Effect of Temperature on l-Pyroglutamic Acid Solubility in Organic Solvents: Experimental, Molecular Dynamics Simulation, and Thermodynamic Analysis

The solubility of l-PGA in 12 monosolvents was determined by the gravimetric method at temperatures ranging from 283.15 to 328.15 K under atmospheric pressure (101.2 kPa). The solubility values in all of the solvents are positively correlated with the temperature. At 298.15 K, the order of l-PGA solubility was methanol, ethanol, isopropanol, n-propanol, isobutanol, n-butanol, 1,4-dioxane, acetone, 2-butanone, acetonitrile, methyl acetate, and ethyl acetate. The largest solubility is in methanol (5.895 × 10–1 at 323.15 K), and the smallest value is observed in ethyl acetate (0.671 × 10–3 at 283.15 K). Molecular modeling including the Hirshfeld surface (HS) analysis and molecular electrostatic potential surface (MEPS) was employed to understand internal interactions. Radial distribution function (RDF) analyses indicated a strong correlation between the rank of solute–solvent interactions and the solubility order of l-PGA in the solvents. Additionally, the solubility data were fitted using the modified Apelblat equation, λh equation, NRTL model, and Margules model. The results indicated that the modified Apelblat equation was the most suitable for correlating l-PGA's solubility. In addition, the NRTL model, known for its high accuracy, was employed to analyze the dissolution thermodynamic characteristics of l-PGA in the selected solvents. The analysis revealed that the dissolution and mixing processes were both spontaneous and entropy-driven.