Solubility of Fmoc-l-glutamic Acid in 14 Monosolvents: Solvent Effects Analysis, Molecular Simulation, Model Correlation, and Comparison with Structurally Similar Substances

Fmoc-l-glutamic acid, as a derivative of glutamic acid, exhibits prominent applicability in biochemical science and medicinal chemistry. In order to improve the relevant database, this study used the static gravimetric method to determine the solubility of Fmoc-l-glutamic acid in 14 single solvents (including methanol, ethanol, n-propanol, n-butanol, isopropanol, n-pentanol, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, dimethyl carbonate, acetone, 2-butanone, and acetonitrile) within the temperature range of 283.15–323.15 K. The experimental data reveal that the dissolution capability of Fmoc-l-glutamic acid is enhanced as the temperature rises in all investigated solvent systems. By combining molecular electrostatic potential surface (MEPS) analysis and interaction energy calculation, this work elucidated the intermolecular interaction mechanism of Fmoc-l-glutamic acid with solvents. Research has confirmed that solvent polarity (E_T(30)), hydrogen bonding, and cohesive energy density mainly affect the solvation behavior. In addition, the solubility of Fmoc-l-glutamic acid in 14 single solvents was evaluated using Hansen solubility parameters (HSPs) and interaction region indicator (IRI). By comparing the solubility behavior of Fmoc-l-glutamic acid and l-glutamic acid 5-methyl ester, the solubility of structurally similar substances in the same solvent was explored.