Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
165 results
Search Results
Item ACYCLIC CUCURBIT[N]URIL MOLECULAR RECEPTORS: SEQUESTRANTS FOR DRUGS, MICROPOLLUTANTS, AND IODINE(2024) Perera, Wahalathanthreege Sathma Suvenika; Isaacs, Lyle; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Molecular containers are extensively utilized for their exceptional molecular recognition capabilities, making them suitable for use as sensors and sequestration agents. Cucurbit[n]urils, in particular, are recognized for their strong binding affinities, especially towards cationic guest molecules. These applications can be further enhanced by adjusting the size and shape of the host and incorporating functional groups.In Chapter 1, the concept of supramolecular chemistry is introduced, with a specific focus on cucurbit[n]urils. The chapter provides an overview of the development of cucurbit[n]urils and their potential applications. It also addresses the challenge of poor water solubility of cucurbit[n]urils, and discusses the enhancement of water solubility through the development of acyclic CB[n]s. Furthermore, the potential application of these containers as sequestration agents is explored. Chapter 2 describes the synthesis of a novel sulfated acyclic CB[n] receptor (Me4TetM0) and its recognition properties towards a panel of drugs of abuse. The obtained results were compared with two other sulfated acyclic CB[n]s (TetM0 and TriM0). Furthermore, in vivo studies were conducted with TetM0 to assess its efficacy as a sequestration agent for methamphetamine. Chapter 3 presents the synthesis of a series of water insoluble acyclic CB[n]-type receptors and studies their function as solid state sequestrants for organic micropollutants. The results are compared with CB[6] and CB[8]. The time course experiments performed with H4 show a rapid sequestration ability of the five micropollutants studied. Furthermore, under identical conditions, the micropollutant removal efficiency is higher than activated charcoal. Chapter 4 investigates the use of water-insoluble acyclic CB[n]-type receptors for the reversible capture of iodine from the vapor phase. H2 exhibits an iodine capture of 2.2 g g-1, equivalent to 12 iodine atoms per H2 molecule. Following iodine uptake, H2 undergoes partial oxidation, and the uptake of I3- and I5- was confirmed through Raman spectroscopy. Chapter 5 details the synthesis of glycoluril dimer bis(cyclic) ether-based hosts with diverse aromatic side walls. The chapter presents a comparative analysis of dye removal from a solid state and delves into the influence of distinct aromatic walls and various attached substituents.Item Photoredox-Active Tertiary N-Oxyammonium Reagents For Selective sp3 C-H Oxidative Functionalization(2023) Hitt, Michael James; Vedernikov, Andrei N; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The C(sp3)-H bond functionalization under photoredox catalysis has been a topic of active research over two last decades. Photoredox catalysis involves the use of light to access catalysts’ excited states allowing for facile single electron transfer (SET) with a hydrogen atom transfer (HAT) agent precursor. One prominent HAT agent precursor is quinuclidine (Q), of which the active radical is the electrophilic radical cation (Q●+) able to abstract a hydrogen atom from a C(sp3)-H bond, so allowing for the bond functionalization. Q has been used by researchers since 2015 in the reductive photoredox catalytic C(sp3)-H functionalization (Chapter 1). In this work we focus primarily on the design of novel N-acyloxyquinuclidinium reagents with the goal of the development of new reaction protocols for the selective oxidative C(sp3)-H bond functionalization that utilize our new reagents under photoredox catalysis. In Chapter 2 we present our new catalytic system that allows for the selective oxidative C(sp3)-H trifluoroacetoxylation of donors of 1o, 2o and 3o benzylic C-H bonds using N-trifluoroacetoxyquinuclidinium trifluoroacetate that can be conveniently generated in situ by mixing quinuclidine N-oxide and trifluoroacetic anhydride in DCM solutions. Under photoredox catalyst under blue LED light, this reagent allows for the unique high-yielding (up to >99%) selective oxidative trifluoroacetoxylation of various (functionalized) alkylarenes used as limiting reactants (22 examples overall, including a pharmaceutical-derived substrate). The proposed reaction mechanism involves Q●+ as a highly selective HAT agent and benzylic carbocations resulting from oxidative radical polar crossover of transient benzylic radicals. In Chapter 3 we introduce a series of isolable N-aroyloxyquinuclidinium tetrafluoroborates (Q-Bz) that allow for the preparation of N-alkylimides in a first of its kind Ritter-Mumm type three-component oxidative imidation of donors of benzylic and cycloalkane C(sp3)-H bonds. In this reaction carbonitriles serve as the source of an imide nitrogen atom and a solvent, whereas the third reaction component, Q-Bz, acts as the oxidant, the source of HAT agents and one of two acyl groups of the imide products. All three reaction components can be varied. 33 different N-alkylimides were prepared using (substituted) alkylarenes as limiting reagents, with product yields up to 94%, and cycloalkanes taken in 3-fold excess with respect to the oxidant. The proposed reaction mechanism involves either Q●+ or aroyloxy radicals as HAT agents, depending on the identity of the aroyl group. Chapter 4 discusses the first example of a Balz-Schiemann – type C(sp3)-H fluorination of alkylarenes and cycloalkanes using N-aroyloxyquinuclidinium tetrafluoroborates (Q-Bz), with tetrafluoroborate anion as the source of the fluorine atom of the resulting alkyl fluorides. The proposed reaction mechanism involves either Q●+ or aroyloxy radicals as HAT agents. Chapter 5 discusses the use of N-trifloxypyridinium salts for Minisci type cross dehydrogenative coupling (CDC) of alkane C-H bonds and pyridine C(sp2)-H bonds. Some limitations and possible future development of this chemistry are presented. Finally, Chapter 6 gives a summary of the results of this work and suggests future directions for the advancement of oxidative C(sp3)-H functionalization chemistry using various N-oxyammonium salts as HAT agent precursors, oxidants, and co-reagents.Item New method for kinetic isotope effect measurements(2023) Kljaic, Teodora; Poulin, Myles B; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Kinetic isotope effect (KIE) measurements are a powerful tool to interrogate the microscopic steps in enzyme catalyzed reactions and can provide detailed information about transition state structures. However, the application of KIE measurements to study enzymatic reactions is not widely applied due to the tedious and complex analytical workflows required to measure KIEs with sufficient precision. In this thesis I described the development of a novel competitive KIE measurement method using MALDI-TOF-MS and the investigation of the transition state of glycosyltransferase enzyme BshA from B. subtilis. We developed a method for the direct measurement of competitive KIEs using a whole molecule matrix assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS). This approach enabled quantitative measurements of both relative isotope abundance of an analyte and fractional conversion F in single measurements without the need for purification prior to analysis. The application of this MALDI-TOF MS approach has demonstrated the precision of KIE measurements comparable to those obtained using competitive radioisotope labelling, and NMR based approaches while requiring smaller amounts of stable isotope labelled substrates. Using two chemoenzymatic approaches, we then synthesized 5 substrates for the application of our method to investigate the transition state of BshA: UDP-GlcNAc (3.1), [1''-13C]UDP-GlcNAc (3.2), [2''-13C]UDP-GlcNAc (3.3), [13C6]UDP-GlcNAc (3.4) and [2''-2H]UDP-GlcNAc (3.5). Finally, we have begun to work on the synthesis of [1''-18O]UDP-GlcNAc and describe an approach to prepare this substrate that is currently underway in the lab. Application of the quantitative whole molecule MALDI-TOF MS approach enabled us to determine multiple competitive KIEs for the enzymatic reaction catalyzed by BshA. While previous studies suggested a front-face SNi (DNAN) TS for the conjugation of UDP-GlcNAc and L-malate, our KIE results show that a stepwise mechanism resulting in the formation of a discrete, though likely short lived, oxocarbenium ion intermediate is more likely. Our method be applied to study other glycosyltransferases whose mechanisms still remain to be elucidated and to design TS based inhibitors for enzymes involved in different bacterial infections. Future work on automation of this method would simplify the KIE measurement process and increase reproducibility making the measurement of KIEs for TS analysis a more experimentally accessible technique for the broader enzymology research community.Item Versatile Strategies for Multifunctional Polyolefins(2023) Fischbach, Danyon Miles; Sita, Lawrence R; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Polyolefins have quickly become one of the world’s most utilized products since their discovery in the 1950s. With 350 million tons produced each year, it is clear that the use of polyolefins is not subsiding in the near future. Instead, it is imperative to develop novel materials that are more efficient than their current counterparts. As the function of a plastic is derived from its properties, creating polyolefins with designable and targetable attributes is a major priority. The Sita group has played a huge role in the development of ‘precision’ polyolefins. The techniques employed allow for the scalable synthesis of a plethora of polyolefins. To do this, input variables such as the monomer, tacticity, molar mass, and molar mass distribution are controlled in an organized manner to affect output properties such as crystallinity, elasticity, and tensile strength. The ability to create diverse plastics is necessary for the functions asked of them, however, the missing element in almost all polyolefin synthesis is chemical functionality. The inert nature of polyolefins leads to limited reactivity, therefore, reducing possible chemical reactions, such as recycling. The goal of this work is to increase the scope of functional polyolefins so that new materials with improved properties can be produced. The first step in adding functionality is choosing the proper functional group. A drawback to many polyolefin functionalities currently under study is that they have a very limited scope. Functional groups are designed and used individually, requiring different compounds for each target functionality. To overcome this obstacle, aryl functional groups were targeted in this report. Phenyl functionalities are known for undergoing a range of chemical transformations leading to a wide variety of possible materials. Described in this report, aryl-functionalized polyolefins were synthesized using three different techniques. Each method has been shown to later undergo post-synthetic transformations to yield new functional groups that can either be used as contact points for macromolecular building blocks or as chromophores for optical observation. The single use or combination of these techniques has led to polyolefin-based materials that may in fact lower the barrier for the next-generation of functional polyolefins.Item DESIGN AND SYNTHESIS OF NEW SULFONATED CNN LIGAND SCAFFOLDS FOR PLATINUM CATALYZED H/D EXCHANGE APPLICATIONS(2023) Kramer, Morgan; Vedernikov, Andrei N; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The use of platinum group metals for the activation and functionalization of C-H bonds has been a topic of substantial interest over the past 60 years. Specifically, platinum-based complexes represent a particularly promising avenue due to their ability to form air- and water-stable species that are capable of reacting with some of the most inert C-H bonds within organic substrates. Over the decades of research contributing to this field, platinum complexes have frequently been angled towards fundamental mechanistic analysis of homogeneous C-H bond activation. In turn, the development of homogenous PtII-based catalytic systems has remained underdeveloped for the practical applications in C-H bond functionalization and, in particular, deuteration of complex organic molecules, including pharmaceuticals. The latter direction is now attracting a significant interest by the pharmaceutical industry. In this work the kinetic and thermodynamic selectivity of our new catalyst, a Pt(II) sulfonated CNN-pincer complex 1.5, in the H/D exchange reaction between aromaticsubstrates and wet TFE-d1 was screened across thirty-four aromatic substrates with the catalysts TON up to 300 (Chapter 2). A kinetic preference of 1.5 for electron-rich C-H bonds and substrates was firmly established and a novel scale of Hammett-like σXM constants was introduced to characterize the reactivity of the substrates’ C(sp2)–H bonds in transition-metal-mediated C-H activation. To greatly enhance our PtII catalysts’ useful life, we used their rigid covalent immobilization to mesoporous silica nanoparticles (immobilized complex 3.5). The resulting robust material served as an efficient H/D exchange catalyst utilizing cheaper sources of exchangeable deuterium, AcOD-d4, and D2O, with the catalyst’s TON up to 1600 (Chapter 3). To understand our novel catalyst’s structure – activity relationship, a series of benzene fragment – R-substituted analogs of 1.5 (R = MeO, tBu, iPr, F, Cl, CF3) were synthesized and explored in the H/D exchange of a series of aromatic compounds (Chapter 4). Surprisingly, the complex 4.1-tBu (R = tBu) stood out as a most robust homogeneous catalyst compatible with AcOD-d4 and D2O at 120 oC as deuterium sources that can work under air. Thanks to this finding, the substrates scope for the H/D exchange with AcOD-d4 catalyzed by 4.1-tBu was expanded to include eight pharmaceuticals, some alkenes, with signs of engagement of some C(sp3)-H bond donors. A novel photo-induced (violet light) room temperature H/D exchange catalyzed by 4.1-OMe was discovered with a substantially different substrate selectivity, as compared to the thermal reaction at 80 oC. These observations may provide some important insight into the mechanism of PtII-mediated C-H activation. Finally, Chapter 5 summarizes the results of this work and suggests some future directions for this area of research.Item Exploring Mechanisms and Predicting Reactivity of Transition Metal-Catalyzed and Photocatalyzed Radical and Polar Organic Transformations(2023) Martin, Robert Thompson; Davis, Jeffery; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The creation of protocols to form novel C-C and C-heteroatom bonds has been the primary goal of organic synthesis since its inception. Chemists have long harnessed both radical and polar reactivities, often as complementary paths to construct these bonds to yield more complex molecular architectures. However, compared to the development of synthetic protocols, development of mechanistic models and enriching of mechanistic understanding of many organic reactions has been limited. Computational studies into the mechanisms of organic transformations provide an avenue by which mechanisms of reactions can be better understood and new patterns of reactivity can be predicted. Herein, quantum-mechanical computational methods e.g., density functional theory (DFT) have been employed in the pursuit of understanding the mechanisms of a series of radical and polar reaction schemes. Specifically, DFT calculations were employed to understand the mechanism and origins of selectivity of two nickel(I)-catalyzed olefin functionalizations. These studies demonstrate a catalyst-control scheme by which selectivity can be induced by the steric properties of the catalyst (Chapter 1). Following this work, two photocatalytic transformations which yield difluorinated products were studied thoroughly with computations. First, a synthesis of difluorinated lactone derivatives revealed a long-lived radical intermediate and motivated mechanistic experiments to isolate this radical. Next, a synthesis of difluorinated oxindole derivatives demonstrated the ability of arenethiols to act as photocatalysts (Chapter 2). Then, computations were used to rigorously explore a copper-catalyzed reductive cross-coupling of imine and allenamides. Specifically, computations were employed to explore the mechanism of the transformation and the origins of stereoselectivity and the divergent formation of urea and diamine products (Chapter 3). Finally, two computational investigations into the mechanisms of transformations catalyzed by first-row transition metals are detailed. In particular, a nickel-catalyzed hydroarylation of gem-difluoroalkenes is explored computationally to determine the order of steps in the reaction. In addition, the mechanism of a cobalt(I)-catalyzed allylic substitution is considered to ascertain the nature of the transformation as either radical or polar (Chapter 4). Given the complexity of the mechanisms of these transformations, computational studies provide an alternative route to acquire useful mechanistic understanding that can support or explain observed experiments and suggest further mechanistic experiments that could provide stronger evidence for a given mechanistic proposal.Item DESIGN AND SYNTHESIS OF POLYOLEFIN MATERIALS FOR NANOSTRUCTURED SELF-ASSEMBLY: BUILDING BLOCKS, COPOLYMERS, AND POLYMER CONJUGATES(2022) Wentz, Charlotte Maria; Sita, Lawrence R; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Polyolefin based materials are essential to today’s society in both simplistic commodity plastics to complex nanostructured materials and optoelectronic devices. In order to better understand these materials and make new impactful innovations, there is a barrier of fabrication, scalability, versatility, and programmability. The answer to the world’s plastic waste problem lies not in removing our use of polymers but relies in better understanding their properties, utilizing them as building blocks in advanced materials, and creating a long-lasting advanced material. Towards the goal of overcoming limitations in fabrication and scalability the work herein presents on utilizing a toolbox of living polymerization techniques such as living chain transfer polymerization (LCCTP) where new functionalities, stereochemical microstructures, optical properties, and physical properties of the polyolefin can be designed and systematically controlled. The polyolefins made through these techniques are scalable and versatile with end-group functionalization creating a seemingly endless choice of polymer building blocks and polymer materials. In line with creating new technologies that are programable the polyolefin building blocks made herein are utilized in multiple conjugates to create and understand methods and mechanisms of solid-state nanostructured self-assembly and access rare nonclassical phases that are highly desirable for their properties and uses in a plethora of applications. The conjugates investigated involve either a sugar-based head group covalently bond to a polymer tail to access rare and misunderstood Frank Kasper phase order-order transitions, or a perylene chromophore core covalently bond on both sides of the core in a linear fashion to polymer domains to create highly florescent or optically active materials that are useful in organic technologies such as solar cells, light emitting diodes, or nanotechnology. These perylene based conjugates can self-assemble into unique columnar phases and single gyroid phase. These results with conjugates provide methods for reliable and programmable access to rich phase behavior through the design of the polyolefin domains.Item AB INITIO MODELING OF THE SELECTIVITY AND REACTIVITY OF BOTH THERMAL AND LIGHT MEDIATED ORGANIC AND ORGANOMETALLIC TRANSFORMATIONS(2022) Dykstraa, Ryan Henry; Gutierrez, Osvaldo; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The mechanism of a reaction is the collection of events that take place that lead to the products of a chemical transformation. Though there are some events in a chemical reaction that can be observed by experiment, such long-lived intermediates, many of the events are too short lived to be measured. Due to these restrictions and the advancements in the development of moderately scaling computational tools, it is becoming commonplace to use quantum mechanical software packages to model the mechanism of a reaction. Here, I used quantum mechanical calculations alongside experimental evidence provided by multiple collaborators to understand the reactivity of both heat- and light-mediated organic transformations. In chapter 2, I investigated the role of electron donor-acceptor complexes in the generation of alkyl and acyl radicals in the presence of visible light. In addition, the pathways to the experimentally observed products, alkyl and acyl thioethers, were modeled. The lowest energy pathway to product, post-radical generation, was radical addition to the radical electron donor-acceptor complex. For a photoredox-catalyzed method to cyclopropanes from a novel halomethyl radical precursor (Chapter 3), computations strongly supported a redox-neutral reductive radical/polar crossover mechanism over radical pathways, consistent with experimental trends. Investigation of the isomerization of cinnamyl chloride to cyclopropane via a commonly used photoredox catalyst (Chapter 4) revealed that the reaction was mediated via dexter energy transfer between photocatalyst and substrate over the more commonly proposed electron transfer, affording diastereoselective product formation. A dual nickel/photoredox-catalyzed coupling of sulfinate salts and aryl halides gave a mixture of aryl sulfide and aryl sulfone products (Chapter 5), suggesting that disproportionation of sulfone radical was leading to the formation of thiyl radical. Modeling the product determining steps indicated that the product distribution was controlled by radical addition of the thiyl radical to the nickel(II) species versus reductive elimination of the sulfone bound to the nickel(III) catalyst. A bicyclo[1.1.1]pentane diborylated with pinacolboryl groups, one at the arm and head position, was found to have reactivity only at the bridgehead position (Chapter 6). Calculations of a hydrozone coupling reaction performed by the Qin group found that the reactivity was due to the unique hybridization of the bridgehead position as well as increased steric interactions at the arm position. Finally, a sulfoxide synthesized from a sulfinate salt could be activated with Grignard reagent, affording coupling of the substituents originally bound to the sulfoxide. DFT calculations validated the role of the sulfurane intermediate acting as a mediator to the coupled product.Item MECHANISMS AND RATIONAL CATALYST DESIGN OF ORGANIC TRANSFORMATIONS FOR THE SYNTHESIS OF NEW C-C AND C-X BONDS(2021) Rotella, Madeline Elizabeth; Gutierrez, Osvaldo; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The creation of new C-C or C-X bonds, where X can be oxygen, nitrogen or fluorine, is vital to organic synthesis and the discovery of new methods for complex molecule synthesis. In many cases, the mechanism of these transformations is not investigated, although an understanding of the underlying mechanism would allow for rational design of new catalysts and would lead to the development of novel reactivity. Computational studies probing the mechanisms of valuable synthetic methods including C-H oxidation, organocatalysis, nickel photocatalysis, alkyne metathesis and multicomponent reactions are presented. Specifically, computational methods were used in the development of a novel tetradentate amine iron (II) catalyst for the promotion of C(sp3)-H oxidation (Chapter 1). Next, the mechanism of an organocatalyzed amination was studied thoroughly with density functional theory (DFT) calculations in combination with molecular dynamics simulations to develop a predictive model for reactivity for use in the creation of new catalysts in the field of amination chemistry (Chapter 2). Additionally, the mechanism of a regio- and enantioselective iridium-catalyzed asymmetric fluorination was studied, with an emphasis on determining the role of the trichloroacetimidate group in the reaction (Chapter 3). Further, the mechanisms of various transition metal-catalyzed C-C bond formations were studied through computationally. First, a photoredox/nickel-dual catalyzed Tsuji-Trost reaction was studied through DFT and DLPNO-CCSD(T) calculations to investigate the stereoselectivity of the reaction as well as the order of reaction events. Next, a photoredox/nickel-dual catalyzed C-C bond formation using oxanorbornadienes as electrophilic coupling partners was investigated computationally (Chapter 4). Additionally, the mechanism of tungsten- and molybdenum-catalyzed alkyne metathesis as well as the difference in reactivity between the two metals was explored (Chapter 5). A nickel-catalyzed diarylation of alkenes was studied computationally, with particular emphasis on the role of the phosphine ligand in controlling regioselectivity (Chapter 6). Finally, an iron-catalyzed dicarbofunctionalization of vinyl ethers with aryl Grignard reagents and alkyl halides or (fluoro)alkyl halides was developed experimentally (Chapter 7).Item Mechanistic Studies of Photochemical Reactions: Photoacid Generators, Photoreleaseable Protecting Groups, and Diarylnitrenium Ions(2021) Zeppuhar, Andrea; Falvey, Daniel E; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The use of light to drive chemical reactions is becoming increasingly popular due to the enhanced spatial and temporal control provided. Because of this, it is important to understand how these photochemical transformations occur from a mechanistic viewpoint in order to aid in the improvement of existing systems as well as in the development of new systems. The work presented in this dissertation will examine the mechanisms of several photochemical systems including photoacid generators, photoreleaseable protecting groups, and diarylnitrenium ions. Chapter 1 will begin with an introduction to organic photochemistry and describe some of the excited state reactions that will be encountered throughout this text. It will also describe laser flash photolysis, a technique critical to studying the reactive intermediates generated in photochemical reactions. Chapter 2 will describe the design and synthesis of photoacid generators that are activated via sequential two-photon absorption. The experiments conducted support a mechanism involving triplet re-excitation providing a more favorable bond scission. Chapter 3 will explore the applications of these newly developed photoacid generators, specifically for photopolymerization. It is shown that these compounds are capable of initiating both cationic and radical polymerizations depending on the intensity of visible light irradiation used. Chapter 4 will examine the 9-phenyl-9-tritylone photoreleaseable protecting group for alcohols to understand the details of its release mechanism. It is shown that the tritylone anion radical is required for alcohol photorelease. Chapters 5 and 6 will explore the behavior of diarylnitrenium ions in aqueous media. Chapter 5 will examine the reactivity of diarylnitrenium ions toward guanosine and it is shown that there is a rapid reaction to generate the C8 adduct, suggesting potential carcinogenicity. Chapter 6 will examine the reactivity of diarylnitrenium ions under acidic aqueous conditions. Under these conditions, a long-lived species is formed, and the experiments conducted indicate this species is the cation radical derived from the diarylnitrenium ion. Mechanistic analysis supports formation via a pathway separate from the nitrenium ion, suggestive of a triplet mechanism.