Sodium Taurodeoxycholate Solutions Research Articles

Analyzing Surfactant Structures on Length and Chirality Resolved (6,5) Single-Wall Carbon Nanotubes by Analytical Ultracentrifugation

The structure and density of the bound interfacial surfactant layer and associated hydration shell were investigated using analytical ultracentrifugation for length and chirality purified (6,5) single-wall carbon nanotubes (SWCNTs) in three different bile salt surfactant solutions. The differences in the chemical structures of the surfactants significantly affect the size and density of the bound surfactant layers. As probed by exchange of a common parent nanotube population into sodium deoxycholate, sodium cholate, or sodium taurodeoxycholate solutions, the anhydrous density of the nanotubes was least for the sodium taurodeoxycholate surfactant, and the absolute sedimentation velocities greatest for the sodium cholate and sodium taurodeoxycholate surfactants. These results suggest that the thickest interfacial layer is formed by the deoxycholate, and that the taurodeoxycholate packs more densely than either sodium cholate or deoxycholate. These structural differences correlate well to an observed 25% increase in fluorescence intensity relative to the cholate surfactant for deoxycholate and taurodeoxycholate dispersed SWCNTs displaying equivalent absorbance spectra. Separate sedimentation velocity experiments including the density modifying agent iodixanol were used to establish the buoyant density of the (6,5) SWCNT in each of the bile salt surfactants; from the difference in the buoyant and anhydrous densities, the largest hydrated diameter is observed for sodium deoxycholate. Understanding the effects of dispersant choice and the methodology for measurement of the interfacial density and hydrated diameter is critical for rationally advancing separation strategies and applications of nanotubes.

Competitive solubilization of cholesterol and six species of sterol/stanol in bile salt micelles

Slight differences in the molecular structures of a category of sterol/stanol species affect the solubility of cholesterol in a bile salt solution. We systematically studied the preferential solubilization of cholesterol and sterol/stanol in sodium taurodeoxycholate solutions using relatively minor plant species of sterol/stanol (brassicasterol and stigmasterol) and a non-plant sterol (cholestanol). As relatively major sterol/stanol species (beta-sitosterol, beta-sitostanol, and campesterol) have already been examined using nearly identical procedures to that used in our system, we were able to sufficiently discuss the cholesterol-lowering effects resulting from the molecular structures of six sterol/stanol species. The results of competitive solubilization revealed that cholestanol has the largest cholesterol-lowering effect, decreasing cholesterol solubility to 33% of that in a single solubilizate system. The molecular structure of cholestanol is also most similar to that of cholesterol. In contrast, brassicasterol and stigmasterol have little ability to decrease cholesterol solubility in a mixed binary system. Both have an unsaturated double bond at the side chain of the steroid ring. By applying thermodynamic analyses to these results, we found that the Gibbs energy changes (DeltaG degrees ) of solubilization for sterol/stanol species with cholesterol-lowering effects show larger negative values than that for cholesterol.

Ionization and solubilization of 4 alkyl benzoic acids and 4 alkyl anilines in sodium taurodeoxycholate solutions.

The aqueous solubility and the extent of solubilization and ionization constant in sodium taurodeoxycholate (NaTDC) solutions of a series of benzoic acid and aniline derivatives were measured as a basis to characterize and thereby help predict the nature of the interaction of drugs with bile aggregates. The aqueous solubility and the solubilization of two series of compounds, 4-alkyl benzoic acids and 4-alkyl anilines, was measured as a function of NaTDC in 0 and 150 mM NaCl. The ionization constants were determined in water and in 50 mM NaTDC at sodium chloride concentration of 0, 75 and 150 mM by spectrophotometric titration. The diffusion coefficients of NaTDC and the solutes were measured by pulsed-field gradient spin echo NMR spectroscopy. The aqueous solubilities decreased with increasing alkyl chain length in both series, and the aniline derivatives had larger solubilities than the benzoic acid derivatives. The number of moles of solute solubilized per mole of bile salt ranged from 0.17 to 0.31 for the benzoic acid derivatives and from 1.3 to 3.0 for the aniline derivatives. The pKa values of the benzoic acid derivatives in the presence of NaTDC were higher relative to the controls, and the difference in the pKa (delta pKa,obs) increased with increasing chain length. With the aniline derivatives, the pKa values were also shifted to higher values in NaTDC relative to the control but only in the absence of salt. The presence of the solute caused a decrease in the diffusion coefficient of NaTDC, and the diffusion coefficients of the solutes decreased with increasing alkyl chain length. With the hexyl derivative, the diffusion coefficient of the solute was smaller than the diffusion coefficient of the bile salt. The chemical shift of the protons attached to carbon 18 and 19 of the salt were decreased to a greater extent in the presence of the solutes than the protons attached to carbon 26. Both the solubilization and ionization behavior of solutes were affected by the presence of bile salt aggregates. The surface potential and effective polarity of NaTDC aggregates were found to be dependent on the alkyl chain length for these two homologous series of solutes. The solubilization ratio was largely independent of alkyl chain length, but the unitary partition coefficient was dependent on both alkyl chain length as well as ionization state. The derivatives reduced the diffusivity of the micelles suggesting the formation of larger size aggregates and the solutes (hexyl derivatives) appear to favor association with the larger sized aggregates. The phenyl ring of the solutes appears to be oriented parallel to the plane of the steroid frame with preferential positioning near the hydrophobic rings.

Chiral separation of trimetoquinol hydrochloride and related compounds by micellar electrokinetic chromatography using sodium taurodeoxycholate solutions and application to optical purity determination

The chiral separation of trimetoquinol hydrochloride, which is a bronchodilator (Inolin), and three related compounds by micellar electrokinetic chromatography was investigated using a bile salt as a chiral surfactant. Enantiomers of these compounds, except laudanosoline, were successfully separated within 12 min using a separation tube of effective length 500 mm × 0.05 rum i.d. and a 0.05 M sodium taurodeoxycholate solution of pH 7.0. The observed theoretical plate numbers of the peaks were ca. 150000. Chiral recognition was affected by the structure of bile salts, the pH of the buffer solutions used and the structure of the solutes. Of four kinds of bile salts, successful chiral separation was achieved only using sodium taurodeoxycholate solution under neutral conditions. The method was applied to the optical purity determination of trimetoquinol hydrochloride. The effects of surfactant concentrations and some additives to the micellar solution are briefly described.

Calorimetric and optical study of micellar aggregates of sodium taurodeoxycholate

Calorimetric measurements, carried out on aqueous solutions of sodium taurodeoxycholate at different NaCl concentrations, show that the molar heat of dilution decreases with the bile salt concentration and, to a lesser extent, with the NaCl concentration. Circular dichroism spectra, recorded from aqueous solutions of bile salt as a function of concentration, change the sign of the molar ellipticity under 230 nm.1H NMR spectra show an increase of the half-height line width of the C18 methyl group with the concentration of both bile salt and NaCl. These results, together with those inferred from viscosity measurements, favour the assumption of a model, observed from the crystal structure of sodium taurodeoxycholate and based on an equilibrium between two types of helices.

A model for micellar aggregates of a bile salt: crystal structure of sodium taurodeoxycholate monohydrate

Crystals of sodium taurodeoxycholate monohydrate, NaC26H44NO6S X H2O, are trigonal, space group P3(1), with a = 18.393(1), c = 7.097(1)A, V = 2079.3(5)A3, and Z = 3. The structure was solved by direct methods and Fourier techniques and refined by full-matrix least-squares calculations. The final R index is 0.051. The side chair of the anion displays an approximate folded-back conformation. The cyclopentane ring assumes an intermediate conformation between the half-chain and the beta-envelope. The sodium ion shows a distorted octahedral coordination with six oxygen atoms, giving rise to ion-ion and ion-dipole interactions. The molecules form helices, characterized by threefold screw axes, with a radius of about 16 A. The helices are packed in such a way as to be embedded in each other as cog-wheels. The helix found in this crystal structure will be used as a model and checked in the study of the micellar solutions of sodium taurodeoxycholate, following the same strategy satisfactorily employed in the case of sodium deoxycholate.

Liquid solubilization dynamics: II. Flux enhancement by interface gel formation

Dynamic solubilization studies were conducted to determine the mechanism of incorporation of oleic acid into aqueous sodium taurodeoxycholate solutions at 37°C in which the apparent diffusion limit of mixed micelles was exceeded. The effects of pH, added NaCl, and surfactant type on the flux of oleic acid were determined by means of a membrane-modified liquid/liquid stirred cell for this model fatty acid digestion system. The apparent enhanced mass transfer of oleic acid into sodium taurodeoxycholate solutions at sufficiently high pH and surfactant concentration can be satisfactorily explained by the formation of an oil/aqueous surfactant liquid crystalline phase at the interface. Under flow conditions this phase may be sheared from the interface and subsequently solubilized in the bulk aqueous phase as a mixed micelle or microemulsion. Experiments conducted under non-flow conditions support the proposed mechanism.

Physico-chemical properties of micellar sodium taurodeoxycholate solutions. Ultrasonic behaviour and viscosity

Ultrasonic absorption and velocity have been measured in sodium taurodeoxycholate solutions, at concentrations ranging between 0.1 and 0.4 mol kg−1 and at temperatures of 25, 35 and 45°C. In addition, viscosity measurements have been performed. The ultrasonic results show that at least two kinetic processes occur in such systems. At high frequency the kinetic processes may be related to monomer-micelle exchange, while at lower frequency they may be related to the change of size and shape of the solute aggregates. The trend of the activation energy of the viscous flow confirms the increase of the aggregation number of the micelles at higher molality.

Liquid solubilization dynamics: Oleic acid in bile salt

The solubilization dynamics of oleic acid by aqueous sodium taurodeoxycholate solutions at 37°C does not conform to previous resistance in series models involving diffusion and interfacial steps. This is especially true as the ionic strength of the aqueous solution is increased by adding NaCl or by increasing the taurodeoxycholate concentration above 2%. Experiments conducted with a liquid/liquid stirred cell show that as the ionic strength is increased, the flux of oleic acid into the aqueous solution exceeds a reasonable value for the diffusion limit, assuming that oleic acid diffuses only in mixed micelles, and that the flux becomes independent of flow at these high ionic strengths. Two alternative models for the solubilization process are proposed. One involves a rapid exchange of oleic acid between mixed micelles and oleic acid free micelles in parallel with mixed micelle diffusion; and the second involves formation of a small emulsion droplet at the interface, which contains significantly more oleic acid than a mixed micelle, and which rapidly dissolves into micellar solution as the droplet leaves the interface.

Linoleic acid solubilization with a spinning liquid disc

The rates of linoleic acid solubilization in aqueous solutions of sodium taurodeoxycholate were measured at 37°C using a spinning liquid disc. The liquid disc is made of a polymer film whose pores contain the liquid being solubilized. Measurements of heptanoic acid dissolution show that the liquid disc behaves like a solid disc of 10% smaller area. Measurements of linoleic acid solubilization show characteristics of diffusion and surface reaction in series. The surface reaction is apparently controlled by bile salt adsorption.

Estimation of Diffusion Coefficients and Molecular Weights of Interacting Colloids from Dissolution-Rate Data

Based on dissolution-rate theory, diffusion coefficients for the salicylamide-micelle species were calculated from dissolution and solubility data obtained in micellar solutions of sodium taurodeoxycholate and sodium taurocholate at 20°. The calculated values were in good agreement with those determined experimentally using a diffusion cell and silver membrane. By assuming that the solubilized drug does not interfere with the organization of the micelle, the Stokes-Einstein equation was employed to estimate the molecular weight of the micelle. Excellent agreement was found between values calculated from dissolution data and those determined directly by ultracentrifugation or light scattering.

The solubility of cholesterol in aqueous solutions of bile salts and lecithin.

The solubility of cholesterol in aqueous solutions of bile salts and lecithin with N/10 phosphate buffer, pH 7.3 has been examined. For the sodium salts of the six bile acids used in the study, the capacity for dissolving cholesterol was found to decrease in the following order: Glycodeoxycholate, Taurodeoxycholate, Glycochenodeoxycholate, Taurochenodeoxycholate, Glycocholate, Taurocholate. The differences with respect to cholesterol dissolving capacity were greatest when no lecithin was present, and decreased as the amount of lecithin increased. Graphical representations (molar ratio bile salt to cholesterol as abscissa, molar ratio lecithin to cholesterol as ordinate) of the limits for solubility of cholesterol in 100 millimolar solutions of each of the six bile salts to which purified egg lecithin is added in amounts varying from zero to approximately 80 millimoles per 100 millimoles bile salt, had the shape of curved lines tending to converge against a point, approximately 3.5, on the vertical axis but without reaching it. (Fig. 1). The starting points of the curves on the horizontal axis (millimoles bile salt required to dissolve 1 millimole of cholesterol in the absence of lecithin) were: for Glycodeoxycholate 19, for Taurodeoxycholate 30, for Glycochenodeoxycholate 34, for Taurochenodeoxycholate 47, for Glycocholate 52, for Taurocholate 62. The graphical representation, as above, of the limit for solubility of cholesterol in a 100 millimolar solution of a mixture of the six bile salts in relative amounts as in human bile, to which lecithin from human bile is added was practically identical to the corresponding curve for a 100 millimolar solution of glycochenodeoxycholate with additions of purified egg lecithin (Fig. 2.). The starting point on the horizontal axis for the curve representing mixed bile salts could be calculated — with fair approximation — from the cholesterol dissolving capacities of the individual bile salts in the mixture. The graphical representations of the limits for solubility of cholesterol in 50 millimolar, 100 millimolar and 200 millimolar aqueous solutions of sodium taurodeoxycholate to which purified egg lecithin was added in varying amounts did not show any certain differences from each other. Two purified egg lecithins of greatly different fatty acid pattern (Table 1) isolated from eggs of hens fed linoleic acid deficient diets and linoleic acid rich diets respectively, did not show any certain difference from each other with respect to cholesterol dissolving capacity when added in varying amounts to a 100 millimolar solution of sodium taurodeoxycholate.

Micellar properties of bile salts. Sodium taurodeoxycholate and sodium glycodeoxycholate.

Surface-tension, light-scattering, and refractometric measurements were made on aqueous solutions of sodium taurodeoxycholate and sodium glycodeoxycholate in the presence of varying amounts of NaCl or NaI (0–0.5 M). Critical micellar concentrations (c.m.c), molecular areas, refractive index increments, micellar molecular weights and aggregation numbers, and effective charges per micelle were obtained. The two conjugated bile salts exhibited rather similar behavior. The micellar properties of bile salts were much like those of typical anionic detergents. The c.m.c. values were of the order of several millimoles per liter in water, and decreased with increasing concentration of electrolyte. Areas per molecule were in the vicinity of 90 Å2, closely corresponding to the area occupied by the steroid nucleus lying flat at the interface. Aggregation numbers varied from 8 in water to about 50 in 0.5 M electrolyte solutions.

The dimensions of the bile salt micelle. Measurements by gel filtration

Gel filtration has been used for the characterization of detergent solutions. Solutions of sodium taurodeoxycholate and sodium dodecylsulfate 0.15 M in sodium ions have been used in column elution or equilibrium experiments using Sephadex gels. Micelles of these detergents are completely excluded from the G-25 and G-50 gels, respectively. The data indicate a radius of the bile salt and dodecylsulfate micelle (if assumed to be spherical) of 16–20 and 35–50 Å, respectively. These figures are appreciably larger than the micellar size reported from light-scattering data. The discrepancies might be explained by an appreciable hydration of the micelles. Gel filtration can be used for the determination of the partition coefficients of solutes between phases of different physical dimensions when one of the phases is partly or completely excluded from the gel.