Reactions of oxazepam with two typical water treatment oxidants in aqueous solutions: Results based on density functional theory.

Pharmaceutical residues in the environment and their transformation mechanism are important challenges in environmental pollution research. The present study investigated the transformation mechanisms and reaction kinetics of oxazepam, a representative of benzodiazepine pharmaceutical, with two typical water treatment oxidants including HOCl and ∙OH in aqueous solution through theoretical calculations and experimental verification. The results showed that oxazepam is a chiral molecule with two enantiomers in equal proportions. The reactions between oxazepam and HOCl can be classified into Cl-substitution, OH-substitution, and bond-fission reactions. Among these substitutions, the Cl-substitution reaction at the N23 site was most likely to occur. The bond-fission reactions were predominated by the cleavage of the C27-N29 bond, which could lead to further bond cleavage reactions. The reactions between oxazepam and ∙OH involved the addition and H-abstraction pathways, with the addition reactions at the C5, C13, and C17 sites being the top three major reaction pathways. The kinetics rate constants obtained by the density functional theory (DFT) calculation were 0.16 and 1.78 × 1011 M-1 s-1 for the reactions of oxazepam with HOCl (kHOCl, M-1 s-1) and ∙OH (k·OH, M-1 s-1) respectively, which are basically consistent with the experimental results. This comprehensive understanding of the reaction mechanisms of oxazepam with HOCl and ∙OH based on quantum chemical calculations is crucial for exploring the chlorination and advanced oxidation of benzodiazepine pharmaceuticals.