Thermodynamic characterization of bile salt aggregation as a function of temperature and ionic strength using isothermal titration calorimetry

The critical micellar concentration (cmc) and the demicellization enthalpy Delta H-demic of the primary aggregates of sodium cholate (NaC) and sodium deoxycholate (NaDC) in water and 0.1 M NaCl at pH 7.5 were determined by is othermal titration calorimetry (ITC). The cmc of NaC and NaDC in water and 0.1 M NaCl at pH 7.5 shows a minimum between 295 and 300 K. With increasing ionic strength, the cmc of the bile salts decreases. Delta H-demic is stro ngly temperature-dependent but shows almost no dependence on the ionic stre ngth. For comparison with other systems, the thermodynamic parameters Delta G(demic) and Delta S-demic associated with the demicellization process wer e calculated using the pseudo-phase-separation model. From the temperature dependence of Delta H-demic, the change in heat capacity Delta Cp-demic for the demicellization process was determined. The data obtained for Delta Cp -demi care positive and at 298 K have values of 250 J.mol(-1).K-1 for NaC a nd 350 J.mol(-1).K-1 for NaDC. These values correspond to changes in the ex posed hydrophobic surface area of 1.1-1.5 nm(2) per molecule. For NaDC, Del ta Cp-demic decreases at 343 K to similar to 250 J.mol(-1).K-1, whereas Del ta Cp-demic for NaC remains essentially unchanged. The calorimetric titrati on curves were simulated using a mass action model including counterion con densation for the aggregation process. The simulation of the titration curv es yielded values for the aggregation number n. In the concentration region of the cmc, n is approximately 4-6 for NaC in water or 0.1 M NaCl and inde pendent of temperature. For NaDC in water values of n of 7 and 12 were obta ined at low temperature (284 K) in water and 0.1 M NaCl, respectively. For NaDC in water and 0.1 M NaCl, the aggregation number n decreases to 5 and 7 , respectively, at 328 K.