Thermodynamic of Transfer and Preferential Solvation of Antibiotic Cephradine in 1,4-Dioxane-Water Mixtures

The ionization constants of cephradine in 0, 10, 20, 30, 40, 50, 60, 70, 80 and 90% ( v/v ) 1,4-dioxane-water mixed solvents were determined using a potentiometric technique and an automatic titrator. The measurements were performed at four different temperatures and 0.1 M KCl, and thus the thermodynamic parameters of ionization and transfer were evaluated. The ionization of cephradine has been found to be endothermic and entropically unfavourable. A non-linear dependence of the ionization Gibbs energies (Δ_dissG^°) on the mole fraction of 1,4-dioxane and the reciprocal of the dielectric constant of the solvent mixtures was observed. The variation of the Δ_dissG^° values (and thus pK_a values) obtained over the whole composition range studied can be explained in terms of preferential solvation of cephradine in 1,4-dioxane–water mixtures. Both Δ_dissG^° and Δ_dissS^° were linearly related to Δ_dissH^°, given isoequilibrium relationships. The Δ_dissH^°–Δ_dissS^° susceptibilities are different for the first and second ionization processes as well as for water-rich and 1,4-dioxane-rich zones. On the basis of the standard Gibbs energies of hydrogen ion from water to 1,4-dioxane-water mixtures, Δ_transG^°(H⁺) and the relative values of ionized and unionized species of cephradine, the effect of solvent on its ionization in 1,4-dioxane–water mixtures is clarified. The Δ_dissG^° values are well correlated with the solvent polarity parameter of Dimroth and Reichardt, E_T(30). The linear solvation energy relationships method (LSER) was also applied to correlate the thermodynamic parameters with the Kamlet and Taft solvatochromic parameters (α, β, π*) of 1,4-dioxane-water mixtures. Thus, calculation of the thermodynamic parameters of ionization and transfer in any 1,4-dioxane-water mixtures up to 90% ( v/v ) can be done using the obtained equations.