Chiral separation by ligand-exchange

Martin G Schmid, Gerald Gübitz


The principle of chiral ligand-exchange, introduced by Davankov, has become a widely used technique for chiral separation in both chromatography and in electromigration techniques. This simple technique makes use of the formation of mixed metal chelate complexes between a chiral selector and both enantiomers of an analyte. In HPLC, the chiral selector can be either bonded to the stationary phase or added to the mobile phase. In CE the chiral selector is simply added to the electrolyte. A relatively new approach represents CEC, where capillaries contain a chiral stationary phase. More than thousand papers appeared in the field of chiral ligand-exchange. To cite all papers would require several books.
The present article gives an overview of both milestones and our activities on chiral separation using the principle of ligand-exchange. Recent advances in chip technology for chiral separations and new approaches regarding improvement of detection sensitivity are mentioned.


ligand-exchange; chiral selectors; chemically bonded phases; dynamically coated phases; monolithic phases; HPLC; capillary electrophoresis; capillary electrochromatography

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Davankov, V. A. and Rogozhin, S. V.: Ligand Chromatography as a Novel Method for Investiga¬tion of Mixed Complexes – Stereoselective Effects in Alpha–Amino Acid Copper(II) Complexes. J. Chromatogr. A, 60, 284–312 (1971).

Rogozhin, S. V. and Davankov, V. A.: USSR patent 308635, (1968).

Rogozhin, S. V. and Davankov, V. A.: Dokl. Akad. Nauk., 193, 94 (1970).

Gübitz, G.: Direct Separation of Enantiomers by High-Performance Ligand-Exchange Chromatog¬raphy on Chemically Bonded Chiral Phases. J. Liq. Chromatogr., 9, 519–535 (1986).

Gübitz, G., Jellenz, W., Löffler, G. and Santi, W.: Chemically Bonded Chiral Stationary Phases for the Separation of Racemates by HPLC. J. High Resol. Chromatogr., 2, 145–146 (1979).

Gübitz, G., Jellenz, W. and Santi, W.: Separation of the Optical Isomers of Amino-Acids by Li¬gand–Exchange Chromatography Using Chemi¬cally Bonded Chiral Phases. J. Chromatogr. A, 203, 377–384 (1981).

Gübitz, G., Juffmann, W. and W., J.: Direct sepa¬ration of amino acid enantiomers by high per¬formance ligand–exchange chromatography on chemically bonded chiral phases. Chromatograph¬ia, 16, 103–106 (1982).

Grobuschek, N., Schmid, M. G., Tuscher, C., Ivanova, M. and Gübitz, G.: Chiral separation of beta-methyl-amino acids by ligand exchange us¬ing capillary electrophoresis and HPLC. J. Pharm. Biomed. Anal., 27, 599–605 (2002).

Gübitz, G. and Mihellyes, S.: Resolution of 2-Hydroxydicarboxylic Acid Enantiomers by Li¬gand–Exchange Chromatography on Chemically Bonded Chiral Phases. J. High. Res. Chrom., 17, 733–734 (1994).

Gübitz, G., Vollmann, B., Cannazza, G. and Schmid, M. G.: Chiral resolution of dipeptides by ligand exchange chromatography on chemically bonded chiral phases. J. Liq. Chromatogr., 19, 2933–2942 (1996).

Gubitz, G. and Juffmann, F.: Resolution of the En¬antiomers of Thyroid-Hormones by High-Perfor¬mance Ligand-Exchange Chromatography Using a Chemically Bonded Chiral Stationary Phase. J. Chromatogr. A, 404, 391–393 (1987).

Gübitz, G., Mihellyes, S., Kobinger, G. and Wutte, A.: New Chemically Bonded Chiral Ligand-Ex¬change Chromatographic Stationary Phases. J. Chromatogr. A, 666, 91–97 (1994).

Roumeliotis, P., Unger, K. K., Kurganov, A. A. and Davankov, V. A.: High-Performance Ligand- Exchange Chromatography of Alpha-Amino-Acid Enantiomers – Studies on Monomerically Bonded 3-(L-Prolyl)Propyl and 3-(L-Hydroxyprolyl)Pro¬pyl Silicas. J. Chromatogr. A, 255, 51–66 (1983).

Davankov, V. A., Navratil, J. D. and Walton, H. F.: Ligand Exchange Chromatography. CRC Press, Inc., Boca Raton, Florida, 1988.

Hyun, M. H., Han, S. C., Lee, C. W. and Lee, Y. K.: Preparation and application of a new ligand exchange chiral stationary phase for the liquid chromatographic resolution of alpha-amino acid enantiomers. J. Chromatogr. A, 950, 55–63 (2002).

Davankov, V. A.: Enantioselective ligand exchange in modern separation techniques. J. Chromatogr. A, 1000, 891–915 (2003).

Davankov, V. A., Bochkov, A. S., Kurganov, A. A., Roumeliotis, P. and Unger, K. K.: Dealing with the Ligand-Exchange Chromatography. 13. Separa¬tion of Unmodified Alpha-Amino-Acid Enantio¬mers by Reversed Phase HPLC. Chromatograph¬ia, 13, 677–685 (1980).

Davankov, V. A., Bochkov, A. S. and Belov, Y. P.: Ligand-Exchange Chromatography of Race¬mates.15. Resolution of Alpha-Amino-Acids on Reversed-Phase Silica-Gels Coated with N-Dec¬yl-L-Histidine. J. Chromatogr. A, 218, 547–551 (1981).

Mohr, S., Kremsmair, C. and Schmid, M. G., in preparation (2010).

Schmid, M. G., Schreiner, K., Reisinger, D. and Gubitz, G.: Fast chiral separation by ligand–ex¬change HPLC using a dynamically coated mono¬lithic column. J Sep Sci, 29, 1470–1475 (2006).

Hare, P. E. and Gil–Av, E.: Separation of D and L Amino Acids by Liquid Chromatography: Use of Chiral Eluants. Science, 204, 1226–1228 (1979).

Lindner, W., Lepage, J. N., Davies, G., Seitz, D. E. and Karger, B. L.: Reversed–Phase Separation of Optical Isomers of Dns-Amino Acids and Peptides Using Chiral Metal Chelate Additives. J. Chro¬matogr. A, 185, 323–343 (1979).

Schmid, M. G.: unpublished results.

Gassmann, E., Kuo, J. E. and Zare, R. N.: Electro¬kinetic Separation of Chiral Compounds. Science, 230, 813–814 (1985).

Gozel, P., Gassmann, E., Michelsen, H. and Zare, R. N.: Electrokinetic Resolution of Amino-Acid Enantiomers with Copper(II) Aspartame Support Electrolyte. Anal. Chem., 59, 44–49 (1987).

Schmid, M. G. and Gübitz, G.: Direct enantiomer separation of underivatized amino acids by cap¬illary zone electrophoresis based on ligand ex¬change. Enantiomer, 1, 23–27 (1996).



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