Chemistry Electronic Theses and Dissertations (UMKC)
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The items in this collection are the theses and dissertations written by students of the Department of Chemistry. Some items may be viewed only by members of the University of Missouri System and/or University of Missouri-Kansas City. Click on one of the browse buttons above for a complete listing of the works.
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Item Benzannulated indoles as drug discovery templates. Efforts towards the total synthesis of a library of therapeutic candidates inspired by Cis-Trikentrin A(2025) Mcatee, William Norman; Buszek, Keith R.The herbindole and trikentrin indole alkaloids are a series of structurally related natural products, characterized by a 6,7-benzannulated indole core – a structural motif rarely observed in nature. Originally isolated from the Trikentrion flabelliforme, and Axinella sp. sponges, these compounds present as attractive targets for synthetic and medicinal chemists, due to their reported antibiotic, cytotoxic, and analgesic properties. Indeed, extensive efforts have been made since 1988 towards novel synthetic routes to the aforementioned natural products. Once accessed, analogues of the trikentrin indoles and herbindole present as ideal drug discovery templates due to their likelihood for bioactivity and high potential for synthetic diversification. Until recently, efforts towards the total synthesis of these deceptively simple herbindole and trikentrin indoles have proven these compounds to be challenging targets. Specifically, extensive substitution at the C4 and C5 positions without substitution at the easily accessible C2 and C3 positions have been of particular challenge to synthetic chemists. Additionally, these diastereomeric properties of the fused 6,7 dimethylcyclopentyl unit provides additional complexity to proposed synthetic routes. Many of these challenges have been alleviated through the discovery of a new class of reactive aryne intermediates. These intermediates allow for the generation of an in-situ 6,7-indole aryne, proving readily susceptible to selective annulation of the indole via [4+2] cycloaddition. Additionally, the tunable selectivity of the indole aryne generation allows for unaffected substituents at the C4 or C5 position, affording a wide variety of coupling reactions. Preliminary cell-based assays of herbindole and trikentrin indole analogue libraries have demonstrated promising anticancer, antiparasitic, and analgesic activity. Additionally, several key intermediates in the synthetic route towards these libraries have demonstrated newly discovered therapeutic value for a rare and aggressive cancer, sinonasal undifferentiated carcinoma (SNUC). Significant advances towards a more practical, accessible, and cost effective synthesis of these early intermediates have been made. Specifically, strategic eliminations of several toxic reagents and solvents (e.g. dichloromethane) as well as alternative synthetic approaches have been implemented. However, more work is needed in order to fully understand the structural activity relationship and maximize the therapeutic potential of these compounds. Recent advancements, described herein, enhance the practicality of the synthetic route towards a cis-Trikentrin A-inspired scaffold, with applications as a drug discovery template.Item An electrochemical pipette with thin-layer design for rapid electrosynthesis and mechanistic study of the catalytic reactions(2025) Punchihewa, Buwanila Tharusha; Rafiee, Mohammad; Gutheil, WilliamIn the past few decades, electrochemical organic synthesis has emerged as a transformative approach to modern organic synthesis. Electrochemical methods enable unique reaction pathways for both direct (electrode-driven) and mediated (redox-catalyst-assisted) systems through controlled electron transfer, access to reactive intermediates, and transformations that are inaccessible to conventional methods. However, traditional electrochemical reaction setups depend on mass transport, and extended electrolysis times limit their application in organic synthesis. Therefore, developing an electrochemical design that is independent of mass transfer, and facilitating fast electrolysis is essential for advancing the field of electrochemical organic synthesis. In this study, we fabricated an electrochemical cell that confines the electrolysis volume to a thin layer of solution, comparable to the thickness of the diffusion layer. The fabricated thin layer electrode (TLE) is independent of mass transfer and allows electrolysis to be performed within minutes owing to its high surface (A)/ volume (v) ratio. The utility of the TLE electrode for parallel electrosynthesis applications was benchmarked using N-hydroxyphthalimide (NHPI) mediated electrochemical C-H functionalization. Rapid electrolysis and generation of microscale volumes make TLE suitable for application in drug metabolism. The application of TLE in drug metabolism has been demonstrated through the oxidative metabolism of acetaminophen under mild basic and acidic conditions. The formation of an N-acetyl-p-benzoquinone imine metabolite (NAPQI) during acetaminophen oxidation and its subsequent chemical reactions during electrolysis were successfully studied. Moreover, the integration of a microelectrode with TLE (combined TLE) enabled the real-time monitoring of redox-active intermediates formed during rapid electrosynthesis. Real-time studies of electrocatalytic cycles allow for a better understanding of electrocatalytic mechanisms and their resting states. The utility of this combined TLE for mechanistic studies of electrochemical synthesis was demonstrated using a Ni-catalyzed biaryl coupling reaction. This approach allowed the real-time monitoring of both closed- and open-shell nickel species generated during nickel-catalyzed biaryl coupling reactions under catalytic conditions. Studying both the closed- and open-shell nickel species generated during the catalysis cycle using spectroscopic methods is challenging. Therefore, this approach assists in understanding the unreported trends in Ni speciation, concentration profiles of key intermediates under different reaction conditions, and reaction progress.Item Toward high thermoelectric performance of solids: ab initio forces within the orthogonalized linear combination of atomic orbitals method(2024) Alzahrani, Nuha; Rulis, Paul Michael, 1976-; Peng, Zhonghua, Ph. D.Toward the long-term goal of predicting the figure of merit of complex thermoelectric materials, we introduce the computational and theoretical groundwork for the calculation of interatomic forces in ab initio calculations using the Orthogonalized Linear Combination of Atomic Orbitals (OLCAO) method. The approach is based on the Hellmann-Feynman (HF) theorem and Pulay forces in the presence of an atomic orbital basis set. To accomplish this, we offered a thorough derivation of a HF theorem that holds for all quantum mechanical systems. This theorem serves as a valuable tool for understanding the nature of chemical bonding in quantum chemistry and solid-state physics. We follow Pulay's suggestion [Mol. Phys.17, 153 (1969)] to update the HF theorem by including contributions from changes in the wave function with respect to nuclear sites. Additionally, we developed the Obara–Saika scheme for evaluating the derivative of different molecular integrals that contribute to the HF force using Gaussian-type orbitals, i.e., electron repulsion integrals, kinetic energy integrals, and nuclear attraction integrals. Once the force calculation was implemented in the OLCAO method, we applied this method to compute the interatomic forces between various pairs of atoms in diatomic molecules such as N2, H2, O2, F2, Cl2, I2, CO, and NO.Item Medieval seismicity on the Himalayan Frontal Thrust Fault at Lal Dhang, Uttarakhand, India(2019) Daniels, Robyn L.; Niemi, Tina M.; Kilway, Kathleen V., 1963-The Himalayan Frontal Thrust Fault (HFT) lies at the active, tectonic boundary between Eurasia and the Indian subcontinent. Continuous convergence between the landmasses causes strain to accumulate on the fault, which is intermittently released during seismic events. Throughout the last two centuries, several large-magnitude earthquakes have occurred on the HFT without producing measurable vertical offsets at the ground surface, leading many to refer to these events as blind-thrust earthquakes. However, large fault scarps along the HFT indicate that past ruptures of the fault were not blind and may have been much greater in magnitude. Recent paleoseismological studies have aimed to characterize the earthquakes that generated these features. One of these studies focused on defining the seismic parameters of a specific segment of the fault by comparing findings across several sites, including the site of Lal Dhang in Uttarakhand, India. The results of this study point to lingering uncertainties specific to the site of Lal Dhang that warrant additional research, including poor temporal constraint of past fault ruptures, disparities in deformational structures when compared to surrounding sites, discrepancies in fault scarp height as compared to apparent net slip measurements, and questions surrounding local interactions between fluvial terrace development and fault scarp generation. The goal of this research was to conduct a comprehensive and detailed analysis of the seismic history at the site of Lal Dhang. The work was distributed across three intersecting objectives: 1) development of an age model for previous earthquakes on the segment of the HFT that includes Lal Dhang, 2) determination of the faulting sequence, timing, and seismic parameters of previous earthquakes at the site, and 3) investigation of the interaction between local tectonic and fluvial landscape development. Data produced through this study have narrowed the constraint on rupture timing at the site of Lal Dhang and along the western section of the CSG. Results presented here include improved estimates for coseismic slip and vertical separation at the site of Lal Dhang, which are comparable to surrounding sites, and a model for local fault scarp generation and associated landscape development. Implications for future research are considered and discussed.Item Advancing the treatment of relativistic theory within the OLCAO package and with application to solar photovoltaic technologies(2024) Alsharef, Mrwah; Rulis, Paul Michael, 1976-; Peng, Zhonghua, Ph. D.Methylammonium lead bromide, known as CH3NH3PbBr3, is a promising perovskite material for the absorption layer in solar cells. While its bulk electronic structure is favorable, its long-term stability and interface design remain as primary concerns before it can be used for commercial production. Although experimental methods such as X-ray photoemission spectroscopy can be used to investigate the surface atomic and electronic structures of such materials (e.g., by observing core-level chemical shifts), theoretical support is vital for interpreting the measured data and for guiding the selection of future experiments. Unfortunately, perovskite solar cell materials often contain high Z-number atoms which require relativistic treatment. Here, we show the development and implementation of scalar relativistic theory within the density functional theory (DFT) based Orthogonalized Linear Combination of Atomic Orbitals (OLCAO) method for electronic structure calculation. We then demonstrate the application of the method to the calculation of core-level chemical shifts of all elements of CH3NH3PbBr3 and compared the results to those obtained with non-relativistic theory to evaluate the effect of scalar relativistic theory. The results of the relativistic calculations were consistent with experimental expectations, enabling us to accurately calculate the chemical shift resulting from changes in the local environment. In addition, the X-ray absorption near-edge structure (XANES) spectra of CH3NH3 and PbBr2 surface models were studied via depth profiling to highlight the influence of the surface effects. The results indicate a shift towards lower energy of the edge onset for Pb-4f and Br-3d atoms in the CH3NH3 surface termination, while the edge onset of Pb-4f and Br-3d does not change for the PbBr2 surface termination. According to the findings, the modifications made on the surface of a material result in alterations in the edge onset.