Replication of the Enzymatic Temperature Dependency of the Primary Hydride Kinetic Isotope Effects in Solution: Caused by the Protein-Controlled Rigidity of the Donor-Acceptor Centers?

The change from the temperature independence of the primary (1°) H/D kinetic isotope effects (KIEs) in wild-type enzyme-catalyzed H-transfer reactions (Δ = - ∼ 0) to a strong temperature dependence with the mutated enzymes (Δ ≫ 0) has recently been frequently observed. This has prompted some enzymologists to develop new H-tunneling models to correlate Δ with the donor-acceptor distance (DAD) at the tunneling-ready state (TRS) as well as the protein thermal motions/dynamics that sample the short DAD's for H-tunneling to occur. While extensive evidence supporting or disproving the thermally activated DAD sampling concept has emerged, a comparable study of the simpler bimolecular H-tunneling reactions in solution has not been carried out.

Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD Analogues in Their Hydride Tunneling Reactions in Solution.

The α-H/D (if available) and remote β-type N-CH/CD 2° kinetic isotope effects (KIEs) on 10-methylacridine (MAH), 9,10-dimethylacridine (DMAH), 1,3-dimethyl-2-phenylbenzimidazoline (DMPBIH) and on the oxidized forms MA and DMA, in their hydride transfer reactions with several hydride acceptors/donors in acetonitrile, were determined. The corresponding equilibrium isotope effects (EIEs) were computed. Hammett correlations of several closely related hydride transfer reactions were constructed using the literature data.