Copper-mediated DNA photocleavage by a tetrapyridoacridine (tpac) ligand.

Bioorg Med Chem Lett

Departamento de Química Inorgánica, Universidad de Valencia, 46100-Burjassot, Valencia, Spain.

Published: June 2008

We have focused our interest on the tetrapyridoacridine ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h: 2''',3'''-j]acridine (tpac), as a model system for the preparation of novel copper-based artificial nucleases. The complex of copper(II)-tpac cleaves supercoiled pUC18 plasmid DNA in an oxidative manner by photoactivation with visible light, exhibiting maximum cleaving efficiency at 1:2 metal-ligand stoichiometric ratio. We propose an interaction of the copper-tpac complex with DNA through both major and minor grooves and a photocleavage mechanism via the formation of hydroxyl radicals and singlet oxygen or singlet oxygen-like species.

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http://dx.doi.org/10.1016/j.bmcl.2008.04.040DOI Listing

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