Enantioselective interactions

The ability of proteins to form enantioselective interactions with a large variety of drugs is used in chiral affinity chromatography. Protein CSPs that are most frequently used for the enantioseparation of pharmaceuticals include bovine serum albumin (BSA), human serum albumin... 

X Zhu, Y Ding, B Lin, A Jakob, B Koppenhoefer. Study of enantioselective interactions between chiral drugs and serum albumin by capillary electrophoresis. Electrophoresis 20 1869-1877, 1999. 

With chiral affinity phases, proteins undergo enantioselective interactions with a great variety of drugs. Thus, the resolution on chiral affinity stationary phases is due to interactions of the enantiomers with proteins bonded to the solid support. Typical proteins used for chiral affinity separa-... 

Chiral recognition at surfaces occurs at different levels and in different ways. Chiral expression becomes especially obvious in the formation of chiral motifs. That is, chirality is transferred from the single molecule into a supramolecular enantiomorphous structure. Moreover, enantioselective interactions between identical or different species are decisive for spontaneous resolution or play an important role in cooperative phenomena. 

Beside the presented supramolecular systems on surfaces, it is worth mentioning that recognition of chiral sites on crystalline surfaces has been reported in biomineralization or at the solid-liquid interface [39-41]. Enantioselective interactions with kink sites of metal surfaces have been demonstrated for the electro-oxidation of R- and S-glucose over Pt and for desorption of chiral molecules from Cu(543) [42,43]. 

To our knowledge, topologically chiral molecules have not yet been resolved into enantiomers. However, we may anticipate that their energy barrier to racemization will be extremely high, compared to Euclidean chiral molecules. Therefore they are expected to be useful in enantioselective interactions or reactions. For example, it has been shown that tetrahedral copper(I) bis-2,9-diphenyl-l,10-phenanthroline complexes (which form the catenate subunits) are good reductants in the excited state [97] therefore the chiral Cu(I) catenates could be used for enantioselective electron-transfer reactions. Alternatively, the resolution of topologically chiral molecules would allow to answer fundamental questions, such as what are the chiroptical properties of molecular trefoil knots ... 

Chiralpak AD or Chiralcel OD) with separation factors up to 19152 but further enantioselective interactions were not described. 

Figure 3.14 Equilibrium isotherms for (R)- and (S)- Propranolol on Cel-7A at increasing pH, see data in Figure 3.13. Plots of the saturation capacity (Left) of the three retention mechanisms and of their binding constants (Right) versus the pH of the mobile phase. Enantioselective interactions of S-propranolol (1) and of R-propranolol (2), and nonselec-tive interactions of either enantiomers (3). NB. In both figures, the left y-axis corresponds to lines 1 and 2 the right y-axis to line 3. Reproduced with permission from T. Fomstedt, G. Gotmar, M. Andersson, G. Guiochon, f. Am. Chem. Soc., 121 (1999) 1164 (Figs. 7 and 8). (g)1999, American Chemical Society.

Longo, P. Proto, A. Grassi, A. Ammendola, P. Stereospecific polymerization of propylene in the presence of homogeneous catalysts ligand-monomer enantioselective interactions. Macromolecules 1991, 24, 4624. 

The susceptibility of the biological machinery to enantioselective interactions, however, is not limited to chiral compounds of endogenous origin. Frequently, biological systems exert substantial levels of stereoselectivity for exogenous chiral molecules, for example, odorants [1], pheromones [2], agrochemicals [3, 4], environmental pollutants [5-7] and, most importantly, drug compounds [8-11]. 

The origin of the favorable effects of these strongly acidic additives remains to be established. The authors suggested that fhe strongly acidic additives may play an essential role in the formation of stable ion pairs, or promote a local pH-effect enhancing the enantioselective interaction wifh fhe binding sites at the polysaccharide-type CSP. 

Hellriegel, C., Skogsberg, U., Albert, K., Laemmerhofer, M., Maier, N. M., Lindner, W. Characterization of a chiral stationary phase by HR/MAS NMR spectroscopy and investigation of enantioselective interaction with chiral ligates by transferred NOE, J. Am. Chem. Soc.,... 

It allows for enantioselective interactions. For example, it has been shown that the interaction of L-DPPC 10 (R = R = n-CjjHji) with (-)-carvone or (/ )- at the air-water interface gives more expanded mono layers than the interaction of this compound with (-H)-carvone or (5)-l This may be relevant to the mechanism of olfactory detection of these... 

This large selectivity correlates with toxicity in vivo where the P(+) isomers are virtually non-toxic. There is little differentiation of the C(-) and C(+) isomers of soman. As discussed in Section XI, the enantioselective interaction of soman isomers with other esterases also effects toxicity in vivo. Tabun and show less enantioselectivity in... 

The derivatised glucose can act as a chiral site and result in diastereomeric interactions with enantiomers which together with the steric fit requirements within the cavity and the different interactions with the cellulose strands provides the basis for enantioselective interaction and subsequent resolution. The acetate, benzoate and phenylcarbamate glucose ester give superior resolution and selectivity compared with the parent material. Hydrophobic mobile phases are most commonly encountered though aqueous based eluants can be used with many versions of these materials. These stationary phase packings have been used to separate a wide range of pharmaceutical compounds [80]. 

Attempts have been made to determine enantiospecific differences between enantiomers and racemates in solution using microcalorimetry [29]. The microcalorimetric method can be used to understand the magnitude of stereoselective interactions that could result from the mixing of solutions of enantiomers of a chiral excipient. The heat evolved or heat of solution (A/T ° ) is measured for the racemate as well as the enantiomers and could be indicative of enantioselective discrimination. However, Horeau and Guette [30] reported that enantioselective interaction in an aqueous medium measured using microcalorimetry may be inconsistent and flawed because of the insufficient purity of the optically active samples used and the insensitivity of the measurement relative to small differences in magnitude of the observed effects. 

The interaction between cyclodextrin and a chiral drug depends on the type of cyclodextrin. Enantioselective interactions, a basis for chiral recognition, may lead to complex supramolecular aggregates. This information can be gathered from NMR studies. For example, the interaction... 

Gidal, B.E. Sorkness, C.A. McGill, K.A. Larson, R. Levine, R.R. Evaluation of a potential enantioselective interaction between ticlopidine and warfarin in chronically anticoagulated patients. Ther. Drug Monit. 1995, 17, 33-38. 

While the migration principle, i.e., the driving forces moving the analytes through the separation capillary, is based on electrophoretic mechanisms the chiral separation is based on enantioselective interactions between the analyte enantiomers and a chiral selector and is, therefore, a chromatographic separation principle. The fact that the selector is in the same phase as the analytes in CE and not part of a stationary phase that is immiscible with the mobile phase as found in chromatography does not represent a conceptional difference between both techniques. The chiral selector in CE is also called pseudophase as it is not a physically different phase and may also possess an electrophoretic mobility. Enantioseparations in CE have also been termed capillary electrokinetic chromatography . 

Crown ethers, especially 18-crown-6 ethers, can complex not only inorganic cations but also alkylammonium compounds. The primary interactions occur between the hydrogens of the ammonium group and the oxygens of the crown ether. The introduction of bulky groups such as binaphtyl onto the exterior of the crown ether provides steric barriers and induces enantioselective interactions with the guest molecule. 

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