Cyclodextrins as chiral selectors

Armstrong and Jin [15] reported the separation of several hydrophobic isomers (including (l-ferrocenylethyl)thiophenol, 1 -benzylnornicotine, mephenytoin and disopyramide) by cyclodextrins as chiral selectors. A wide variety of crown ethers have been synthesized for application in enantioselective liquid membrane separation, such as binaphthyl-, biphenanthryl-, helicene-, tetrahydrofuran and cyclohex-anediol-based crown ethers [16-20]. Brice and Pirkle [7] give a comprehensive overview of the characteristics and performance of the various crown ethers used as chiral selectors in liquid membrane separation. 

Perrin, C., Vander Heyden, Y, Maftouh, M., Massart, D.L. Rapid screening for chiral separations by short-end injection capillary electrophoresis nsing highly sulfated cyclodextrins as chiral selectors. Electrophoresis 2001, 22, 3203-3215. 

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... 

Ropivacaine hydrochloride is a long-acting local anesthetic, which is manufactured as the pure S-enantiomer. The enantiomeric purity is determined by CZE, using heptakis-(2,6-di-0-methyl)-j5-cyclodextrin as chiral selector. A resolution of 3.7 between the two enantiomers is required for the system suitability solution. The percentage R-enantiomer is calculated relative to the S-enantiomer in the same electropherogram, and should not exceed 0.5%. In Eigure 5, a representative electropherogram is presented. 

Rudaz, S., Calleri, E., Geiser, L., Gherkaoui, S., Prat, J., and Veuthey, J. L. (2003). Infinite enantiomeric resolution of basic compounds using highly sulfated cyclodextrin as chiral selector in capillary electrophoresis. Electrophoresis 24, 2633—2641. 

T Schmitt, H Engelhardt. Charged and uncharged cyclodextrins as chiral selectors in capillary electrophoresis. Chromatographia 37 475-481, 1993. 

Y Tanaka, S Terabe. Enantiomer separation of acidic racemates by capillary electrophoresis using cationic and amphoteric f -cyclodextrins as chiral selectors. J Chromatogr A 781 151-160, 1997. 

G Galaverna, R Corradini, A Dossena, R Marchelli. Histamine-modified cationic /3-cyclodextrins as chiral selectors for the enantiomeric separation of hydroxy acids and carboxylic acids by capillary electrophoresis. Electrophoresis 20 2619-2629, 1999. 

A Shibukawa, DK Lloyd, IW Wainer. Simultaneous chiral separation of leu-covorin and its major metabolite 5-methyltetrahydrofolate by capillary electrophoresis using cyclodextrins as chiral selectors. Estimation of the formation constant and mobility of the solute—cyclodextrin complex. Chromatographia 35 419-429, 1993. 

A Amini, N Merclin, S Bastami, D Westerlund. Determination of association constants between enantiomers of orciprenaline and me thy 1-/3-cyclodextrin as chiral selector by capillary zone electrophoresis using a partial filling technique. Electrophoresis 20 180-188, 1999. 

A number of CE/MS applications have been published in the field of chiral separations, mostly using cyclodextrins as chiral selectors. In some cases the partial-filling technique was used (see earlier). The importance of... 

A Amini, U Paulsen-Sorman. Enantioseparation of local anaesthetic drugs by capillary zone electrophoresis with cyclodextrins as chiral selectors using a partial-filling technique. Electrophoresis 18 1019-1025, 1997. 

Better results for the enantioanalysis of S-perindopril were obtained when the carbon paste was impregnated with a-, /i- and y-cyclodextrins as chiral selectors [29]. There had been improvements in detection limits (lower with unsubstituted CDs as chiral selectors), enantioselec-tivity (higher especially when a-CD was used as chiral selector) and the values of the slope of the electrodes (higher especially when a-CD and y-CD were used as chiral selectors). 

Kataky et al. described the design of a PYC membrane based on a-, fi-and y-cyclodextrins as chiral selectors [35]. The enantiomers of aryl ammonium ions of pharmaceutical importance can be discriminated and assayed with low limits of detection and high sensitivities using these electrodes. 

To establish chiral separation method for donepezil hydrochloride enantiomers by capillary electrophoresis (CE) and to determine the two enantiomers in plasma [39], alkalized plasma was extracted by isopropa-nol-n-hexane (3 97) and L-butefeina was used as the IS. Enantioresolution was achieved using 2.5% sulfated-beta-cyclodextrin as chiral selector in 25 mmol/1 triethylammonium phosphate solution (pH 2.5) on the uncoated fused-silica capillary column (70 cm x 50 fim i.d.). The feasibility of the method to be used as quantitation of donepezil HC1 enantiomers in rabbit plasma was also investigated. Donepezil HC1 enantiomers were separated at a baseline level under the above condition. The linearity of the response was evaluated in the concentration range from 0.1 to 5 mg/1. The linear regression analysis obtained by plotting the peak area ratio (A(s)/A(i)) of the analyte to the IS versus the concentration (C) showed excellent correlation coefficient The low limit of detection was 0.05 mg/1. The inter- and intra-day precisions (RSD) were all less than 20%. Compared with chiral stationary phase by HPLC, the CE method is simple, reliable, inexpensive, and suitable for studying the stereoseletive pharmacokinetics in rabbit. 

Gao et al. [27] described enantiomeric resolution of FITC-labeled basic drugs (baclofen, norfenefrine, and tocainide) by NCE using several neutral cyclodextrins as chiral selectors. FITC-baclofen enantiomers were separated completely by y-CD while resolution of FITC-norfenefrine enantiomers was achieved by dimethyl-(3-cyclodextrins. Furthermore, the authors studied the feasibility of using one chiral selector to separate multiple racemic samples on a four-channel chip. Figure 9.8 indicates the role of some chiral selectors for enantiomeric resolution of FITC-baclofen and FITC-norfenefrine race-mates. A perusal of this figure indicates that HP-a-CD and HP-0-CD are... 

Capillary Electrophoresis (CE) and Micellar Electrokinetic Chromatography (MEKC). - Di(2-ethylhexyl) thiophosphoric acid (DEHTPA) has been earlier characterised by potentiometric titration, and quantified by capillary zone electrophoresis with carbonate buffer, operating at —20 kV, and using UV detection at 210 nm. ° Also, a comparison has been made of capillary electrophoresis (CE) and liquid chromatography (LC) for the enantiomeric separation of a-phosphonosulfonic acids, where CE used 3-cyclodextrin as chiral selector in a borate electrolyte. Alkylphosphonic acids, at trace levels in water, have been determined by CE coupled online with flame photomeric detection, and alkylphosphonic acid esters have been separated and determined by CE using indirect UV detection. 

Gilar, M., Uhrova, M.,Tesarova, E. Enantiomer separation of dihydropyridine calcium antagonists with cyclodextrins as chiral selectors structural correlation, J. Chromatogr. B., 1996, 681, 133-141. 

M Blanco, J Coello, H Iturriaga, S Maspoch, C Perez-Maseda. Separation of profen enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors. J Chromatogr A 793 165-175, 1998. 

KL Sutton, RM Sutton, AM Stalcup, JA Caruso. A comparison of vancomycin and sulfated beta-cyclodextrin as chiral selectors for enantiomeric separations of selenoamino acids using capillary electrophoresis with UV absorbance detection. Analyst 125 231-234, 2000. 

Tang W, Muderawan IW, Ng S-C, Chan HSO. 2006. Enantioselective separation in capillary electrophoresis using a novel mono-6 -propylammonium-P-cyclodextrin as chiral selector. Analytica Chimica Acta 555(1 ) 63-67. 

Capillary electrophoresis (CE) features increasingly in chiral separations. The use of cyclodextrins as chiral selectors is commonplace. Micellar electro-kinetic chromatography (MEKC) was used for the chiral separation of enantiomers of l,r-binaphthyl-2,2 -diyl hydrogen phosphate. ... 

Frovatriptan, using cyclodextrin as chiral selector. J. Pharm. Biomed Anal., 41,1447-1452 (2006). Zhou S., Ouyang J., Baeyens W.R.G, Zhao H., Yang Y, Chiral separation of four fluoroquinolone compounds using capillary electrophoresis with hydroxypropyl-fS-cyclodextrin as chiral selector. 

Jin, L. J., Rodriguez, 1., and Li, S. R Y, Enantiomeric separation of amino acids derivatized with fluores-ceine isothiocyanate isomer I by micellar electrokinetic chromatography using b- and g-cyclodextrins as chiral selectors. Electrophoresis, 20, 1538, 1999. 

For method optimization of chiral separations the type and concentration of the chiral selector has to be specifically considered in addition to factors also important in achiral CE such as pH, molarity and type of the background electrolyte, and buffer additives. When using randomly substituted cyclodextrins as chiral selectors testing of different batches of the cyclodextrin and samples from different suppliers is... 

In particular, the resolution of dansyl-o- and L-amino acids by reversed-phase TLC using aqueous mobile phases containing methanol or acetonitrile and p-cyclodextrin as chiral selector is very useful for stereochemical analysis of amino acids from small peptides, since a significant number of naturally occurring peptides and peptide antibiotics isolated from plants and microorganisms contain at least one amino acid in D-configuration. ... 

Source From New derivatives of cyclodextrins as chiral selectors for the capillary electrophoretic separation of dichlorprop enantiomers, in J. Chromatogr. 

Zerbinati, O. Trotta, F. Giovannoh, C. Baggiani, C. Giraudi, G. Vanni, A. New derivatives of cyclodextrins as chiral selectors for the capillary electrophoretic separation of dichlor-prop enantiomers. J. Chromatogr. A, 1998, 810, 193-200. 

Zhang XH, Wang Y, Jin WJ (2008) Enantiomeric discrimination of l,l -binaphthol by room temperature phosphorimetry using y-cyclodextrin as chiral selector. Anal Chim Acta 622 157-162... 

Table 9.4 The chiral resolution of phenoxy acid herbicides (underivatized and deriva-tized with 7-aminonaphthalene-l,3-disulfonic acid) using various cyclodextrins as chiral selectors [37]...

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... 

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