Two-Dimensional NMR Study on the Structures of Micelles of Sodium Taurocholate

Abstract

The aggregation behavior of sodium taurocholate (TC) in deuterium oxide without salt was investigated by one-and two-dimensional NMR spectroscopy. Analysis of the concentration dependence of the chemical shift suggests that TC forms a dimer and a pentamer. The equilibrium constants of dimerization and pentamerization are close to those already determined by chromatography in the presence of 154 mM sodium chloride. The structure of the dimer is estimated from the NOESY and ROESY spectra of a 8 mM TC solution and molecular mechanics calculations. The inter-proton distances calculated from the molecular mechanics structure are consistent with the NOE and ROE intensities, whereas those calculated from the X-ray crystal structure (hydrogen-bonded structure) are inconsistent. The molecular mechanics structure is stabilized by hydrophobic interactions between the steroid nuclei and by reduced electrostatic repulsion between the sulfonate ions. The local structures of the pentamer are estimated on the basis of the ROESY spectrum of a 30 mM TC solution. The pentamer of TC is formed mainly by hydrophobic interactions. Thus, a novel NMR method in surfactant chemistry has provided the first step to resolve the 20-year debate about the structures of dimers and micelles of TC. This novel approach in surfactant chemistry will serve to estimate the structures of micelles of other natural and synthetic surfactants.

Study on Micelle Formation of Bile Salt Using Nuclear Magnetic Resonance Spectroscopy

“…5, the pair of 18 and 19 methyl groups can mutually interact with each other and induce aggregation. This antiparallel aggregation model with back-to-back faces has been discussed in previous reports 4,10,12,15,16 . Of course, aggregates or the basic units are not composed of only 2 molecules, but are contain a large number of bile salt molecules.…”

“…In particular, two-dimensional 1 H-NMR was used to directly determine the key protons involved in micelle formation 12,15,17 .…”

Spectral investigation of the conformation of primary and secondary micelles of sodium cholate and the impact of pH and salt concentration.

“…2D spectra for 1 mM and 8 mM naTC were compared and additional cross-peaks were observed suggesting the dimerization of TC. 47 Increasing the concentration to 30 mM showed new cross-peaks that were not observed at 8 mM, at this higher concentration these new contacts were due to the presence of primary micelles. 47 Similar studies were conducted for sodium taurodeoxycholate (NaTDC) using one-and two-dimensional NMR.…”

“…47 Increasing the concentration to 30 mM showed new cross-peaks that were not observed at 8 mM, at this higher concentration these new contacts were due to the presence of primary micelles. 47 Similar studies were conducted for sodium taurodeoxycholate (NaTDC) using one-and two-dimensional NMR. 8 NaTDC and NaTC are bile salts that differ only in the number of hydroxyl groups.…”

“…Six possible dimeric fragments of NaTC and NaTDC micelles were considered for dimerization shown in Figure 1-7. 8,47 There are three types of interactions that stabilize these dimers.…”