Theoretical Parameters to Characterize Antioxidants. Part 1. The case of vitamin E and analogs

The objectives of ibis 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, Ep, and rate constant of the reaction with a free radical log ks). AM1 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, ΔHox and ΔHabs) were fairly well correlated with the experimental antioxidant activities (Ep and ks). 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.