Formation and Cytotoxicity of Halophenylacetamides: A New Group of Nitrogenous Aromatic Halogenated Disinfection Byproducts in Drinking Water

Nitrogenous aromatic halogenated disinfection byproducts (DBPs) in drinking water have received considerable attention recently owing to their relatively high toxicity. In this study, a new group of nitrogenous aromatic halogenated disinfection byproducts, halophenylacetamides (HPAcAms), were successfully identified for the first time in both the laboratory experiments and realistic drinking water. The formation mechanism of HPAcAms during chlorination of phenylalanine in the presence of Br- and I-, occurrence frequencies, and concentrations in authentic drinking water were investigated, and a quantitative structure-activity relationship (QSAR) model was developed based on the acquired cytotoxicity data. The results demonstrated that HPAcAms could be formed from phenylalanine in chlorination via electrophilic substitution, decarboxylation, hydrochloric acid elimination, and hydrolysis. The HPAcAm yields from phenylalanine were significantly affected by contact time, pH, chlorine dose, and temperature. Nine HPAcAms with concentrations in the range of 0.02-1.54 ng/L were detected in authentic drinking water samples. Most tested HPAcAms showed significantly higher cytotoxicity compared with dichloroacetamide, which is the most abundant aliphatic haloacetamide DBP. The QSAR model demonstrated that the cellular uptake efficiency and the polarized distributions of electrons of HPAcAms play essential roles in their cytotoxicity mechanisms.

Automated summary

This study successfully identified a new group of nitrogenous aromatic halogenated disinfection byproducts, halophenylacetamides (HPAcAms), in laboratory experiments and realistic drinking water for the first time. The study investigated the formation mechanism, occurrence frequencies, and concentrations of HPAcAms in authentic drinking water, and developed a quantitative structure-activity relationship (QSAR) model based on cytotoxicity data. The results showed that HPAcAms could form from phenylalanine during chlorination and their yields were influenced by various factors. Multiple HPAcAms were detected in authentic drinking water samples and showed higher cytotoxicity compared to the most abundant aliphatic haloacetamide DBP.