Preferential Solvation in 2-Propanol/Water Mixtures: Relationship between Solvatochromic Parameters and Ionization and Transfer Thermodynamics of Nalidixic Acid Antibiotic

Precise ionization constants for nalidixic acid have been obtained in various binary 2-propanol/water mixtures at four different temperatures using a potentiometric method. The thermodynamic parameters of ionization and transfer of nalidixic acid from water to aquo-organic solvents were calculated. The variation of pK_a (or free energy of ionization Δ_ionG°) with the inverse of dielectric constant of the solvent is non-linear revealing preferential solvation of nalidixic acid. To identify the solvent characteristics affecting the ionization equilibria, the results are discussed in terms of solute-solvent and solvent-solvent interactions. Correlations of the ionization and transfer thermodynamic functions with the molecular-microscopic properties of solvents were also examined and were found to be much better than the corresponding correlations with macroscopic ones. The linear solvation energy relationships of Kamlet and Taft’s multiparametric method were also used to relate the pK_a and various thermodynamic parameters with solvatochromic parameters of aquo-organic mixtures. Thus, the derived equations give a precise method of obtaining pK_a and various thermodynamic parameters for nalidixic acid in any binary solvent composition, up to 80% volume fraction in organic solvent. The observed pronounced maximum in Δ_transS°-composition profile has been guided mainly from the water structure promotion caused by alkyl group of alcohol, followed by breakdown of this structure by increasing alcohol content. Moreover, the entropy of transfer of nalidixic acid is proposed as a sensitive and useful probe for the elucidation of solvent structure.