Selective DNA Strand Scission with Binuclear Copper Complexes: Implications for an Active Cu₂−O₂ Species

A homologous series of binuclear copper(II) complexes [CuII2(Nn)(Y)2]2+ (1−3) (n = 3−5 and Y = (ClO4)- or (NO3)-) were studied to investigate the intermediate(s) responsible for selective DNA strand scission in the presence of MPA/O2 (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 H2O2. Spectroscopic and reactivity studies with [CuII2(N4)(Y)2]2+ (2) and H2O2 are consistent with DNA oxidation mediated by formation of a side-on peroxodicopper(II) (Cu2−O2) complex.