Solubility of L-Isoleucine in 12 Organic Solvents: Solvent Effects, Molecular Simulations, and Model Correlations

The solubility of L-isoleucine (I form) in 12 neat solvents, including alcohols, was measured using the static gravimetric method from 283.15 to 323.15 K. The solubility order of L-isoleucine was ranked as ethyl acetate > methyl acetate > isopropanol > isobutanol > 1,4-dioxane > methanol > 2-butanone > ethanol > n-propanol > acetonitrile > n-butanol > acetone. The maximum solubility was found in methyl acetate at 323.15 K (5.451 × 10–3), and the minimum was found in acetone at 283.15 K (0.121 × 10–4). Hirshfeld surface (HS) analysis and molecular electrostatic potential surfaces (MEPs) were used to investigate the solubility of L-isoleucine in 12 monosolvents. IRI and interaction energy indicated that the solubility of L-isoleucine has a negative trend with the increase in the carbon chain length of the solvents. This research will provide basic data for the production of L-isoleucine in the pharmaceutical industry.