Experimental solubility evaluation and thermodynamic analysis of biologically active D-tryptophan in aqueous mixtures of N,N-dimethylformamide and several alcohols

Abstract

The D-tryptophan solubility in aqueous solutions of methanol, ethanol, isopropanol and N,N-dimethylformamide (DMF) was measured by the saturation shake-flask method at temperatures ranging from 283.15 K to 333.15 K. The maximum solubility was found in water for alcohol (1) + water (2) mixtures, and in neat DMF for DMF (1) + water (2) mixture. When the same temperature and mass fraction of the water is given, the highest mole fraction solubility of D-tryptophan was found in (DMF + water). The solid phases were tested by X-ray powder diffraction (XPRD) showing no polymorphic transformation, solvate formation or crystaltransition. Three solubility models, i.e. the Jouyban-Acree, van’t Hoff-Jouyban-Acree and Apelblat-Jouyban-Acree were employed to correlate the experimental solubility values so as to obtain thermodynamic parameters. The RAD and RMSD data were no more than 1.65% and 9.40 × 10−5, respectively. Linear solvation energy relationship analysis based on Kamlet-Taft parameters indicated that the variation of D-tryptophan solubility depended on π∗ for methanol (ethanol, isopropanol) (1) + water (2), and cavity term for DMF (1) + water (2). The preferential solvation parameters (δx1,3) for methanol, ethanol, isopropanol and DMF derived by means of the inverse Kirkwood–Buff integrals were negative in the four solvent mixtures with intermediate and alcohol-rich compositions, which indicated that D-tryptophan was preferentially solvated by water. The higher solvation by water could be explained in terms of the higher acidic behaviour of the solvents interacting with the Lewis basic groups of the D-tryptophan. However D-tryptophan is preferentially solvated neither by water nor by DMF in DMF + water mixture.