A homologous series of binuclear copper(II) complexes [Cu-2(II)(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/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 H2O2. Spectroscopic and reactivity studies with [Cu-2(II)(N4)(Y)(2)](2+) (2) and H2O2 are consistent with DNA oxidation mediated by formation of a side-on peroxodicopper(II) (Cu-2-O-2) complex.