Chiral Selector In Capillary Electrophoresis Research Articles

Designed combination of chiral selectors for adjustment of enantioseparation selectivity in capillary electrophoresis.

In this study an attempt has been made to explain the reasons for changing the enantioseparation selectivity in some dual cyclodextrin (CD) systems compared to the use of single chiral selectors in capillary electrophoresis (CE). An explanation for selectivity changes is proposed based on the effect of the chiral selector on the mobility of the analyte. In order to support the proposed mechanism, several dual systems were designed on the basis of the known recognition pattern of enantiomers for individual CDs. In most cases the separation selectivity could be adjusted in a designed way. There was no experimental evidence for simultaneous binding of a given chiral analyte with both chiral selectors or of chiral recognition of an analyte complex with one CD by another CD.

Enantiomeric separations of dansyl amino acids using the macrocyclic antibiotic A35512B as a chiral selector in capillary electrophoresis.

The macrocyclic antibiotic A35512B was examined as a chiral selector for capillary electrophoresis (CE) using thirteen racemic dansyl amino acids as test analytes. The chiral selectivity of A35512B was evaluated as a function of the run buffer pH, antibiotic concentration, and organic modifier composition. After optimizing these parameters, the macrocylic antibiotic A35512B provided high resolutions of all the enantiomers for the thirteen dansyl amino acids tested in this study.

Evaluation of quail egg white riboflavin binding protein as a chiral selector in capillary electrophoresis by applying a modified partial filling technique.

A preliminary evaluation of the enantioselective properties of quail egg yolk riboflavin binding protein (qRfBP) was carried out in capillary electrophoresis by using the complete filling technique. The most promising results obtained by this screening of nineteen chiral drugs were singled out with the aim of optimizing enantiomer separations by applying the partial filling technique, which allows operating at much higher protein concentrations without detection problems. The building of the separation zone in the partial filling technique has been modified in order to enable on-line monitoring, before each run, of the actual protein plug application velocity and, consequently, the building of a plug of the desired length. The electrophoretic conditions chosen gave opposite migration directions for the chiral selector and the analytes, with qRfBP migrating away from the detector. A polyvinyl alcohol-coated capillary was first totally filled with protein and the optimal plug length was obtained by further applying negative pressure together with positive voltage for the time needed. Separations of basic drugs were optimized by using protein concentrations ranging from 200 microM up to 900 microM and different plug lengths, while the running buffer pH (6.0), temperature (25 degrees C) and operating voltage (+20 kV) were kept constant. The enantioresolution of all solutes was affected by both the chiral selector concentration and protein plug length. Baseline separations were obtained for oxprenolol, prilocaine and bupivacaine.

Vinylpyrrolidine-β-cyclodextrin copolymer: A novel chiral selector for capillary electrophoresis

The synthesis and characterization of a novel polymer consisting of an alkyl backbone and pendant β-cyclodextrin units, obtained by radical copolymerization of vinylpyrrolidone and methacryloyl-β-cyclodextrin (PVP-β-CD), was reported. The ability of this copolymer to act as a capillary electrophoresis (CE) chiral selector was investigated in the separation of a mixture of basic drugs. The influence of polymeric cyclodextrin concentration, temperature, and pH on the separation of the test analytes was assessed and the advantage of using the polymeric selector over native β-cyclodextrin was demonstrated.

Vinylpyrrolidine-beta-cyclodextrin copolymer: a novel chiral selector for capillary electrophoresis.

The synthesis and characterization of a novel polymer consisting of an alkyl backbone and pendant beta-cyclodextrin units, obtained by radical copolymerization of vinylpyrrolidone and methacryloyl-beta-cyclodextrin (PVP-beta-CD), was reported. The ability of this copolymer to act as a capillary electrophoresis (CE) chiral selector was investigated in the separation of a mixture of basic drugs. The influence of polymeric cyclodextrin concentration, temperature, and pH on the separation of the test analytes was assessed and the advantage of using the polymeric selector over native beta-cyclodextrin was demonstrated.

Evaluation of quail egg white riboflavin binding protein as a chiral selector in capillary electrophoresis by applying a modified partial filling technique

Evaluation of quail egg white riboflavin binding protein as a chiral selector in capillary electrophoresis by applying a modified partial filling technique

Avoparcin, a new macrocyclic antibiotic chiral run buffer additive for capillary electrophoresis.

Avoparcin, like vancomycin, teicoplanin, and ristocetin A, belongs to the family of macrocyclic glycopeptide antibiotics. These antibiotics have all been used as effective chiral selectors for capillary electrophoresis (CE), thin-layer chromatography (TLC), and high performance liquid chromatography (HPLC). The present work focuses on avoparcin, which has been shown to be an excellent chiral selector for the CE enantioseparation of many N-blocked amino acids, as well as several anti-inflammatory drugs of pharmaceutical importance. The use of avoparcin as a chiral run buffer additive in CE is discussed, as well as the effects of changing experimental parameters, like avoparcin concentration, pH, organic modifiers, etc. Comparisons of enantioseparations of some N-3,5-dinitrobenzoyl-derivatized amino acids, using either avoparcin, ristocetin A, teicoplanin, or vancomycin in the run buffer, are also made. In general, vancomycin had the longest migration times, and ristocetin A the shortest, while avoparcin was intermediate. Generally, at least one of the four chiral selectors produced an excellent separation, while a different macrocyclic antibiotic produced a poor separation. Currently, we see no way to predict which chiral run buffer additive will be best or worst for an individual solute.

Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis

Chemically oversulfated galactosaminoglycans with potential as therapeutic agents (inhibitors of human leukocyte elastase) were tested as chiral selectors in capillary electrophoresis of basic racemates. The high anionic character of these compounds provides them with anodic mobility in acidic buffer; using uncoated capillaries, the enantioresolution of racemic basic drugs was obtained at pH 2.5. Dimethindene, chloroquine and chlorpheniramine were enantioresolved applying negative voltage (−15 kV) while the other analytes (propranolol, pindolol, tetrahydrozoline and cloperastine) exhibited catodic migration. The addition of organic solvents to the running buffer was evaluated in order to increase the resolution; methanol provides the best results and in general, baseline separation of the analytes was reached. The studied oversulfated mucopolysaccharide, shows the same ionic character of heparin but presents different stereochemistry and sites of sulfation. A comparison with heparin, used in the same acidic conditions, may underline the role of ionic, spatial and steric features of glycosaminoglycans in the enantiorecognition.

Combinatorial Synthesis of Highly Selective Cyclohexapeptides for Separation of Amino Acid Enantiomers by Capillary Electrophoresis

Cyclic peptide libraries dissolved in the electrolyte solution can be used as chiral selectors in capillary electrophoresis. In the present investigation, the resolution obtained in capillary electrophoresis for a set of dinitrophenyl-d,l-amino acids was the parameter used to screen for the most effective selectors contained in a mixture of thousands of components of a cyclic hexapeptide sublibrary with three randomized positions. The deconvolution procedure was simplified by fractionating the sublibrary components according to the hydrophobicity of the amino acids in the randomized positions through reversed-phase HPLC. By comparing the resolution obtained with the separated fractions, a set of hydrophobic amino acids was recognized as essential to achieve adequate enantioselectivity. The whole deconvolution process, which made it possible to select two highly selective cyclopeptides, required the synthesis and the evaluation of 15 sublibraries instead of the 54 syntheses required by a classical procedure of serial deconvolution.

Dermatan sulfate as useful chiral selector in capillary electrophoresis

Dermatan sulfate (DS), a complex, polydispersed, sulfated polysaccharide was investigated as a useful chiral selector in capillary electrophoresis for the enantioresolution of a variety of drugs. Analysis was carried out in a fused-silica capillary column of 48.5 cm length (40 cm to detector window)×50 μm I.D., and the separation buffer consisted of citric acid–Tris containing DS; the applied voltage was 15 kV and the detection wavelength was 220 nm. The effects of buffer pH, the dermatan concentration and run temperature on the enantioseparation and migration were examined. The method was applied to the enantioresolution of a representative set of twenty basic drugs. At all pH values used (3.0, 4.5 and 6.5) the addition of DS resulted in an increased migration time due to analyte–DS interaction. Using DS concentration of 2% (w/w), at pH 4.5, enantiomeric separations could be obtained for more than 50% of the examined drugs; resorcinic moiety was found to be a very favourable structural feature for obtaining high enantioresolution values.

Use of a Hepta‐tyr glycopeptide antibiotic as chiral selector in capillary electrophoresis

A new glycopeptide antibiotic, MDL 63,246 (Hepta-tyr), of the teicoplanin family, has been evaluated in capillary electrophoresis for the resolution of chiral compounds of pharmaceutical and environmental interest. Electrophoretic separations were carried out in a polyacrylamide-coated capillary using the partial filling-counter current mode with aqueous-organic buffers in the pH range 4-6. Experimental parameters affecting resolution, such as antibiotic concentration, buffer pH, organic modifier type and capillary temperature, were studied. The Hepta-tyr antibiotic exhibited a high enantiorecognition capability towards the studied compounds at very low concentrations (1-2 mg/mL). The optimum experimental conditions were achieved by using a buffer at pH 5 containing acetonitrile at 25 degrees C.

Chiral Separation of (R,S)-1,1′-Binaphthyl-2,2′-diyl Hydrogenphosphate by Capillary Electrophoresis Using Monosaccharides as Chiral Selectors

Monosaccharides were investigated as chiral selectors in capillary electrophoresis of binaphthyl compounds. Among monosaccharides tested, glucose, mannose and their derivatives, except for methyl-β-D-glucopyranoside, were found to be effective for direct separation of racemic mixture of 1,1′-binaphthyl-2,2′-diyl hydrogenphosphate (BNP). D-Forms of galactose, sorbose, fructose, ribose, arabinose and xylose failed chiral separation of BNP. We tentatively concluded that monosaccharides (in the case of D-forms) must satisfy the following structural requirements for successful chiral separation of BNP enantiomers: (1) oxygen atom at C-1 is in α-configuration, (2) -OH group at C-4 is downward configurated and (3) the presence of a -CH2OH or -CH3 group at C-5. Thus, in the case of D-glucose, the chiral separation of BNP is anticipated to be achieved predominantly through the hydrogen bonding between oxygen atom at C-1 and hydrogen atom of -OH group at C-4 on D-glucose and hydrogenphosphate moiety of BNP.

Comparative capillary electrophoresis and NMR studies of enantioseparation of dimethindene with cyclodextrins

Enantioseparation of the antihistaminic drug dimethindene (DIM) (as maleate and tartrate salts) was studied using various cyclodextrins (CD) as chiral selectors in capillary electrophoresis (CE). NMR spectroscopy was used in order to elucidate the reason for the opposite migration order of the enantiomers of dimethindene (DIM) when native β-CD or commercially available carboxymethyl-β-CD (CM-β-CD) were used. This study demonstrated that the complexation-induced chemical shift of enantiomers does not always definitely show the chiral recognition pattern. The binding constants between the analyte and chiral selector need to be determined. NMR spectroscopy provided clear evidence on the multimodal (at least bimodal) complexation between DIM and CM-β-CD. These complexes seem to have a different stoichiometry. Moreover, the chiral recognition of DIM seems to be opposite in these complexes. The effect of additives such as urea on the interaction between DIM and β-CD was studied with both techniques.

Capillary Electrophoretic Enantiomeric Separations of Nonsteroidal Anti-inflammatory Compounds Using the Macrocyclic Antibiotic Actaplanin A and 2-Methoxyethanol

Actaplanin A, a macrocyclic antibiotic, was examined as a chiral selector in capillary electrophoresis (CE) for the enantioseparation of several racemic nonsteroidal antiinflammatory compounds. The chiral selectivity of this macrocyclic antibiotic was evaluated as a function of the run buffer pH, chiral selector concentration, and organic modifier composition. Optimized conditions using 15-30% of 2-methoxyethanol and 0.5 mM actaplanin A in 40 mM phosphate buffer (pH 6) were successful in separating all of the enantiomers from the racemic compounds tested in this study.

Enantioseparation of atropisomeric 1,1?-binaphthyl-2,2?-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis

Twelve different disaccharides and a series of noncyclic malto- and cello-oligosaccharides were used as chiral selectors in capillary electrophoresis (CE). Most saccharides resolved the enantiomers of atropisomeric 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BDHP) depending on the type (alpha or beta) and position of the linkage between monosaccharides. The effect of chain length of malto- and cello-oligosaccharides on enantioseparation of BDHP was also investigated. The nature of cations in background electrolytes affected significantly the separation of BDHP enantiomers.

Enantioseparation of atropisomeric 1,1?-binaphthyl-2,2?-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis

Enantioseparation of atropisomeric 1,1?-binaphthyl-2,2?-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis

Enantioseparation of atropisomeric 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate in capillary electrophoresis by using di‐ and oligosaccharides as chiral selectors: di‐ and oligosaccharide chiral selectors in capillary electrophoresis

Enantioseparation of atropisomeric 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate in capillary electrophoresis by using di‐ and oligosaccharides as chiral selectors: di‐ and oligosaccharide chiral selectors in capillary electrophoresis

Evaluation of Two Amine-Functionalized Cyclodextrins as Chiral Selectors in Capillary Electrophoresis: Comparisons to Vancomycin

Two different amine-functionalized β-cyclodextrins were evaluated as chiral selectors in capillary electrophoresis. The first selector was a monosubstituted 6-ethylenediamine-derivatized β-cyclodextrin, and the other was quaternary ammonium hydroxypropyl-β-cyclodextrin. The former compound was more widely useful as a chiral selector and had less effect on the electroosmotic flow than the latter compound. Both tended to resolve anionic compounds. The primary attractive interaction between these host chiral selectors and their enantiomeric guests were charge–charge (ionic) and hydrophobic inclusion. Additional interactions involved hydrogen bonding and/or steric repulsions. The cationic cyclodextrins were not as widely useful in resolving anionic compounds as was vancomycin. However, they tended to be more stable and were comparatively transparent to near-UV light.

Enantioseparation using selected polysaccharides as chiral buffer additives in capillary electrophoresis

Selected water-soluble, native polysaccharides – such as amylose, laminaran, pullulan – and derivatized polysaccharides – methyl cellulose, hydroxypropyl cellulose, and carboxymethyl amylose sodium salt (CM-Am) – were investigated as chiral selectors in capillary electrophoresis. Effects of degree of polymerization and concentration of amylose on the separation of enantiomers of 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BDHP) and a chiral cardiovascular drug cis-diltiazem were also studied. Pullulan and amyloses used in this study showed the same migration order for enantiomers of BDHP. In contrast, the migration order of BDHP enantiomers for cellulose derivatives and laminaran as well as with β-cyclodextrin was opposite to that for amylose and pullulan. The enantioseparation of several chiral drugs was also performed using high-molecular-mass amylose (Am-4900) and CM-Am.