Thermodynamic Characterization of Bile Salt Aggregation as a Function of Temperature and Ionic Strength Using Isothermal Titration Calorimetry

Abstract

The critical micellar concentration (cmc) and the demicellization enthalpy ΔH 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 isothermal 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. ΔH demic is strongly temperature-dependent but shows almost no dependence on the ionic strength. For comparison with other systems, the thermodynamic parameters ΔG demic and ΔS demic associated with the demicellization process were calculated using the pseudo-phase-separation model. From the temperature dependence of ΔH demic, the change in heat capacity ΔCp demic for the demicellization process was determined. The data obtained for ΔCp demic are positive and at 298 K have values of 250 J·mol-1·K-1 for NaC and 350 J·mol-1·K-1 for NaDC. These values correspond to changes in the exposed hydrophobic surface area of 1.1−1.5 nm2 per molecule. For NaDC, ΔCp demic decreases at 343 K to ∼250 J·mol-1·K-1, whereas ΔCp demic for NaC remains essentially unchanged. The calorimetric titration curves were simulated using a mass action model including counterion condensation for the aggregation process. The simulation of the titration curves 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 independent of temperature. For NaDC in water values of n of 7 and 12 were obtained 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.

Anionic surfactant aggregation with (Hydroxypropyl)cellulose in the presence of added salt

“…Also in agreement with the unchanged micropolarity between the free bile salts and aggregates, 30,31 an alternative interaction could be the polymer adsorption on the hydrophobic exposed surfaces of the free bile salts that is about 60-80% of total hydrophobic surface. 16 As can be seen by the dynamic light scattering results, the behavior of the bile salts/HPC systems seems to support the process of polymer adsorption since there is dissolution of polymer clusters already at surfactant concentrations lower than the critical aggregation concentration C 1 . This effect may also be interpreted as follows: at first bile salt unimers attach to the HPC chain and in a second step bile salt micelle-like aggregates further bind to it.…”

“…The critical surfactant concentration without polymer or critical micellization concentration (CMC) was obtained for each surfactant at 298 K in good agreement with literature values. 16,27 In the presence of 0.5% HPC the C 1 decreases with respect to CMC observed for the SDS/HPC 2,28 and DC/HPC systems whereas an opposite trend is observed for CS/HPC. An earlier study 22 on the system DC/HPMC/NaCl 0.01 mol L -1 indicated no changes with respect to CMC of DC but in our work the higher ionic strength may have contributed to decrease the solubility of the system leading to aggregation at lower concentration.…”

“…11 Nevertheless only a few types of surfactants have been investigated, most of them formed by long alkyl chains with a polar head group. [13][14][15][16] We have previously studied different anionic surfactants with respect to the aggregation with the low molar mass, non charged flexible polymer poly (ethylene oxide), 17 including some natural anionic surfactant bile salts, namely, sodium cholate (CS) and sodium deoxycholate (DC), that are carboxylic polyhydroxy derivatives from cholesterol 18 and the wellknown sodium dodecylsulfate (SDS) that is a long chain alkylsulfate. The molecular shape of the bile salts exhibits a planar polarity due to spatial distribution of lateral groups in their steroid backbone.…”

Thermodynamics of micellisation: Sodium dodecyl sulfate/sodium deoxycholate with polyethylene glycol and model drugs

“…It is for this reason that caution should be observed, particularly in the case of NaDC, where a primary aggregation phenomenon has been reported at a concentration not much lower than the main CMC [9]. Furthermore, even the drugs themselves are potentially capable of self-aggregating which has been previously observed for similar compounds [17].…”

“…Sodium deoxycholate (NaDC) is a more complex surfactant than SDS, with published data often referring to a second aggregation event, similar in concentration to that for the main micellisation [9].…”