Metal-mediated activation of hydrogen peroxide and dioxygen by copper complexes in aqueous solution

Abstract

Dinuclear Cu(II) complexes [CuII2(Nn)Y2]2+ (n=4, Y = ClO4-; n = 5, Y = NO3-) (Nn = -(CH2)n- (n = 3-5) linked bis[2-(2-pyridyl)ethyl]amine) were recently found to cleave DNA specifically in the presence of a reducing thiol and O2 or in the presence of H2O2 alone. However, a closely-related [CuII2(N3)Y]2+ (n = 3, Y = ClO4-) and their mononuclear analogue, [CuII(MePY2)(CH3CN)(ClO4-)]1+ (MePY2 = bis[2-(2-pyridyl)ethyl]methylamine), exhibited no selective cleavage under either condition. To clarify the nature of the intermediate(s) involved in cleavage, the reactivity of these copper complexes was investigated in aqueous solutions.

Spectroscopic studies indicated that an intermediate with an absorption band at 376 nm was generated either from [CuII2(N4,5)Y2]2+ in the presence of H2O2 or from its corresponding Cu(I) complexes in the presence of O2. Formation of this intermediate was pH, phosphate and temperature dependent. This intermediate decayed exponentially at room temperature with concomitant degradation of ligand. Its decay was temperature dependent, but was independent of H2O2 concentration and a series of added electron donors. This intermediate was not formed with [CuII2(N3)Y2]2+ and its corresponding

Cu(I) complex, and only formed with mononuclear Cu(II) complex under high concentrations of H2O2 and the copper complex. A highly sensitive method was employed to test for the formation of reactive species produced during the intermediate decay. Methyl radical was detected in the presence of either DMSO or methane. The relative yield of methyl radical from DMSO and methane confirmed unequivocally the involvement of hydroxyl radical. The stoichiometry of hydroxyl radical production with respect to the concentration of the intermediate was 1:1 for both [CuII2(N4,5)Y2]2+ and mononuclear Cu(II) complex.

Our results suggested that this intermediate is most likely a Cu(II)(hydro)peroxo complex, of as yet, unknown structure, which decays through a rate-limiting intramolecular electron transfer from the ligand to the metal peroxo center thereby producing a hydroxyl radical and a ligand-based radical. The results also imply that DNA cleavage does not result from direct reaction with a metal-peroxo intermediate, but instead arises from reaction with either the hydroxyl radical or ligand-based radicals.