A trinuclear copper complex, [Cu-3(II)(L)(H2O)(3)(NO3)(2)](NO3)(4).5H(2)O (1) (L = 2,2',2"-tris(dipicolyl-amino)triethylamine), with pyridyl and alkylamine coordination exhibits a remarkable ability to promote specific strand scission at junctions between single-and double-stranded DNA. Strand scission occurs on the 3' overhang at the junction of a hairpin or frayed duplex structure and is not dependent on the identity of the base at which cleavage occurs. Target recognition minimally requires a purine at the first unpaired position and a guanine at the second unpaired position on the 5' strand. Incorporation of the necessary recognition elements into an otherwise unreactive junction resulted in specific strand scission at that new target and helped to confirm the predictive nature of this complex. Selective strand scission requires both a reductant and dioxygen, suggesting activation of O-2 by the reduced form of 1. The reaction utilizing the trinuclear complex does not appear to involve a diffusible radical species as suggested by its high specificity of target oxidation and its lack of sensitivity to radical quenching agents. Comparisons between the trinuclear copper complex, mononuclear analogues of 1, and [Cu(OP)(2)](2+) (OP = 1,10-phenanthroline) indicate that recognition and reactivity described in this report are dependent on the multiple metal ions within the same complex which together support its unique activity.