Reactivity of Diethylstilbestrol Toward Electrogenerated Superoxide in N,N-Dimethylformamide Through Proton-Coupled Electron Transfer

Abstract

The superoxide radical anion (O₂^•−) scavenging mechanism of diethylstilbestrol (DesH₂) was investigated using in situ UV–vis spectroelectrochemistry, cyclic voltammetry, and DFT/TD-DFT calculations. While thermodynamic evaluation indicates that all tested stilbene derivatives possess favorable free energy changes for scavenging O₂^•−, comparative cyclic voltammetry revealed that only DesH₂ and 4,4′-dihydroxystilbene exhibit distinct scavenging waves. On the electrochemical timescale, effective scavenging requires a 1:1 stoichiometric proton-coupled electron transfer (PCET) mechanism involving the transfer of two protons and one electron from a single molecule. Thermodynamic and mechanistic analyses supported this PCET pathway. Crucially, the diethyl substituents in DesH₂ stabilize the generated radical anion and maintain the structural integrity of the stilbene core, enabling further two- to four-electron oxidation. Furthermore, subsequent chemical steps (e.g., adduct decomposition or OH addition) pull the reaction equilibrium forward to dynamically drive the initial PCET process.