Rashid_2023_Toxicol.Rep_10_27

Although the hydrolysis mechanism of the nerve agents, which is the main decontamination pathway, has been studied experimentally and theoretically, the reliable theoretical prediction method for the hydrolysis rate is not studied yet. Furthermore, after the CWC (Chemical Warfare Agent) list is updated, Novichok candidate structures can be more than 10,000 structures, for which it is not possible to perform the experiment for all of them for synthesizing and getting the hydrolysis rate. Therefore, developing a reliable theoretical method for hydrolysis rate prediction is crucial to prepare for the forthcoming usage of new types of nerve agents. Herein, by using DFT (Density Functional Theory), we successfully developed a new method of predicting the hydrolysis rate on nerve agents by investigating the electrophilicity index (EI) of the various A-, V-, and G-series nerve agents and found a suitable correlation with the experimental hydrolysis rate. Among the several DFT methods, wb97xD predicts the EI with the lowest % deviation of the studied nerve agents. Our results show that EI can be a good indicator to predict the hydrolysis rate of the anticipated nerve agents. Based on the result, we predicted the hydrolysis rate on another type of Novichok candidates, which could be the firm basis for developing a decontaminant and antidote with much fewer experimental efforts on new types of nerve agents.