Catalytic Chain-Breaking Pyridinol Antioxidants.

The synthesis of 3-pyridinols carrying alkyltelluro, alkylseleno, and alkylthio groups is described together with a detailed kinetic, thermodynamic, and mechanistic study of their antioxidant activity. When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzcnc two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcystcine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than a-socopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent. in homogeneous phase, inhibition of styrene autoxidation absolute rate constants kin5 for quenching of peroxyl radical were as large as 1 x 107 M-1 s-1, thus outperforming the best phenolic antioxidants including co-tocopherol. Tellurium-containing 3-pyridinolt could be quantitatively regenerated in homogeneous phase by N-tert-butoxycarbonyl cysteine methyl ester, a lipid-soluble analogue of N-acetylcysteine. In the presence of an excess of the thiol, a catalytic mode of action was observed, similar to the one in the two-phase system. Overall, compounds bearing the alkyltclluro moiety ortho to the OH group were much more effective antioxidants than the corresponding isara isomers. The origin of the high reactivity of these compounds was explored using pulse-radiolysis thermodynamic measurements, and a mechanism for their unusual antioxidant activity was proposed. The tellurium-containing 3-pyridinols were also found to catalyze reduction of hydrogen peroxide in the presence of thiol reducing agents, thereby acting as multi-functional (preventive and chain-breaking) catalytic antioxidants. [ABSTRACT FROM AUTHOR]