Oxidation of polyunsaturated fatty acids and lipids through thiyl and sulfonyl radicals: reaction kinetics, and influence of oxygen and structure of thiyl radicals.

Thiyl free radicals have been shown to react with polyunsaturated fatty acids via abstraction of bisallylic hydrogen, forming pentadienyl radicals, and via addition to the double bonds. In the absence of oxygen, the latter pathway leads to regeneration of thiyl radicals through beta-elimination or "repair" of the adduct radicals by thiols. In the presence of oxygen, fixation of thiyl-induced damage occurs through reaction of O2 with the pentadienyl radical (yielding conjugated dienyl peroxyl radicals) and also with the thiyl-to-double bond adduct radical. A quantitative reaction scheme evaluated from these data considers abstraction, addition, rearrangement, and repair reactions, and the evaluation of rate constants for the individual steps. Absolute rate constants have been measured, in particular, for reactions of thiyl free radicals from glutathione, cysteine, homocysteine, N-acetylcysteine, cysteine ethyl ester, penicillamine, captopril, mercaptoethanol, and dithiothreitol with polyunsaturated fatty acids (PUFAs) ranging from 18:2 to 22:6, and the lipids trilinolein and trilinolenin. The rate constants for hydrogen abstraction were found to be typically of the order of 10(7) mol-1 dm3 s-1 and to increase with increasing lipophilicity of the attacking thiyl radical. Thioperoxyl radicals, RSOO., were found to be rather unreactive toward PUFAs, in contrast to the isomer sulfonyl radicals, RSO2., which not only abstract hydrogen from the bisallylic methylene groups of the PUFAs (although only at relatively small yield) but also readily add to the PUFA double bonds (major pathway). Specific information was obtained on the optical properties of the thiyl radical derived from the ACE inhibitor captopril, CpS. (lambda max = 340 nm, epsilon = 460 +/- 50 mol-1 dm3 cm-1), and its conjugate disulfide radical anion (CpS:.SCp) (lambda max = 420 nm).