Atom-Driven and Knowledge-Based Hydrolysis Metabolite Assessment for Environmental Organic Chemicals

The metabolism of environmental organic chemicals often relies on the catalytic action of specific enzymes at the nanoscale, which is critical for assessing their environmental impact, safety, and efficacy. Hydrolysis is one of the primary metabolic and degradation reaction pathways. Traditionally, hydrolysis product identification has relied on experimental methods that are both time-consuming and costly. In this study, machine-learning-based atomic-driven models were constructed to predict the hydrolysis reactions for environmental organic chemicals, including four main hydrolysis sites: N-Hydrolysis, O-Hydrolysis, C-Hydrolysis, and Global-Hydrolysis. These machine learning models were further integrated with a knowledge-based expert system to create a global hydrolysis model, which utilizes predicted hydrolysis site probabilities to prioritize potential hydrolysis products. For an external test set of 75 chemicals, the global hydrolysis site prediction model achieved an accuracy of 93%. Additionally, among 99 experimental hydrolysis products, our model successfully predicted 90, with a hit rate of 90%. This model offers significant potential for identifying hydrolysis metabolites in environmental organic chemicals.