Solubility Measurement, Correlation, and Computational Analysis of Methyl l‑Leucinate Hydrochloride in 12 Pure Solvents

The solubility of methyl l-leucinate hydrochloride in 12 pure solvents (methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, dimethyl carbonate, n-butanol, n-pentanol, acetonitrile, acetone, 2-butanone, n-hexane, and 1,4-dioxane) was determined by a gravimetric method under atmospheric pressure (101.2 kPa) and temperature ranging from 283.15 to 323.15 K. Furthermore, the solvent thermodynamic functions were derived by van’t Hoff model. The values of Δ sol G°, Δ sol H°, and Δ sol S° are positive in selected 12 solvents, indicating that the dissolution process of methyl l-leucinate hydrochloride is endothermic and driven by entropy. In addition, the contributions of multiple physicochemical properties of solvents to the solubility of methyl l-leucinate hydrochloride were evaluated. The solvents had a strong tendency to form a hydrogen bond with methyl l-leucinate hydrochloride. The solid phase of methyl l-leucinate hydrochloride in the investigated solvent systems was characterized by powder X-ray diffraction test. The increasing temperature exhibits a positive effect on the methyl l-leucinate hydrochloride solubility in pure solvents. The dissolution behavior was affected by the combined effects of four factors consisting of solvent polarity, formation of hydrogen bonds, solvent–solvent intermolecular interactions (represented by cohesive energy density), and molecular structures of solvents and the solute. Additionally, the Yaws model and the modified Apelblat model were utilized to fit the data of solubility, and the values of ARD as well as RMSD were calculated to evaluate the relative applicability of the two solubility models. The results show that the modified Apelblat model could give a better correlation result for the solubility data than the Yaws model. The results could facilitate the crystallization operation of methyl l-leucinate hydrochloride for purification and separation.