Chiral enantioselective binding

Nair, U.B. et al.. Elucidation of vancomycin s enantioselective binding site using its copper complex. Chirality, 8, 590, 1996. 

Gagne and coworkers utilized this combination to discover enantioselec-tive receptors for (-)-adenosine [12]. A racemic dipeptide hydrazone [( )-pro-aib] generated a stereochemically diverse DCL of n-mer. The dimers were composed of two chiral (DD/LL) and one achiral isomer (DL), the four trimers (DDD, LLL, DDL, and LLD), the tetramers of four chiral and two achiral isomers, etc. Two techniques were used to measure the enan-tio-imbalance that was caused by the enantioselective binding of the chiral analyte to the enantiomeric receptors (Fig. 5.11). Since the unperturbed library is optically inactive, the optical enrichment of each library component could be measured by a combined HPLC optical rotation detection scheme (laser polarimeter, LP). LP detection differentiated unselective binding (amplification but not optical enrichment) from enantioselective recognition of the analyte (amplification and optical enrichment). In this manner the LL dimer (SS) of the dipeptide was amplified and identified as the enantioselective match for (-)-adenosine. 

B. Capillary Electrophoresis Methods for Determination of Enantioselective Binding Constants Between Chiral Drugs and Cyclodextrins... 

Similar equations can be written for both enantiomers of chiral analyte. Based on Eq. (14), nonlinear regression techniques allow one to determine the enantioselective binding constants (KR and Ks) and the mobilities of related transient diastereomeric complexes (/4°mplex and /x ""plex). 

The frontal analysis technique has been used for the determination of enantioselective binding constants of chiral drugs such as warfarin, verapamil, nilvadipine, and semotidil with proteins such as bovine serum albumin (BSA), human serum albumin (HSA), and plasma lipoproteins (45-51). 

III. APPLICATION OF CAPILLARY ELECTROPHORESIS FOR DETERMINATION OF ENANTIOSELECTIVE BINDING CONSTANTS OF CHIRAL DRUG/CYCLODEXTRIN COMPLEXES... 

Thus, as shown earlier, CE represents a suitable technique for the determination of enantioselective binding constants between chiral drugs and cyclodextrins. The results obtained under appropriate conditions are reasonable and can be applied for optimization purposes as well as for a better understanding of the fine nuances of chiral CE separations. On the other hand, some care must be taken for the proper application of CE methods for the determination of the binding constants as well as when applying these data. A critical review of the calculation of stability constants for the chiral selector-enantiomer interactions from electrophoretic mobilities has been published by Vespalec and Bocek (40). 

The enantioselective binding properties of certain chiral crown ethers have been employed in the resolution of amino add racemates. The racemic amino ester is adsorbed onto silica gel as its ammonium salt and eluted by a chloroform solution of the chiral crown ether. An excellent separation of the two enantiomers is achieved by this method (74JA7100). 

It has also been reported from circular dichroism (CD) studies [36] that polysaccharide-based CSPs can induce chirality in enantiomeric guests such as (4Z,15Z)-bilirubin-Ixoc (BR) (Fig. 5). Although not optically active, BR has two enantiomeric helical conformations maintained by six intramolecular hydrogen bonds between two carboxylic acid moieties and two pyrromethenone — NH— protons. These (R)- and (5)-helical conformers are in dynamic equilibrium in an achiral solution [37], but some optically active compounds can enantioselectively bind to BR to induce CD spectra in solution [38-40]. A significant induced CD... 

A chiral molecular cavity, admitting the possibility of enantioselective binding and catalysis. 

In 1992, de Mendoza and coworkers reported the synthesis of the bifunction-alized chiral bicyclic guanidinium 34 for the purpose of enantioselectively binding zwitterionic aromatic amino acids (i.e., tryptophan and phenylalanine) [55]. By including binding elements for the carboxylate and ammonium of the amino acids which were noncomplementary, they hoped to avoid the potential... 

S)-amino acicis, mexiule C, two stereoisomers, and tethered to polystyrene via mcxlule B, two stereoisomers) was prepared by encoded split synthesis on 100 pm polystyrene synthesis beads so that different library members were segregated on different beads (i.e. one bead, one chiral SO). This library was then screened by a two-colour differential binding method amino acid SAs were labelled via a linker with red ((/ )-amino acids) and blue ((S)-amino acids) dyes and the chiral beads treated with an equimolar mixture of the labelled SA enantiomers. Enantioselective binding beads are either red or blue, whereas unselective beads are brown. 

The enantioselective binding of tryptophan (16) is a result of differential binding at site II, which is held to be the more enantioselective of the major drug binding sites (29). However, enantioselective binding at site I has been proposed for chiral drugs binding there, such as warfarin (19,30-33). 

Enantioselective Binding of Chiral 1,4-Benzodiazepines to Site If of Serum Albumin... 

Figure 78 A chiral, water-soluble cyclophane for enantioselective binding [104]...

The observation of enantioselective binding properties of polysaccharides dates back to the early SOs. At this time Kotake [95] and Dalgliesh [96] achieved thin layer chromatographic separation of amino acid enantiomers on cellulose carriers. However, the poor chiral recognition capacity of native polysaccharides hampered further developments. 

The observation of enantioselective binding of chiral molecules to certain classes... 

HSA bears structural and functional resemblance to BSA, and HSA-type CSPs [164] also show similar enantioselective binding preferences for acidic and neutral drug molecules, such as 2-aryloxypropanoic acids [165], warfarin [166] and benzodiazepines [167]. The chiral recognition mechanism of HSA has been the subject of a number of investigations [168], which revealed that enantioselective binding occurs primarily at two well-defined hydrophobic sites. Acidic drugs have been shown to bind preferentially to the so-called warfarin-azapropazone (site I) and neutral drugs to the indol-benzodiazepine site (site II). 

---