Critical micellar temperature bile salts

On the basis of surface and bulk interaction with water. Small [85] classified bile acids as insoluble amphiphiles and bile salts as soluble amphiphiles. On account of the undissociated carboxylic acid group, the aqueous solubility of bile acids is limited [35] in contrast, many bile salts have high aqueous solubilities as monomers [33] and, in addition, their aqueous solubilities are greatly enhanced by the formation of micelles [5,6]. Because many bile salts are weak electrolytes, their ionization and solubility properties are more complicated than those of simple inorganic or organic electrolytes [5,35]. For example, the p/Tj, values of bile acids in water vary markedly as functions of bile salt concentration and, because micelles formed by the A (anionic) species can solubilize the HA (acid) species [5,35], the equilibrium precipitation pH values of bile acids also vary as functions of bile salt concentration. Finally, certain bile salts are characterized by insolubility at ambient temperatures [2,5,6,86,87], only becoming soluble as micelles at elevated temperatures (the critical micellar temperature) [6]. 

Fig. 12. Partial phase diagrams for the dilute region of aqueous solutions of the disodium salts of sulfated monohydroxy bile salts glycolithocholate sulfate (GLCS at pH 10.0) and taurolithocholate sulfate (TLCS at pH 7.0, inset). The solid solubility curves and the interrupted CMC curves demarcate areas where crystals (and monomers), micelles (and monomers), and monomers alone are found. The critical micellar temperature (CMT) represents an equilibrium between micelles and hydrated crystals connected via the monomer concentration at the CMC. The Krafft point is a triple point and only represents the CMT at the CMC. (After ref. 6 with permission.)...

We have carried out similar experiments with saturated fatty acid soaps as the first soap and bile acids (as the sodium salt) as the second soap (66). The bile acids behave as typical ionic detergents with critical micellar temperatures well below 0°C (Fig. 10). For any saturated fatty acid soap, its critical micellar temperature decreases as the chain length shortens. Thus, at 37°C, more of a short-chain soap will be solubilized for a given amount of bile acid present, or, to paraphrase, the molar ratio of soap/bile acid will be much higher for short-chain soaps at 37°C. One carries out these experiments by incubating a series of different molar ratios of soap/bile acid. The bile acid is micellar, and the soap is crystalline. Over a few degrees of temperature range, the crystalline soap completely dissolves. No satisfactory quantitative description of these experiments has, as yet, been proposed. 

Fig. 10. Phase equilibria of the bile acid (as sodium salt)-fatty acid soap-water phase diagram at constant water concentration in relation to temperature. Mixtures with varying molar ratios of bile acid/sodium soap (total concentration 40 mM) were incubated, and the temperature at which the system became clear was plotted solutions were buffered top i 12. The curves indicate the critical micellar temperature of the system and have also been termed mixed Krafft points (46). The CMT of the bile acids is extremely low.

Fig. 36. Critical micellar temperature (CMT) of alkaline metal salts of lithocholic acid as a function of the atomic volume of the alkaline metal. CMT vertical axis, atomic volume horizontal axis. Percent solids refers to the total amount of bile salt in g/100 ml water. Note that as the atomic volume of the alkaline metal decreases, the Krafft point for any given concentration of bile salt increases. There is a striking rise with lithium, which has the smallest atomic volume.

The physical chemistry of micellar structure and formation has been reviewed extensively elsewhere[40,45-47], and is only briefly summarized. The concentration at which micellar aggregation of bile salts molecules occurs (critical micellar concentration, CMC) is affected by bile salt structure, pH, temperature and a variety of other factors. Conjugated bile salts have a higher CMC than the unconjugates, and the CMC for trihydroxycholanates (cholic acid) is higher than for the dihydroxy derivatives. Among the latter, deoxy-cholate forms micelles at a lower CMC than does chenodeoxycholate. 

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