An Edge Selection Mechanism for Chirally Selective Solubilization of Binaphthyl Atropisomeric Guests by Cholate and Deoxycholate Micelles.
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.
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania, USA.
Kyle W
KW
Eckenroad
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania, USA.
Gregory A
GA
Manley
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania, USA.
Jenna B
JB
Yehl
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania, USA.
Ross T
RT
Pirnie
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania, USA.
Timothy G
TG
Strein
Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania, USA.
David
D
Rovnyak
D020355:Cholates / Q000737:chemistry*; D020374:Chromatography, Micellar Electrokinetic Capillary; D003840:Deoxycholic Acid / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D009281:Naphthalenes / Q000737:chemistry*; D009284:Naphthols / Q000737:chemistry; D010755:Organophosphates / Q000737:chemistry*; D012995:Solubility; D013237:Stereoisomerism
D020355:Cholates; D009281:Naphthalenes; D009284:Naphthols; D010755:Organophosphates; D003840:Deoxycholic Acid; C107195:1,1'-binaphthyl-2,2'-diyl hydrogen phosphate; C412332:1,1'-bi-2-naphthol
bile acid; chenodeoxycholic acid; cholic acid; deoxycholic acid; micellar electrokinetic capillary chromatography (MEKC); nuclear magnetic resonance (NMR)