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.

Cellular uptake and cytotoxicity of PEGylated MXene nanomaterials mediated by protein corona.

A stringent analysis of the biocompatibility of MXene is a necessary condition for assessing the biological risk of MXene. Owing to high surface free energy, MXene is capable of adsorbing a large amount of blood proteins to form MXene-protein corona complexes, however, a comprehensive understanding of the relationship between MXene and cellular physiological systems remains limited. Therefore, we investigated the cellular uptake and cytotoxicity effect of MXene Ti3C2Tx and PEGylation Ti3C2Tx mediated by human serum protein corona in THP-1 cells. It was found that PEGylation can alter the interaction between Ti3C2Tx and serum proteins, inducing a significant transformation in the fingerprint of the protein corona. Following protein corona formation, both Ti3C2Tx and PEGylated Ti3C2Tx predominantly accumulated at lysosomal sites within THP-1 cells. Further analysis revealed that clathrin-mediated endocytosis was the primary mechanism of Ti3C2Tx internalization by THP-1 cells. There was no significant effect on cell viability. However, we found that Ti3C2Tx plays a dual role as both a stimulus and scavenger of ROS within THP-1 cells, influenced by its PEGylation and the formation of a protein corona. This study provides important insights for biocompatibility evaluation and rational design of nanoproducts based on Ti3C2Tx in the future.