Ligand exchange chromatography

Achiral Columns Together with Chiral Mobile Phases. Ligand-exchange chromatography for chiral separation has been introduced (59), and has been appHed to the resolution of several a-amino acids. Prior derivatization is sometimes necessary. Preparative resolutions are possible, but the method is sensitive to small variations in the mobile phase and sometimes gives poor reproducibiUty. 

An extensive review of ligand-exchange chromatography has been given by Davankov.40... 

Ligand exchange chromatography. H. F. Walton, Ion Exch. Solvent Extr., 1973, 4,121-153 (58). 

Galli, B. et al., Enantiomeric separation of DNS-amino acids and DBS-amino acids by ligand exchange chromatography with (5) - and (R)-phenylalaninamide modified silica gel, J. Chromatogr. A, 666,11, 1994. 

Chiral ligand-exchange chromatography (CLEC) ° separates enantiomers by the formation of diastereomeric metal complexes. In a first instance the technique was mainly used for the separation of amino acids. Impressive results of the first separations gave rise to intensive investigation in the field and numerous publications appeared in the literature, which have been reviewed. 

TABLE 4 Examples of Chiral Separations in Chiral Ligand-Exchange Chromatography... 

Based on preliminary results from Helfferich130, further developments by Davankov and co-workers5 131 133 turned the principle of chelation into a powerful chiral chromatographic method by the introduction of chiral-complex-forming synlhetie resins. The technique is based on the reversible chelate complex formation of the chiral selector and the selectand (analyte) molecules with transient metal cations. The technical term is chiral ligand exchange chromatography (CLEC) reliable and complete LC separation of enantiomers of free a-amino acids and other classes of chiral compounds was made as early as 1968 131. 

Figure 19. Resolution of analytes by chiral ligand exchange chromatography (CLEC). A hydroxy acids (reprinted with permission from ref 138) B dansyl amino acids (reprinted with permission from ref 139),...

Ligand Exchange Chromatography, V. A. Da-vankov, J. D. Navratil, H. F. Walton, Eds., CRC Press, Boca Raton 1988. 

C Tao, TB Huang. Resolution of DL-a-amino acids on a L-hydroxyproline chiral phase by ligand-exchange chromatography. Chin Chem Lett 6 383-384, 1995. 

A useful extension of the ion-exchange concept is ligand-exchange chromatography. 

A modification of the pyridoxal—amino acid reaction (mentioned above) has been made for automatic analysis of amino acids by ligand-exchange chromatography [95]. This technique involves separation of the amino acids prior to fluorimetric reaction and determination. As the amino acids are eluted from the column, they are mixed with the pyridoxal-zinc(II) reagent to produce a highly fluorescent zinc chelate. Amounts of as low as 1 nmole of amino acid may be detected. The first reaction involved is the formation of the pyridoxyl-amino acid (Schiff base) as in Fig.4.46. The zinc then forms a chelate which probably has the structure shown in Fig. 4.48. 

With the development of the chiral ligand exchange chromatography by Davan-kov, this technique has been used frequently for the chiral resolution of racemic compounds containing electron-donating atoms. It is useful for providing the basic information on the chiral resolution and, hence, is still in use. In spite of this, there are some limitations with this chiral resolution technique. The most... 

Davankov VA, Navratil JD, Walton HF. Ligand Exchange Chromatography, CRC Press, Boca Raton, FL (1988). 

Davankov, V.A. (1980) Resolution of racemates by ligand exchanges chromatography, Adv. Chromatogr. 18, 139-195. 

V. A. Davankov and A. A. Kurganov, The role of achiral sorbent matrix in chiral recognition of amino acid enantiomers in ligand-exchange chromatography, Chromatographia, 77 696 (1983). 

Chiral ligand-exchange chromatography resolves enantiomers on the basis of their ability to complex with transition metal ions, such as copper, zinc, and cadmium, as illustrated by the separation of amino acid racemates using copper102 (Fig. 2.21). The principle of exchange is similar to that... 

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