A Quantitative Approach to the Free Radical Interaction Between Alpha-Tocopherol and the Coantioxidants Eugenol, Resveratrol or Ascorbate

Abstract

The regeneration of alpha-tocopherol (vitamin E; VE) by coantioxidants such as phenolics and ascorbate has been studied in homogeneous hydrocarbon solution and in biological systems. However, VE phenoxyl radicals (VE^●) may be sufficiently reactive to cooxidize phenolic compounds and ascorbates. The coantioxidant behavior of some relevant phenols such as eugenol (EUG), isoeugenol (IsoEUG), 2,6-di-tert-butyl-4-methoxyphenol (DTBMP), trans-resveratrol (RES) and L-ascorbyl-2,6-dibutyrate (ASDB; an ascorbate derivative) with the antioxidant VE at a molar ratio of 1:1 was investigated by the induction period (IP) method in the kinetics of polymerization of methyl methacrylate (MMA) initiated by the thermal decomposition of 2,2′-azobis(isobutyronitrile) (AIBN; a source of alkyl radicals, R^●) or benzoyl peroxide (BPO; a source of peroxy radicals, PhCOO^●) under nearly anaerobic conditions. Synergism, implying regeneration of VE by the coantioxidant, was observed with only two of these combinations, VE/EUG with PhCOO^● and VE/DTBMP with R^●. For other mixtures of VE with a phenolic coantioxidant, VE was able to cooxidize the phenolic. Regeneration can only be observed if the bond dissociation energy (BDE) of the coantioxidant is lower than, or at least close to, that of VE. The driving force for regeneration of VE by EUG may be removal of the semiquinone radical of EUG by VE, leading to the formation of VE and EUG-quinonemethide, even though the BDE value of EUG is greater by 5.8 kcal/mol than that of VE. Further evidence for this mechanism of regeneration is provided by the value of approximately 2 for the stoichiometric factor (n) of EUG induced by PhCOO^●, but not by R^●, again implying the formation of EUG-quinonemethide. The regeneration of VE by DTBMP in the R^● system may result from their much smaller difference in BDE (0.1-1.3 kcal/mol). Since VE is rapidly oxidized by PhCOO^●, regeneration of VE by DTBMP was not found in this system. The observed IP for the VE/ASDB mixture in the R^● system was much lower than that for VE alone, whereas the IP for VE/ASDB in the PhCOO^● system was similar to that of VE. In the R^● system, VE^● was sufficiently reactive to cooxidize ASDB and, in addition, the prooxidation of VE may be promoted by the catalytic action of the ascorbate derivative. The present system, under nearly anaerobic conditions, is relatively biomimetic, since oxygen in living cells is sparse. Such studies could help to explain the mechanism of regeneration of VE by coantioxidants such as phenolic compounds and vitamin C in vivo.