Thermodynamics Research Center / ThermoML | Fluid Phase Equilibria

ABSTRACT

The examination of physicochemical properties of selected protein kinase CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt), 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole (2-Me-TBBi) was performed. The study includes modification of synthesis method and determination of compounds' thermal properties, the solid-liquid phase equilibria and pKa. Thermal properties (melting temperature, enthalpy of fusion, temperature and enthalpy of phase transitions) were determined by means of differential scanning calorimetry (DSC). For solid-liquid phase equilibria study, as a solvent, three liquids were used independently: water, ethanol and 1-octanol. In order to elicit the inhibitors' solubility with alcohols (ethanol and 1-octanol), the dynamic method was applied. In the case of poorly soluble inhibitors in water, equilibria were determined by spectrophotometric method. Based on a phase diagram obtained results were interpreted and correlated using three equations: Wilson equation, NRTL equation and UNIQUAC equation. pKa values of studied polybrominated benzoazoles were estimated by the spectrophotometric Bates-Schwarzenbach method at two constant temperatures: 298.15 K as a room temperature and 310.15 K as a human body temperature. Obtained results are very important for further design of CK2 inhibitors, because they provide information about the solubility of pharmacophore in binary systems: active compound (1) + solvent (2), that may be used in differentiating the way how to apply potential drug. Moreover, all values of dissociation constants bring valuable guidelines to establish the therapeutic dose of pharmaceutics.