Solubility modeling, Hansen solubility parameter, solvation thermodynamics and enthalpy–entropy compensation of 5-chlorooxine (form I) in several aqueous cosolvent solutions

Abstract

The current contribution was dedicated to solubility profile, solvation behavior, and inter- and intramolecular interactions for the binary systems formed by 5-chlorooxine (I) in aqueous solutions of ethanol, N-methyl-2-pyrrolidinone (NMP), isopropanol and N,N-dimethylformamide (DMF) together with numerous computational approach. A shake-flask method conducted all experiments under local pressure p = 101.2 kPa over temperatures ranging from 278.15 to 323.15 K. For each cosolvent system, the highest equilibrium solubility of 5-chlorooxine (I) was recorded in neat cosolvent at temperature of T = 323.15 K; and the lowest one, in neat solvent of water at 278.15 K. The solubility performance was investigated by the use of the Hansen solubility parameter and extended Hildebrand solubility approach. Numerous models, e.g. mixture response surface, Jouyban–Acree, modified Wilson and Jouyban–Acree–van’t Hoff acceptably correlated the obtained mole fraction solubility with relative average deviations (RAD) no greater than 7.25 %. The relative contribution of solute–solvent and solvent–solvent interactions to equilibrium solubility variation of 5-chlorooxine (I) at the temperature of 298.15 K was analyzed quantitatively by employing the linear solvation energy relationships, indicating that the dipolarity-polarizability and solubility parameter of solvent systems were predominantly responsible for the 5-chlorooxine (I) solubility. The solvation behavior was inspected by the extended Hildebrand solubility approach applied to the solubility data at 298.15 K, gaining RAD of no more than 3.15 %. In addition, preferential solvation of 5-chlorooxine (I) was quantitatively analyzed by the method of inverse Kirkwood–Buff integrals in terms of some available solution properties. The positive preferential solvation parameters for 5-chlorooxine (I) in intermediate and cosolvent-rich solutions suggests that the solute 5-chlorooxine (I) is preferentially solvated by cosolvents. It is speculated that 5-chlorooxine (I) performs as a Lewis acid behavior with cosolvent molecules in above composition districts. The dissolution of 5-chlorooxine (I) in all aqueous solution systems was entropy-driven and endothermic process.