The purpose of this research is to investigate the quantum mechanical concept of tunneling in hydride-transfer reactions in solution. It is to support the contemporary Marcus-like H-tunneling model and further support the concept of donor-acceptor distances (DAD) about the tunneling-ready-state (TRS). The change from the temperature independence of the primary (1°) H/D kinetic isotope effects (KIEs) in wild-type enzyme-catalyzed H-transfer reactions (∆Ea = EaD - EaH ~ 0) to strong temperature dependence with the mutants (∆Ea >> 0) have recently been frequently observed. We study the structural effects on the temperature dependence of primary (1°) KIEs for H-transfer reactions in solution in an attempt to compare with well-studied enzymatic H-transfer reactions. The hypothesis is that a greater temperature dependence of 1° KIEs should be observed in H/D-transfer reaction systems that have a loosely associated TRS, which allows donor-acceptor distance (DAD) sampling. Hydride transfer reactions from several dihydropyridines to various hydride acceptors, in acetonitrile, were studied to investigate this hypothesis. The relationship between structures and ΔEa(D-H) are compared for reactions in solution vs. enzymes. The reactions take place by an H-tunnelling mechanism, irrespective of the reaction media. It appears that the more rigid donor-acceptor complexes that are more sterically hindered and more tightly associated would give rise to a weaker temperature dependence of 1° KIEs. This is consistent with the trend observed in wild-type enzymes vs. mutants, in which the active site of the wild-type enzyme is tightly packed and does not readily allow DAD sampling, thus resulting in weak temperature dependence of 1° KIEs. Our results replicate the enzyme observations and support the new concept that the local thermal motions promote the enzyme catalysis.
|Commitee:||Luesse, Sarah, O'Brien, Leah|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 81/3(E), Masters Abstracts International|
|Keywords:||Tunneling-ready-state, Donor-acceptor distances, H-transfer reactions|
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