Antioxidant Activity of trans-Resveratrol toward Hydroxyl and Hydroperoxyl Radicals: A Quantum Chemical and Computational Kinetics Study

In this work, we have carried out a systematic study of the antioxidant activity of trans-resveratrol toward hydroxyl ((OH)-O-center dot) and hydroperoxyl ((OOH)-O-center dot) radicals in aqueous simulated media using density functional quantum chemistry and computational kinetics methods. All possible mechanisms have been considered: hydrogen atom transfer (HAT), proton-coupled electron transfer (PCET), sequential electron proton transfer (SEPT), and radical adduct formation (RAF). Rate constants have been calculated using conventional transition state theory in conjunction with the Collins-Kimball theory. Branching ratios for the different paths contributing to the overall reaction, at 298 K, are reported. For the global reactivity of trans-resveratrol toward (OH)-O-center dot radicals, in water at physiological pH, the main mechanism of reaction is proposed to be the sequential electron proton transfer (SEPT). However, we show that trans-resveratrol always reacts with (OH)-O-center dot radicals at a rate that is diffusion-controlled, independent of the reaction pathway. This explains why trans-resveratrol is an excellent but very unselective (OH)-O-center dot radical scavenger that provides antioxidant protection to the cell. Reaction between trans-resveratrol and the hydroperoxyl radical occurs only by phenolic hydrogen abstraction. The total rate coefficient is predicted to be 1.42 x 10(5) M-1 s(-1), which is much smaller than the ones for reactions of trans-resveratrol with (OH)-O-center dot radicals, but still important. Since the (OOH)-O-center dot half-life time is several orders larger than the one of the (OH)-O-center dot radical, it should contribute significantly to trans-resveratrol oxidation in aqueous biological media. Thus, trans-resveratrol may act as an efficient (OOH)-O-center dot, and also presumably (OOR)-O-center dot, radical scavenger.