Oxidative DNA Cleavage, Formation of μ-1,1-Hydroperoxo Species, and Cytotoxicity of Dicopper(II) Complex Supported by a -Cresol-Derived Amide-Tether Ligand.

Metal complexes to promote oxidative DNA cleavage by HO are desirable as anticancer drugs. A dicopper(II) complex of known -cresol-derived methylene-tether ligand Hbcc [Cu(bcc)] did not promote DNA cleavage by HO. Here, we synthesized a new -cresol-derived amide-tether one, 2,6-bis(1,4,7,10-tetrazacyclododecyl-1-carboxyamide)--cresol (Hbcamide). A dicopper(II) complex of the new ligand [Cu(μ-OH)(bcamide)] was structurally characterized. This complex promoted the oxidative cleavage of supercoiled plasmid pUC19 DNA (Form I) with HO at pH 6.0-8.2 to give Forms II and III. The reaction was largely accelerated in a high pH region. A μ-1,1-hydroperoxo species was formed as the active species and spectroscopically identified. The amide-tether complex is more effective in cytotoxicity against HeLa cells than the methylene-tether one.