Enantiomer-selective interaction

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. 

An interesting and practical example of the use of thermodynamic analysis is to explain and predict certain features that arise in the application of chromatography to chiral separations. The separation of enantiomers is achieved by making one or both phases chirally active so that different enantiomers will interact slightly differently with the one or both phases. In practice, it is usual to make the stationary phase comprise one specific isomer so that it offers specific selectivity to one enantiomer of the chiral solute pair. The basis of the selectivity is thought to be spatial, in that one enantiomer can approach the stationary phase closer than the other. If there is no chiral selectivity in the stationary phase, both enantiomers (being chemically identical) will coelute and will provide identical log(Vr ) against 1/T curve. If, however, one... 

The substantial difference between these two chromatograms was a clear proof that CSP 13 interacted differently with the mixtures of l and d enantiomers. This also indicated the presence of at least one pair of enantiomers that interacted selectively with the CSP. Unfortunately, a tedious synthesis of 16 sublibraries (eight l and eight d) containing decreasing numbers of blocks had to be prepared to deconvolute the best selector. A comparison of the chromatograms obtained from these sublibraries in each deconvolution step was used again, and those selectors for which no difference was observed were eliminated. This procedure enabled the identification... 

With a 3,3-heterodihalogeno substitution of the (3-lactam ring, a selective interaction of each enantiomer of the chiral azetidinone with the enzyme active site is expected. The enantiomer 3R of the 3F, 3Br derivative indeed has a more favorable kinetic parameter k-JK, than the enantiomer 3S.33 The partition ratio kCA /kt (=k3/k4, Eq. 11.1) for the inactivation is also higher. Therefore, enantiomer 3R is a better suicide substrate for HLE since a lower partition ratio corresponds to abetter suicide substrate.20... 

The binding sites of most enzymes and receptors are highly stereoselective in recognition and reaction with optical isomers (J, 2 ), which applies to natural substrates and synthetic drugs as well. The principle of enantiomer selectivity of enzymes and binding sites in general exists by virtue of the difference of free enthalpy in the interaction of two optical antipodes with the active site of an enzyme. As a consequence the active site by itself must be chiral because only formation of a diasteromeric association complex between substrate and active site can result in such an enthalpy difference. The building blocks of enzymes and receptors, the L-amino acid residues, therefore ultimately represent the basis of nature s enantiomer selectivity. 

Enantiomer-selective deactivation of racemic catalyts by a chiral deactivator affects the enantiomer-selective formation of a deactivated catalyst with low catalytic activity (Scheme 8.2). Therefore, it is crucial for a chiral deactivator to interact with one enantiomer of a racemic catalyst (Scheme 8.2a). As the chiral deactivator does not interact with the other enantiomer of racemic catalyst, the enantiomeri-cally enriched product can be obtained. Therefore, the level of enantiomeric excess (% ee) could not exceed that attained by the enantiopure catalyst. On the other hand, nonselective complexation of a chiral deactivator would equally and simultaneously deactivate both catalyst enantiomers, thereby yielding a racemic product (Scheme 8.2b). Although this strategy tends to use excess chiral poison relative to the amount of catalyst, it offers a significant advantage in reducing cost and synthetic difficulty since readily available racemic catalysts and often inexpensive chiral poisons are used. 

Later, Klemm and co-workers [86,87] achieved partial resolution of aromatic compounds by low-pressure chromatography on silica gel impregnated with TAPA. The separation was attributed to n-n complexation between TAPA and the enantiomers. Mikes et al. [88] used a column packed with an (i )-(-)-TAPA aminopropyl-bonded silica support to accomplish the full resolution of helicenes. The authors extended their study to other homologues of TAPA (Figure 22-19). These compounds were coated on silica gel or ion-paired to an aminopropyl-bonded phase, and they were used in the HPLC separation of helicenes. To describe the selective interactions that occur between the stationary phase and the helicenes, the authors assumed that the 2,4,5,7-tetranitro-9-fluorenylidene moieties of the selector are laying down on the silica surface, while the X groups point away from the surface and above the plane of the fluorenyl ring. 

B. Feibush, A. Balan, B. Altman, and E. Gil-Av, Chiral solute-solvent systems. Selective interaction between V-lauroyl-L-valine amides and V-trifluoroactyl esters of enantiomers of 2-amino-alkan-l-ols, a-, P-, and y-amino acids, /. Chem. Soc. Perkin Trans II9 (1979), 1230. 

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... 

The first observation of biological enantioselectivity was made by Pasteur himself. He found, in 1858, that when solutions of racemic ammonium tartrate were fortified with organic matter (i.e., a source of microorganisms) and allowed to stand, the solution fermented and (-I-)-tartaric acid was consumed rapidly while (-)-tartaric acid was left behind unreacted. Eventually the (-)-enantiomer was also metabolized, but considerably more slowly than (-t)-tartrate [50]. In later experiments Pasteur showed that the common mold Penicillium glaucum metabolized (-I-)-tartaric acid with high enantioselectivity [51]. He correctly theorized that the enantioselective destruction of tartaric acid by microorganisms involves selective interaction of the tartrate enantiomers with a key chiral molecule within the microorganism [50, 51]. 

Many of the chiral stationary phases have been developed by systematically applying the principle of reciprocity to the enantiomer binding interactions. A number of diverse racemates are analyzed on a chiral stationary phase containing as chiral selector the immobilized target molecule for the enantiomers of which a new selector is desired. The racemate showing the highest enantioselectivity in this system is selected, and... 

Stirling and coworkers incorporated a chiral sulphoxide group in a gold-thiol mono-layer (23). Quick exposure of this chiral monolayer to the vapours of ( )-ethyl lactate shows non-selective adsorption of both enantiomers. However, prolonged exposure at 40 °C results in adsorption of exclusively one enantiomer . The interactions can be followed by SPR . ... 

Still and coworkers prepared the highly selective, D2-synnnetric receptor 37 for amino acids and small peptides by simple condensation of (/ , )-cyclohexane-1,2-diamihe and trimesic acid. ° Complexes are held together by four intermolecular hydrogen bonds and resemble a peptidic three-strand (1-sheet. A further, enantiomer-discriminating interaction is based on steric complementarity between the amino acid side chain and the cleft-type cavity of the receptor. 

Summarizing, the separation of enantiomeric pairs is achieved by the close selective interaction of one enantiomer with a stationary phase chiral center, resulting in stronger molecular interactions between the enantiomer and the neighboring groups or atoms round the stationary phase chiral center. 

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