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The interaction of myoglobin with H2O2 leads via a two-electron oxidation process to the formation of ferryl myoglobin. Metmyoglobin is more readily activated than oxymyoglobin to the ferryl states, which are capable of inducing peroxidative damage to membranes. E.p.r. and optical spectroscopic studies show that the thiol-containing compounds N-(2-mercaptopropionyl) glycine and N-acetylcysteine and the trihydroxamate desferrioxamine attenuate these processes by reducing the ferryl myoglobin species to metmyoglobin, with the formation of thiyl radicals and the desferrioxamine nitroxide radical respectively. Biochemical investigations of the potential for myoglobin in ruptured myocytes to be involved in radical generation, when under oxidative stress, and of the nature of the resulting species, were also undertaken. E.p.r. spectroscopic studies revealed the formation of a radical species which is capable of inducing membrane lipid peroxidation. The interaction of the thiol compounds and desferrioxamine with components of myocardial tissue under these conditions results in the generation of thiol-derived radical species and the desferrioxamine nitroxide radical respectively. These data, along with those obtained using optical spectrocopy, support the assignment of the identity of the radical species generated from the myocytes as the ferryl myoglobin radical.

The development of a 1-hydroxybenzotriazole linker for the synthesis of heterocyclic derivatives is described, utilizing analytical construct methodology to facilitate the analysis of resin samples. A UV-chromophore-containing analytical construct enabled the accurate determination of resin loading and the automated monitoring of key reactions using only small quantities of resin. The syntheses of an array of isoxazole derivatives are reported.

1056BIOCHEMICAL SOCIETY TRANSACTIONS established, the mechanism by which /?-carotene exerts a protective function against cancer remains unknown. However, there are several lines of evidence which suggest that the generation of reactive oxygen species may play an important role in the development of cancer [14]. The present work emphasizes that attention should be extended from /?-carotene to lycopene and other carotenoids. Lycopene has a plasma concentration slightly higher than /?-carotene and both these carotenoids were found in lowdensity lipoproteins [ IS].The relative physical quenching abilities of the tocopherol homologues decreased in the following order: a, /?, y, and &tocopherol. With the tocopherols, the ability of '02 quenching depends on a free hydroxyl group in position 6 of the chromane ring. Chemical reactivity of the tocopherol homologues were low, accounting for 0.1 to 1.5"/0 of the physical quenching. Among the biological thiols, cysteine was the most effective quencher of lo,, followed by lipoate (disulphide form of the dithiol lipoate), coenzyme A, glutathione, cysteamine and dihydrolipoate. Pharmacologically active thiols like Nacetylcysteine, mesna, WR-1065 and captopril significantly differed in their quenching abilities. The pD dependence of the chemical quenching indicated that '0, reacts with the thiolate anion. As compared to their overall quenching abilities, cysteine, WR-1065, cysteamine, mesna and dihydrolipoate had significant chemical quenching abilities. other thiols tested had a chemical quenching rate less than S%, most of them less than I%, of their overall quenching ability.Compared to carotenoids, other classes of compounds, e.g. bilirubin, tocopherols and thiols were less active in singlet oxygen quenching. But these may also be biologically important in '02 quenching because of their higher concen-tration and/or different subcellular location in biological targets, besides solubility characteristics.

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