Solubility of Fmoc-l-valine in Fourteen Monosolvents: Characterization, Determination, Analysis, and Model Correlation

Abstract

The mole fraction solubility of Fmoc-l-valine in 14 pure solvents (methanol, ethanol n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, n-pentanol, isopentanol, butyl acetate, acetone, acetonitrile, 2-butanone, dimethyl carbonate) was determined by the static gravimetric method at a temperature range of 283.15 to 323.15 K under a pressure of 101.2 kPa. Among the 14 monosolvents, solubility increased with the increase of absolute temperature. The order of solubility is as follows: acetone (0.06274 mol/mol) > 2-butanone (0.05704 mol/mol) > methanol (0.03966 mol/mol) > ethanol (0.03124 mol/mol) > sec-butanol (0.02749 mol/mol) > n-propanol (0.02535 mol/mol) > n-butanol (0.02445 mol/mol) > n-pentanol (0.02335 mol/mol) > butyl acetate (0.02088 mol/mol) > isopropanol (0.02038 mol/mol) > isopentanol (0.01916 mol/mol) > isobutanol (0.01525 mol/mol) > dimethyl carbonate (0.01078 mol/mol) > acetonitrile (0.004770 mol/mol). The equilibrium solid phase of Fmoc-l-valine in the solvent systems was characterized by powder X-ray diffraction analysis. The solubility data were fitted using the modified Apelblat model, NRTL model, UNIQUAC model, and Margules model; at the same time, the model parameters and data deviation values were calculated. The results showed that the modified Apelblat model had better correlation results. Interaction energy, interaction region indicator (IRI), and molecular electrostatic potential surface (MEPS) were used to determine the internal interactions within Fmoc-l-valine solutions. The Hansen solubility parameters (HSPs) was utilized to assess the solvents’ capability and to elucidate its ability to dissolve Fmoc-l-valine. Furthermore, the mixing thermodynamic characteristics of Fmoc-l-valine in selected solvents were calculated using the NRTL model, which revealed that the mixing process was spontaneous and entropy-driven. The solubility data can be used for the preparation and optimization of the Fmoc-l-valine crystallization processes.