Solubility of N-Acetyl-L-glutamine in twelve Mono-solvents: Characterization, Determination, Analysis, and model correlation

Abstract

In this work, the solid–liquid equilibrium solubility and solvent effects of N-acetyl-L-glutamine in twelve mono-solvent systems (water, methanol, ethanol, n-propanol, n-butanol, isobutanol, sec-butanol, acetonitrile, acetone, ethyl acetate, 2-butanone, methyl acetate) were reported at the pressure of 101.2 kPa (at T = 283.15–––323.15 K). Among the twelve mono-solvents, the solubility increased with the increase of absolute temperature, the order is: water > methanol > ethanol > sec-butanol > n-propanol > 2-butanone > isobutanol > acetone > methyl acetate > ethyl acetate > n-butanol > acetonitrile. The modified Apelblat model, Wilson model, NRTL model and UNIQUAC model were employed to correlate the experimental solubility, and the fitting results of the four models were all satisfactory. In addition, through comparison of the average ARD and RMSD values of the four models, the modified Apelblat model achieved the best correlation result. Hirshfeld surface analysis (HS) and molecular electrostatic potential surface (MEPS) were used to determine the internal interactions within N-acetyl-L-glutamine solutions. The Hansen solubility parameters (HSPs) and the coverage Pearson correlation coefficients (PCC) heatmap were utilized to assess the solvents’ capability and to elucidate its ability to dissolve N-acetyl-L-glutamine. Furthermore, mixing thermodynamic characteristics of N-acetyl-L-glutamine in selected solvents were calculated by the NRTL model, which revealed that the mixing process was spontaneous and entropy-driven. These experimental results could be utilized for the purification, crystallization, and industrial applications of N-acetyl-L-glutamine as well as similar substances.