Redox cycling of quinones reduced by ascorbic acid

In aqueous solutions containing ascorbic acid and O₂, many quinones undergo reduction to the semiquinone followed by reoxidation. This redox cycling mediates the oxidation of ascorbic acid and the reduction of O₂ to superoxide and ultimately hydrogen peroxide. For that reason, redox cycling has attracted attention as a source of reactive oxygen species. This redox cycling is paradoxical, however, because the one-equivalent reduction potentials of the reactants are unfavorable, so the concentrations of the products, monodehydroascorbate and superoxide, must be kept extremely low. Disproportionation is not fast enough to eliminate these products. We have investigated the mechanism of ascorbate-driven redox cycling by monitoring the redox status of the quinone and the rate of redox cycling in parallel. Evidence is presented for a mechanism in which monodehydroascorbate is oxidized by the semiquinone. The result is that cycling of the semiquinone and hydroquinone mediates a rapid disproportionation of monodehydroascorbate. This mechanism accounts for the dependence of the redox cycling rate on quinone and ascorbate concentrations as well as on the reduction potential of the quinone. Therefore, it predicts how fast ascorbate-driven redox cycling will generate hydrogen peroxide under a variety of conditions and with different quinones.