Substituent Effects on Temperature Dependence of Kinetic Isotope Effects in Hydride-Transfer Reactions of NADH/NAD⁺ Analogues in Solution: Reaction Center Rigidity Is the Key

Abstract

Substituent effects on the temperature dependence of primary kinetic isotope effects, characterized by ΔEa = EaD – EaH, for two series of the title reactions in acetonitrile were studied. The change from ΔEa ≈ 0 for a highly rigid system to ΔEa > 0 for systems with reduced rigidities was observed. The rigidities were controlled by the electronic and steric effects. This work replicates the observations in enzymes and opens a new research direction that studies structure−ΔEa relationship.