Selective DNA strand scission with binuclear copper complexes: implications for an active Cu2-O2 species

A homologous series of binuclear copper(II) complexes [Cu(II)(2)(Nn)(Y)(2)](2+) (1-3) (n = 3-5 and Y = (ClO(4))(-) or (NO(3))(-)) were studied to investigate the intermediate(s) responsible for selective DNA strand scission in the presence of MPA/O(2) (MPA = 3-mercaptopropanoic acid). While the N3 complex does not react, the N4 and N5 analogues show comparable activity with strand scission occurring at a single-strand/double-strand junction. Identical reactivity is also observed in the alternate presence of H(2)O(2). Spectroscopic and reactivity studies with [Cu(II)(2)(N4)(Y)(2)](2+) (2) and H(2)O(2) are consistent with DNA oxidation mediated by formation of a side-on peroxodicopper(II) (Cu(2)-O(2)) complex.