Influence of ionization and position of substituents on the solubility, solvation and transfer processes: A thermodynamic study of hydroxybenzamide and acetamidobenzoic acid isomers

• Solubility of hydroxybenzamide and acetaminobenzoic acid isomers was determined in relevant pharmaceutically solvents. • Thermodynamic functions of dissolution and solvation were estimated. • The transfer processes from n -hexane to solvents and from buffers to 1-octanol were studied. Solubility of i -hydroxybenzamides and i -acetamidobenzoic acids ( i = 2, 3, 4) in buffer solutions (pH 2.0 and 7.4), 1-octanol and n -hexane were measured by the isothermal saturation method in the temperature range (293.15–315.15 K). The following order of the solubility was revealed (in mole fraction): 1-octanol > buffer pH 7.4 > buffer pH 2.0 > n -hexane. The solubility was correlated by the van’t Hoff and Apelblat equations. The best result was achieved with the van’t Hoff model. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor–acceptor capacity of the molecules on drug solubility has been studied. The thermodynamic parameters of solubility, solvation and transfer processes were calculated and discussed in view of solute–solvent interactions. A diagram approach was used to analyze the enthalpy and entropy contributions to the Gibbs energy of transfer processes from n -hexane to solvents and from buffer solutions to 1-octanol for the substances studied.