Theoretical parameters to characterize antioxidants .1. The case of vitamin E and analogs

The objectives of this work were a) to evaluate parameters obtained by quantum-mechanical calculations as predictors of antioxidant activities, and b) to obtain information on the molecular mechanism(s) underlying the antioxidant effects of vitamin E and analogs. To this effect, we selected a large series of tocopherol analogs for which some experimental antioxidant activities were available in the literature (i.e., peak of oxidation potential, E-p, and rate constant of the reaction with a free radical log k(s)). AMI Semi-empirical calculations were performed, the results of which were validated by ab initio calculations on a subset of compounds. The quantum chemical descriptors considered here (HOMO, Delta H-ox and Delta H-abs) were fairly well correlated with the experimental antioxidant activities (E-p and k(s)). Moreover, these theoretical parameters were intercorrelated, suggesting that vitamin E analogs may act by a dual mechanism of single-electron transfer (SET) and direct H-atom abstraction.