Cyclodextrins as Dominant Chiral Selective Agents in the Capillary Separation Techniques (original) (raw)
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Single isomer cyclodextrins as chiral selectors in capillary electrophoresis
Journal of Chromatography A
Since decades, cyclodextrins are one of the most powerful selectors in chiral capillary electrophoresis for the enantioseparation of diverse organic compounds. This review concerns papers published over the last decade (from 2009 until nowadays), dealing with the capillary electrophoretic application of single isomer cyclodextrin derivatives in chiral separations. Following a brief overview of their synthetic approaches, the inventory of the neutral, negatively and positively charged (including both permanently ionic and pH-tunable ionizable substituents) and zwitterionic CD derivatives is presented, with insights to underlying structural aspects by NMR spectroscopy and molecular modeling. CE represents an ideal tool to study the weak, non-covalent supramolecular interactions. The published methods are reviewed in the light of enantioselectivity, enantiomer migration order and the fine-tuning of enantiodiscrimination by the substitution pattern of the single entity selector molecules, which is hardly possible for their randomly substituted counterparts. All the reviewed publications herein support that cyclodextrin-based chiral capillary electrophoresis seems to remain a popular choice in pharmaceutical and biomedical analysis.
Journal of Pharmaceutical and Biomedical Analysis, 1999
A simple, systematic method was developed for rapidly screening potential capillary electrophoresis (CE) separation conditions for small, amine-containing enantiomers. During method development, 39 pairs of enantiomers were investigated and partial or complete separation was achieved in every case. Baseline resolution was achieved by these initial screening conditions in over half of the cases. The screening strategy uses a bare fused silica capillary and a pH 2.5 amine-modified phosphate buffer containing one of the selected cyclodextrins (CD): dimethyl-b-CD, hydroxypropyl-b-CD, hydroxypropyl-a-CD, hydroxypropyl-g-CD and sulfated-b-CD. An additional set of compounds have been screened by this approach to demonstrate the validity of the method. The paper outlines the experimental work carried out to develop the screen and describes how one might implement it for a new compound.
Application of Sulfated Cyclodextrins to Chiral Separations by Capillary Zone Electrophoresis
Analytical Chemistry, 1996
Mixtures of randomly substituted sulfated cyclodextrins (degree of substitution, ∼7-10) were successfully used as chiral additives for the enantioseparation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antihypertensives, antimalarials, relaxants, and bronchodilators. The separations were accomplished at pH 3.8, with the anode at the detector end of the column. Under these conditions, in which electroosmotic flow is directed toward the injection end of the column and the electrophoretic mobility of the negatively charged cyclodextrin is toward the detector, none of the analytes reached the detector in the absence of the sulfated cyclodextrin. Most (40) of the successfully resolved enantiomers contained basic functionality and a stereogenic carbon. However, the versatility of this sulfated cyclodextrin additive was also demonstrated by the fact that three atropisomers, 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate, 1,1′-binaphthyl-2,2′-diol, and Troger's base, and several neutral analytes were also successfully enantioresolved under these conditions. The separation mechanism seems to involve inclusion complexation.
Molecules
In order to better understand the chiral recognition mechanisms of positively charged cyclodextrin (CD) derivatives, the synthesis, the pKa determination by 1H nuclear magnetic resonance (NMR)-pH titration and a comparative chiral capillary electrophoretic (CE) study were performed with two series of mono-substituted cationic single isomer CDs. The first series of selectors were mono-(6-N-pyrrolidine-6-deoxy)-β-CD (PYR-β-CD), mono-(6-N-piperidine-6-deoxy)-β-CD (PIP-β-CD), mono-(6-N-morpholine-6-deoxy)-β-CD (MO-β-CD) and mono-(6-N-piperazine-6-deoxy)-β-CD (PIPA-β-CD), carrying a pH-adjustable moiety at the narrower rim of the cavity, while the second set represented by their quaternarized, permanently cationic counterparts: mono-(6-N-(N-methyl-pyrrolidine)-6-deoxy)-β-CD (MePYR-β-CD), mono-(6-N-(N-methyl-piperidine)-6-deoxy)-β-CD (MePIP-β-CD), mono-(6-N-(N-methyl-morpholine)-6-deoxy)-β-CD (MeMO-β-CD) and mono-(6-N-(4,4-N,N-dimethyl-piperazine)-β-CD (diMePIPA-β-CD). Based on pH-depende...
Journal of Pharmaceutical and Biomedical Analysis, 2010
Preparation of (6-monoureido-6-monodeoxy) permethylated -cyclodextrin bonded chiral stationary phase from permethylated 6-monoamino-6-monodeoxy--cyclodextrin is described. The optimized chiral stationary phase was evaluated by using HPLC separation of racemates of coumarin derivatives. Column characterization was performed by solid-state 13 C, 15 N, 29 Si NMR using cross-polarization at the magic angle spinning. The development process was supported by CE experiments where the complex formation between cyclodextrins and warfarin was investigated. The results demonstrate good enantio-discrimination for coumarin derivatives.
A persubstituted cationic beta-cyclodextrin for chiral separations
Analytical Chemistry
The applications of a novel polycationic derivative of beta-cyclodextrin (beta-CD), heptakis(6-hydroxyethylamino-6-deoxy-beta-cyclodextrin) (beta-CD-EA), as a chiral host--guest additive for the enantioseparation of various classes of chiral anionic analytes are presented. The cationic beta-CD described in this paper is persubstituted with seven ethanolamine side arms at the primary rim of each cyclodextrin (CD) molecule. It is found that the electrophoretic mobility of beta-CD-EA can be adjusted to influence the chiral selectivity by changing the pH of the background electrolyte. Most of the observed CD capillary zone electrophoresis (CZE) separations of anionic drugs and herbicides were accomplished in the pH range of 4.0-7.0 with a reverse polarity configuration. At pH 5.0, enantioseparation of a mixture of three structurally related antiinflammatory agents (fenoprofen, flurbiprofen, and ibuprofen) was possible in about 30 min. However, other chiral acids, such as a series of phe...
Structural studies on the chiral selector capacity of cyclodextrin derivatives
Journal of Biochemical and Biophysical Methods, 2008
Chromatographic separation of enantiomers to assure or enhance chiral purity is of considerable importance and can be achieved by the use of selectors of great structural variety. Cyclodextrins are an important and frequently used class, and they are multimodal selectors since multiple chiral interactions are possible by very different mechanisms. Here, the results of a preliminary examination on the possible value of computational molecular modeling approaches for the predictability of cyclodextrin selector effects for compounds that possess both geometrical and optical isomerism are presented. Interactions between various cyclodextrins and pyrethroic acids are modeled, interpreted, and compared to experimental capillary electrophoresis data.
Chromatographia, 2010
Three 2,3-di-O-allyl-6-O-acyl-b-cyclodextrins, 2,3-di-O-allyl-6-O-valeryl-b-cyclodextrin, 2,3-di-O-allyl-6-O-heptanoyl-b-cyclodextrin, and 2,3-di-O-allyl-6-O-octanoyl-b-cyclodextrin, were synthesized and their chromatographic properties were investigated. 2,3-di-Oallyl-6-O-acyl-b-cyclodextrins cannot only separate the enantiomers of methyl 2-chloropropionate, methyl 2-bromopropionate, methyl 2-hydroxypropionate, allethrone acetate, propargyllone acetate, and 1-(2,4-dichlorophenyl)ethanol, but also possess enantiomer separation abilities to some enantiomers of pyrethroic acid methyl esters and epoxides. The enantiomer separation results on the three 2,3-di-O-allyl-6-O-acyl-b-CDs were used to draw some empirical rules about enantiomer separation together with the enantiomer separation results on other CDs. Acyl groups on CDs, especially 3-position acyl groups on CDs, are favorable for the enantiomer separation of pyrethroic acid methyl esters, while acyl groups on 6-position of CDs are beneficial for the enantiomer separation of epoxides, but allyl on CDs are less favorable for enantiomer separation than pentyl. The empirical rules summarized here have some practice significances in selecting CGC chiral stationary phase for solving enantiomer separation problems. Also, the three 2,3-di-O-allyl-6-O-acyl-b-CDs may be used in practical chiral analysis.
A Persubstituted Cationic β-Cyclodextrin for Chiral Separations
Analytical Chemistry, 1997
The applications of a novel polycationic derivative of -cyclodextrin ( -CD), heptakis(6-hydroxyethylamino-6deoxy--cyclodextrin) ( -CD-EA), as a chiral host-guest additive for the enantioseparation of various classes of chiral anionic analytes are presented. The cationic -CD described in this paper is persubstituted with seven ethanolamine side arms at the primary rim of each cyclodextrin (CD) molecule. It is found that the electrophoretic mobility of -CD-EA can be adjusted to influence the chiral selectivity by changing the pH of the background electrolyte. Most of the observed CD capillary zone electrophoresis (CZE) separations of anionic drugs and herbicides were accomplished in the pH range of 4.0-7.0 with a reverse polarity configuration. At pH 5.0, enantioseparation of a mixture of three structurally related antiinflammatory agents (fenoprofen, flurbiprofen, and ibuprofen) was possible in about 30 min. However, other chiral acids, such as a series of phenoxypropionic acid herbicides and dansylated amino acids (glutamic acid and aspartic acids), were best separated at pH 6.0 or 7.0. An impressive separation of a mixture of six structurally related anionic herbicides [(()-2-phenoxypropionic acid, (()-2-(2-chlorophenoxy)propionic acid, (()-2-(3-chlorophenoxy)propionic acid, (()-2-(4-chlorophenoxy)propionic acid, (()-2-(2,4-dichlorophenoxy)propionic acid, and (()-2-(2,4,5-trichlorophenoxy)propionic acid] was achieved for the first time in about 15 min during a single run with 20 mM -CD-EA. The analytical applicability of this cationic CD molecule for chiral separations is discussed in detail.