Equilibrium solubility of amrinone in aqueous co-solvent solutions reconsidered: Quantitative molecular surface, inter/intra-molecular interactions and solvation thermodynamics analysis

Abstract

Two powerful tools of quantum-chemical parameters, minimum negative surface electrostatic potential together with minimum surface average local ionization energy, were employed in this communication to illustrate the electrostatic characteristics of acidity and basicity from a microscopic point of view, correspondingly. The -N = and > NH groups of amrinone molecule are primary sites of electrophilic and nucleophilic attacks. With the help of the famous method of inverse Kirkwood–Buff integrals, preferential solvation analysis was executed based on the reported amrinone solubility in four solution systems of EG (1) + water (2), ethanol (1) + water (2), DMF (1) + water (2) and methanol (1) + water (2). In rich water concentrations, amrinone was surrounded preferentially by water; while in intermediate and rich EG/ethanol/DMF/methanol compositions, EG/ethanol/DMF/methanol solvated preferentially amrinone. High basicity of EG/ethanol/DMF/methanol that favored interactions with the acidic groups of amrinone resulted in selective solvation of amrinone by the co-solvent. Deep investigation on the amrinone solubility behavior was done by the partial Hansen solubility parameters. The inspection of molecular interactions on amrinone solubility variation was made in the light of the well-known linear solvation energy relationships, identifying the solubility parameter, hydrogen-bond acidity and dipolarity-polarizability of solutions presented dominant contributions to the solubility variation. The transfer and thermodynamic dissolution properties including entropy, enthalpy and Gibbs free energy change were also derived and deeply discussed. Thermodynamic enthalpy–entropy compensation analysis validated a shift of prevailing mechanism of dissolution from entropy-driven (in rich water compositions) to enthalpy-driven (in rich co-solvent compositions).