论文部分内容阅读
卤代醌是一类具有致癌活性的化合物.最近,它们作为氯代消毒副产物在饮用水中被检测到.有机氢过氧化物(ROOH)可通过自由基和酶促反应氧化多不饱和脂肪酸产生.先前的研究表明,ROOH可被过渡金属催化分解产生烷氧自由基,从而启动脂质过氧化或进一步分解生成α,β-不饱和醛.然而,目前还不清楚卤代醌能否不依赖过渡金属离子与ROOH以类似方式生成烷氧自由基.综合采用电子自旋共振-自旋捕获、高分辨液相色谱质谱联用及其他分析方法,结果发现,2,5-二氯-1,4-苯醌(DCBQ)可显著增强典型的有机氢过氧化物叔丁基过氧化氢(t-BuO OH)分解,以不依赖金属离子的方式生成叔丁氧自由基.在以上发现的基础上,我们检测和鉴定出一类新型的以碳为中心的醌酮自由基,其是我们之前推测的以氧为中心的醌氧自由基的自旋异构体.我们进而将研究扩展到更具生理意义的内源性脂质氢过氧化物13-过氧羟基-9,11-十八碳二烯酸(13-HPODE)中,发现DCBQ也可以显著增加13-HPODE的分解,产生脂质烷基自由基和具有基因毒性的4-羟基-2-壬烯醛.其他卤代醌也具有类似作用.研究表明,致癌性卤代醌能通过一类新型的不依赖于金属离子的亲核取代和均裂分解的机制,促进有机氢过氧化物分解并生成具有较强反应活性的烷氧、醌酮和脂质烷基自由基,及具有基因毒性的4-羟基-2-壬烯醛.以上研究结果可部分解释卤代醌及其酚类前驱物为何具有潜在的基因毒性和致癌性.
Haloquinones are a class of compounds that have oncogenic activity and have recently been detected in drinking water as a byproduct of chlorinated disinfection Organic hydroperoxides (ROOH) oxidize polyunsaturated fatty acids by free radical and enzymatic reactions Previous studies have shown that ROOH can be catalytically decomposed by transition metals to produce alkoxy radicals, thereby initiating lipid peroxidation or further decomposition to form alpha, beta-unsaturated aldehydes.However, it is unclear whether haloquinones are not Dependent on the transition metal ions and ROOH in a similar manner to generate alkoxy radicals.Combination of electron spin resonance - spin capture, high resolution liquid chromatography mass spectrometry and other analytical methods, found that 2,5-dichloro-1 , 4-benzoquinone (DCBQ) can significantly enhance the decomposition of t-butyl hydroperoxide (t-BuO OH), a typical organic hydroperoxide, Based on this, we detected and identified a new class of carbon-centered quinone-based free radicals, which are our previously hypothesized oxygen-centered spin-isomers of quinone oxygen free radicals. We then extend the study to More physiologically important endogenous lipids In peroxide 13-peroxyhydroxy-9,11-octadecadienoic acid (13-HPODE), DCBQ was also found to significantly increase the decomposition of 13-HPODE to produce lipid alkyl radicals and genotoxic 4-hydroxy-2-nonenal, and other haloquinones also have similar effects. Studies have shown that carcinogenic halogenated quinones can be promoted by a new class of mechanisms that are not dependent on the nucleophilic substitution and the cleavage of the metal ions Organic hydroperoxides decompose and produce highly reactive alkoxides, quinones and lipid alkyl radicals, and genotoxic 4-hydroxy-2-nonenal. The above results can be partially explained halogenated Why quinones and their phenolic precursors are potentially genotoxic and carcinogenic.