Chiral selectors recognition mechanisms

The chiral recognition mechanism for these types of phases was attributed primarily to hydrogen bonding and dipole—dipole interactions between the analyte and the chiral selector in the stationary phase. It was postulated that chiral recognition involved the formation of transient five- and seven-membered association complexes between the analyte and the chiral selector (117). 

In another study, the authors reported a comparative study of the enantiomeric resolution of miconazole and the other two chiral drugs by high performance liquid chromatography on various cellulose chiral columns in the normal phase mode [79], The chiral resolution of the three drugs on the columns containing different cellulose derivatives namely Chiralcel OD, OJ, OB, OK, OC, and OE in normal phase mode was described. The mobile phase used was hexane-isopropanol-diethylamine (425 74 1). The flow rates of the mobile phase used were 0.5, 1, and 1.5 mL/min. The values of the separation factor (a) of the resolved enantiomers of econazole, miconazole, and sulconazole on chiral phases were ranged from 1.07 to 2.5 while the values of resolution factors (Rs) varied from 0.17 to 3.9. The chiral recognition mechanisms between the analytes and the chiral selectors are discussed. 

Various endeavors have been undertaken to get insight into the 3D selector-selectand complex structures and to elucidate chiral recognition mechanisms of cinchonan carbamate selectors for a few model selectands (in particular, DNB-Leu). Such studies comprised NMR [92-94], ET-IR [94-96], X-ray diffraction [33,59,92,94], and molecular modeling investigations (the latter focusing on molecular dynamics [92,93,97], and 3D-QSAR CoMFA studies [98]). 

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. 

Several CD derivatives (charged and uncharged) are available which should allow the separation of most chiral molecules with at least one of them. However, due to the complexity of chiral recognition mechanisms, the determination of the best selector based on the analyte structure is challenging. Eurthermore, separations using CDs are influenced by numerous factors, so that no general rule can be applied for the successful resolution of enantiomers. ... 

More than 100 CSPs are commercially available nowadays, which should make the separation of any pair of enantiomers feasible. However, the enantiorecognition mechanisms involved in the chiral recognition between the analytes and the CSPs are complex and therefore the selection of the appropriate CSPs, depending on the structure of the analyte, is a difficult task. A common approach to develop a new enantioseparation is the stepwise trial-and-error approach based on detailed consideration of the enantiorecognition mechanisms between the chiral selector and the analyte, or on the analyst s experience, or on the consultation of literature or databases. However, this approach is time-consuming and often unsuccessful owing to the fact that achieving enantioresolution is often purely empirical... 

Many researchers have put a considerable amount of effort into studies of the chiral recognition mechanisms (using, e.g., NMR and molecular modeling), but yet the choice of chiral selector or chiral phase for a new compound is often based on trial and error. Different strategies for chiral method development have been presented by many of the retailers of chiral columns as a service for the customers. In addition to the information supplied by these retailers, another source of knowledge is Chirbase, a database that contains more than 50,000 HPLC separations of more than 15,000 different chiral substances [61], which also can provide guidance to the analytical chemist. 

The last column of Table 7 contains the chiral selector and the third column describes the type of interaction between the selector and the substrate, i.e., the mechanism of the chiral recognition involved. 

Bhushan and Parsad [65] resolved dansyl amino acids on erythromycin impregnated thin-layer chromatographic (TLC) silica plates. The mobile phase used was different ratios of 0.5 M aqueous NaCl-acetonitrile-methanol. Further, Bhushan and Thiong o [66] achieved the chiral resolution of dansyl amino acids on silica TLC plates impregnated with vancomycin chiral selector. The mobile phase used for this study was acetonitrile-0.5 M aqueous NaCl (10 4 and 14 3, v/v). The chiral recognition mechanisms of antibiotic CSPs in sub-SFC, SFC, CEC, and TLC modes of chromatography were found to be similar to HPLC. 

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