Chiral discrimination, using cyclodextrins

H Yamamura, A Akasaki, Y Yamada, K Kano, T Katsuhara, S Araki, M Kawai, T Tsuda. Capillary zone electrophoretic chiral discrimination using cationic cyclodextrin derivative determination of velocity and association... 

Lin X, Zhao M, Qi X, Zhu C, Hao A. Capillary zone electrophoretic chiral discrimination using 6-0-(2-hydroxy-3-tri-methylammoniopropyl)-p-cyclodextrin as a chiral selector. Electrophoresis 2006 27 872-879. 

Lyotropic polymeric LC, formed by dissolving two aromatic polyamides in concentrated sulphuric acid, have been studied using variable-director 13C NMR experiments.324 The experimental line shapes at different angles w.r.t the external field were used to extract macromolecular order and dynamic in these ordered fluids. An interesting application of lyotropic LC is for the chiral discrimination of R- and S-enantiomers, and has recently been demonstrated by Courtieu and co-workers.325 The idea was to include a chiral compound 1-deutero-l-phenylethanol in a chiral cage (e.g., /1-cyclodextrin) which was dissolved and oriented by the nematic mean field in a cromolyn-water system. Proton-decoupled 2H NMR spectrum clearly showed the quad-rupolar splittings of the R- and S-enantiomers. The technique is applicable to water-soluble solutes. 

RJ Tait, DO Thompson, VJ Stella, JF Stobaugh. Sulfobutyl ether /3-cyclodextrin as a chiral discriminator for use with capillary electrophoresis. Anal Chem 66 4013-4018, 1994. 

Reversible inclusion-type complexation, forming diastereomeric [SO-SA] molecule associates, is a favored resolution principle which has also been adapted for CE and MECK126 129. Cyclodextrin and derivatives are superior materials if extremely high efficiency capillary techniques are used. Small chiral discrimination effects are often sufficient for baseline resolution127. 

A variety of chiral alignment media for organic solvents is known with the most widely used and best characterized being the poly(amino acids) PBLG and PCBLL. Both polymers form lyotropic mesophases and possess ot-helical structures for which many examples of enantiomeric differentiation have been shown. In addition to chiral poly(amino acids), it was demonstrated that achiral media with chiral cages like cyclodextrines serve as alignment media with the potential of chiral discrimination.121... 

FITC-labeled amino acids as model compounds were separated in sodium dodecyl sulfate/borate buffer at pH 9.4 with y-cyclodextrin as chiral discriminator. Separation speed achieved with the microchip was one order of magnitude faster than that with conventional CE. Bailey and co-workers demonstrated chiral and achiral separation of amphetamine and analogous compounds labeled with 4-fluoro-7-nitrobenzofurazane on an S-folded separation channel. Phosphate buffer with sulfated y-cyclodextrin and sodium dodecyl sulfate as additives was used. It is expected that chiral separations on microfabricated electrophoresis devices with high speed and high throughput will find its way into pharmaceutical and biomedical sciences as well as into other areas. 

Reliable techniques exist for liquid-liquid extraction of ephedrine from alkaline tissue samples. Gas chromatography-mass spectrometry measurement requires pentafluoropropionic acid derivatization. Blood and tissue measurements have been reported in several ephedrine-related deaths, and in clinical trials with therapeutic doses of the drug (Backer et al., 1997). More recently capillary electrophoresis has been used to separate and identify all 10 stereoisomers of the ephedrine family found in nutritional supplements. Chiral discrimination is effected by using hydroxypropyl-P-cyclodextrin (Flurer et al., 1995). 

Phenoxy acid herbicides, sulfonyl ureas, quaternary ammonium derivatives (quats), and aryloxy propanoic acids are the main classes of compounds subjected to capillary zone electrophoresis (CZE). Triazines are also separated using nonaqueous CZE, while low pfCa characterized chlorotriazines require an ion-pair-like solubilization using cationic surfactants (tetradecylammonium bromide, dodecyltrimethyl-ammonium bromide). Chiral selectors are added in CZE for obtaining enantioselectivity. Chiral selectors used for herbicide enantiomeric discrimination are vancomycin, y-cyclodextrin, ethyl carbonate -cyclo-dextrin, cyclohexyl-alkyl-)S-D-maltoside, sulpropyl ether a-cyclodextrin, and hexakis(2,3-di-0-methyl)-a-cyclodextrin. 

As an alternative, papers have appeared in the thin-layer literature using TLC for chiral separations by putting the chiral discrimination reagent (antibiotic, cyclodextrin, etc.) into the mobile phase. The separations work as well as if the reagents had been coated or bonded to the silica gel (or in some cases, the reversed bonded phase). 

A new chiral reagent, NSP-Cl was synthesized and used to derivatize amino acids and the resulting diastereomers were resolved by TLC (166), Chiralplate with MeCN-MeOH-HjO (4 1 1) as mobile phase was used to evaluate reaction products in the synthesis of modified phe and tyr derivatives (167), and also to separate aspartame and its precursor stereoisomers (168). Tryptophans and substituted tryptophans were separated on cellulose layers developed with copper sulphate solutions (169) when excess of Cu " ions decreased the chiral discrimination of the system, and with aq a-cyclodextrin (1 to 10%) plus NaCl solutions (O.IM, 0.5M, l.OM) when the best results were... 

Kataky et al. described the design of a PYC membrane based on a-, fi-and y-cyclodextrins as chiral selectors [35]. The enantiomers of aryl ammonium ions of pharmaceutical importance can be discriminated and assayed with low limits of detection and high sensitivities using these electrodes. 

The FITC labeling method was also applied to chiral separations of amino acids on a microchip to determine the enantiomeric ratios of amino acids found on a meteorite [27], Since biotic amino acids are normally single enantiomers, chiral separations of amino acids are not truly clinical in nature, but illustrate the potential for chiral separations of small molecules of clinical interest. Ma-thies and co-workers used this technique to search for evidence of life in extraterrestrial environments. Enantiomeric forms of Val, Ala, Glu, and Asp could be discriminated by addition of a-, (3-, or y-cyclodextrin (CD) to the run buffer. Improved resolution with faster separations was found with respect to conventional CE. This method has been modified, by addition of SDS to the buffer, to perform cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) [28]. Increasing the SDS concentration decreased the magnitude of elec-troosmotic flow (EOF), increasing the effective migration distance, and therefore the resolution on the microchips. 

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