The equilibrium solubility of 6-chloroguanine in four co-solvent mixtures of dimethyl sulfoxide (DMSO) (1) + water (2), N,N-dimethylformamide (DMF) + water (2), isopropanol (1) + water (2) and 1,4-dioxane (1) + water (2) over the temperature range from (278.15 to 333.15) K were reported. At the same temperature and composition of DMSO, DMF, isopropanol or 1,4-dioxane, the mole fraction solubility of 6-chloroguanine was highest in DMSO (1) + water (2) mixtures, and lowest in 1,4-dioxane (1) + water (2) mixtures. By using the Jouyban-Acree, van't Hoff-Jouyban-Acree and Apelblat-Jouyban-Acree models, 6-chloroguanine solubility was well correlated obtaining RAD lower than 5.83% and RMSD lower than 4.82 x 10(4). Quantitative values for the local mole fraction of DMSO (DMF, isopropanol or 1,4-dioxane) and water around the 6-chloroguanine were computed by using the Inverse Kirkwood-Buff integrals method applied to the determined solubility data. For the DMF (1) + water (2) mixture with composition 0.20 < x(1) < 0.69, DMSO (1) + water (2) mixture with composition 0.20 < x(1) < 1 and 1,4-dioxane (1) + water (2) mixture with composition 0.18 < x(1) <0.35, 6-chloroguanine is preferentially solvated by the co-solvent. For the isopropanol (1) + water (2) mixture with composition 0.25 < x(1) < 0.70, 6-chloroguanine is preferentially solvated neither by isopropanol nor by water. However, in the other regions for the four co-solvent mixtures, 6-chloroguanine is preferentially solvated by water. The dissolution process of 6-chloroguanine in solvent solutions was endothermic. Furthermore, transfer Gibbs energy (Delta(tr)G degrees), enthalpy (Delta H-tr degrees), and entropy (Delta S-tr degrees) were calculated, demonstrating that the solubilization capacity was more favorable with the increase in the co-solvent concentration. (C) 2019 Elsevier Ltd.