卤代乙酰胺类消毒副产物的形成路径及毒性作用的化学机制

Haloacetamides (HAcAms) are an emerging class of nitrogenous disinfection byproducts (DBPs). They are widely detected in chlorinated or chloraminated drinking water. HAcAms are much more toxic than the currently regulated DBPs, such as trihalomethanes (THMs) and haloacetic acids (HAAs), causing high health risk to human. So far the experimental results about the formation pathway of these chemicals are still controversial, and the chemical mechanism of toxicity is not clear either, calling for further research. Basing on the current studies, this project will employ 15NH2Cl isotopic tracer experiment and quantum chemical computation method to identify the formation pathway as well as the nitrogen source of HAcAms in chloramination, and clarify the chemical mechanism of the formation reaction; furthermore, use chemoassay and quantum mechanics/molecular mechanics (QM/MM) hybrid approach to investigate the interaction of typical HAcAms with glutathione (GSH) under the catalysis of glutathione transferase, and reveal the molecular mechanism of their toxicity; finally to develop virtual screening models of genotoxicity and cytotoxicity for these chemicals basing on the mechanism analysis. The results of this project will give us scientific guidance for optimizing disinfection processes and pollution control of HAcAms, and also provide basic data for ecological risk assessment of these chemicals.

卤代乙酰胺（HAcAms）是一类新兴含氮消毒副产物，在氯或氯胺消毒的饮用水中广泛检出。HAcAms的毒性远高于三卤甲烷和卤乙酸等常规消毒副产物，带来巨大的健康风险。但迄今为止，该类物质的形成机理还存在争议，毒性作用的化学机制也不清楚，是急需解决的重要科学问题。鉴于此，本项目拟使用15NH2Cl同位素示踪实验和量子化学计算方法阐明HAcAms在氯胺消毒过程中的形成路径及氮元素来源，构建完整的生成反应的化学机理；并使用chemoassay实验和量子力学与分子力学耦合方法（QM/MM）揭示代表性HAcAms在谷胱甘肽转移酶的催化作用下与谷胱甘肽（GSH）的相互作用，揭示HAcAms毒性作用的分子机制；在此基础上构建基于机理的基因毒性和细胞毒性的虚拟筛选模型。本项目的研究结果将会为优化消毒工艺和HAcAms的污染控制提供科学指导，并为该类化合物的生态风险评价提供基础数据。

卤代乙酰胺（HAcAms）是一类新兴含氮消毒副产物，在氯或氯胺消毒的饮用水中广泛检出。HAcAms的毒性远高于三卤甲烷和卤乙酸等常规消毒副产物，带来巨大的健康风险。但迄今为止该类物质的形成机理还存在争议，毒性作用的化学机制也不清楚，是急需解决的重要科学问题。鉴于此，本项目使用15NH2Cl同位素示踪实验和量子化学计算方法阐明了天冬氨酸等代表性氨基酸在氯胺消毒过程中形成HAcAms的路径以及氮元素的来源，构建了完整的生成反应的化学机理；使用chemoassay实验和计算模拟研究了9种HAcAms与GSH反应的产物和动力学特征，鉴定了中间产物，阐明了HAcAms与GHS相互作用而导致毒性的作用机制；基于分子模拟揭示的作用机制，选取具有明确物理化学意义的分子结构参数表征相互作用，使用多元线性回归分析，构建了基于机理的遗传毒性和细胞毒性的虚拟筛选模型。本项目的研究结果将会为优化消毒工艺和污染控制提供科学指导，并为该类化合物的健康风险评价提供基础数据。