Generation of 2'-deoxyadenosine N6-aminyl radicals from the photolysis of phenylhydrazone derivatives.
Nitrogen-centered radicals are major species generated by the addition of hydroxyl radicals and the one-electron oxidation of adenine derivatives. Aminyl radicals are also generated in the decomposition of adenine chloramines upon reaction of hypochlorite. Here, we report the photochemistry of modified 2'-deoxyadenosine (dAdo) containing photoactive hydrazone substituents as a model to investigate the chemistry of dAdo N(6)-aminyl radicals. Derivatives of dAdo containing a phenylhydrazone moiety at N6 displayed UV absorption between 300 and 400 nm. Upon UV photolysis in the presence of a H-donor, that is, glutathione, two major products were formed, dAdo and benzaldehyde, indicating efficient homolytic cleavage to dAdo N(6)-aminyl radicals and benzylidene iminyl radicals. dAdo N(6)-phenylhydrazone was photolyzed in the presence of a molar excess of nonmodified dAdo to mimic the reactions taking place in DNA, and the major photoproducts were identified by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. The formation of 2-(benzylideneamino)-2'-deoxyadenosine as well as a more extensive oxidation product may be explained by the recombination of initial dAdo N(6)-aminyl and benzylidene iminyl radicals. The formation of 2'-deoxyinosine may be explained by hydrolytic deamination of dAdo N(6)-aminyl radicals. Interestingly, a dimeric product containing two dAdo moieties was identified in the photolysis mixture. The present studies demonstrate the ability of dAdo N(6)-aminyl radicals to undergo H-abstraction to give dAdo, deamination to give 2'-deoxyinosine, and addition to the adenine moiety to give dimers.
Kuttappan-Nair
Vandana
V
Departement de Medecine Nucleaire et Radiobiologie, Faculte de Medecine, 3001 12e Avenue Nord, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
Samson-Thibault
Francois
F
Wagner
J Richard
JR
D002851:Chromatography, High Pressure Liquid; D003839:Deoxyadenosines / Q000737:chemistry*; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry; D010084:Oxidation-Reduction; D010782:Photolysis; D021241:Spectrometry, Mass, Electrospray Ionization; D014466:Ultraviolet Rays
D003839:Deoxyadenosines; D006835:Hydrazones; C012483:phenylhydrazone; D017665:Hydroxyl Radical; C058118:2'-deoxyadenosine