Atomic oxygen-induced oxidative degradation of carbamazepine: Mechanistic insights from reactive molecular dynamics

Abstract Carbamazepine (CBZ) is a persistent pharmaceutical contaminant that is poorly removed by conventional wastewater treatment processes. Although non-thermal plasma can promote efficient CBZ degradation, the elementary molecular mechanisms governing its initial oxidative transformation remain incompletely understood. In this work, atomic-oxygen-induced CBZ oxidation was investigated using DFTB-based reactive molecular dynamics (RMD) simulations combined with stationary thermochemical and reaction-path analyses. One hundred independent trajectories revealed 23 distinct reaction subtypes, comprising hydroxylation (72%), epoxide-type oxygen addition (15%), ring expansion (8%), peroxide/hydroperoxide formation (4%), and CO2-releasing fragmentation (1%). Representative R1-R5 structures were independently optimized and characterized by vibrational analysis and gas-phase RRHO thermochemistry, showing that all five overall transformations are exergonic under the adopted reference convention. CI-NEB calculations identified electronic barriers of 47.3 kJ mol-1 for the R3 epoxide-like intermediate-to-ring-expanded product step and 22.6 kJ mol-1 for the R4 peroxy-to-hydroperoxide hydrogen-transfer step. No unique overall activation barrier was assigned to R1, R2, or the strongly dissociative R5 pathway. Analysis of the trajectory ensemble showed a mean reaction-onset time of 6.49 ± 7.96 ps, demonstrating rapid but heterogeneous early-stage reactivity under the simulated conditions. Overall, the results reveal strongly site-selective and mechanistically diverse atomic-O-induced CBZ oxidation and provide an atomistic framework for interpreting early-stage plasma-assisted degradation chemistry.

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