Solubility modelling and preferential solvation of adenine in solvent mixtures of (N,N-dimethylformamide, N-methyl pyrrolidone, propylene glycol and dimethyl sulfoxide) plus water

Abstract The equilibrium solubility of adenine in solvent mixtures of N,N-dimethylformamide (DMF) + water, N-methyl pyrrolidone (NMP) + water, propylene glycol (PG) + water and dimethyl sulfoxide (DMSO) + water were determined experimentally by using shake-flask method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). Linear solvation energy relationships concept was used to describe the variation in the solubility based on the solvent effect. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. The preferential solvation parameters (δx1,3) for DMF, NMP, PG or DMSO were negative in the four solvent mixtures with water-rich compositions, which indicated that adenine was preferentially solvated by water. Temperature has little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behavior of the solvents interacting with the Lewis basic groups of the adenine. Besides, the solubility of this drug was mathematically represented by using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.23% for correlative studies. The standard dissolution enthalpies of adenine in the solvent mixtures were obtained. Positive values of the standard molar enthalpy demonstrated that the dissolution process of adenine was endothermic, and the entropy was driving force for the dissolution process.