Structural Effects on the Temperature Dependence of Hydride Kinetic Isotope Effects of the NADH/NAD Model Reactions in Acetonitrile: Charge-Transfer Complex Tightness Is a Key.

It has recently frequently been found that the kinetic isotope effect (KIE) is independent of temperature () in H-tunneling reactions in enzymes but becomes dependent on in their mutants. Many enzymologists found that the trend is related to different donor-acceptor distances (DADs) at tunneling-ready states (TRSs), which could be sampled by protein dynamics. That is, a more rigid system of densely populated short DADs gives rise to a weaker dependence of KIEs.

Solvent Effects on the Temperature Dependence of Hydride Kinetic Isotope Effects: Correlation to the Donor-Acceptor Distances.

Protein structural effects on the temperature () dependence of kinetic isotope effects (KIEs) in H-tunneling reactions have recently been used to discuss about the role of enzyme thermal motions in catalysis. Frequently observed nearly -independent KIEs in the wild-type enzymes and -dependent KIEs in variants suggest that H-tunneling in the former is assisted by the naturally evolved protein constructive vibrations that help sample short donor-acceptor distances (DADs) needed. This explanation that correlates the -dependence of KIEs with DAD sampling has been highly debated as simulations following other H-tunneling models sometimes gave alternative explanations.