OH-Initiated Oxidation of N-Methyl-2-Pyrrolidone: Kinetics, Environmental Fate, and Implications for Biological Interactions.

Abstract

N-Methyl-2-pyrrolidone (NMP) is an industrial solvent of global concern due to its widespread use and potential toxicity; however, its atmospheric and aqueous transformation pathways remain poorly understood. In this study, we present the first comprehensive investigation of the reaction between NMP and OH radicals in both gas and aqueous phases over a wide range of conditions (200-2000 K, 0.76-760,000 Torr). High-level electronic structure calculations [CCSD(T)/cc-pVTZ//M06-2X/aug-cc-pVTZ] combined with stochastic RRKM-master equation modeling provided validated rate coefficients and product branching ratios, in good agreement with available experimental data. We demonstrate that NMP degrades rapidly in the atmosphere (lifetime ≈ approximately 12 hours) but persists in water (lifetime ranging from days to decades), highlighting contrasting environmental behaviors. Under ambient conditions, the dominant products are (2-oxopyrrolidin-1-yl)methyl (P4) in air and both P4 and 1-methyl-5-oxopyrrolidin-2-yl (P3) in water. These intermediates further transform into N-formylpyrrolidinone (FP) and N-methylsuccinimide (NMS), which we identify as long-range transported atmospheric products. Molecular docking and dynamics simulations reveal that FP and NMS, unlike NMP, exhibit stronger and more persistent interactions with bromodomain proteins (BRD4), suggesting unrecognized risks to developmental and reproductive health. By integrating quantum chemical kinetics, atmospheric fate modeling, and biological interaction analysis, this work provides new insights into the persistence and potential health impacts of NMP and its degradation products, informing risk assessment and regulatory considerations for this widely used solvent.