A Novel Mechanism for Metal-independent Hydroxyl Radical Production by Hydrogen Peroxide and Halogenated Quinones

The hydroxyl radical ((center dot)OH) has been considered to be one of the most reactive oxygen species that are produced in biological systems. Frequently, (center dot)OH formation is ascribed to the transition metal-catalyzed Fenton reaction. During the study of the molecular mechanism for the genotoxicity of the wood preservative pentachlorophenol (PCP), we found that (center dot)OH could be produced by H(2)O(2) and PCP metabolite tetrachloro-1,4-benzoquinone (TCBQ) independent of transition metal ions. Further studies showed that TCBQ, but not its corresponding semiquinone radical, is essential for (center dot)OH production. Metal-independent production of (center dot)OH could also be observed with other halogenated quinones and H(2)O(2). Based on these data, we propose that (center dot)OH production by TCBQ and H(2)O(2) is not through a semiquinone-dependent organic Fenton reaction, but rather through a novel nucleophilic substitution and homolytical decomposition mechanism. This represents a novel mechanism for (center dot)OH production not requiring the catalysis of redox-active transition metal ions, and may partly explain the potential carcinogenicity of the widely used biocides such as PCP and other polyhalogenated aromatic compounds.