Fenton-like copper redox chemistry revisited: Hydrogen peroxide and superoxide mediation of copper-catalyzed oxidant production

Abstract

Copper toxicity has been attributed to its potential as a catalyst for oxidative damage to tissues through redox cycling between Cu(I) and Cu(II), particularly in the presence of H2O2, a by-product of oxygen metabolism. In this study, the reactions of nanomolar concentrations of Cu(I) and Cu(II) with H2O2 have been investigated in 2.0mM NaHCO3 and 0.7M NaCl at pH 8.0. Measurements of both the formation of the hydroxylated phthalhydrazide chemiluminescent product and the degradation of formate in the absence and presence of compounds with well-known reactivity with HO indicated that the reaction between Cu(I) and H2O2 did not result in the production of HO but involved the formation of a higher oxidation state of copper, Cu(III). The Cu(III) so-formed reacts with the substrates that were present at much slower rates compared to those of HO. The rate of formation of HO from the dissociation of Cu(III) was extremely slow at pH 8.0 with the result that HO is not an important oxidant in this system. The rapid rate of reaction of Cu(III) with Cu(I) contributes significantly to the redox cycle of copper and the associated oxidizing capacity of the Cu(I)/Cu(II)/H2O2/O2 system with exogenous input of H2O2 and O2- exhibiting the ability to mediate ongoing copper-catalyzed production of the powerful oxidant, Cu(III).