Fmoc- l -Isoleucine Solubility in 12 Monosolvents: Solvent Effects, Molecular Simulation, Thermodynamic Modeling, and Comparison of Structurally Similar Substances

At present, there is a lack of comprehensive solubility data and thermodynamic analysis, which limits the optimization of crystallization and purification process of Fmoc-l-isoleucine. In this study, the solubility of Fmoc-l-isoleucine in 12 pure solvents in the temperature range of 283.15–325.15 K was measured, and it was found that it was positively correlated with temperature. The solubility in acetone is the highest (8.604 × 10–2 mol/mol at 323.15 K), and the solubility in water is the lowest. The thermodynamic correlation of the four semiempirical models shows that the Yaws model has the best fitting degree, and the average relative deviation (100ARD) is only 1.31%. Molecular simulations (HS, MEPS, and IRI) quantitatively confirmed that the hydrogen bonding between the carboxyl/ester group of the solute and the active site of the solvent is the main driving force of the dissolution process. This study could provide a key thermodynamic basis for industrial process design.