Chiral selectors interaction with solute

Additional substances (buffer additives) are often added to the buffer solution to alter selectivity and/or to improve efficiency, and the wall of the capillary may be treated to reduce adsorptive interactions with solute species. Organic solvents, surfactants, urea and chiral selectors are among the many additives that have been recommended (table 4-24). Many alter or even reverse the EOF by affecting the surface charge on the capillary wall, whilst some help to solubilize hydrophobic solutes, form ion-pairs, or minimize solute adsorption on the capillary wall. Chiral selectors enable racemic mixtures to be separated by differential interactions with the two enantiomers which affects their electrophoretic mobilities. Deactivation of the capillary wall to improve efficiency by minimizing internet ions. with solute species can be achieved by permanent chemical modification such as silylaytion or the... 

Affinity liquid chromatography and chiral separations (enantiomer separations) require similar analyte properties. The solutes may have interactions through hydrogen-bonding, ligand formation, or Coulombic forces with the surface of stationary phase materials or the sites of additives however, the selectivity is controlled by the steric effects of the structures of the analyte molecules and the recognition molecules (chiral selectors). 

CSPs has, overall, a hydrophobic character (very similar to RP phases with C4-C8 ligands) which stems from contributions of the chiral selectors itself and (capped) linker groups (only a portion of the linkers are utilized for selector attachment) which constitutes a kind of hydrophobic basic layer on the support surface. Hence under typical RP-conditions, hydrophobic interactions between lipophilic residues of the solute and hydrophobic patches of the sorbent may be active and thus a reversed-phase like partition mechanism may be superimposed upon the primary ion-exchange process k = A rp -I- A ix). This A Rp-retention contribution may be especially important for eluents with high aqueous content. 

The chiral recognition of enantiomers can be of three types (i) desionoselective, (ii) ionoselective, or (iii) duoselective, in which only the non-dissociated, the dissociated or both forms (charged and uncharged), respectively, of the enantiomers selectively interact with the chiral selector. In the case of ionoselective and duoselective interactions, a reversal of the migration order of the enantiomers is theoretically possible by the appropriate selection of CD concentration and the pH of the BGE. The addition of organic modifier to the BGE can also change selectivity by modifying the solubility of the chiral selector and/or of the solute, the complex equilibrium, the conductivity of the BGE and the electroendos-motic flow (EOE) level. Several other factors, such as the temperature, the type and the concentration of the BGE, and the level of the EOE can influence the separation. 

The use of a charged chiral selector is probably the best solution to improve the classical PET when CE is hyphenated with MS. Better solubility, additional electrostatic interactions, and improvement of the stereoselective separation power afforded by the self-mobility of the chiral additives into the BGE are among the numerous advantages of these charged selectors. When electromigration of the chiral species and the analytes are opposite (PFT-countercurrent approach), the mobility difference between free and complexed analytes is increased, leading to a higher resolution than with a neutral chiral selector. In optimized countercurrent... 

Enantiomeric separations of amino acids and short peptides are performed using either a direct or the indirect approach [10]. The indirect approach employs chiral reagents for diasteromer formation and their subsequent separation by various modes of CE. The direct approach uses a variety of chiral selectors that are incorporated into the electrolyte solution. Chiral selectors are optically pure compounds bearing at least one functional group with a chiral center (usually represented by an asymmetric carbon atom) which allows sterically selective interactions with the two enantiomers. Among others, cyclodextrins (CDs) are the... 

Capillaries with chiral polymer coatings have been applied in CE for resolution of enantiomers. Possibly because of its inclusive effect, cyclodextrin seems to be an effective chiral selective agent when bonded to a fused-silica capillary surface. In this case, the purpose of the modification is to induce interactions with the chiral material on the surface. Certainly, the cyclodextrin moiety lowers EOF like other wall modifications because it diminishes the number of silanols. The lower EOF allows for slower migration of the solute through the column and, hence, more time for interaction with the chiral selector. The diminished number of silanols also results in less nonspecific interactions with the fused-silica surface, which would tend to degrade the enantiomeric separation. 

In 1992 Mayer and Schurig showed for the first time the possibility of enantioseparations in open tubular capillaries modified with a permethylated CyD derivative. This technique was used later with different chiral selectors but did not mature to become the method of choice for CEC enantioseparations, most likely due to the following conflict inherent in this technique. For a separation which occurs on the mobile phase/stationary phase interface and not in the bulk solution, retention of the analyte on the capillary wall (chiral stationary phase) is necessary for achieving a separation. On the other hand, any retentive analyte-capillary wall interactions are associated with a drastic decrease in peak efficiency in capillary electromigration techniques. However, this study stimulated research in both capillary enantioseparation techniques and in the use of CyD-based CSPs for CEC enantioseparations. 

Enantiomeric ions can be separated in normal phase liquid-solid systems with one antipode of a chiral counter-ion added to the non-polar mobile phase. The chiral selector should have properties such that several interaction points with the enantiomeric solutes are obtained. Electrostatic interaction, hydrogen bonding and a steric influence from a bulky structure in the vicinity of the asymmetric centre seem to be needed. Pettersson has developed systems for the separation of enantiomers of amino alcohols used as /8-adrenoceptor blocking drugs, with (-l-)-lO-camphorsulfonic acid [54] and a dipeptide derivative, N-benzoxycarbonylglycyl-L-proline [25], as selectors, the latter giving higher chiral selectivity. 

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