Generation of 2'-deoxyadenosine N6-aminyl radicals from the photolysis of phenylhydrazone derivatives.

Chem Res Toxicol

Departement de Medecine Nucleaire et Radiobiologie, Faculte de Medecine, 3001 12e Avenue Nord, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.

Published: January 2010

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.

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http://dx.doi.org/10.1021/tx900268rDOI Listing

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Generation of 2'-deoxyadenosine N6-aminyl radicals from the photolysis of phenylhydrazone derivatives.

Chem Res Toxicol

January 2010

Departement de Medecine Nucleaire et Radiobiologie, Faculte de Medecine, 3001 12e Avenue Nord, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.

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.

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