Explaining Kinetic Isotope Effects in Proton-Coupled Electron Transfer Reactions

Proton-coupled electron transfer (PCET) is essential for a wide range of chemical and biological processes. Understanding the mechanism of PCET reactions is important for controlling and tuning these processes. The kinetic isotope effect (KIE), defined as the ratio of the rate constants for hydrogen and deuterium transfer, is used to probe PCET mechanisms experimentally but is often challenging to interpret. Herein, a theoretical framework is described for interpreting KIEs of concerted PCET reactions. The first step is to classify the reaction in terms of vibronic and electron–proton nonadiabaticities, which reflect the relative time scales of the electrons, protons, and environment. The second step is to select the appropriate rate constant expression based on this classification. The third step is to compute the input quantities with computational methods.