Abstract
Contemporary H-tunneling theories predict that a longer donor-acceptor distance (DAD) corresponds to a larger kinetic isotope effect (KIE). Herein, hydride-tunneling reactions of NADH/NAD(+) analogues in acetonitrile were used to examine the KIE-DAD relationship. Reaction pairs of similar tunneling-ready conformations were selected, so that additional factors influencing KIEs would be relatively fixed. Positive results were obtained, with some reaction pairs displaying a reversal of the traditional KIE-ΔG° relationship in favor of the KIE-DAD relationship, lending strong support to the latter.