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

The hydroxyl radical (˙OH) has been considered to be one of the most reactive oxygen species that are produced in biological systems. Frequently, ˙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 ˙OH could be produced by H2O2 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 ˙OH production. Metal-independent production of ˙OH could also be observed with other halogenated quinones and H2O2. Based on these data, we propose that ˙OH production by TCBQ and H2O2 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 ˙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.