A machine learning-based QSAR model reveals important molecular features for understanding the potential inhibition mechanism of ionic liquids to acetylcholinesterase

The broad application of ionic liquids (ILs) has been hindered by uncertainties surrounding their ecotoxicity. In this work, a Quantitative Structure-Activity Relationship (QSAR) model was devised to predict the inhibition of ILs towards the activity of AChE, employing both Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) machine learning approaches. Fourteen kings of essential molecular feature descriptors were screened from an initial roster of 244 descriptors through the application of a feature importance index and they showed a significant impact on the activity of AChE activity. The two models based solely on the 14 most critical molecular descriptors could maintain model's robustness and reliability. The correlation analysis between these 14 descriptors and the inhibition of AChE activity revealed the potential impact of the molecular characteristics on ILs toxicity. The results underscored the main influence of cations in ILs on the inhibitory activity towards the AChE enzyme. Specifically, cations exhibiting hydrophobicity properties were found to exert more potent inhibitory effects on the AChE enzyme. In addition, some other properties of the cations, such as the degree of branching, atomic weight and partial charge also modulated their inhibition potential. This study enhances the comprehension of the structure-activity relationship between ILs and AChE inhibition, providing a reference for designing safer and greener ILs.