EPR spin-trapping studies of radicals generated from the FeII-catalysed degradation of nucleobase, nucleoside, RNA and DNA hydroperoxides†

Abstract

Nucleobase, nucleoside, RNA and DNA hydroperoxides have been generated by exposure of the parent compounds to high energy electrons in the presence of oxygen; EPR spin-trapping experiments using 2-methyl-2-nitrosopropane (MNP) and 5,5-dimethyl-4,5-dihydro-3H-pyrrole N-oxide (DMPO) have been employed to study the reactions of alkoxyl radicals generated from their reaction with Fe²⁺. Alkoxyl radicals generated from the pyrimidine hydroperoxides (nucleobases and nucleosides) are shown to be capable of reacting with a variety of substrates, which include the pyrimidine nucleobases and nucleosides themselves and histone proteins. Attack on the parent pyrimidine compounds involves addition to the C(5) and C(6) atoms of the pyrimidine ring; reaction with the histone proteins, amino acids and peptides gives carbon-centred species, providing direct evidence for transfer of damage via hydrogen-atom abstraction. Rapid reactions with antioxidants are also demonstrated.