Electrochemical and Computational Studies Show That Vitamin C Assists Resveratrol, Piceatannol and Oxyresveratrol in Superoxide Scavenging, Suggesting a Superoxide Dismutase Mechanism

In this study, we combine experimental and computational approaches to elucidate a density functional theory (DFT)-derived mechanism for superoxide scavenging by resveratrol, piceatannol, and oxyresveratrol. Using rotating ring–disk electrode (RRDE) hydrodynamic voltammetry, the superoxide radicals are generated in situ, allowing direct measurement of antioxidant activity. Data show that the catechol-containing piceatannol is approximately four times more active than resveratrol, while resveratrol and oxyresveratrol exhibit similar efficiencies, indicating that the additional 2′-OH group in oxyresveratrol has minimal impact. Vitamin C (ascorbic acid) facilitates scavenging by acting as a proton donor for resveratrol, piceatannol, and 4′-OH oxyresveratrol, but it is unable to deprotonate the 2′OH group of oxyresveratrol. The experimental results suggest a superoxide dismutase (SOD)-like mechanism, obtained from energetically feasible DFT calculations, in which these stilbenes convert two superoxide anions into H2O2 and O2, helped by vitamin C. Mechanistically, the first superoxide is reduced by abstracting a hydroxyl-group hydrogen atom, while the second undergoes oxidation via π–π interaction with the aromatic system, releasing O2. Notably, resveratrol can be regenerated through a catalytic cycle involving vitamin C. These data underscore the SOD-mimicking properties of dietary polyphenols and suggest a need to reevaluate resveratrol’s clinical utility regardless of its low bioavailability.