Enantiomeric separations by use of polymeric surfactant electrokinetic chromatography

This review surveys the enantiomeric separation of drugs by electrokinetic chromatography using polymeric chiral surfactant pseudostationary phases. These phases have recently been shown to provide better mass transfer and increased rigidity and stability than regular micelles in micellar capillary electrophoresis. Characterization of the polymeric chiral surfactants is presented. Solution interactions of the pseudostationary phases via thermodynamics and fluorescence probe studies are evaluated. Also, case studies of enantiomeric separation of drugs using a single amino acid surfactant and the synergistic effect of the addition of γ-cyclodextrin to the buffer is discussed. The use of dipeptide surfactants for chiral drug separations is described as well. Copyright (C) 2000 Elsevier Science B.V

Capillary Zone Electrophoresis of Bile Acids with Indirect Photometric Detection

Investigations in our laboratory have demonstrated that capillary zone electrophoresis (CZE) with indirect photometric detection is a viable approach to the separation and identification of free bile acids along with their taurine and glycine derivatives. Various parameters such as pH, organic solvent concentrations, column temperature, and type of chromophore electrolyte were investigated to optimize the electrophoretic separation and to maximize the peak capacity. The quality of separation of bile acids can be dramatically improved by incorporating y-cyclodextrin (γ-CD) in the running electrolyte. This improvement in resolution is accompanied by a decreased migration time, suggestive of an increase in association of γ-CD with bile acids. As a result, a CZE separation of all 15 bile acids was possible in ∼30 min using 5 mM adenosine 5′-monophosphate, 7 mM γ-CD in 75% (v/v) methanol at pH 7.0

Characterization and thermodynamic studies of the interactions of two chiral polymeric surfactants with model substances: Phenylthiohydantoin amino acids

Analytical ultracentrifugation is used for determination of the molecular weights and the sedimentation coefficients of poly(sodium undecanoyl-L-valinate) (PSUV) and poly(sodium undecanoyl-L-threoninate) (PSUT) at different temperatures. Plots of absorbance as a function of radius indicates that both PSUV and PSUT are highly monodispersed. A method for evaluating the partial specific volumes using density measurements is presented. The partial specific volumes of PSUV are slightly higher than those of PSUT. In addition, the temperature dependence of the retention factor in electrokinetic chromatography was used to estimate the enthalpy, the entropy, and the Gibbs free energy of the surfactant/analyte complexes. Five phenylthiohydantoin-DL-amino acids were separated and each enantiomeric pair was completely resolved. Comparison of the thermodynamic values obtained with PSUV vs PSUT using a van\u27t Hoff relationship suggests that PSUT, with a less favorable free energy change (i.e., less negative A(AG)), generates a more positive entropy change, hence slightly less chiral resolution

Capillary electrophoretic separation of binaphthyl enantiomers with two polymeric chiral surfactants: \u3csup\u3e1\u3c/sup\u3eH-nuclear magnetic resonance and fluorescence spectroscopy study

The use of the water-soluble polymeric chiral surfactants (PCS), sodium N-undecanoyl-L-valinate (poly-L-SUV) and sodium undecanoyl-L-isoleucinate (poly-L-SUI) as buffer additives in electrokinetic chromatography (EKC) afforded the separation of racemic mixtures of 2,2\u27-dihydroxy-1,1\u27-binaphthyl (BOH) and 1,1\u27-binaphthyl-2,2\u27-diyl hydrogen phosphate (BNP). The apparent binding constants of the PCS to the enantiomers of BNP and BOH were obtained through 1H-nuclear magnetic resonance (1H-NMR) titrations and fluorescence spectroscopy, respectively. The 1H-NMR titration studies show that the BNP enantiomers are localized in the hydrophobic micellar pockets of PCS and form complexes of a 1:1 stoichiometry. The binding constants of PCS of BOH were determined from a Benesi-Hildebrand treatment of the fluorescence data. The EKC data corroborate those of the binding constants, supporting the formation of inclusion complexes. A model rationalizing the chiral discrimination of the enantiomers of BNP is proposed based on the intermolecular interactions observed in 1H-NMR data

Chiral separation with dipeptide-terminated polymeric surfactants: The effect of an extra heteroatom on the polar head group

Chiral recognition of two binaphthyl derivatives and three benzodiazepines were studied by use of polymeric surfactants in electrokinetic chromatography. Four specific dipeptide terminated (multichiral) micelle polymers were synthesized for this study. These include poly (sodium-N-undecanoyl-L-alanyl-leucinate)-(poly L-SUAL), poly (sodium-N- undecanoyl-L-valyl-leucinate) (poly L-SUVL), poly (sodium-N-undecanoyl-L- seryl-leucinate) (poly L-SUSL), and poly(sodium-N-undecanoyl-L-threonyl- leucinate) (poly L-SUTL). In addition to the chiral separation study, the physicochemical properties (critical micelle concentration and specific rotation) of each polymer were investigated. The molecular weights of the various dipeptide-terminated micelle polymers were determined using analytical ultracentrifugation. These dipeptide-terminated micelle polymers were designed to study the effect of the extra heteroatom at the polar head group of the micelle polymer (i.e., poly L-SUSL compared to poly L-SUAL and poly L-SUTL compared to poly L-SUVL) on the enantiomeric separation of the binaphthyl derivatives and benzodiazepines. The synergistic effect of three chiral centers (poly L-SUTL) provided improved resolution over that of two chiral centered dipeptide-terminated micelle polymer in the case of (±)- temazepam, (±)-oxazepam, (±)binaphthol, and (±)-binaphthol phosphate. The chiral recognition mechanisms in these cases were additionally controlled by the presence of the extra heteroatom located on the polar head group of the micelle polymers

GR 24 enantiomers: Synthesis, NMR spectroscopy, X-ray crystallography, and separation by chiral electrokinetic capillary chromatography

Chiral discrimination of enantiomers of 2-methyl-4-(2-oxo-2,3,3a,8b-tetrahydro-4H-indeno[1,2b]furan-3-yl-idenemethoxy )but-2-en-4-olide (commonly referred to as GR 24) by three polymeric chiral surfactants (PCS) is studied by use of chiral polymeric surfactant capillary electrophoresis (CPSCE). The CPSCE results indicate that the optical configurations of valine residues on the PCS backbone affect chiral resolution and elution order of GR24 stereoisomers. The L- and D-forms of poly(sodium N-undecanoyl valinate) provide baseline separation of all four enantiomers while the DL-form separates diastereomers of GR 24 (1). A model is presented rationalizing the migration behavior and chiral resolution of 1 in CPSCE. The actual configuration of the stereogenic centers of GR 24 and 3-[(2,5-dihydro-3-methyl-2-oxo-5-furanyl)oxo]-methylene-3,3a,6,6a-tetrahydro- 2H-cyclopenta[b]furan-2-one (GR 7) is established by a concerted application of high-resolution nuclear magnetic resonance spectroscopy and X-ray crystallography

Spectroscopic studies of cyclodextrin complexes with 2,5-bis-(4-methylphenyl)oxazole

The complexation of γ-cyclodextrins (γ-CDs) with the guest molecule 2,5-bis-(4-methylphenyl)oxazole (MPPO) has been studied by use of fluorescence spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and dynamic light scattering (DLS). The changes in the 1H NMR aromatic signals of MPPO in aqueous γ-CD provide evidence of complexation and inclusion. DLS was used to confirm the existence of a distribution of the aggregates in the nanometer range. Excimer fluorescence was pronounced in the presence of γ-CD. The evidence of the existence of two species was shown through fluorescence lifetime data. The emission intensities of the steady state fluorescence and the fluorescence anisotropies of the linear aggregates revealed a phase transition temperature of 60 °C