization of trifluoromethylarenes will be provided. Chapter two will describe the initial discovery, development, and mechanistic investigation of the defluoroallylation reaction reported by the Bandar group. This discovery led to the identification of a new strategy to achieve reductive coupling through the use of Lewis base activated organosilanes, which provides the basis for the reactions discovered and developed in chapters three and four. Chapter three will describe the discovery, development, and mechanistic investigation of a reductive coupling reaction of trifluoromethylarenes with formamides. This reaction generates a silylated hemiaminal product which is a valuable synthetic intermediate to access a broad scope of ⍺,⍺-difluorobenzylic derivatives. Mechanistic investigations support the generation of a ⍺,⍺-difluorobenzylsilane intermediate in the reaction. Isolated of the ⍺,⍺-difluorobenzylsilane and subsequent derivatizations further broaden the scope of transformations accessible via this reductive coupling process. Chapter four will describe the discovery and preliminary development of the mono-selective hydrodefluorination of trifluoromethylarenes using hydrosilanes activated by a Lewis basic catalyst. Two different catalytic systems are demonstrated that operate via different mechanisms, which provides access to different reaction scopes. A short discussion on the future work of this project will also be provided, where a junior graduate student is developing conditions to enable the mono-selective hydrodefluorination of electron-neutral trifluoromethylarenes.Item Open Access Site-selective functionalization of azines and polyazines via heterocyclic phosphonium salts(Colorado State University. Libraries, 2020) Dolewski, Ryan D., author; McNally, Andrew, advisor; Paton, Robert, committee member; Henry, Chuck, committee member; Kanatous, Shane, committee memberPyridine and diazines are frequently found in FDA approved drugs, biologically active compounds, agrochemicals, and materials. Given the importance of these structural motifs, direct methods that selectively functionalize pyridine and diazine scaffolds have been developed. These methods and their associated challenges are discussed in chapter one. In chapter two, a strategy to directly and selectively functionalize pyridines and diazines via heterocyclic phosphonium salts is presented. The process is broadly applicable for pyridines and diazines and the late-stage functionalization of pharmaceuticals. Four reaction manifolds are amenable to transforming heterocyclic phosphonium salts into valuable derivatives. In chapter three, inherent factors that control site-selectivity in polyazine systems are described along with mechanistically driven approaches for site-selective switching, where the phosphonium ion can be predictably installed at other positions in a polyazine system. The fourth chapter focuses on a new strategy to selectively alkylate pyridines via a traceless dearomatized phosphonium salt intermediate. Preliminary studies show this protocol is amenable to building-block pyridines, drug-like fragments and pharmaceuticals. A late-stage methylation strategy is also presented.Item Open Access Sustainable polymer synthesis through the design of organic photoredox catalysts and development of poly(norbornane trithiolanes)(Colorado State University. Libraries, 2023) Price, Mariel Jene, author; Miyake, Garret, advisor; Paton, Robert, committee member; Zadrozny, Joseph, committee member; Herrera-Alonso, Margarita, committee memberThere are many avenues through which the sustainability synthesis, use, and disposal of polymeric materials can be approached. One of the two approaches explored in this work is the sustainable design and use of polymerization catalysts. Proper employment of catalysis can greatly decrease the energy input required to synthesize polymers and intentional design of those catalysts can enable their use in small quantities without compromising their effectiveness or the sustainability with which they are made and used. Herein, the development of a new class of metal-free photoredox catalysts (made from abundant elements) which can use visible wavelengths of light (a readily available, replenishable, and mild source of energy) to control the polymerization acrylate monomers is reported. Through this work we provide insight into how catalyst structure can be tuned to achieve desired properties and what properties might render certain catalysts more effective at lower loadings. The second approach explored herein towards improving the sustainability of polymer synthesis, use, and disposal is related to the recyclability of the polymeric materials. In addition to sustainable synthesis through catalysis, one way to improve the sustainability of polymeric materials is to increase their viable economic lifetime. Polymeric materials that are readily recyclable prevent the loss of materials through disposal. In the work reported herein methods for the synthesis and polymerization of sulfur-containing monomers to generate polymeric materials with intrinsic recyclability are investigated, approaches for efficient depolymerization of such polymers improved, and the scope of these materials expanded.Item Embargo Synthesis and characterization of biologically relevant redox-active molecules(Colorado State University. Libraries, 2023) Kostenkova, Kateryna, author; Crans, Debbie, advisor; Zadrozny, Joseph, committee member; Paton, Robert, committee member; Worley, Deanna, committee memberRedox chemistry is fundamental to several essential life processes, such as energy metabolism, respiration, and free radical formation. Many redox-active inorganic and organic molecules are promising agents to combat difficult-to-treat diseases, including cancer and tuberculosis. This dissertation covers the syntheses, studies of the fundamental chemical and biological properties of two vastly different classes of redox-active molecules, inorganic and organic molecules. Most of this work has investigated the fundamental development of hydrophilic, hydrophobic and amphiphilic redox-active vanadium complexes for the treatment of different types of cancer. The last chapter of this dissertation describes the studies of the fundamental properties of demethylmenaquinones which are biosynthetic precursors to menaquinones, lipid electron carriers essential for anaerobic bacterial respiration of several types of bacteria, including Escherichia coli, Actinomadura madurae and pathogenic Mycobacterium tuberculosis. Targeting bacterial electron transport chain disrupts respiration of pathogenic Mycobacterium tuberculosis, thus, studying the properties of demethylmenaquinone analogs is of great interest. Chapter one, an introductory chapter, presents a comprehensive review of the developments in vanadium anticancer therapeutics over the last five years. The structural diversity of the vanadium-containing anticancer compounds, potential applications to various cancer cell lines, and different modes of delivery of highly cytotoxic vanadium species are described in detail. Vanadium gained interest for its anticancer applications after bis(maltolato)oxovanadium(IV), an antidiabetic complexes studied in Phase II clinical trials, went off patent in September 2011. Previous studies with vanadium antidiabetic complexes, however, provided valuable information to understand the action of novel vanadium anticancer complexes, as cancer and diabetes target the same metabolic pathways. Chapters two and three describe the syntheses, spectroscopic characterization, and cytotoxic studies of novel vanadium(V) catecholate complexes with pyridine-containing Schiff base ligands. According to previous reports, vanadium(V) Schiff base catecholate complexes are promising agents for glioblastoma treatment, and herein we investigated whether the presence of the pyridine ring on the Schiff base scaffold improves cytotoxicity and hydrolytic stability of the vanadium catecholato complexes. The studies showed that the presence of the pyridine ring improves hydrolytic stability of the V(V) catecholate complexes, yet it decreases their uptake into glioblastoma cells which result in the decrease of cytotoxicity of the complexes. Even though the stability increased and the compounds have enough time to get into cells, the efficacy of these complexes decreased. Chapter three further explores the redox properties and the redox reaction mechanism of vanadium(V) Schiff base catecholate complexes with pyridine-scaffolds and tert- butyl substituted catecholate ligands. Chapter four describes the speciation studies and testing of vanadium(V) dipicolinate that enhance the effects of oncolytic viruses, non-pathogenic viruses that can infect and kill cancer cells. Additionally, the chapter describes 1H and 51V NMR studies carried out in model membrane interfaces. The data show that V(V) dipicolinates hydrolyze under physiological conditions and generate vanadate which ultimately enhances the spread of the oncolytic viruses. V(V) dipicolinates are located on the interface of the aqueous pool and hydrophobic region of model membranes which also contributes to their hydrolysis. Chapter five describes PtIV and MoVI monosubstituted decavanadates, monoplatino(IV)nonavanadate(V) ([H2PtIVVV9O28]5-, V9Pt), and monomolybdo(VI)-nonavanadate(V) ([MoVIVV9O28]5-, V9Mo), and their ability to initiate signal transduction on the luteinizing hormone receptor (LHR) in CHO cells and their speciation chemistry under the biological experiments. The PtIV and MoVI monosubstituted decavanadates are large vanadium- oxo clusters that are structurally similar to decavanadate but have different charges. The results showed that both V9Mo and V9Pt affect LHR expression and do not inhibit cell growth which is different than the decavanadate ([V10O28]6−, abbreviated V10). Although all the clusters hydrolyze under the assay conditions lifetimes are different, and this was characterized using spectroscopic methods. Using the washing experiments, we were able to show that the V9Pt and V9Mo monosubstituted decavanadates do not associate with the cells and, hence, do not negatively affect cell growth, however, they are more effective in initiating signaling. Chapter six describes initial efforts to study the fundamental properties of two truncated demethylmenaquinones, biosynthetic precursors for menaquinones. The studies are important to understand the fundamental differences between the chemical properties of menaquinones and demethylmenaquines which include 3D conformation and redox potential. Indeed, the development of inhibitors of MenG, a methyltransferase enzyme that coverts demethylmenaquines to form menaquinones, is a known target for drug development for antitubercular applications. Therefore, we investigated whether non-native demethylmenaquines would convert to menaquinones by the relevant enzymes present in the membrane preparations. In summary, the first five chapters demonstrate 1) the diversity of applications of vanadium compounds for treatment of different types of cancer and 2) the efforts to develop vanadium- based anticancer therapeutics to treat different types of cancer. The final chapter describes efforts in fundamental studies preparing and characterizing the chemical properties the truncated demethylmenaquinones. In addition, we demonstrated that the membrane preparations of mycobacteria concerted the synthesized truncated demethylmenaquinone-2 and demethylmenaquinone-3 are processed to form menquinone-2 and menaquinone-3.Item Embargo The design and synthesis of super reducing organic photocatalysts through mechanistic understanding with application towards unactivated arene activation(Colorado State University. Libraries, 2024) Green, Alexander Richard, author; Miyake, Garret, advisor; Paton, Robert, committee member; Bailey, Travis, committee member; Reisfeld, Brad, committee memberThe work described in this dissertation focuses on the understanding of an organic photocatalyst system through a degradation and mechanistic study, leading to development of a new class of organic photocatalyst and improved application. The design of new organic photocatalysts is crucial for eliminating the need to use rare and expensive ruthenium and iridium that have dominated the field of photoredox catalysis for the past decade. Additionally, most of the catalysts describe here-in operate through a unique two electron, one proton activation mechanism to generate a closed shell species which enables direct quenching towards unactivated arenes such as benzene, without the use of a stoichiometric amount of reductant such as solvated electrons coming from pyrophoric metals. The progress described within this dissertation provides a deeper understanding of tunable organic reductants and their function.