Solid-liquid equilibrium behavior, thermodynamic analysis and molecular simulation of dimetridazole in twelve organic solvents

The molecular structure properties of Dimetridazole (DMZ) were investigated both in the solid and liquid phases. Molecular electrostatic potential surface and Hirshfeld surface analysis were respectively used to investigate the overall charge distribution and the intermolecular interaction of DMZ. In addition, the solubility of DMZ in twelve mono organic solvents, including methanol, ethanol, 1-propanol, 2-propanol, 2-butanol, 1-pentanol, acetone, 2-butanone, cyclohexanone, ethyl acetate, propyl acetate and isopropyl acetate, was investigated using the gravimetric method at temperature ranging from 283.15 K to 323.15 Kunder atmospheric pressure. The solubility of DMZ in all solvents were monotonously rising with increasing temperature as expected. Furthermore, the Apelblat equation, lambda h equation, van't Hoff equation and NRTL model were selected to check and correlate the experimental solubility data, respectively, in which the Apelblat equation showed the best fitting performance. Besides, the solvent properties including polarity, hydrogen bond and solubility parameter (cohesive energy density) were performed to analyze the solid-liquid equilibrium behavior of DMZ. Meanwhile, the standard thermodynamic properties of mixing (Delta(mix)G, Delta H-mix and Delta S-mix) were calculated, and the results indicated that the mixing process of DMZ in different solvents is spontaneous, endothermic and entropy-driving. To further confirm this conclusion, the molecular simulations involving solvation free energy and radial distribution function analysis were employed to successfully analyze the interactions between solute-solvent and solvent-solvent. (C) 2021 Elsevier B.V. All rights reserved.