Suppression of radical-induced lipid peroxidation in a model system by alkyl esters of cinnamate quaternary ammonium salts

Three new groups of phenolic antioxidants, quaternary ammonium salts with a phenol ring and alkyl chains of different length (pyrrolidine ethyl esters of 3,5-di-t-butyl-4-hydroxydihydrocinnamic acid n-alkoxymethylchlorides (P YE-n) or n-alkylbromides (PYA-n) and 2-dimethylaminoethyl ester n-alkylbrom ides (PPA-n), were synthesized. Some of them were previously found to effic iently protect yeast cells against oxidants and to inhibit the production o f thiobarbituric acid-reactive substances in whole yeast cells and in isola ted membrane lipids. The new antioxidants (at 1-100 muM) abolished or dimin ished peroxidation of oliwe oil emulsions caused by the OH.-producing Fe2and RO. and ROO.-producing tert-butylhydroperoxide (TBHP) and the azo compo unds 2,2'-azobis-(amidinopropane)dihydronitrile (AAPH) and 1,1'-azobis-(1-c yclohexanecarbonitrile) (ACHN): all present at 10 mM. The efficiency of ind ividual both antioxidants was examined in relation to the type of lipid per oxidation inducer, the site of antioxidant incorporation into the emulsion lipid phase, the length of the alkyl chain, and the maximum concentration o f effective antioxidant monomers given by its critical micelle concentratio n. PYA-n class compounds were highly efficient against all peroxidation ind ucers and their efficiency did not depend on the position of their molecule s in the lipid phase and/or on the aliphatic chain length. In contrast, the efficiency of PYE-n and PPA-n class compounds depended both on the type of oxidant and on the length of their aliphatic chain. Their potency against Fe2+ and ACHN increased with increasing alkyl chain length whereas with AAP H it dropped with increasing alkyl chain length. A similar pattern was foun d with the action of PYE-n against TBHP whereas in the PPA-n group an exten ding alkyl chain reduced the anti-TBHP efficiency. These relationships may not be entirely straightforward and other factors (chemical nature of each compound, its possible interaction with fluorescent probes used for diagnos tics, etc.) may play a considerable and not yet quite clear role. PPA-n cla ss antioxidants have the lowest critical micelle concentration, which may l imit their efficiency. Nevertheless, these phenolic antioxidants can be con veniently employed as highly efficient inhibitors of lipid peroxidation.