Hydrophobic self-association of sodium taurochenodeoxycholate and tauroursodeoxycholate

The aggregation patterns of sodium taurochenodeoxycholate (TCDC) and tauroursodeoxycholate (TUDC) in an isotonic sodium chloride solution are investigated by frontal chromatography on Sephadex G-10 columns at 298.2 K and are quantitatively analyzed on the basis of stepwise aggregation models. The micellar aggregation numbers, critical micelle concentrations (cmc's), stepwise aggregation constants, and micelle size distributions of TCDC and TUDC are determined and compared to those of sodium taurocholate and taurodeoxycholate. The logarithms of gel-water partition coefficients, dimerization constants, and reciprocal cmc values for the four bile salts exhibit linearity with their hydrophobic molecular surface areas, and the slopes are close to that of the logarithms of reciprocal cmc values against the hydrophobic molecular surface areas of lecithins. This fact shows that the gel adsorption, dimerization, and micellization of bile salts are driven mainly by hydrophobic interactions and that the Small model for the micellization of bile salts is better than models based on hydrophilic interactions. The micelle of TUDC grows less cooperatively than that of TCDC, an epimer of TUDC. This result suggests that the 7 beta-hydroxyl group of TUDC inhibits micellar growth because of increased intermolecular mismatching contact with the hydrophobic surface and decreased intermolecular hydrogen bonds in the micelle.