Chiral separation mechanism cavities

Chemically modiHed soibents] soibents and precoated layers for ion-exchange chromatography, 115-119 Chiral separation mechanism direct separation of enantiomers on TLC plates coated with chiral compounds, 635 enantiomeric separation on adsorbents with chiral cavities, 622-626... 

LI Separations in the reversed-phase mode — chiral recognition mechanisms and structural features of selectands. The primary mechanism of interaction between the macrocyclic selectors and the selectands in the reversed-pha.se mode (employing aqueous buffered mobile phases) is (partial) inclusion of hydrophobic molecules or parts of the molecules, such as (substituted) aromatic rings, into the apolar cavity of the CD. It is clear that the dimensions of the CD cavity play a dominant role to facilitate this... 

Furthermore, this separation problem, which is theoretically simple, is also highly relevant to the pharmaceutical industry. An example is the separation of mixtures of N-benzoyl-D- and L-alanine on immobilized BSA (see Figures 11.20). We have explained in Chapters 3 and 4 (i) that a competitive bi-Langmuir isotherm can be employed to account for the competitive behavior of these components (Figure 4.25c) and (ii) that, because the chiral selective retention mechanism involves adsorption of the enantiomers in the hydrophobic cavity of BSA, the column saturation capacity of the chiral selective mechanism is the same for the two enantiomers. This competitive bi-Langmuir isotherm model is simply derived from the parameters obtained from single-component isotherm measurements. 

Enantiomeric resolution of solutes that fit within the molecular cavity, which is chiral, results in the formation of an inclusion complex (Ref. 169 and Fig. 4). In general, the enantiomers are separated on the basis of formation constants of the host-guest complexes. The enantiomer that forms the more stable complex has a greater migration time because of this effect. The chiral recognition mechanism for cyclodextrin enantioseparation has been discussed in several works (163-168). 

Lipkowitz [63] used molecular dynamics simulations to answer the following questions a) What are the intermolecular forces responsible for analyte binding to the CSP b) Where on or in the host does the analyte bind c) What are the differential interactions giving rise to chiral discrimination d) What differences do R and S-enantiomers experience in the CD cavity e) Are existing chiral recognition mechanisms valid His computational work was based on experimental separations... 

Mechanism of Separation. There are several requirements for chiral recognition. (/) Formation of an inclusion complex between the solute and the cydodextrin cavity is needed (4,10). This has been demonstrated by performing a normal-phase separation, eg, using hexane—isopropanol mobile phase, on a J3-CD column. The enantiomeric solute is then restricted to the outside surface of the cydodextrin cavity because the hydrophobic solvent occupies the interior of the cydodextrin. (2) The inclusion complex formed should provide a rdatively "tight fit" between the hydrophobic species and the cydodextrin cavity. This is evident by the fact that J3-CD exhibits better enantioselectivity for molecules the size of biphenyl or naphthalene than it does for smaller molecules. Smaller compounds are not as rigidly held and appear to be able to move in such a manner that they experience the same average environment. (5) The chiral center, or a substituent attached to the chiral center, must be near to and interact with the mouth of the cydodextrin cavity. When these three requirements are fulfilled the possibility of chiral recognition is favorable. 

It was found that polar enantiomers could be separated with CDs in nonaqueous polar medium (e.g., 99% acetonitrile with 1% methanol). In this situation, inclusion complexation is unlikely, the solvent molecules occupying the CD cavity. The chiral mechanism involves H-bonds with the spatially oriented hydroxyl groups at the rims of the cavity and other interactions with the numerous asymmetric carbons of the glucopyranose units [36]. Polar organic mobile phases were tried with other CSPs and greatly extended their usefulness enhancing the role of H-bond interactions that were screened by water molecules. 

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