Hirschi, Jennifer Sue (2007-12). Application of kinetic isotope effects and theoretical calculations to interesting reaction mechanisms. Doctoral Dissertation. Thesis uri icon

abstract

  • A variety of biological and organic reaction mechanisms are studied using powerful tools from experimental and theoretical chemistry. These tools include the precise measurement of kinetic isotope effects (KIEs) and the use of theoretical calculations to predict KIEs as well as determine factors that contribute to reaction acceleration and selectivity. Theoretical analysis of the Swain-Schaad relationship involves the prediction of a large number of isotope effects and establishes the semiclassical boundaries of the relationship. Studies on the mechanism of oxidosqualene cyclase involve the determination of a large number of precise KIEs simultaneously. Transition state models for the Sharpless asymmetric epoxidation have been developed that explain the versatility, high selectivities, and ligand accelerated catalysis of the reaction. Theoretical predictions on the proposed enzymatic mechanism of flavin dependent amine oxidation suggest a hydride transfer mechanism and rules out mechanisms involving covalent intermediates. Finally, a theoretical analysis of Diels-Alder reactions successfully describes the unexpected exo selectivity in some of these reactions.
  • A variety of biological and organic reaction mechanisms are studied using
    powerful tools from experimental and theoretical chemistry. These tools include the
    precise measurement of kinetic isotope effects (KIEs) and the use of theoretical
    calculations to predict KIEs as well as determine factors that contribute to reaction
    acceleration and selectivity.
    Theoretical analysis of the Swain-Schaad relationship involves the prediction of
    a large number of isotope effects and establishes the semiclassical boundaries of the
    relationship. Studies on the mechanism of oxidosqualene cyclase involve the
    determination of a large number of precise KIEs simultaneously. Transition state models
    for the Sharpless asymmetric epoxidation have been developed that explain the
    versatility, high selectivities, and ligand accelerated catalysis of the reaction. Theoretical
    predictions on the proposed enzymatic mechanism of flavin dependent amine oxidation
    suggest a hydride transfer mechanism and rules out mechanisms involving covalent
    intermediates. Finally, a theoretical analysis of Diels-Alder reactions successfully
    describes the unexpected exo selectivity in some of these reactions.

publication date

  • December 2007