Abstract
Computational chemistry is growing more versatile in assisting in understanding chemical phenomena. As computing power becomes more expeditious, so can the complexity and rigor of quantum mechanical (QM) calculations. The goal of this thesis is to demonstrate through computational procedures that QM calculations can help predict and explain the complexities of the chemical phenomena within reaction mechanisms. The first system to be studied was the catalytic mechanism of deformylation by the metalloenzyme peptide deformylase, which is a potential antibacterial target. A biomimetic model was used for the active site that was modified with varying substituents. Hammett plots were used to examine trends in reaction energies with the varying substituents, which were tracked to changes in the bond orders between the metal center and substrate throughout the reaction. As the substituents became more electron-donating, the reaction became more thermodynamically favorable, and as the substituents became more electron-donating or electronwithdrawing the rate of reaction decreased. The second project examined competing pathways of electron transfer (inner sphere versus outer sphere) between multiple metal-salens (Ni(II), Zn(II), Cu(II), and Co(II)) and electron-deficient alkenes (methyl acrylate and acrylamide). Overall, the order of thermodynamic favorability for electron transfer was found to be Zn(II)>Ni(II)»Co(II)>Cu(II). Results indicate a vi kinetic preference for OS electron transfer, which holds generally across the different metal centers and alkenes. The reduced Ni(II)- and Zn(II)-salen have significantly lower OS electron transfer barriers versus reduced Cu(II)- and Co(II)-salen, consistent with the higher oxidation potentials for reduced Ni(II)- and Zn(II)-salen. Reduced Ni(II)- and Zn(II)-salen likewise show a much lower activation energy for IS electron transfer, which is attributed to ligand- versus metalbased reduction of the neutral salen in the Ni(II) and Zn(II) cases. The last project was to design a theoretical enzyme active site (theozyme) for a Morita- Baylis-Hillman reaction that would be lower in activation energy compared to a tertiary amine catalyzed reaction as well as an uncatalyzed reaction. Single amino acids were placed around a transition state complex between p-nitrobenzaldehyde and acrylamide in order to stabilize the formation of charges as well as to coordinate the reactants to an optimal arrangement. The amino acids that stabilized the transition state the most at each position would have their individual stabilization energies combined, and this overall stabilization then compared to the energy barriers of the literature mechanisms. The final theozyme arrangement lowered the energy barrier of the uncatalyzed reaction by nearly 50 kcal*mol-1, and was lower in activation energy by over 20 kcal*mol-1 compared to the literature tertiary amine catalyzed mechanisms.