Hydrogen peroxide and dioxygen activation by dinuclear copper complexes in aqueous solution: Hydroxyl radical production initiated by internal electron transfer

Dinuclear Cu(II) complexes, (Cu2Nn)-N-II (n = 4 or 5), were recently found to specifically cleave DNA in the presence of a reducing thiol and O-2 or in the presence of H2O2 alone. However, (Cu2N3)-N-II and a closely related mononuclear Cu(II) complex exhibited no selective reaction under either condition. Spectroscopic studies indicate an intermediate is generated from (Cu2Nn)-N-II (n = 4 or 5) and mononuclear Cu(II) solutions in the presence of H2O2 or from (Cu2Nn)-N-I (n = 4 or 5) in the presence of O-2. This intermediate decays to generate OH radicals and ligand degradation products at room temperature. The lack of reactivity of the intermediate with a series of added electron donors suggests the intermediate discharges through a rate-limiting intramolecular electron transfer from the ligand to the metal peroxo center to produce an OH radical and a ligand-based radical. These results imply that DNA cleavage does not result from direct reaction with a metal-peroxo intermediate but instead arises from reaction with either OH radicals or ligand-based radicals.