Solvent Effects on Medicinal Structure and 15N NMR Shielding of Medazepam

The Density Functional Theory (DFT) and Tomasi’s Polarized Continuum Model (PCM) were used to investigate the effects of solvent dielectric constant on the structural stability and 15N NMR tensors of Medazepam (MDZ) drug. The results revealed that the structural stability of MDZ in polar protic solvents was higher than that in the polar aprotic and non-polar solvents; and its value depended on the solvent dielectric constant and its structure. so that in most cases, relative stability increased by increasing the solvent dielectric constant and the most stable structures were observed in water media at DFT level and in methanol at MP2 level. In this regard, natural bond orbital (NBO) interpretation showed that the tetravalent N1 nucleus of diazepine ring in the MDZ structure had the highest value of negative charge and the resonance energy related to LP (1)  N1 → σ* and π* delocalizations among heteroatoms of MDZ structure in the tested solvents. The findings reported that with an increase in the solvent dielectric constant, the resonance energy related to LP (1) N1 → σ* and π* delocalizations increased and the highest value of resonance energy was observed in water media. Furthermore, NMR results represented that the N1 nucleus had a higher value of chemical shielding than the trivalent N4 nucleus in all of the tested media. However, it may be concluded that by increasing the accumulation of negative charge and lone pair electrons participation of nitrogen nuclei in the resonance delocalizations, isotropic chemical shielding around them increase.