An Edge Selection Mechanism for Chirally Selective Solubilization of Binaphthyl Atropisomeric Guests by Cholate and Deoxycholate Micelles

Abstract

Combining micellar electrokinetic capillary chromatography (MEKC) and nuclear magnetic resonance (NMR) experimentation, we shed light on the structural basis for the chirally selective solubilization of atropisomeric binaphthyl compounds by bile salt micelles comprised of cholate (NaC) or deoxycholate (NaDC). The model binaphthyl analyte R,S-BNDHP exhibits chirally selective interactions with primary micellar aggregates of cholate and deoxycholate, as does the closely related analyte binaphthol (R,S-BN). Chiral selectivity was localized, by NMR chemical shift analysis, to the proton at the C12 position of these bile acids. Correspondingly, MEKC results show that the 12α-OH group of either NaC or NaDC is necessary for chirally selective resolution of these model binaphthyl analytes by bile micelles, and the S isomer is more highly retained by the micelles. With NMR, the chemical shift of 12β-H was perturbed more strongly in the presence of S-BNDHP than R-BNDHP. Intermolecular NOEs demonstrate that R,S-BNDHP and R,S-BN interact with a similar hydrophobic planar pocket lined with the methyl groups of the bile salts, and are best explained by the existence of an antiparallel dimeric unit of bile salts. Finally, chemical shift data and intermolecular NOEs support different interactions of the enantiomers with the edges of dimeric bile units, indicating that R,S-BNDHP enantiomers sample the same binding site preferentially from opposite edges of the dimeric bile unit. Chirality 28:525-533, 2016. © 2016 Wiley Periodicals, Inc.

Direct Measurement of the Thermodynamics of Chiral Recognition in Bile Salt Micelles

“…39 The small enthalpic differences that correlate with chiral recognition are on the order of small changes in van der Waals interactions between Rand S-BNDHP binding by bile micelles. Together with NMR data indicating that R-and S-BNDHP utilize the same binding pocket but with only slight changes in binding affinity, 40 these small enthalpic changes appear to support a model that localizes the heat of chiral selection to contacts between the guest and the bile micelle that are not in the common binding pocket. That is, the thermodynamic data are consistent with a model in which one naphthyl ring is inserted into a conserved binding site, but the other ring has subtle differences in contacts with the micelle surface and/or the solvent shell around the system, and it is the latter interactions that give rise to the observed difference in heat.…”

Bile Salts in Chiral Micellar Electrokinetic Chromatography: 2000–2020

“…These were called the primary and the secondary micelles. This was confirmed by Rovnyak and co-workers in a series of four papers using data gathered from MEKC and proton nuclear magnetic resonance spectroscopy ( 1 H NMR) [ 16 , 17 , 32 , 33 ]. They used R,S -binaphthyl-1,1′-diylhydrogenphosphate as an analyte.…”

“…These compounds act to emulsify and solubilize fatty acids, monoglycerides, cholesterol and fat-soluble vitamins in human and mammalian digestive systems [ 12 , 13 ]. As such, they have also been shown to solubilize various lipophilic molecules, such as drugs [ 14 , 15 ], vesicles [ 13 ] and model compounds [ 16 ]. Following the use of bile salts as CS in MEKC, other naturally derived chiral surfactants such digitonin and saponins and synthetic surfactants such as amino-acid-based surfactants, glycosidic surfactants and molecular micelles have been utilized for the chiral MEKC of small molecules.…”

Oxidation of Sodium Deoxycholate Catalyzed by Gold Nanoparticles and Chiral Recognition Performances of Bile Salt Micelles

“…It should be noted that for R,S-BNDHP in a higher concentration of NaDC solution the Cotton effect at the short wavelength was gradually weakened (Figure 6b), which meant that the coupling effect of transition dipoles between the two naphthyl moieties was weakened. It is well known that NaDC molecules form micelles at high concentrations, which provides a hydrophobic environment capable of accommodating guest molecules [41][42][43][44][45][46][47]. It is supposed that one of the naphthyl moieties of the BNDHP is embedded in the micelles, which results in the weakening of the coupling between the two naphthyl moieties.…”