Capillary chiral recognition

GC-GC has typically been employed for complex samples or those requiring additional chemistry, such as chiral recognition, to be employed along with classical GC separation. Typical GC-GC systems employ multiple capillary columns connected... 

Kuhn, R., Emi, F., Bereuter, T., and Hausler, J., Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis, Anal. Chem., 64, 2815, 1992. 

Phinney et al. [Ill] investigated the application of citrus pectins, as chiral selectors, to enantiomer separations in capillary electrophoresis. Successful enantioreso-lution of primaquine and other antimalarials, was achieved by utilizing potassium polypectate as the chiral selector. Changes in pH, chiral additive concentration, and capillary type were studied in relation to chiral resolution. The effect of degree of esterification of pectin materials on chiral recognition was evaluated. 

Lim, J. M., Nakagama, T, Uchiyama, K., and Hobo, T. (1997). Temperature effect on chiral recognition of some amino acids with molecularly imprinted polymer filled capillary electrochromatography. Biomed. Chromatogr. 11, 298-302. 

B Chankvetadze, G Endresz, G Schulte, D Bergenthal, G Blaschke. Capillary electrophoresis and H NMR studies on chiral recognition of atropisomeric binaphthyl derivatives by cyclodextrin hosts. J Chromatogr A 732 143-150,... 

A chiral selector can also be dissolved in the IL solvent and be subsequently coated on the capillary wall [38]. In this approach, the achiral [C4CiIm]Cl was used to dissolve permethylated p-cyclodextrin (p-PM) and dimethylated P-cyclodextrin (p-DM). The chromatographic separations obtained from these two columns were compared to two commercially available CSPs based on p-PM and p-DM dissolved in polydimethylsiloxane. From a set of 64 chiral molecules separafed by fhe commercial p-PM column, only 21 of the molecules were enantioresolved by the IL-based p-PM column. Likewise, from a collecfion of 80 analytes separated by the p-DM column, only 16 analytes could be separated on the IL-based p-DM column. The authors also noted a considerable enhancement in the separation efficiency of fhe IL-based CSPs. This resulf, coupled to fhe loss of enantioselecfivify for mosf separations, suggests that the imidazolium cation may occupy the cavity of the cyclodextrin preventing the analyte-cyclodextrin inclusion complex-ation that is crucial for chiral recognition. The ability for ILs to form inclusion complexes wifh cyclodextrin molecules has been recently studied by Tran and coworkers using near-infrared spectromefry [39]. 

Figure 26-33 Separation of enantiomers of eight p blocker drugs by micellar electrokinetic chromatography at pH 8.0 in a 120-cm capillary at 30 kV. Micelles were formed by a polymer surfactant containing L-leucinate substituents for chiral recognition. The structure of one compound is shown. [From C. Akbay. S, A. A. Rizvi. and S. A. Shamsi, "Simultaneous Enantiosepcration and Tandem UV-MS Detection of Eight p-Blockers in Micellar Electrokinetic Chromatography Using a Chiral Molecular Micelle Anal. Chem. 2005, 77.1672.]...

Since Pasteur separated crystalline sodium ammonium tartrate manually in 1848, many researchers have worked on the subject of enantiomeric separation. In 1939 Henderson and Rule fully separated derivatives of camphor by column chromatography using lactose as a stationary phase material [1]. Gil-Av et al. [2] were able to separate amino acid derivatives on a polysiloxane-based stationary phase by gas chromatography (GC) in 1966. Since then many approaches for a successful distinction between enantiomers have been developed for capillary GC and liquid chromatography [3]. It is still a current topic for researchers searching for chiral separation with SciFinder [4] results in 812 hits and searching for chiral recognition leads to 285 hits for the year 2003 only. 

The chiral recognition mechanisms in NLC and NCE devices are similar to conventional liquid chromatography and capillary electrophoresis with chiral mobile phase additives. It is important to note here that, to date, no chiral stationary phase has been developed in microfluidic devices. As discussed above polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, proteins, crown ethers, ligand exchangers, and Pirkle s type molecules are the most commonly used chiral selectors. These compounds... 

Hui, F. (2004) High Performance Liquid Chromatography and Capillary Electrophoresis Chiral Recognition Mechanisms Using Glycopeptide Macrocyclic Antibiotics as Selectors, Fenxi Huaxue 32, 964-968. 

There have also been examples of ligand-exchange CSPs. Schmid et al. [159] used a ligand-exchange monomer as a chiral selector. The chiral selector, monomer, cross-linker, and charged monomer were polymerized to produce monolithic capillaries capable of chiral recognition and generation of EOF. The separation is achieved due to the differences in the stability between the ternary mixed copper complexes formed by the enantiomers and the CSP. 

Blaschke, G. Separation of brompheniramine enantiomers by capillary electrophoresis and study of chiral recognition mechanisms of cyclodextrins using NMR spectroscopy, UV spectrometry, electrospray ionization mass spectrometry and X-ray crystallography. J. Chromatogr., A 2000, 875, 471-484. 

The enantiomeric separation of some racemic antihistamines and antimalar-ials, namely (+/-)-pheniramine, (+/-)-bromopheniramine, (+/-)-chlorophen-iramine, (+/-)-doxylamine, and (+/-)-chloroquine, were investigated by capillary zone electrophoresis (CZE). The enantiomeric separation of these five compounds was obtained by addition of 7 mM or 1 % (w/v) of sulfated P-cyclo-dextrin to the buffer as a chiral selector. It was found that the type of substituent and degree of substitution on the rim of the cyclodextrin structure played a very important part in enhancing chiral recognition (174). The use of sulfated P-cyclo-dextrin mixtures as chiral additives was evaluated for the chiral resolution of neutral, cyclic, and bicyclic monoterpenes. While there was no resolution of the monoterpene enantiomers with the sulfated P-cyclodextrin, the addition of a-cyclodextrin resulted in mobility differences for the terpenoid enantiomers. Resolution factors of 4-25 were observed. The role of both a-cyclodextrin and sulfated P-cyclodextrin in these separations was discussed (187). The enantiomeric separation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antimalarials, relaxants, and broncodilators, was studied. The separations were obtained at pH 3.8 with the anode at the detector end of the capillary. Most of the 40 successfully resolved enantiomers contained a basic functionality and a stereogenic carbon (173). 

A commercial CE system and a micropacked capillary was used to separate N—, O—, and S-containing heterocyclic compounds. Migration time reproducibility, linearity, and detector response was found to be comparable to HPLC. A study of the heterocyclic compound s elution order followed that predicted by the octanol-water partition coefficients (354). While chiral CEC provides improved resolution and higher efficiencies, additional work is needed since chiral CEC capillaries are not available commercially. The separation principles and chiral recognition mechanism for the separation of enantiomers have been reviewed (355). Furthermore, a comprehensive collection of drug applications and other compounds of interest has been reported (356). Direct enantiomeric separations by CEC were studied using a capillary packed with alpha-1-acid glycoprotein chiral stationary phase (357). Chiral resolution was achieved for enantiomers of benzoin, hexobarbital, pentobarbital, fosfamide, disopyramide, methoprolol, oxprenolol, and propanolol. The effects of pH, electrolyte concentration, and con-... 

LJ Jin, SF Li. Comparison of chiral recognition capabilities of cyclodextrins for the separation of basic drugs in capillary zone electrophoresis. J Chromatogr B 708 257-266, 1998. 

The computational studies described above are representative examples meant to illustrate the diversity of computational techniques used to assess chiral recognition by cyclodextrins in chiral chromatography. Other published examples include the use of molecular mechanics to describe shapes of aminoalkylphosphonic acids binding to a covalently linked acetylated cyclodextrin [72], the computation of free energies of atenolol binding to a perphenylcarbamate-p-cyclodextrin likewise covalently bound to silica gel [73], and studies of cyclodextrins used as chiral mobile phase additives in reverse-phase HPLC [74] and in capillary electrophoresis [75]. 

Chromatography is one of the most important methods for direct studies of molecular and chiral recognition by CyDs. Today it has split into several branches, e.g. gas chromatography, GC, high-performance liquid chromatography, HPLC, and capillary electrophoresis and other electromigration techniques, that enable us not only to detect the recognition but also to estimate the complex stoichiometry and formation constant and, consequently, the enthalpies and entropies of complex for-... 

Lin, J.M. Nakagama, T. Wu, X.-Z. Uchiyama, K. Hobo, T. Capillary electrochroma-tographic separation of amino acid enantiomers with molecularly imprinted polymers as chiral recognition agents. Fresenius J. Anal. Chem. 1997, 357, 130-132. 

Figure 2 Enantiomer separation of aliphatic oxiranes by com-plexation gas chromatography on nickel(ii) bis[3-(heptafluoro-butanoyl)-(1S)-19-ethylidene-camphorate] (0.125molkg in OV-101) between 70°C and 90°C. Column 25m x 0.25mm (i.d.) glass capillary. (From Schurig V and Betschinger F (1992) Metal-mediated enantioselective access to unfunctionalized aliphatic oxiranes prochiral and chiral recognition. Chemical Reviews 92 873-888.)...

Chiral recognition for 1-phenylethylamine perchlorate(6). Extraction of aqueous 1-phenylethylamine perchlorate(6) with crown ethers(4) and the determination of the amount of extracted amine was carried out by the same procedure as described for a-phenylglycine methyl ester perchlorate. Another 10 ]ll portion of organic phase was derivatized with (-)-(L) N-trifluoroacetylalanine and used for the determination of CRF by GLC(OV-17 coated glass capillary column at 160 °C). 

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