An Jibin, Li Guiying, An Taicheng, Nie Xiangping
State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, People's Republic of China.
University of Chinese Academy of Sciences, Beijing, People's Republic of China.
Environ Toxicol Chem. 2016 Mar;35(3):584-92. doi: 10.1002/etc.3238. Epub 2016 Feb 9.
Acyclovir and penciclovir, 2 antiviral drugs, are increasingly detected in aquatic environments. The present study explores the natural photochemical transformation mechanisms and fate of these drugs, examining direct and indirect photochemical transformation under simulated sunlight irradiation. The 2 antiviral drugs are photostable under certain conditions but significantly degrade in the presence of chromophoric dissolved organic matter (DOM). The degradation rate associated with the drugs' indirect photochemical transformation scaled with chromophoric DOM concentration. Quenchers and sensitizers were used to identify indirect photochemical transformation mechanism. Results suggested that both pharmaceuticals could be transformed by reacting with (1)O2, (•)OH, and excited chromophoric DOM. The (1)O2 played an important role in indirect photochemical transformation. Furthermore, the reaction kinetics between their substructural molecules, guanine, isocytosine, and imidazole, with different reactive oxygen species were evaluated to determine which substrate functionalities were most susceptible to singlet oxygenation. Imidazole was identified as the reaction site for (1)O2, and preliminary (1)O2 oxidation mechanisms were further evaluated based on liquid chromatographic-tandem mass spectrometric results. Finally, aquatic ecotoxicity assessment of phototransformed solutions revealed that the degradation of acyclovir and penciclovir may not ultimately diminish environmental risk because of either formation of more toxic intermediates than parent pharmaceuticals or some synergistic effects existing between the intermediates.
阿昔洛韦和喷昔洛韦这两种抗病毒药物在水生环境中越来越多地被检测到。本研究探讨了这些药物的自然光化学转化机制和归宿,研究了模拟阳光照射下的直接和间接光化学转化。这两种抗病毒药物在某些条件下是光稳定的,但在存在发色溶解有机物(DOM)的情况下会显著降解。与药物间接光化学转化相关的降解速率与发色DOM浓度成比例。使用猝灭剂和敏化剂来确定间接光化学转化机制。结果表明,这两种药物都可以通过与单线态氧(¹O₂)、羟基自由基(•OH)和激发态发色DOM反应而发生转化。¹O₂在间接光化学转化中起重要作用。此外,评估了它们的亚结构分子鸟嘌呤、异胞嘧啶和咪唑与不同活性氧物种之间的反应动力学,以确定哪些底物官能团最易受到单线态氧氧化作用的影响。咪唑被确定为¹O₂的反应位点,并根据液相色谱 - 串联质谱结果进一步评估了初步的¹O₂氧化机制。最后,对光转化溶液的水生生态毒性评估表明,阿昔洛韦和喷昔洛韦的降解可能最终不会降低环境风险,因为形成的毒性更强的中间体比母体药物更多,或者中间体之间存在一些协同效应。