De novo prediction strategy based on multi-step synergy of computation and experimentation

Sertraline, a wide-used antidepressant in medicine, is often detected in environmental water samples and has become a new pollutant of considerable concern because of its accumulation in the environment due to its leakage during the production process and incomplete metabolic excretion by organisms. However, there is a lack of research on the environmental health effects of sertraline. Dr. Cheng Shiyang, a young faculty member at School of Environment and Spatial Informatics, used de novo prediction strategy based on multi-step synergy of computation and experimentation to conduct quantum chemical computational prediction of reactivity sequence evolution of amino functional groups of sertraline and confirmed the presence of the suspected mutagenic metabolite sertraline oxaziridine by high-resolution mass spectrometry in the incubation of human liver microsomes and exposure experiments of zebrafish embryos, and detected the sertraline oxaziridine DNA addition product in vivo experiments in mice. And based on the Bell-Evans-Polanyi principle, it was revealed that the desaturation pathway is widely present in aliphatic amine micropollutants that use sertraline as a model substrate, such as the pesticide atrazine and the tire antioxidant 6PPD. The ab initio prediction method developed in this work is expected to support the scientific assessment of the environmental health risk of new pollutants during the whole life cycle. The results of this work were summarized in a paper titled “Insight into chemically reactive metabolites of aliphatic amine pollutants: A de novo prediction strategy and case study of sertraline”, which has been published online in Environmental International, the top academic journal in the field of environmental health (IF=11.8, Chinese Academy of Sciences, Region I, Top).

Jin Lingmin, a PhD student of Class of 2022 of CUMT, is the first author of the paper, and Dr. Cheng Shiyang is the co-first author and co-corresponding author of the paper, and the main participants include Prof. Ji Li of School of Environment and Spatial Informatics of CUMT, and Prof. Rudi van Eldik of University of Erlangen-Nuremberg, Germany. This research was supported by the National Natural Science Foundation of China Youth Fund (22106168), General Program Fund (22176211), and the Inter-Organizational Cooperation Project between the National Natural Science Foundation of China and the Polish National Funding Council (42361134581).

It is reported that School of Environment and Spatial Informatics has set up the environmental health research group since 2021, and through the initiatives of basing on the international academic frontiers, carrying out scientific research for the major national needs and strengthening the cultivation of young scientific and technological talents in environmental health, it has published a number of high-level papers consecutively in the top academic journals in the field of international environmental health, such as Environmental Science & Technology, and Environmental International. The members of the research group have been selected as members of Expert Committee on Environmental Risk Assessment of Chemical Substances of the Ministry of Ecology and Environment. At present, the research group has accumulated a large academic influence in the field of new pollutant management at home and abroad.