Stepwise Self-Association of Sodium Taurocholate and Taurodeoxycholate As Revealed by Chromatography

Abstract

From frontal chromatograms and derivatives of sodium taurocholate (TC) and taurodeoxycholate (TDC) on Sephadex G-10 columns in 0.154 M sodium chloride, monomer concentrations (Cl), weight and number average aggregation numbers excluding and including the monomer contribution, critical micelle concentrations (cmc's), and minimum multimerization concentrations have been determined as a function of the total concentration (C). Since the micellization of TC occurs rather noncritically, the cmc values obtained from the same centroid volume data depend on the data treatment. The definition of cmc, that cmc is the total concentration at the inflection on the C1 vs C curve, is applicable to TC and TDC as well as surfactants. The dimerization of TC and TDC has been proven by several pieces of chromatographic evidence, and their dimerization constants are determined independently from centroid volume and peak volume data. The stepwise aggregation constants are determined and are used to calculate micelle size distributions. Micelles of TC and TDC grow above the cmc more gradually than those of surfactants. This gradual growth is the main reason for inconsistencies in the literature of bile salt micellization. Since TDC is more hydrophobic than TC, the dimerization constant and aggregation numbers of TDC are larger than those of TC. This result supports the Small model for small micelles of bile salt.

Kinetics of formation of bile salt micelles from coarse-grained Langevin dynamics simulations

“….10), which are almost non-existent for other surfactants. 21,22,[24][25][26][28][29][30][31][32] Molecular dynamics simulations using all-atom [28][29][30] and coarse-grained 31 models, indicate that both oligomers and micelles are primarily stabilized by hydrophobic interactions, in agreement with experimental data that indicates that micellization is entropy-driven because of the release of water molecules from the hydrophobic face of the bile salts. [32][33][34] While the static properties of pure bile micelles are reasonably well characterized as summarized above, considerably less is known about their mechanism of formation.…”

Self-assembly in aqueous bile salt solutions

“…600 mM) for dihydroxy, but not trihydroxy, bile salts [4,18,28,29,40]. The aggregation number typically increases with bile salt concentration and then seems to saturate at about 30 mM for CDC and DC, and about 50 mM for C and UDC [8][9][10][11][12]18,39].…”

“…Upon increasing the total bile salt concentration, the monomer concentration first increases and then saturates around the critical micellar concentration (cmc) [8][9][10][11][12]. Also around the cmc, bile salt molecules start to self-assemble into aggregates, similar to classical amphiphiles.…”

“…The cmc of bile salts has been extensively determined under various conditions [8][9][10][11][12][13][14][20][21][22][23][24][25][26][27][28]. The cmc values show similar general trends on solution parameters, such as ionic strength, pH or temperature, as classical amphiphiles.…”

“…The aggregation number also depends on the bile salt species and typically follows the order DC ≳ CDC N C ≳ UDC [5,[8][9][10][11]21,23,40], which reflects the sequence of the cmc values. As in the related case of the cmc (Section 3, Fig.…”