Reactions of sulphonyl peroxyl radicals with DNA and its components: Hydrogen abstraction from the sugar backbone versus addition to pyrimidine double bonds

The reactions of sulphonyl peroxyl radicals with DNA and its components at low temperatures are investigated through use of electron spin resonance spectroscopy. Radiolysis of cysteine sulphinic acid solution in oxygenated aqueous 5 mol dm(-3) LiCl glass has been employed to generate sulphonyl peroxyl radicals, CysSO(2)OO(.). The mechanism of production is a two-step process involving the oxidation of the sulphinate (CysSO(2)(-)) to the sulphonyl radical (CysSO(2)(.)) by radiolytically produced Cl-2(-) followed by oxygen addition to CysSO(2)(.). Sulphonyl peroxyls are shown to be reactive towards DNA and nucleotides in low temperature glasses, giving rise to carbon-based peroxyl radicals. However, of the DNA bases only thymine was found to react readily. The thymine methyl group contains a relatively weak C-H bond which makes it easily abstractable. DNA nucleosides and nucleotides are likely attacked by CysSO(2)OO(.) by abstraction from the sugar C-H bonds. The C(1) position of deoxyribose ring of model nucleosides is suggested to be a preferred site for attack at low temperatures. The reaction with double-stranded DNA at higher temperatures may occur at the more accessible C(4) position. CysSO(2)OO(.) is also shown to react with a number of methyl substituted uracils, producing the highly persistent 5-oxouracil-6-yl radicals. The reaction mechanism proposed involves the addition of CysSO(2)OO(.) to pyrimidine 5,6-double bonds followed by elimination of cysteine sulphonic acid.