Graduate Thesis Or Dissertation


Strategic Application of Computations to Diverse Chemical Systems Public Deposited

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  • My work has focused on streamlining the study of organic compound structure, properties, and reactions by 1) understanding and using available computational software, 2) developing software packages to facilitate data manipulation as well as augment public programs, and 3) applying public and in-house developed software to further the understanding of organic chemistry phenomena. An evaluation of the strengths and weaknesses of parameters while modeling complex, flexible compounds with molecular mechanics led to several suggestions to help harness the computer-driven portion of conformational searching. Several case studies were used to show the practical considerations for modeling both ground and transition state structures. A comprehensive joint experimental and computational investigation into a supramolecular host/guest binding event led to the observation of an emergent equilibrium isotope effect (EEIE). Computations were used to fragment the detector into key components to identify the origin of the H/D isotope effect and to explore the non-classical C-H/D hydrogen bonding. However, the fragments were unable to reproduce the isotope effect observed in the full detector, leading to the hypothesis that the whole detector is more than the sum of its parts. A continuation of the supramolecular detector work was carried out to understand the unusual binding behavior when conformationally flexible hosts bind disparate oxoanion guests. Experiments showed all three hosts exhibit similar affinities for all three oxoanion guests when in a mixed, less polar solvent system (10% DMSO/90% H2O-saturated CHCl3). However, computations predict the binding affinity between all host/guest combinations to closely resemble the trends in pKa of the conjugate acid of the guest in a range of density functional theory (DFT) methods and solvents. The trend in experimental association constant better matches the computational predictions when a simple, more polar solvent system is used (acetonitrile). Entropic and solvation effects likely explain the discrepancy between computational and experimental results in the mixed solvent system. A study on the stereocontrol of the first highly selective hydroboration of alkyl-substituted aldimines to provide medicinally-relevant a-amidoboronates illustrates the importance of subtle hydrogen contacts. A ferrocenyl group on the planar-chiral N-heterocyclic carbene (NHC) ligand stabilizes the copper-BPin species and is responsible for the bulk of the reaction selectivity. A joint experimental and computational investigation into the mechanism for the formation of perfluoroalkyl-substituted b-lactones using an isothiourea catalyst emphasizes the importance of superimposing experimental and computational results. Computations provided both a stepwise aldol/lactonization process and a concerted [2+2] process depending on the DFT method used. Natural abundance kinetic isotope effect (KIE) studies were used to disseminate the operative mechanism in which computations and experiments corroborate a concerted [2+2] process.
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