Chiral analyte, interaction

In the author s opinion the most useful application of molecular modeling and molecular mechanics calculations to enantioselective analyte-CyD interactions would be a computation of individual intermolecular forces based on the structure, dynamics, and population of the complexes determined by instrumental techniques. Researchers working on molecular modeling of enantioselective CyD-chiral analyte interactions may use CE as a very powerful experimental technique for evaluating the reliability of their calculations. This may significantly contribute to further refinement of calculation techniques. 

Traditionally, chiral separations have been considered among the most difficult of all separations. Conventional separation techniques, such as distillation, Hquid—Hquid extraction, or even some forms of chromatography, are usually based on differences in analyte solubiUties or vapor pressures. However, in an achiral environment, enantiomers or optical isomers have identical physical and chemical properties. The general approach, then, is to create a "chiral environment" to achieve the desired chiral separation and requires chiral analyte—chiral selector interactions with more specificity than is obtainable with conventional techniques. 

Nonpolar organic mobile phases, such as hexane with ethanol or 2-propanol as typical polar modifiers, are most commonly used with these types of phases. Under these conditions, retention seems to foUow normal phase-type behavior (eg, increased mobile phase polarity produces decreased retention). The normal mobile-phase components only weakly interact with the stationary phase and are easily displaced by the chiral analytes thereby promoting enantiospecific interactions. Some of the Pirkle-types of phases have also been used, to a lesser extent, in the reversed phase mode. 

Table 2-2. The relative strength of potential interactions between glycopeptide CSPs and chiral analytes.

Many times an analyte must be derivatized to improve detection. When this derivatization takes place is incredibly important, especially in regards to chiral separations. Papers cited in this chapter employ both precolumn and postcolumn derivatization. Since postcolumn derivatization takes place after the enantiomeric separation it does not change the way the analyte separates on the chiral stationary phase. This prevents the need for development of a new chiral separation method for the derivatized analyte. A chiral analyte that has been derivatized before the enantiomeric separation may not interact with the chiral stationary phase in the same manner as the underivatized analyte. This change in interactions can cause a decrease or increase in the enantioselectivity. A decrease in enantioselectivity can result when precolumn derivatization modifies the same functional groups that contribute to enantioselectivity. For example, chiral crown ethers can no longer separate amino acids that have a derivatized amine group because the protonated primary amine is... 

When the analyte is chiral, however, the stereochemical issues evolve to how a chiral host interacts with a chiral guest. The nature and magnitude of these diastereomeric interactions ultimately control the DCL evolution and what types of hosts are amplified. 

Cyclodextrins have significantly contributed to the development of enantioseparations in CE, where they represent the most widely used chiral selectors. On the other hand, due to its inherently high separation efficiency and diverse technical advantages, CE has contributed enormously to the better understanding of affinity interactions between CDs and chiral analytes. The following text summarizes the recent developments in this field (3-60). 

An advanced type of column selectivity is chiral discrimination. Since enantiomers have identical physical properties they are not separable on conventional GC columns. However, if chiral analytes are allowed to interact with a chiral environment they will form transitory diastereomeric complexes which result in their being retained by the column to a different extent. As increasing numbers of enantiomerically pure drugs are synthesised in order to reduce side-effects, this type of separation will become increasingly important. 

Apart from the above-discussed parameters for HPLC optimization of chiral resolution on antibiotic CSPs, some other HPLC conditions may be controlled to improve chiral resolution on these CSPs. The effect of the concentrations of antibiotics (on stationary phase) on enantioresolution varied depending on the type of racemates. The effect of the concentrations of teicoplanin has been studied on the retention (k), enantioselectivity (a), resolution (Rs), and theoretical plate number (N) for five racemates [21]. An increase in the concentration of teicoplanin resulted in an increase of a and Rs values. The most surprising fact is that the theoretical plate number (N) increases with the increase in the concentration of teicoplanin. It may be the result of the resistance of mass transfer resulting from analyte interaction with free silanol and/or the linkage chains (antibiotics linked with silica gel). This would tend to trap an analyte between the silica surface and the bulky chiral selector adhered to it. This is somewhat... 

Polysaccharide derivatives used as CSPs interact with chiral analytes in much the same manner as cyclodextrins. These molecules have been shown to exhibit high chiral recognition ability in HPLC [155]. The main advantage of CEC over HPLC is the enhanced efficiency. In chiral separations, slow mass transfer kinetics between the CSP and chiral analytes have somewhat diminished the efficiency advantage of the technique. The goal of using polysaccharide derivatives... 

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