Solubility modelling, solvent effect, preferential solvation and solution thermodynamic of thymine form AH A° in ten mono solvents and two solvent mixtures

Abstract The solid-liquid equilibrium solubility of thymine form AH A° at temperature from 283.15 to 323.15 K in methanol, ethanol, 1,4-dioxane, 1-butanol, acetone, 1-propanol, 2-propanol, acetonitrile, N,N-dimethylformamide (DMF), 2-butanone and two mixed solvents (DMF + methanol and DMF + ethanol), solvent effect in mono-solvent systems, preferential solvation in mixed solvent systems, thermodynamic properties and model correlation parameters are reported. The sequence of the mole fraction solubility is DMF > 1,4-dioxane > methanol > ethanol > propanol > -propanol > 1-butanol > acetone > 2-butanone > acetonitrile. Solvent effect had been studied in mono-solvents, and the solubility depended on hydrogen bonding donor (HBD) and hydrogen bonding acceptor (HBA) interactions of solvents with solute and nonspecific dipolarity/polarizability interactions. A dimensionless quantity (δ) was employed to represent the deviation of log x12 values from the mole fraction average, the solute (thymine form AH A°) exhibits preferential solvation, DMF is preferred over methanol or ethanol in the neighborhood of the thymine form AH A°, and the equilibrium constant of the process of solvent exchange (Kps) was used to explain the preferential solvation. The modified Apelblat, Wilson, Jouyban-Acree and CNIBS/R-K models were used as correlation models to correlate the solubility values. The maximum values of relative average deviation (RAD) and root-mean-square deviation (RMSD) for mono-solvent systems were 1.86 × 10−2 and 1.42 × 10−4 and for mixed solvent systems were 3.74 × 10−2 and 3.54 × 10−4. These four models can correlate the solubility of thymine form AH A° in mono-solvents or mixed solvents well. In addition, the thermodynamic properties for the dissolution processes of thymine form AH A° were also calculated based on van't Hoff and Gibbs equations. The results show that the dissolution of thymine form AH A° is the endothermic and entropy-driven process.