The role of non-covalent interactions in the solvation dynamics of metronidazole in water: A theoretical study

Metronidazole, the medicine with the brand name Flagyl, is used to treat the gastrointestinal infection and the activity against anaerobic bacteria like protozoa. The current work describes the interaction of metronidazole drug with water solvent needed for oral ingestion, which is the most common and convenient pathway for the administration of the drug in the body. Computational calculations are performed to optimize the metronidazole drug having solvent (water) at different positions. NBO and AIM calculations employed to determine the strength of intermolecular hydrogen bonding interactions between metronidazole and solvent (water). The second perturbation energy was calculated and the result was a maximum of 67 kJ mol-1 for O?H???O hydrogen bonding interaction. The solvation energy of the metronidazole drug, determined using the solvation model based on density (SMD) model, is found to be ?69.2 kJ mol-1. The bonding parameters of the solvated drug have been analysed through critical point calculations based on the atom-in-molecule (AIM) theory. Furthermore, an ab initio molecular dynamics (AIMD) study reveals that the lowest decomposition energies of metronidazole in the presence of water, considering all pores and different pores, are ?927.86 and ?699.003 a.u., respectively.