Investigating the Dissociation Mechanisms of Nitroimidazole Ions Via Direct Dynamics Simulations

ABSTRACT Nitroimidazoles represent an important class of compounds due to their distinct biological activities and potential therapeutic applications. Among them, 2‐nitroimidazole (2‐NI) is known for its radiosensitizing effects in radiation therapy, while 4‐nitroimidazole (4‐NI) exhibits notable antimicrobial activity. Despite their significance, the fragmentation chemistry of nitroimidazole ions remains poorly understood. In this study, the fragmentation behavior of protonated and deprotonated 2‐NI and 4‐NI ions was investigated using electronic structure calculations combined with direct dynamics simulations under collision‐induced dissociation (CID) conditions. All dynamics simulations were performed at the density functional M06‐2X/6‐31+G* level of theory. Ion activation was modeled through collisions with an Ar atom, and the resulting fragment ions were thoroughly analyzed. The simulations revealed a wide variety of dissociation pathways and product ions. Notably, the CID trajectories were dominated by a direct, non‐statistical shattering mechanism, leading to deviations from experimental fragmentation patterns. To account for these differences, statistical unimolecular dissociation simulations were also conducted at fixed total energies. The resulting product branching ratios showed improved agreement with experimental observations, offering deeper insight into the underlying dissociation mechanisms.