Conformational, vibrational and DFT studies of a newly synthesized arylpiperazine-based drug and evaluation of its reactivity towards the human GABA receptor

This study reports a computational assessment of important biochemical properties and vibrational assignments for the synthesized 1-(4-(3-methoxy-4-nitrophenyl)piperazin-1-yl)ethanone (MNPE). MNPE is related to the commonly used arylpiperazine-based drugs that exhibit a wide range of pharmacological activities. The characterization of MNPE is based on the readily sighted 1363 cm−1 infrared band (associated with piperazine ring stretching), 1308 cm−1 Raman line (associated with the phenyl ring breathing), 1242 cm−1 Raman line and 1092 cm−1 infrared band (both associated with CN stretching) as key modes in its vibrational spectra. First principle calculations revealed that MNPE could exist in sixteen different plausible conformations, which were used as basis to understand the possible molecular docking mechanism of the molecule as an agonist in the human GABAA receptor. The best binding scenarios showed the presence of intramolecular hydrogen bonding in MNPE and was comparable with the most stable configuration. It was further evaluated for its reactivity properties by utilizing the concepts of Average Local Ionization Energies (ALIE) and Fukui functions. The autoxidation and hydrolysis degradation likelihood of MNPE estimated from the computed bond dissociation energies and radial distribution functions predicted that MNPE is to be readily biodegradable in aqueous solutions.