Journal of the American Chemical Society, Vol.137, No.20, 6653-6661, 2015
Steric Effects on the Primary Isotope Dependence of Secondary Kinetic Isotope Effects in Hydride Transfer Reactions in Solution: Caused by the Isotopically Different Tunneling Ready State Conformations?
The observed 1 degrees isotope effect on 2 degrees KIEs in H-transfer reactions has recently been explained on the basis of a H-tunneling mechanism that uses the concept that the tunneling of a heavier isotope requires a shorter donor-acceptor distance (DAD) than that of a lighter isotope. The shorter DAD in D-tunneling, as compared to H-tunneling, could bring about significant spatial crowding effect that stiffens the 2 degrees H/D vibrations, thus decreasing the 2 degrees KIE. This leads to a new physical organic research direction that examines how structure affects the 1 degrees isotope dependence of 2 degrees KIEs and how this dependence provides information about the structure of the tunneling ready states (TRSs). The hypothesis is that H- and D-tunneling have TRS structures which have different DADs, and pronounced 1 degrees isotope effect on 2 degrees KIEs should be observed in tunneling systems that are sterically hindered. This paper investigates the hypothesis by determining the 1 degrees isotope effect on alpha- and beta-2 degrees KIEs for hydride transfer reactions from various hydride donors to different carbocationic hydride acceptors in solution. The systems were designed to include the interactions of the steric groups and the targeted 2 degrees H/D's in the TRSs. The results substantiate our hypothesis, and they are not consistent with the traditional model of H-tunneling and 1 degrees/2 degrees H coupled motions that has been widely used to explain the 1 degrees isotope dependence of 2 degrees KIEs in the enzyme-catalyzed H-transfer reactions. The behaviors of the 1 degrees isotope dependence of 2 degrees KIEs in solution are compared to those with alcohol dehydrogenases, and sources of the observed "puzzling" 2 degrees KIE behaviors in these enzymes are discussed using the concept of the isotopically different TRS conformations.