Reaction of singlet oxygen with 2'-deoxyguanosine and DNA. Isolation and characterization of the main oxidation products.
The reaction of singlet molecular oxygen with 2'-deoxyguanosine and DNA was studied. Emphasis was placed on the identification and characterization of the main methylene blue mediated type II (singlet oxygen) oxidation products of 2'-deoxyguanosine and its corresponding 3',5'-di-O-acetylated derivative. Two major oxidation products of 2'-deoxyguanosine were isolated and characterized by mass spectrometry analysis and extensive 1H and 13C NMR measurements as the two 4R* and 4S* diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine. The addition of 1O2 was also found to occur to the base moiety of the corresponding 3',5'-di-O-acetylated derivative. Methylene blue mediated photosensitization of 2'-deoxyguanosine led also to the production of 7,8-dihydro-8-oxo-2'-deoxyguanosine, but in a relatively lower yield with respect to the two above diastereomers. The participation of singlet oxygen in the mechanism of formation of these oxidation products was confirmed. A reasonable mechanism involving the transient formation of an unstable endoperoxide produced through a Diels-Alder 1,4-cycloaddition of singlet oxygen to the purine ring is suggested. Quantitative analysis allowed us to demonstrate that the two diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine are the main singlet oxygen oxidation products of the guanine moiety within nucleosides, whereas 7,8-dihydro-8-oxoguanine was found to be the major 1O2 oxidation product of guanine in double-stranded DNA.
Ravanat
J L
JL
CEA/Département de Recherche Fondamentale sur la Matière Condensée/SESAM/LAN, Grenoble, France.
Cadet
J
J
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D010777:Photochemistry; D013057:Spectrum Analysis
D004247:DNA; D003849:Deoxyguanosine; D010100:Oxygen