| Popis: |
Halogenated quinones are a class of carcinogenic intermediates and newly identified chlorination disinfection byproducts in drinking water. Organic hydroperoxides (ROOH) can be produced both by free radical reactions and enzymatic oxidation of polyunsaturated fatty acids. ROOH have been shown to undergo transition metal-catalyzed decomposition to alkoxyl radicals, which may initiate lipid peroxidation or further decompose to the reactive α, β-unsaturated aldehydes. However, it is not clear whether halogenated quinones react in a similar fashion with ROOH to produce alkoxyl radicals independent of transition metals. By complementary applications of ESR spin-trapping, HPLC/high resolution mass spectrometric and other analytical methods, we found that 2,5-dichloro- 1,4-benzoquinone (DCBQ) could markedly enhance the decomposition of a model ROOH tert -butylhydroperoxide, leading to the formation of t -butoxyl radicals independent of transition metals. Based on the above findings, we detected and identified, for the first time, an unprecedented carbon-centered quinone ketoxy radical, which is the spin isomer of the proposed oxygen-centered quinone enoxy radical. Then we extended our study to the more physiologically relevant endogenous lipid hydroperoxide 13-hydroperoxy-9,11-octadecadienoic acid, and found that DCBQ could also markedly enhance its decomposition to produce the reactive lipid alkyl radicals and the genotoxic 4-hydroxy-2-nonenal (HNE). Analogous results were observed with other halogenated quinones. In summary, these findings demonstrated that halogenated quinoid carcinogens can enhance the decomposition of ROOH and formation of reactive alkoxyl, quinone ketoxy, lipid alkyl radicals and genotoxic HNE via a novel metal-independent nucleophilic substitution coupled with homolytic decomposition mechanism, which may partly explain their potential genotoxicity and carcinogenicity. |
