Chiral separations with cyclodextrins

Rawjee, Y.Y., Stark, D.U., Vigh, G. Capillary electrophoretic chiral separations with cyclodextrin additives I. acids Chiral selectivity as a function of pH and the concentration of P-cyclodextrin for fenoprofen and ibuprofen. J. Chromatogr. 1993, 635, 291-306. 

F Lelievre, P Gareil, A Jardy. Selectivity in capillary electrophoresis application to chiral separations with cyclodextrins. Anal Chem 69 385—392, 1997. 

Matthijs, N., Perrin, C., Maftouh, M., Massart, D.L., Vander Heyden, Y. Knowledge-based system for method development of chiral separations with capillary electrophoresis using highly sulphated cyclodextrins. J. Pharm. Biomed. An. 2002, 27, 515-529. 

F Lelievre, P Gareil, Y Bahaddi, H Galons. Intrinsic selectivity in capillary electrophoresis for chiral separations with dual cyclodextrin systems. Anal Chem 69 393-401, 1997. 

Investigation with the two optical transduction principles mentioned before confirmed the preferential enrichment of the S-enantiomer resulting in more than ninefold higher signals, which is the highest separation factor found for chiral separation on cyclodextrins up to now. The good agree-... 

Huynh, T.K.X. Lederer, M. Adsorption chromatography on cellulose. XL Chiral separations with aqueous solutions of cyclodextrins as eluents. J. Chromatogr. 1994, 659, 191-197. 

F Wang, MG Khaledi. Non-aqueous capillary electrophoresis chiral separations with sulfated beta-cyclodextrins. J Chromatogr B 731 187-197, 1999. 

Wang F, Khaledi M (1998) Nonaqueous capillary electrophoresis chiral separations with quaternary ammonium P-cyclodextrin. J Chromatogr A 817 121-128... 

Catechin and epicatechin are two flavanols of the catechin family. They are enantiomers. The capillary zone electrophoresis (CE) methods with UV-detection were developed for quantitative determination of this flavanols in green tea extracts. For this purpose following conditions were varied mnning buffers, pH and concentration of chiral additive (P-cyclodextrin was chosen as a chiral selector). Borate buffers improve selectivity of separation because borate can make complexes with ortho-dihydroxy groups on the flavanoid nucleus. 

Figure 3.7 [continued) (b) Chromatograms of (iii) the dichloromethane extract of strawberry fruit yoghurt analysed with an apolar primary column, with the heart-cut regions indicated, and (iv) a non-racemic mixture of y-deca-(Cio) and 7-dodeca-Cj2 lactones isolated by heart-cut transfer, and separated by using a chiral selective modified cyclodextrin column. Reproduced from A. Mosandl, et al J. High Resol. Chromatogr. 1989, 12, 532 (39f. 

Righetti and co-workers [11] were one of the first to demonstrate the utility of classical isoelectric focusing for the chiral separation of small molecules in a slab gel configuration. In their system, dansylated amino acids were resolved enan-tiomerically through complexation with (i-cyclodextrin. Preferential complexation between the cyclodextrin and the derivatized amino acid induced as much as a 0.1 pH unit difference in the pK s of the dansyl group. 

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

Walhagen, A., Edholm, L.E. (1991). Chiral separation of achiral stationary phases with different functionalities using P-cyclodextrin in the mobile phase and applications to bioanalysis and coupled columns. Chromatographia 32, 215-223. 

Lin et al. [95] used capillary electrophoresis with dual cyclodextrin systems for the enantiomer separation of miconazole. A cyclodextrin-modified micellar capillary electrophoretic method was developed using mixture of /i-cyclodextrins and mono-3-0-phenylcarbamoyl-/j-cyclodextrin as chiral additives for the chiral separation of miconazole with the dual cyclodextrins systems. The enantiomers were resolved using a running buffer of 50 mmol/L borate pH 9.5 containing 15 mmol/L jS-cyclodextrin and 15 mmol/L mono-3-<9-phcnylcarbamoyl-/j-cyclodextrin containing 50 mmol/L sodium dodecyl sulfate and 1 mol/L urea. A study of the respective influence of the /i-cyclodcxtrin and the mono-3-(9-phenylcarbamoyl-/i-cyclodextrin concentration was performed to determine the optical conditions with respect to the resolution. Good repeatability of the method was obtained. 

Anions and uncharged analytes tend to spend more time in the buffered solution and as a result their movement relates to this. While these are useful generalizations, various factors contribute to the migration order of the analytes. These include the anionic or cationic nature of the surfactant, the influence of electroendosmosis, the properties of the buffer, the contributions of electrostatic versus hydrophobic interactions and the electrophoretic mobility of the native analyte. In addition, organic modifiers, e.g. methanol, acetonitrile and tetrahydrofuran are used to enhance separations and these increase the affinity of the more hydrophobic analytes for the liquid rather than the micellar phase. The effect of chirality of the analyte on its interaction with the micelles is utilized to separate enantiomers that either are already present in a sample or have been chemically produced. Such pre-capillary derivatization has been used to produce chiral amino acids for capillary electrophoresis. An alternative approach to chiral separations is the incorporation of additives such as cyclodextrins in the buffer solution. 

Liu, L., Nussbaum, M.A. Systematic screening approach for chiral separations of basic compounds by capillary electrophoresis with modihed cyclodextrins. J. Pharm. Biomed. An. 1999,19, 679-694. 

Extensive comparisons between GC and SFC have been reported in chiral separation [63-66]. Zoltan investigated the performance of SFC and GC using the same chiral capillary columns coated with cyclodextrin-based stationary phases. It was observed that chiral selectivity was higher in GC than in SFC using the same open tubular column at the identical temperature (e.g., >100°C). However, the selectivity in SFC was significantly increased at low temperatures, especially for polar compounds [67]. 

Analysis using a CMPA is usually resolved on a nonchiral column. A transient diastereomeric complex is formed between the enantiomer and the chiral component in the mobile phase, similar to the complexes formed with chiral stationary phases. A review by Liu and Liu (2002) cites several papers where addition of CPMAs has been used in analyzing amphetamine-related compounds. Some CPMAs include amino acid enantiomers, metal ions, proteins, and cyclodextrins. Advantages of this method of analysis include the use of less expensive columns and more flexibility in the optimization of chiral separation (Misl anova and Hutta, 2003). 

CE has been applied extensively for the separation of chiral compounds in chemical and pharmaceutical analysis.First chiral separations were reported by Gozel et al. who separated the enantiomers of some dansylated amino acids by using diastereomeric complex formation with Cu " -aspartame. Later, Tran et al. demonstrated that such a separation was also possible by derivatization of amino acids with L-Marfey s reagent. Nishi et al. were able to separate some chiral pharmaceutical compounds by using bile salts as chiral selectors and as micellar surfactants. However, it was not until Fanali first showed the utilization of cyclodextrins as chiral selectors that a boom in the number of applications was noted. Cyclodextrins are added to the buffer electrolyte and a chiral recognition may... 

---