Portal de Periódicos da CAPES

Generation of 2′-Deoxyadenosine N 6 -Aminyl Radicals from the Photolysis of Phenylhydrazone Derivatives

2009; American Chemical Society; Volume: 23; Issue: 1 Linguagem: Inglês

10.1021/tx900268r

1520-5010

Vandana Kuttappan-Nair, François Samson-Thibault, J. Richard Wagner,

Per- and polyfluoroalkyl substances research

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 N6-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 N6-aminyl radicals and benzylidene iminyl radicals. dAdo N6-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 N6-aminyl and benzylidene iminyl radicals. The formation of 2′-deoxyinosine may be explained by hydrolytic deamination of dAdo N6-aminyl radicals. Interestingly, a dimeric product containing two dAdo moieties was identified in the photolysis mixture. The present studies demonstrate the ability of dAdo N6-aminyl radicals to undergo H-abstraction to give dAdo, deamination to give 2′-deoxyinosine, and addition to the adenine moiety to give dimers.