Cascade proton relays facilitate electron transfer across hydrogen‐bonding network

Functioning as both hydrogen-bonding donor and acceptor, the imidazole group of histidine holds a unique position in the proton transfer cascade of biological systems. For example, a histidine residue in the oxygen-evolving photosystem II participates in the proton-coupled electron transfer (PCET) reaction to facilitate light-triggered one-electron oxidation of a nearby tyrosine residue. As a minimalist synthetic model of such His-Tyr functional diad, three structural variants of benzimidazole-phenol conjugate were studied. We found that an increasing number of hydrogen bonds facilitate reversible one-electron oxidation of the phenol ring. The reaction coordinates of this intriguing PCET process were mapped out by density functional theory computational studies to reveal oxidation-driven conformational switching as an entry point to cascade proton relays stabilizing the phenoxyl radical. Strategic placement of hydrogen bonds thus tightly regulates the energy windows of electron transfer, which is an effective strategy for biological redoxphores of seemingly limited structural diversity.