Chiral stationary phases enantiomer recognition

A number of specialised stationary phases have been developed for the separation of chiral compounds. They are known as chiral stationary phases (CSPs) and consist of chiral molecules, usually bonded to microparticulate silica. The mechanism by which such CSPs discriminate between enantiomers (their chiral recognition, or enantioselectivity) is a matter of some debate, but it is known that a number of competing interactions can be involved. Columns packed with CSPs have recently become available commercially. They are some three to five times more expensive than conventional hplc columns, and some types can be used only with a restricted range of mobile phases. Some examples of CSPs are given below ... 

For example22, separation of enantiomers of chiral molecules (amines, alcohols, amino acids) is possible by using a chiral stationary phase obtained from 10-undecenyl esters of Af-(2-naphthyl)-a-amino acids (4). Amino groups are of fundamental importance in this practical application of the chiral recognition. 

This method is based on the fact that molecular association may lead to an efficient chiral recognition leading to enantiomeric separation when a chiral stationary phase (e.g. cyclodextrins) is used in GC. The gas (mobile phase, e.g. hydrogen, helium, nitrogen) is carrying the chiral analyte through the stationary phase. The enantiomers to be analyzed... 

The notion of reciprocity in chiral recognition has played an important role in the design of chiral selectors. In principle, if a single molecule of a chiral selector has different affinities for the enantiomers of another substance, then a single enantiomer of the latter will have different affinities for the enantiomers of the initial selector. In an effort to design a chiral stationary phase capable of separating naproxen, Pirkle et al. [97] first designed two stationary phases in which the carboxyl function of naproxen was linked to a silica matrix... 

Before starting a preparative chiral separation it is essential to identify a chiral stationary phase (CSP) exhibiting good chiral recognition ability. This is usually done with an analytical column because it is less substance- and time-consuming. A stationary phase mostly composed of silica gel with only a few chiral elements will be rapidly overloaded. In this event, even if the phase exhibits useful properties for analytical purposes, it will not be appropriate for preparative applications this is the case for protein-based phases [102, 103], Most chiral stationary phases have relatively low saturation capacity, so the enantiomer separations are usually done under strongly nonlinear conditions [103], Accordingly, the accurate determination of the adsorption isotherms of the two enantiomers on a CSP is of fundamental importance to allow computer-assisted optimization to scale up the process. 

Direct enantiomer separation methodologies circumvent the rather laborious formation of covalent diastereomers, but instead exploit subtle energetic differences of reversibly formed, noncovalent diastereomeric complexes for chiral recognition. Direct chromatographic enantiomer separation may be achieved in two different modes, the chiral mobile phase additive and the chiral stationary phase mode. 

A commercial CE system and a micropacked capillary was used to separate N—, O—, and S-containing heterocyclic compounds. Migration time reproducibility, linearity, and detector response was found to be comparable to HPLC. A study of the heterocyclic compound s elution order followed that predicted by the octanol-water partition coefficients (354). While chiral CEC provides improved resolution and higher efficiencies, additional work is needed since chiral CEC capillaries are not available commercially. The separation principles and chiral recognition mechanism for the separation of enantiomers have been reviewed (355). Furthermore, a comprehensive collection of drug applications and other compounds of interest has been reported (356). Direct enantiomeric separations by CEC were studied using a capillary packed with alpha-1-acid glycoprotein chiral stationary phase (357). Chiral resolution was achieved for enantiomers of benzoin, hexobarbital, pentobarbital, fosfamide, disopyramide, methoprolol, oxprenolol, and propanolol. The effects of pH, electrolyte concentration, and con-... 

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