Cyclodextrins dual systems

Often dual chiral recognition systems ]462,463] involving mixtures of chiral SOs have been shown to enhance enantioselectivity. With dual systems of cyclodextrins (CDs), cationic mono(6-amino-6-deoxy)-p CD and a neutral CD (trimethyl-p-CD or dimethyl-p CD), it could be illustrated that arylpropionic acid enantiomers were baseline resolved, while with a single SO, no or insufficient separation of the enantiomers could be achieved [462J. 

Abushoffa AM, Fillet M, Marini RD, Hubert PH, Crommen J (2003) Enantiomeric separation of aminoglutethimide by capillary electrophoresis using native cyclodextrins in single and dual systems. J Sep Sci 26 536-542... 

DUAL CYCLODEXTRIN SYSTEMS Applying Only One CD in CE occasionally is insufficient to completely resolve chiral compounds as can be seen above. Therefore, either another CD or a combination of two CDs in dual systems can be tested to enhance both enantioselectivity and resolution. The second CD then provides enantioselectivity itself, competes with the other CD, or provides a differential migration rate. A dual system usually combines a neutral and a charged CD, or more rarely either two charged or two neutral CDs. CDs might also be combined with carbohydrates, ion-pairing reagents, surfactants, crown ethers,... 

Elek J, Mangelings D, Ivanyi T, Lazar I, Vander Heyden Y. Enantioselective capillary electrophoretic separation of tryptophane and tyrosine-methylesters in a dual system with a tetra-oxadiaza-crown-ether derivative and a cyclodextrin. J. Phartn. Biotned. Anal. 2005 38 601-608. 

Recently, multidimensional GC has been employed in enantioselective analysis by placing a chiral stationary phase such as a cyclodextrin in the second column. Typically, switching valves are used to heart-cut the appropriate portion of the separation from a non-chiral column into a chiral column. Heil et al. used a dual column system consisting of a non-chiral pre-column (30 m X 0.25 mm X 0.38 p.m, PS-268) and a chiral (30 m X 0.32 mm X 0.64 p.m, heptakis(2,3-di-(9-methyl-6-(9-tert-butyldimethylsilyl)-(3-cyclodextrin) (TBDM-CD) analytical column to separate derivatized urinary organic acids that are indicative of metabolic diseases such as short bowel syndrome, phenylketonuria, tyrosinaemia, and others. They used a FID following the pre-column and an ion trap mass-selective detector following the... 

Lin et al. [95] used capillary electrophoresis with dual cyclodextrin systems for the enantiomer separation of miconazole. A cyclodextrin-modified micellar capillary electrophoretic method was developed using mixture of /i-cyclodextrins and mono-3-0-phenylcarbamoyl-/j-cyclodextrin as chiral additives for the chiral separation of miconazole with the dual cyclodextrins systems. The enantiomers were resolved using a running buffer of 50 mmol/L borate pH 9.5 containing 15 mmol/L jS-cyclodextrin and 15 mmol/L mono-3-<9-phcnylcarbamoyl-/j-cyclodextrin containing 50 mmol/L sodium dodecyl sulfate and 1 mol/L urea. A study of the respective influence of the /i-cyclodcxtrin and the mono-3-(9-phenylcarbamoyl-/i-cyclodextrin concentration was performed to determine the optical conditions with respect to the resolution. Good repeatability of the method was obtained. 

Matthijs, N., Van Hemehyck, S., Maftouh, M., Massart, D.L., Vander Heyden, Y. Electrophoretic separation strategy for chiral pharmaceuticals using highly-snlfated and neutral cyclodextrins based dual selector systems. An. Chim. Acta 2004, 525, 247-263. 

Hammitzsch, M., Rao, R. N., and Scriba, G. K. E. (2006). Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system. Electrophoresis 27(21), 4334—4344. 

F Lelievre, P Gareil, Y Bahaddi, H Galons. Intrinsic selectivity in capillary electrophoresis for chiral separations with dual cyclodextrin systems. Anal Chem 69 393-401, 1997. 

Dual cyclodextrin systems can be developed to provide impressive selectivity of separation [30—32], A typical recipe uses 0.5-1 mM of a charged CD and 5-10 mM of a neutral CD. The development of a dual-CD system chiral separation of secondary amine drug substances is illustrated in Figure 4 using various blends of CDs. A complete separation is only found in run (d), where the buffer contained 5 mM of a neutral and 1 mM of a charged CD. 

Abushoffa AM, Fillet M, Hubert P, Crommen J. Prediction of selectivity for enantiomeric separations of uncharged compounds by capillary electrophoresis involving dual cyclodextrin systems. J Chromatogr A 2002 948 321. 

Synergistic effects in terms of efficiency of CE enantioseparation have been observed when a second (not necessarily chiral) selector is added in the same buffer system. It has been demonstrated that a combination of 18-crown-6 and )-cyclodextrin can achieve or enhance enantioselective separations of nonpolar amines, which are rarely observed with cyclodextrins alone <1997JCH(781)129, 1997JCH(695)157>. The formation of a ternary sandwich complex (dual complex) is postulated to be responsible for such a beneficial effect. 

Jakubetz H, Juza M, Schurig V (1998) Dual chiral recognition system involving cyclodextrin derivatives in capUlaiy electrophoresis II. Enhancement of enantioselectivity. Electrophoresis 19 738—744... 

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