The environmental fate of Novichok degradation products: application of in silico methods for the prediction of hydrolysis and biodegradation

Abstract

Novichoks are highly toxic organophosphorus nerve agents, and their environmental degradation products remain poorly understood. This study presents the first comprehensive in silico evaluation of hydrolysis and biodegradation potential for six identified Novichok degradation products using QSAR Toolbox, EPI Suite (Biowin), VEGA QSAR, Deep-PK, and ADMET Predictor. Hydrolysis modeling showed that MOPAA, EOPAA, MOPGA, and EOPGA degrade rapidly (half-life approximate to 2.6 days), while MPAA and MPGA hydrolyze more slowly (halflife approximate to 38.6 days). The predicted hydrolysis rate constants (Kn) ranged from 1.73/day to 7.53/day. Biodegradation predictions from Biowin models indicated moderate persistence, with ultimate degradation occurring within weeks to months and no compound classified as readily biodegradable under OECD 301C. VEGA, DeepPK, and ADMET Predictor confirmed these outcomes, with 76-95 % confidence. Anaerobic biodegradation potential was also moderate. Structure-activity relationship analysis revealed that smaller alkyl groups and phosphate residues promoted faster degradation, whereas phosphonates and branched structures conferred greater stability. These results indicate that some degradation products may persist in the environment and pose long-term risks. The study enhances understanding of Novichok byproducts' environmental fate and demonstrates the value of computational methods in toxicological risk assessment and chemical defense planning. Experimental validation is recommended to confirm the predictions.