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首页> 外文期刊>Journal of mass spectrometry: JMS >Chlorine substitution promotes phenyl radical loss from C8-phenoxy-2 '-deoxyguanosine adducts: implications for biomarker identification from chlorophenol exposure
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Chlorine substitution promotes phenyl radical loss from C8-phenoxy-2 '-deoxyguanosine adducts: implications for biomarker identification from chlorophenol exposure

机译：氯取代促进C8-苯氧基-2'-脱氧鸟苷加合物的苯基自由基损失：氯酚暴露对生物标志物鉴定的意义

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摘要

Chlorophenols are persistent organic pollutants, which undergo peroxidase-mediated oxidation to afford phenolic radical intermediates that react at the C8-site of 2-deoxyguanosine (dG) to generate oxygen-linked C8-dG adducts. Such adducts are expected to contribute to chlorophenol toxicity and serve as effective dose biomarkers for chlorophenol exposure. Electrospray ionization mass spectrometry (ESI-MS) was employed to study collision induced dissociation (CID) for a family of such phenolic O-linked C8-dG adducts. Fragmentation of the deprotonated nucleosides demonstrates that an unexpected homolytic cleavage of the ether linkage to release phenyl radicals and a nucleoside distonic ion with m/z 281 competes effectively with commonly observed breakage of the glycosidic bond to release the deprotonated nucleobase. Increased chlorination of the phenyl ring enhances phenyl radical loss. Density functional theory calculations demonstrate that Cl-substitution decreases phenyl radical stability but promotes homolytic breakage of the C8-phenyl bond in the C8-dG adduct. The calculations suggest that phenyl radical loss is driven by destabilizing steric (electrostatic repulsion) interactions between the ether oxygen atom and ortho-chlorines on the phenyl ring. The distonic ion at m/z 281 represents a unique dissociation product for deprotonated O-linked C8-dG adducts and may prove useful for selective detection of relevant biomarkers for chlorophenol exposure by tandem mass spectrometry using selective reaction monitoring. Copyright (c) 2015 John Wiley & Sons, Ltd.
机译：氯酚是持久性有机污染物，它们会受到过氧化物酶介导的氧化作用，以提供酚类自由基中间体，这些中间体在2-脱氧鸟苷（dG）的C8位反应，生成氧连接的C8-dG加合物。预期此类加合物会导致氯酚毒性，并用作氯酚暴露的有效剂量生物标志物。电喷雾电离质谱法（ESI-MS）用于研究这类酚O-连接的C8-dG加合物的碰撞诱导解离（CID）。去质子化的核苷的碎裂表明，醚键的意外均质裂解以释放苯基和具有m / z 281的核苷二糖离子与通常观察到的糖苷键断裂有效竞争，从而释放出去质子化的核碱基。苯环氯化的增加会增加苯基的损失。密度泛函理论计算表明，Cl取代可降低苯基自由基的稳定性，但会促进C8-dG加合物中C8-苯基键的均质断裂。这些计算表明，苯基自由基的损失是由醚氧原子与苯环上邻氯之间的空间（静电排斥）相互作用失稳驱动的。 m / z 281处的二阶离子代表用于去质子化的O-连接的C8-dG加合物的独特解离产物，并可能证明可通过串联质谱使用选择性反应监测对氯酚暴露的相关生物标记物进行选择性检测。版权所有（c）2015 John Wiley＆Sons，Ltd.

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