Systematic thermodynamic study of clorsulon dissolved in ten organic solvents: Mechanism evaluation by modeling and molecular dynamic simulation

Abstract The thermodynamic properties of clorsulon were systematically studied through solubility measurement, calculation with modeling and molecular dynamics simulations. The equilibrium solubility of clorsulon in ten organic solvents (methanol, ethanol, n-propanol, n-butanol, iso-butanol, ethylene glycol, dichloromethane, acetonitrile, methyl acetate, ethyl acetate) was measured by employing the dynamic method at the temperature from 293.15 to 333.15 K at 0.1 MPa. Especially, the solubility of clorsulon in ethylene glycol shows extreme sensitivity to temperature due to the dihydroxy structure, which was revealed via analysis of hydrogen bond formation between solvent molecules and solute molecules. Subsequently, the experimental solubility values were correlated well with four thermodynamic models, including the modified Apelblat model, λh equation, van't Hoff equation, and Wilson model, among which the modified Apelblat model gives the best fit. The miscibility of clorsulon-solvents and the solvent effect were explored by analyzing the polarity of solvents, Hansen solubility parameters and KAT-LSER model. The derived thermodynamic parameters showed an endothermic, entropy-driven, and non-spontaneous dissolution process of clorsulon via van't Hoff equation. Through molecular dynamic simulation based on the mechanism of intermolecular interaction, the optimized unit cell structure of clorsulon was established, and the solvation free energies were accurately calculated. The results show that the absolute value of calculated solvation free energy was positively correlated with solubility.