Cyclodextrins diastereomeric complexes

Analysis using a CMPA is usually resolved on a nonchiral column. A transient diastereomeric complex is formed between the enantiomer and the chiral component in the mobile phase, similar to the complexes formed with chiral stationary phases. A review by Liu and Liu (2002) cites several papers where addition of CPMAs has been used in analyzing amphetamine-related compounds. Some CPMAs include amino acid enantiomers, metal ions, proteins, and cyclodextrins. Advantages of this method of analysis include the use of less expensive columns and more flexibility in the optimization of chiral separation (Misl anova and Hutta, 2003). 

CE has been applied extensively for the separation of chiral compounds in chemical and pharmaceutical analysis.First chiral separations were reported by Gozel et al. who separated the enantiomers of some dansylated amino acids by using diastereomeric complex formation with Cu " -aspartame. Later, Tran et al. demonstrated that such a separation was also possible by derivatization of amino acids with L-Marfey s reagent. Nishi et al. were able to separate some chiral pharmaceutical compounds by using bile salts as chiral selectors and as micellar surfactants. However, it was not until Fanali first showed the utilization of cyclodextrins as chiral selectors that a boom in the number of applications was noted. Cyclodextrins are added to the buffer electrolyte and a chiral recognition may... 

Cyclodextrins are neutral compounds which migrate at the same rate as the EOF. They have large hydrophobic cavities in their structures into which molecules can fit. The ease with which a molecule fits into the cavity of the cyclodextrin is dependent on its stereoehemistry. Cyelodextrins have been used as additives both in chiral, where opposite enantiomers form transient diastereomeric complexes with the optically active cyclodextrins, and non-chiral separations where the cyclodextrins affect diastereoisomers to a different extent. 

Cyclodextrins (CDs) are chiral compounds which interact with enantiomers via diastereomeric interactions. The separation is achieved because of the difference in stabilities of the resulting diastereomeric complexes formed between each enantiomer and the CD. In the first CEC experiments incorporating CDs, di-methylpolysiloxane containing chemically bonded permethylated (3- or y-CD (Chirasil-DEX) was chemically bonded to the inner walls of fused silica capillaries [139,140]. Electoosmotic flow is generated in these capillaries in the same manner as in fused silica capillaries. The Chirasil-DEX does not mask all the silanol groups, so while EOF is decreased, it is not entirely diminished by the coating. Since that time, CDs or CD derivatives have been bonded to silica particles which were then packed into capillaries, and the CD has been incorporated into continuous polymer beds known as monoliths. Table 3 shows some different CSPs, enantiomers separated, resolution, and the number of theoretical plates per meter. 

Pirkle or brush type bonded phases Helical chiral polymers (polysaccharides) Cyclodextrins and crown ethers Immobilised enzymes Amino acid metal complexes Three-point interaction Attractive hydrophobic bonding Host guest interaction within chiral cavity Chiral affinity Diastereomeric complexation... 

To obtain further information on the preferential inclusion of the aromatic residue of one of the two enantiomers electronic and c.d. spectra were recorded in the UV-vis region. The inclusion of several chromophores in the cyclodextrin cavity has been shown to produce induced circular dichroism (i.c.d.), due to the presence of many chiral centres. In several cases, it has been possible to correlate theoretically both the sign and the intensity of the observed i.c.d. and the orientation of the transition moment related to the cyclodextrin axis [S0-S2]. It is expected both that the differential inclusion of the aromatic residue of the amino acid in the CD cavity restricts the conformational mobility of the participating groups and that the different orientation of the transition vectors in the two diastereomeric complexes causes the opposite sign in c.d. activity. 

The chiral resolution of environmental pollutants by CE depends on the formation of diastereomeric complexes and, therefore, the stmctures and sizes of the chiral pollutants are responsible for their enantiomeric resolution. To study this aspect, phenoxy acid herbicides (see Table 9.4) may be considered as the best class of chiral pollutant. Mechref and El Rassi [40] studied these herbicides using cyclodextrins as chiral selectors. It has been reported that the chiral resolution of these herbicides was in the order 2-PPA > 2,2-CPPA > 2,3-CPPA. 2-PPA has no chlorine atom on the phenyl ring, while 2,2-CPPA and 2,3-CPPA have chlorine atoms in the ortho- and meta- positions, respectively. Therefore, it may be concluded that the chlorine atom creates some sort of hindrance in the formation of diastereomeric complexes. Furthermore, it may be observed that the ortho- position creates a greater strain in comparison to the meta- position in the formation of diastereoisomeric complexes, and hence the above-mentioned order of resolution is observed. Briefly, the steric effect due to... 

Several of the GC chiral columns used in the pharmaceutical industry are listed in Table 6. Chiral GC typically uses bonded cyclodextrins to trap the volatile chiral components and resolve the stereoisomers based on their stereospecific affinity for the bonded cyclodextrin. The mechanism would be the same as seen with chiral capillary electrophoresis (CE), except cyclodextrin phases is bonded to the GC column support the diastereomeric complex does not elute. As the dia-stereomeric complex partitions between the cyclodextrin stationary phase and carrier gas mobile phase, stereoselectivity is achieved. 

Reversible inclusion-type complexation, forming diastereomeric [SO-SA] molecule associates, is a favored resolution principle which has also been adapted for CE and MECK126 129. Cyclodextrin and derivatives are superior materials if extremely high efficiency capillary techniques are used. Small chiral discrimination effects are often sufficient for baseline resolution127. 

Direct separation of racemate by using natural chiral stationary phases (e.g., cellulose and -cyclodextrin [/3-CD]) effected by the formation of diastereomeric association complexes. 

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