Thermodynamic aspects of solubility and partitioning processes of some sulfonamides in the solvents modeling biological media

• Solubility processes of some sulfonamide isomers in water and 1-octanol were investigated.
• Transfer processes from water to 1-octanol were evaluated by analysis of enthalpic and entropic terms.
• Impact of various substituents in phenyl rings on solubility and transfer processes was studied.

The thermodynamic aspects of solubility processes of sulfonamides (SAs) with the general structures 4-NH2–C6H4–SO2NH–C6H2(R1)(R2)-R3 (R1 = 2-CH3, 2-Cl; R2 = 4-CH3, 4-Cl; R35-H, 5-Cl), 4-NH2-2-Cl–C6H3–SO2NH–C6H3(R1)-R2 (R1 = 2-H, 2-Cl; R2 = 4-H, 4-Cl) and 4-NH2-2-CH3–C6H3–SO2NH–C6H3(R1)-R2 (R1 = 2-H, 2-Cl, 2-NO2; R2 = 4-H, 4-Cl) in water and 1-octanol (as phases modeling various drug delivery pathways) were studied using the isothermal saturation method. For the sulfonamides with various substituents in phenyl rings the processes of transfer from water to 1-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight that the contribution of these terms is different for different molecules (entropy- or enthalpy-determined). Thus, in contrast to the interpretation of only the Gibbs energy of transfer (extensively used for pharmaceuticals in the form of the partition coefficient, logP), the analysis of thermodynamic functions of the transfer process provides additional mechanistic information. This may be important for further evaluation of the physiological distribution of drug molecules and may provide a better understanding of biopharmaceutical properties of drugs.

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