Electron Spin Resonance Studies of the Reactions of • OH and SO 4 •- Radicals with DNA, Polynucleotides and Single Base Model Compounds

Abstract

Results of studies by esr spectroscopy and pulse radiolysis on the reactions of OH and SO 4 •- in aqueous solution with nucleobases, nucleosides, nucleotides and polynucleotides of the pyrunidine series are reported. The esr parameters of a large number of radicals are presented and several of the chemical pathways leading to their formation are discussed. Upon reaction of SO 4 •- with ribose nucleosides and nucleotides a fast transfer of the radical site from the base to the sugar is observed. Tentatively a base radical cation is assumed to be the highly reactive intermediate formed by reaction of SO 4 •- , with the base moieties. A relatively long-lived radical cation is identified from the reaction of SO4 •- with tetramethyluracil. No transfer reaction is observed with the 2’-deoxyribose-derivatives. Differences in sugar ring puckering may explain these results. Upon reaction of• OH radicals with polyuridylic acid [poly(U)] the C(5)-OH adduct radical of the uracil moiety was observed at neutral pH but a sugar radical at pH 3.5. This result is in agreement with pulse conductivity measurements showing a 100-fold increase in the rate of strand break formation of poly(U) upon lowering the pH. From esr spectroscopic parameters of the sugar radical of poly(U) it can be concluded that H abstraction occurs from position 2’ of the sugar by base radicals. This is evidence for the C(2’)-pathway leading to strand break formation in poly(U) as postulated earlier on the basis of pulse radiolysis work. Results obtained with purines are briefly discussed. With polyadenylic acid [poly(A)] and with DNA long-lived radicals (t½> 10 s) are observed which are inert to oxygen.