Low molecular weight selector

Different classifications for the chiral CSPs have been described. They are based on the chemical structure of the chiral selectors and on the chiral recognition mechanism involved. In this chapter we will use a classification based mainly on the chemical structure of the selectors. The selectors are classified in three groups (i) CSPs with low-molecular-weight selectors, such as Pirkle type CSPs, ionic and ligand exchange CSPs, (ii) CSPs with macrocyclic selectors, such as CDs, crown-ethers and macrocyclic antibiotics, and (iii) CSPs with macromolecular selectors, such as polysaccharides, synthetic polymers, molecular imprinted polymers and proteins. These different types of CSPs, frequently used for the analysis of chiral pharmaceuticals, are discussed in more detail later. 

Low-molecular-weight selectors/ Pirke-type selectors [29]... 

The most frequently used CSPs for biological applications in the reversed-phase mode are based on macrocyclic antibiotics, proteins, or oligosaccharides, but some of the applications utilize phases based on polysaccharides, low-molecular-weight selectors, crown ethers, or columns based on immunoaffinity techniques (Table 17.5). 

In a different concept chiral ion-exchange type CSPs based on low molecular weight selectors have been developed. These systems have certain advantages, as listed below. 

In addition to the classification of liquid chromatographic enantioseparation methods by technical description, these methods could further be classified according to the chemical structure of the diverse CSPs. The chiral selector moiety varies from large molecules, based on natural or synthetic polymers in which the chirality may be based on chiral subunits (monomers) or intrinsically on the total structure (e.g., helicity or chiral cavity), to low molecular weight molecules which are irreversibly and/or covalently bound to a rigid hard matrix, most often silica gel. 

Due to the low molecular weight of the selector, high molar SO coverages can be achieved in the immobilization step, leading to high loadability in (semi)preparative separations. 

Recent strategies in CSP development and optimization related to the Pirkle concept and to low molecular weight synthetic chiral selectors. In the attempt to proceed more effectively with the development of new tailor-made CSPs, solid-phase syntheses and combinatorial chemistry approaches involving SO and/or CSP libraries have been tested. 

A CSP consists of a chiral selector, which either alone constitutes the stationary phase or which has been immobilised to a solid phase. The chiral selector is a low molecular weight compound or a polymer, either synthetic or natural. A broad range of CSPs has been developed. Examples of CSPs that have been used successfully include polysaccharides, such as cellulose and its derivatives [6] and cyclodex-trins [7], and proteins, e.g. bovine serum albumin, aj-acid glycoprotein, cellulase, trypsin and a-chymotrypsin [8]. Several different synthetic polymers have also proven to be useful CSPs, for example the Blaschke-type CSPs (polyacrylamides and polymethacrylamides) [9] and the Pirkle-type CSPs [10]. 

Rizkov et al. ° used L-and D- 3-amino alcohols for the enantioseparation of, among others, dansylated (Dns) AAs by CZE in a low-molecular-weight organogel (LMOG)-filled capillary. This LMOG is a fibrillar gel of trans-(15,2S)-l,2-bis-(dodecylamido) cyclohexane in MeOH. Bare fused-silica capillaries with an i.d. of 100 fim and a total length of 60.0 cm (52.0 cm effective length) were used. The BGE contained 10-mM 3-amino alcohol and 5-mM cupric acetate monohydrate in MeOH with pH 5. The selector copper-valinol (2 1) performed best compared... 

Rizkov D, Mizrahi S, Cohen S, Lev O. (i-Amino alcohol selectors for enantioselective separation of amino acids by ligand-exchange capillary zone electrophoresis in a low molecular weight organogel. Electrophoresis 2010 31 3921-3927. 

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