Mechanism of chiral recognition

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

Alcaro, S et al., Glycopeptide-containing CSP new synthesis, apphcations and insight into mechanism of chiral recognition, presented at 22 hit. Symp. on Chromatography, Roma, September 13-18, 1998, 39. 

A significant ability to discriminate between chiral amines based on the quenching of S-di-2-naphthylprolinol fluorescence emission was reported by Diamond et al. [32], fl-Phenylethylamine (PEA) was seen to have a much greater efficiency as a quencher than the S-enantiomer. l- and D-norephedrine, which have structural conformation similarities to PEA, were also observed to have an enantiomeric selectivity. The mechanism of chiral recognition is proposed to be a combination of hydrogen bonding and 3D chirally restricted space. 

In this report, we focus primarily on recent developments in liquid-phase enantiosep-arations. but in particular on liquid chromatography (LC). Mechanisms of chiral recognition will be discussed together with aspects related to the separation technique and to methodological characteristics. Due to the rapidly growing and immense number of publications in this field, it is not our intention to comprehensively review all the published literature, it is rather a selective review of latest developments with emphasis on the last 5 years. 

The macromolecular nature and structural heterogeneity of the polymeric SOs allow the existence of several different binding sites this holds in particular for proteins which are quite heterogeneous by nature. As a consequence they have usually a broad spectrum of applicability, but their or-values are rather mtxlerate and are typically between 1 and 3. In addition, it is difficult to study the mechanism of chiral recognition and to identify the site of chiral recognition. The exact arrangement of the SA in the active chiral recognition site remains still widely unknown. 

Selection of a certain operational mode is guided by the structure of analytes (SAs) to be separated. It will influence the mechanism of chiral recognition. 

The mechanism of chiral recognition in permethyl-p-cyclodextrin has been thoroughly studied by Lipkowitz et al. [269] employing a molecular modelling approach. Not surprisingly, the host s most enantiodiscriminating domain was found to be inside the macrocyclic cavity. 

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. 

The mechanism of chiral recognition of the enantiomers in series of clathrochelates was studied in research reported in Ref. 311, in which [Sb2(cZ-tart)2]2- anion was employed as a chiral eluent. It was established that in the majority of cases, A-enantiomer is eluted first, and that bulky alkyl capping groups increase the degree of resolution. 

Some optically active cationic and racemic anionic complexes were examined to elucidate the mechanism of chiral recognition of cations and anions capable of forming hydrogen bonds [313]. The chromatographic study showed that enantiomers of some anionic complexes form favourable ion pairs with cationic A-complexes (Table 31). 

D. Sanchez, S. AUenmark, Reprint from Poster presented at the Euchem-Con-ference on Mechanisms of Chiral Recognition and the Design of Chiral Phase Systems, 1995, Gdteborg, Bohus (Sweden). 

Because so few type V CSPs have well established molecular structures, most scientists are forced to use a series of probe molecules and some sort of regression analysis to divulge pertinent information about the mechanism of chiral recognition. For example, Norinder and Hermansson [85] separated thirty-five N-aminoalkylsuc-cinimides, 36, on an ai-acid glycoprotein (AGP) column. 

Commercially available silica gel plates coated with acid or basic chiral selectors [o-galacturonic acid, l-(- -)-tartaric acid, L-lactic acid, (-)-brucine] were used for the separation of racemic ephedrine, atropine, neutral amino acids, and their 3-phenyl-2-thiohydantoins (PTH) derivatives. The use of amino acids as chiral selectors involved further possibilities of enantiomer separation owing to the simultaneous presence of basic and acidic groups. In fact, L-aspartic acid, L-lysine, L-histidine, L-arginine, and L-ser-ine resolved racemic alkaloids, (3-blockers, profens, some amino acids, and their Dns derivatives. Macrocyclic antibiotics [i.e., (-)-erythromycin and (-)-vancomycin] were also used as chiral agents for the separation of enantiomeric DNs amino acids. The mechanisms of chiral recognition was investigated by Aboul-Enein, El-Awady, and Heard they hypothesized that the formation of... 

Lu, Y. Li, Ch. Zhang, H. Liu, X. Study on the mechanism of chiral recognition with molecularly imprinted polymers. Anal. Chem. Acta 2003,489, 33 3. 

Structure-Stereoselectivity Relationships and Mechanisms of Chiral Recognition... 

The many data which have accumulated through chromatographic studies of resolution permit a) to single out systems which seem suitable for more detailed investigations of the intimate molecular mechanism of chiral recognition by methods such as X-ray crystallography and b) to correlate the influence of structural factors of selectors and selectands on stereoselectivity. 

For the derivatives soluble in CHCI3, a detailed discussion on the mechanism of the chiral recognition is made possible by the NMR spectral measurements in this solvent [57, 58]. Other methods have also been used to understand the mechanism of chiral recognition by the polysaccharide derivatives [59]. 

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