SOD-Like Activity of 5-Membered Ring Nitroxide Spin Labels
Although Superoxide anion mediated redox reactions have been extensively studied, only a few studies involving radical-radical reactions of Superoxide with nitroxides have been so far reported1–8. Superoxide can act as a one-electron reductant with many species, including the biochemical and toxicological interesting reactions with ferricytochrome c9, tetranitromethane10, or nitroblue-tetrazolium11. Oxidation reactions involving Superoxide are less common and usually involve complex multi-electron steps such as oxidation of sulfite or epinephrine12 where O 2 ∸ may serve as an initiator and propagator of free radical chain reactions. One of the few one-electron oxidations mediated by O 2 ∸ is the conversion of secondary hydroxylamines into nitroxides1. The hydroxylamine, 2-ethyl-l-hydroxy-2,5,5 trimethyl-3-oxazolidine (OXANOH), is readily oxidized by O 2 ∸ to a stable radical, 2-ethyl 2,5,5-trimethyl-3-oxazolidinoxyl (OXANO) and this oxidation has been employed to detect and assay Superoxide2. Recently O 2 ∸ has been found to also be capable of reducing OXANO to OXANOH13. Through the combined reduction and oxidation of O 2 ∸ , the OXANO / OXANOH couple exhibited a Superoxide dismutase-like activity13. This low molecular weight, cell permeable, non-immunogenic, non-cytotoxic, metal-independent SOD-mimic was found, in the present study, to protect mammalian cells against oxidative damage. To determine if other nitroxides have similar properties we investigated a series of nitroxide derivatives for their reactions with O 2 ∸ by using electron spin resonance spectrometry. The 5-membered ring nitroxides were reduced by O 2 ∸ to the corresponding hydroxylamines, which in turn were re-oxidizable to the parent nitroxides. The results indicate that SOD-like activity is not limited to OXANO but is shared by nitroxide spin-labels in general.
KeywordsXanthine Oxidase Free Radical Chain Reaction Stable Nitroxides Milk Xanthine Oxidase Ring Nitroxides
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