Solubility modelling, solvent effect and preferential solvation of 6-chloropurine in several aqueous co-solvent mixtures between 283.15 K and 328.15 K

Abstract

The mole fraction solubility of 6-chloropurine in aqueous mixtures of methanol, ethanol, N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) was measured by a saturation shake-flask method over the temperature range of (283.15–328.15) K at pressure of 101.2 kPa. The solubility of 6-chloropurine increased positively with increasing temperature at a given solvent composition and decreased with increasing mass fraction of water in each binary system. The maximum solubility was found in neat methanol, ethanol, DMF and DMA. Given the same temperature and mass fraction of the organic solvent, the solubility of 6-chloropurine was greater in (DMF + water) than in the other three solvent mixtures. The X-ray power diffraction (XPRD) analysis showed that no polymorphic transformation, solvate formation or crystal transition took place during the experiments. 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 using inverse Kirkwood–Buff integrals. The preferential solvation parameters (δx1,3) for methanol, ethanol, DMF and DMA were negative in the four solvent mixtures with water-rich compositions, which indicated that 6-chloropurine 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 6-chloropurine. Furthermore, several mathematical cosolvency models were adopted to correlate the measured solubility values. The relative average deviation and root-mean-square deviation were no more than 2.36% and 1.026 × 10−3, respectively.