Lone Pair−π and π−π Interactions Play an Important Role in Proton-Coupled Electron Transfer Reactions

Proton-coupled electron transfer (PCET), a class of formal hydrogen atom transfer (HAT) reactions, is of widespread interest because it is implicated in a broad range of chemical and biochemical processes. PCET is typically differentiated from HAT by the fact that it occurs when a proton and electron are transferred between different sets of molecular orbitals. Previous theoretical work predicted that hydrogen bonding between reactants is a necessary but not sufficient condition for H exchanges to take place by PCET. This implies that HAT is the only mechanism for H exchange between two carbon atoms. In this work, we present computational results that show that the H exchange in the tert-butylperoxyl/phenol couple, a prototypical antioxidant exchange reaction, occurs by PCET and that the transfer of the electron can occur via an oxygen lone pair-ring pi overlap. We then show that the H exchange in a model for the tyrosyl/tyrosine couple, which is implicated in ribonucleotide reductase chemistry, occurs via PCET and that one path for the electron transfer is provided by a strong pi-stacking interaction. Finally, we show that a pi-stacking interaction in the benzyl/toluene couple, a system in which there is no H-bonding, can result in this exchange occurring via PCET to some extent. Collectively, these results indicate that PCET reactions are not unique to systems that can engage in H-bonding and that lone pair-pi and pi-pi interactions in these systems may be more important than previously understood.