Enzymatic H Transfers: Quantum Tunneling and Coupled Motion from Kinetic Isotope Effect Studies

Abstract

AbstractMany hydrogen transfer processes exhibit nonclassical behavior due to inherent quantum mechanical properties of the hydrogen. Investigation of various enzymes under physiological conditions indicates that hydrogen transfer processes often show significant quantum mechanical behavior. Traditionally, this phenomenon was treated in terms of a tunneling correction to classical or semiclassical models. However, more recently, it has been observed that increasing numbers of enzymes yield data that cannot be rationalized by tunneling correction models. Observations such as large kinetic isotope effects (KIEs) with unusual temperature dependence, isotope effects on Arrhenius preexponential factors with values different from semiclassical predicted ranges, and small temperature‐independent KIEs for processes with significant energy of activation, could only be explained with full tunneling models for H transfer. Full tunneling models presume that the solvent or protein fluctuations generate a reactive configuration along the heavy‐atom coordinate, from which the hydrogen is transferred through quantum mechanical tunneling. These models are sometimes denoted as environmentally coupled tunneling (ECT) or Marcus‐like models, and they link protein dynamics to the catalyzed H transfer. Several enzymatic systems (dihydrofolate reductase, thymidylate synthase, and soybean lipoxygenase) are presented as case studies of proton, hydrogen, and hydride transfer.