Solubility of edaravone in water/cosolvent mixtures of some alcohols revisited: IKBI preferential solvation analysis and thermodynamic properties

To better understand edaravone (EDA), its solubility behaviour in water-alcohol mixtures (methanol (MeOH), and ethanol (EtOH)) at various temperatures (293.15–323.15 K) was studied. Moreover, it was revealed that the dissolution of EDA is an endothermic process mainly induced by enthalpy changes, where these contributions (over 76%) are common in all solvent systems. The negative Gibbs free energy of transfer values indicates that EDA has a higher thermodynamic affinity for alcohol – water mixtures than for pure water, which is consistent with the increase of its solubility in co-solvent media. According to the inverse Kirkwood – Buff integrals (IKBI) method of preferential solvation, EDA is selectively solvated by alcohol molecules, with the degree of solvation decreasing in the order EtOH > MeOH. The maximal preferential solvation was found in the medium region of alcohol mole fraction (x1 = 0.30–0.40), where solvation occurs due to alcohol molecules replacing water molecules at the non-polar part of EDA.