The Synergy between Glutathione and Phenols-Phenolic Antioxidants Repair Glutathione: Closing the Virtuous Circle-A Theoretical Insight.

Glutathione (GSH) and phenols are well-known antioxidants, and previous research has suggested that their combination can enhance antioxidant activity. In this study, we used Quantum Chemistry and computational kinetics to investigate how this synergy occurs and elucidate the underlying reaction mechanisms. Our results showed that phenolic antioxidants could repair GSH through sequential proton loss electron transfer (SPLET) in aqueous media, with rate constants ranging from 3.21 × 10(6) M(-1) s(-1) for catechol to 6.65 × 10(8) M(-1) s(-1) for piceatannol, and through proton-coupled electron transfer (PCET) in lipid media with rate constants ranging from 8.64 × 10(6) M(-1) s(-1) for catechol to 5.53 × 10(7) M(-1) s(-1) for piceatannol. Previously it was found that superoxide radical anion (O(2)(•-)) can repair phenols, thereby completing the synergistic circle. These findings shed light on the mechanism underlying the beneficial effects of combining GSH and phenols as antioxidants.