Abstract

The increasing presence of chemotherapeutic drug residues in aquatic environments poses serious challenges due to their poor biodegradability and toxicity. Methotrexate (MTX), a widely used anti-cancer drug, is largely excreted from the body unmetabolized and ends up in wastewater, often untreated by traditional treatment methods. Advanced oxidation processes have been investigated for MTX removal, with non-thermal plasma (NTP) emerging as a promising, sustainable alternative. Experimental studies using a pencil plasma jet have demonstrated substantial degradation and mineralization of MTX, yet the molecular-level pathways remain insufficiently understood. In this study, we employ reactive molecular dynamics simulations to examine oxidative degradation of MTX by NTP-generated oxygen atoms, a key reactive oxygen species. The simulations reveal hydroxylation, ring opening, fragmentation, and CO<inf>2</inf> release as dominant mechanisms, showing how oxygen radicals progressively destabilize and decompose MTX. These findings are qualitatively consistent with experimental observations and highlight how integrating computational and experimental approaches deepens mechanistic understanding of plasma-induced pharmaceutical degradation, supporting the development of optimized wastewater treatment strategies.