There is a high demand for the development of processes for the conversion of ubiquitous molecules into industrially useful commodities. Transition metal catalysts are often utilized for the activation and functionalization of small organic molecules due to their diverse nature and proven utility with a myriad of chemical transformations. The functionalization of methane (CH4) and dinitrogen (N2) to methanol (CH3OH) and ammonia (NH3) respectively is of particular interest; however, both methane and dinitrogen are essentially inert due to the inherit strength of their bonds. In this dissertation a series of computational studies is performed to better understand the fundamental chemistry behind the functionalization of methane and the activation of dinitrogen in a homogeneous environment. A catalytic cycle is proposed for the oxy-functionalization of methane to methanol. The cycle consists of two key steps: (1) C-H activation across a metal-alkoxide bond (M-OR), and (2) regeneration of the M-OR species through an oxy-insertion step utilizing external oxidants. The C-H activation step has been extensively studied; however, the latter step is not as well understood with limited examples. For this work, we focus on the oxy-insertion step starting with a class of compounds known to do C-H activation (i.e., Pt(II) systems). Computational studies …

Our country continues to demand clean renewable energy to meet the growing energy needs of our time. Thus, natural gas, which is 87% by volume of methane, has become a hot topic of discussion because it is a clean burning fuel. However, the transportation of methane is not easy because it is a gas at standard temperature and pressure. The usage of transition metals for the conversion of small organic species like methane into a liquid has been a longstanding practice in stoichiometric chemistry. Nonetheless, the current two-step process takes place at a high temperature and pressure for the conversion of methane and steam to methanol via CO + H2 (syngas). The direct oxidation of methane (CH4) into methanol (CH3OH) via homogeneous catalysis is of interest if the system can operate at standard pressure and a temperature less than 250 C. Methane is an inert gas due to the high C-H bond dissociation energy (BDE) of 105 kcal/mol. This dissertation discusses a series of computational investigations of oxy-insertion pathways to understand the essential chemistry behind the functionalization of methane via the use of homogeneous transition metal catalysis. The methane to methanol (MTM) catalytic cycle is made up of two key …

Polymeric nanoparticles were designed, synthesized, and loaded with metal ions to explore the therapeutic potential for transition metals other than platinum found in cisplatin. Nanoparticles were synthesized to show the potential for polymer based vectors. Metal loading and release were characterized via Inductively Coupled Plasma Mass Spectrometry (ICP MS), Energy Dispersive X-Ray Spectroscopy (EDX), X-Ray Photoelectron Spectroscopy (XPS), and Elemental Analysis. Targeting was attempted with the expectation of observed increased particle uptake by cancer cells with flow cytometry and fluorescence microscopy. Results demonstrated that a variety of metals could be loaded to the nano-sized carriers in an aqueous environment, and that the release was pH-dependent. Expected increased targeting was inconsistent. The toxicity of these particles was measured in cancer cells where significant toxicity was observed in vitro via dosing of high copper-loaded nanoparticles and slight toxicity was observed in ruthenium-loaded nanoparticles. No significant toxicity was observed in cells dosed with metal-free nanoparticles. Future research will focus on ruthenium loaded polymeric nanoparticles with different targeting ligands dosed to different cell lines for the aim of increased uptake and decreased cancer cell viability.

Organometallic catalysis has attracted significant interest from both industry and academia due to its wide applications in organic synthetic transformations. Example of such transformations include the reaction of a zinc carbenoid with olefins to form cyclopropanes. The first project is a computational study using both density functional and correlated wavefunction methods of the reaction between ethylene and model zinc carbenoid, nitrenoid and oxenoid complexes (L-Zn-E-X, E = CH2, NH or O, L = X = I or Cl). It was shown that cyclopropanation of ethylene with IZnCH2I and aziridination of ethylene with IZnNHI proceed via a single-step mechanism with an asynchronous transition state. The reaction barrier for the aziridination with IZnNHI is lower than that of cyclopropanation. Changing the leaving group of IZnNHI from I to Cl, changes the mechanism of the aziridination reaction to a two-step pathway. The calculation results from the epoxidation with IZnOI and ClZnOCl oxenoids suggest a two-step mechanism for both oxenoids. Another important example of organometallic catalysis is the formation of alkyl arenes from arenes and olefins using transition metal catalysis (olefin hydroarylation). We studied with DFT methods the mechanism of a novel Rh catalyst (FlDAB)Rh(TFA)(η2–C2H4) [FlDAB = N,N’ -bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA = trifluoroacetate] that converts …

Human glutathione synthetase (hGS) is a homodimeric enzymes that catalyzes the second step in the biological synthesis of glutathione, a critical cellular antioxidant. The enzyme exhibits negative cooperativity towards the γ-glutamylcysteine (γ-GC) substrate. In this type of allosteric regulation, the binding of γ-GC at one active site significantly reduces substrate affinity at a second active site over 40 Å away. The presented work explores protein-protein interactions, substrate binding, and allosteric communication through investigation of three regions of hGS: the dimer interface, the S-loop, and the E-loop. Strong electrostatic interactions across the dimer interface of hGS maintain the appropriate tertiary and quaternary enzymatic structure needed for activity. The S-loop and E-loop of hGS form walls of the active site near γ-GC, with some residues serving to bind and position the negatively cooperative substrate. These strong interactions in the active site serve as a trigger for allosteric communication, which then passes through hydrophobic interactions at the interface. A comprehensive computational and experimental approach relates hGS structure with activity and regulation. ATP-grasp enzymes, including hGS, utilize ATP in the nucleophilic attack of a carboxylic acid in a reaction thought to proceed through the formation of an acylphosphate intermediate. Small metal cations are known …

As fossil fuel resources become more and more scarce, attention has been turned to alternative sources of fuels and energy. One promising prospect is the conversion of methane (natural gas) to methanol, which requires an initial activation of a C-H bond and subsequent formation of a C-O bond. The most well studied methodologies for both C-H activation and C-O bond formation involve oxidation of the metal center. Metal complexes with facile access to oxidation states separated by four charge units, required for two subsequent oxidations, are rare. Non-oxidative methods to perform C-H bond activation or C-O bond formation must be pursued in order for methane to methanol to become a viable strategy. In this dissertation studies on redox and non-redox methods for both C-H activation and C-O bond formation are discussed. In the early chapters C-O bond formation in the form of reductive functionalization is modeled. Polypyridine ligated rhodium complexes were studied computationally to determine the properties that would promote reductive functionalization. These principles were then tested by designing an experimental complex that could form C-O bonds. This complex was then shown to also work in acidic media, a critical aspect for product stabilization. In the later chapters, non-oxidative C-H …