Mechanistic aspects of the oxidation of DNA constituents mediated by singlet molecular oxygen

The present paper focussed on the mechanistic aspect of the reaction of singlet oxygen (1O2), in its lowest excited state (1Δg), toward DNA constituents. It is well known that 1O2 is able to react with the guanine moiety of DNA to produce almost specifically 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). However, when 2′-deoxyguanosine (dGuo), free in solution, is the substrate, additional modified nucleosides are detected upon 1O2-mediated oxidation. The combined use of the thermolysis of a water-soluble naphthalene endoperoxide as a generator of 18O-singlet oxygen and the sensitivity of electrospray ionization–tandem mass spectrometry has allowed us to better understand the reactivity of 1O2 toward dGuo and 8-oxodGuo. As a striking observation, the secondary oxidation reaction of 8-oxodGuo, a main 1O2 oxidation product of dGuo, may explain, at least partly, the observed mutagenicity of 1O2.