Chiral recognition advantages

The dependence of chiral recognition on the formation of the diastereomeric complex imposes constraints on the proximity of the metal binding sites, usually either an hydroxy or an amine a to a carboxyHc acid, in the analyte. Principal advantages of this technique include the abiHty to assign configuration in the absence of standards, enantioresolve non aromatic analytes, use aqueous mobile phases, acquire a stationary phase with the opposite enantioselectivity, and predict the likelihood of successful chiral resolution for a given analyte based on a weU-understood chiral recognition mechanism. 

Another important issue that must be considered in the development of CSPs for preparative separations is the solubility of enantiomers in the mobile phase. For example, the mixtures of hexane and polar solvents such as tetrahydrofuran, ethyl acetate, and 2-propanol typically used for normal-phase HPLC may not dissolve enough compound to overload the column. Since the selectivity of chiral recognition is strongly mobile phase-dependent, the development and optimization of the selector must be carried out in such a solvent that is well suited for the analytes. In contrast to analytical separations, separations on process scale do not require selectivity for a broad variety of racemates, since the unit often separates only a unique mixture of enantiomers. Therefore, a very high key-and-lock type selectivity, well known in the recognition of biosystems, would be most advantageous for the separation of a specific pair of enantiomers in large-scale production. 

Polysaccharide derivatives used as CSPs interact with chiral analytes in much the same manner as cyclodextrins. These molecules have been shown to exhibit high chiral recognition ability in HPLC [155]. The main advantage of CEC over HPLC is the enhanced efficiency. In chiral separations, slow mass transfer kinetics between the CSP and chiral analytes have somewhat diminished the efficiency advantage of the technique. The goal of using polysaccharide derivatives... 

Additional chiral recognition sites can be introduced via the substituents of deriva-tized p-CD-bonded CSPs thus facilitating SO-SA inclusion complexation and/or enhancing chiral separation of SAs which are poorly or not separated on native CD type CSPs. For example, the hydroxyl groups of hydroxypropyl-derivatized P-CD CSP may be advantageous for the binding of certain SAs, offering a sterically more favourable... 

The primary mechanism of chiral recognition in CE in aqueous conditions seems to be inclusion complexation [464] as discussed above for CD-based CSPs under reversed-phase conditions. Moreover, one of the main advantages of CDs and CD-derived chiral selectors is that they do not carry chromogenic groups, thus being quasi-UV transparent. Therefore, there is no interference regarding detection sensitivity. 

CTA-I can be used as an analytical and a preparative support and has been employed for the preparation of various racemic drugs or drug intermediates (9-11,41-43). The advantages of this phase have been delineated by Francotte and Wolf (41). They are (1) easy preparation of the phase (2) practically unlimited source (3) high loading capacity (4) high chiral recognition (5) broad applicability (6) low production costs. 

The major advantage of these phases is the ability to manipulate structure and the reciprocity of chiral recognition. The reciprocity approach is not readily available for the naturally occurring polymeric CSPs such as cellulose, proteins, and others. Those solutes not containing the complementary re-acid or re-base functionality can often be derivatized to incorporate these features into the molecules of interest. 

The biopolymer CSPs are attractive owing to the ready availability of the chiral precursors. Offsetting this advantage is an innate complexity that more or less baffles one s ability to deduce the details of the operative chiral recognition processes. Moreover, one cannot easily alter or "fine tune" the structure of the CSP to enhance selectively. Finally, there may well be limitations as to the mobile phases which can be used owing to possible swelling, shrinking, denaturation, or dissolution. 

CyDs offer several advantages as chiral selectors for CE. The most important is that these macrocydic molecules possess a quite universal chiral recognition ability for many different dasses of organic compounds. In addition, CyDs are water soluble, transparent in the UV range, relatively inexpensive, and nontoxic. All of these contribute significantly to the status of CyDs as one of the most useful chiral selectors in CE. Free hydroxyl groups on the outer rim of CyDs offers various derivatiza-tion possibilities for introduction of nonionic and ionic groups into the structure of CyDs. Several CyD derivatives developed to be used in enantioseparations are presented in Chapter 2. 

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