Mobile-phase-additive ligand-exchange

In view of the importance of chiral resolution and the efficiency of liquid chromatographic methods, attempts are made to explain the art of chiral resolution by means of liquid chromatography. This book consists of an introduction followed by Chapters 2 to 8, which discuss resolution chiral stationary phases based on polysaccharides, cyclodextrins, macrocyclic glyco-peptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ethers. The applications of other miscellaneous types of CSP are covered in Chapter 9. However, the use of chiral mobile phase additives in the separation of enantiomers is discussed in Chapter 10. 

TABLE 3 Chiral Resolution of Some Racemic Compounds Using Ligand Exchangers as the Mobile Phase Additives... 

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... 

The ligand-exchange process has been applied as a mobile-phase-additive technique for enantioseparations. It involves the formation of a dissociable diastereoisomeric complex between a homochiral additive and a heterochiral solute about a central metal ion (Fig. 28). The mobile phase contains both the homochiral ligand and the metal ion as additive components. These species probably exist as the fully complexed species with at least two molecules of the homochiral... 

Since enantiomer separation requires the Intervention of some chiral agent, one may utilize either chiral mobile phase additives (CMPA) or chiral stationary phases (CSPs). While the requirement that one add a chiral substance to the mobile phase has obvious limitations for preparative separations, it is not a serious problem for analytical separations. Indeed, for some types of compounds (e.g. amino acids) this approach may be preferred. Quite an extensive literature exists for the use of mobile phases containing chiral bidentate ligands and copper ions for the "ligand exchange" resolution of underlvatized amino acids (1, 2) and for N-dansyl derivatives of amino acids Tartaric acid derivatives have also been used as CMPAs (5). 

Type IV includes chiral phases that usually interact with the enantiomeric analytes through the formation of metal complexes. There are usually used to separate amino acid enantiomers. These types of phases are also called ligand exchange phases. The transient diastereomeric complexes are ternary metal complexes between a transitional metal (usually Cu +), an amino acid enantiomeric analyte, and another compound immobilized on the CSP which is able to undergo complexation with the transitional metal (see also the ligand exchange section. Section 22.5). The two enantiomers are separated based on the difference in the stability constant of the two diastereomeric species. The mobile phases used to separate such enantiomeric analytes are usually aqueous solutions of copper (II) salts such as copper sulfate or copper acetate. To modulate the retention, several parameters—such as the pH of the mobile phase, the concentration of the copper ion, or the addition of an organic modifier such as acetonitrile or methanol in the mobile phase—can be varied. 

Fig. 9.5. Some coordination complexes of copper, cobalt and zinc formed during ligand exchange chromatography. 1 and 3 represent those immobilised on silica. Proline is a popular ligand and is also used as a chiral additive to the mobile phase.

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