Thermodynamic Study of the Solubility of Some Sulfonamides in Cyclohexane

Sulfonamides are drugs extensively used for the treatment of certain infections caused by gram-positive and gram-negative microorganisms, some fungi, and certain protozoa. Several physical and chemical parameters of these compounds have been correlated with their chemotherapeutic activity: pK a , protein binding, and electronic charge distribution, among others. Unfortunately, no single parameter can explain the action of sulfonamides. The information known so far does not allow the proposition of suitable mechanisms for the process of transfer of sulfonamides between immiscible liquid phases or between aqueous media and biological membrane models, which would explain their differences in biological activity as a function of their molecular structure. However, the temperature dependence of the solubility may be used to account for these differences. Mauger et al. have determined the solubility of sulfadiazine, sulfisomidine, sulfadimethoxine, and sulfisoxazole in some alcohols at 25, 30, and 37 °C, while Regosz et al., have evaluated the aqueous solubility of a variety of sulfonamides at several temperatures. Martínez and Gómez have studied the thermodynamics of solution of some sulfonamides in octanol, water, and the mutually saturated solvents. In order to have systematic and more complete physicochemical information about the transfer of sulfonamides between aqueous and organic phases, in this work the solubility of eight structurally related sulfonamides in cyclohexane was determined at several temperatures, and the related thermodynamic functions were calculated. Cyclohexane and octanol have been used as standard organic media for partitioning experiments in the study of quantitative structure–activity relationships (QSAR). Cyclohexane is a non-polar lipophilic hydrocarbon solvent, and therefore it is used in the evaluation of hydrophobic interactions. The theoretical thermodynamic aspects of the solubility of solid solutes have been discussed elsewhere.