LAUSR

The change from 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 mutated enzymes (∆Ea >> 0) have recently been frequently observed. This has prompted some enzymologists to develop new H-tunneling models to correlate ∆Ea with the donor-acceptor distance (DAD) at the tunneling-ready state (TRS) as well as the protein thermal motions/dynamics that sample the short DADTRS's for H-tunneling to occur. While evidence supporting or disproving the thermally activated DAD sampling concept has extensively emerged, comparable study on the simpler bimolecular H-tunneling reactions in solution has not been carried out. Especially, small ∆Ea's (~ 0) have not been found. In this paper, we report a study of the hydride transfer reactions from four NADH models to the same hydride acceptor in acetonitrile. The ∆Ea's were determined, which are 0.37 (small), 0.60, 0.99, and 1.53 kcal/mol (large), respectively. The α-2° KIEs on the acceptor that serve as a ruler for the rigidity of reaction centers were either previously reported or determined. All possible productive reactant complex (PRC) configurations were computed to provide insight into the structures of the TRS's. Relationships among structures, 2° KIEs, DADPRC's, and ∆Ea's were discussed. The more rigid system with more suppressed 2° C-H vibrations at the TRS and more narrowly distributed DADPRC's in PRCs gave a smaller ∆Ea. Results replicated the trend observed in enzymes versus mutated enzymes, and appeared to support the concepts of different thermally activated DADTRS sampling processes in response to the rigid versus flexible donor-acceptor centers.