Calorimetry studies of chlorpromazine hydrochloride in solution

The self-association of the tranquilizer chlorpromazine hydrochloride in aq ueous solution was studied.. Using isothermal titration calorimetry, the cr itical micelle concentration and solvent-micelle interactions were evaluate d as a function of temperature, ionic strength, and pH. The enthalpy of dem icellization, Delta H-demic, was directly measured from the experimental en thalpy values, which showed that the spontaneous demicellization of chlorpr omazine hydrochloride is a highly endothermic process under all experimenta l conditions studied. The thermodynamic parameters were subsequently calcul ated from the temperature dependent thermograms. At 25 degrees C, the criti cal micelle concentration was determined to be 3.2 mM at pH 6.5 with a Delt a H-demic of 12.5 kJ/mol, a Delta G(demic) of 24.3 kJ/mol, and a T Delta S- demic of -10.1 kJ/mol. Our results suggest that the enthalpy-entropy compen sation theory may be applied to these micelles. In addition, using differen tial scanning calorimetry, a broad endothermic demicellization peak was obs erved in postmicelle solutions during heating scans at approximately 45 deg rees C. Cooling scans revealed a very broad peak centered around 40 degrees C that corresponds to the heat of micellization.