Chiral ligand exchange micellar electrokinetic chromatography using borate anion as a central ion

Three compounds having 1,2-diol structure (1-phenyl-1,2-ethanediol, 3-phenoxy-1,2-propanediol, and 3-benzyloxy-1,2-propanediol) were enantioseparated by ligand exchange MEKC using (5S)-pinanediol (SPD) as a chiral selector and borate anion as a central ion together with SDS. When (S)-1,2-propanediol, (S)-1,2,4-butanetriol, or (S)-3-tert-butylamino-1,2-propanediol were used as the chiral ligand instead of SPD, these three compounds were not enantioseparated. When borate was replaced with 2-aminoethane-1-sulfonate or N-cyclohexyl-3-aminopropanesulfonate, no chiral separation was achieved. Therefore, the hydrophobic interaction between the chiral selector and the chiral analytes within the transient diastereomeric complex may play an important role in the enantioseparation achieved by the proposed method.     

Chiral separation of sympathomimetics by ligand exchange capillary electrophoresis.

A rapid and simple approach to the chiral separation of sympathomimetic drugs with amino alcohol structure by ligand exchange capillary electrophoresis is described. An N-(2-hydroxyoctyl)-L-4-hydroxyproline/copper(II) complex is used as chiral selector. Thirteen sympathomimetics were resolved, nine with baseline resolution. The influence of pH and composition of the electrolyte on resolution was investigated. The optimal pH for complexation of these amino alcohols was found to be 12.     

Chiral resolution of monosaccharides as 1-phenyl-3-methyl-5-pyrazolone derivatives by ligand-exchange CE using borate anion as a central ion of the chiral selector

Six reducing monosaccharides (mannose, galactose, fucose, glucose, xylose, and arabinose) were derivatized with 1-phenyl-3-methyl-5-pyrazolone (PMP) and chiral resolution of these racemic PMP-monosaccharides was studied by ligand-exchange CE using borate anion as a central ion of the chiral selector and (S)-3-amino-1,2-propanediol (SAP) as a chiral selector ligand. PMP-mannose, PMP-galactose and PMP-fucose were successfully enantioseparated. Lowering the capillary temperature increased the resolution of PMP-mannose system, but decreased that of PMP-galactose and PMP-fucose systems. Whereas the maximum resolution was obtained at pH 8.9 in the PMP-mannose system, resolution increased gradually with pH in the PMP-galactose and PMP-fucose systems. Expecting the formation of the ternary borate complexes with SAP and PMP-monosaccharide in the CE experiments, the optimized structures of the borate diastereomers were obtained by semiempirical molecular orbital calculations to discuss the structural difference of the diastereomers in connection with the enantioseparation behaviors.     

Chiral separation using capillary electromigration techniques based on ligand exchange principle

Over the last couple of decades, researchers have developed diverse chiral separation methods emerged from a few chiral separation principles. This review article is primarily focused on the application of chiral ligand-exchange (CLE) principle in capillary electromigration techniques, such as capillary electrophoresis (CE) and capillary electrochromatography (CEC). First, the most commonly used CLE-CZE separation mode by using different kinds of central ions, such as Cu(II), Zn(II), borate ion, and other metal ions, has been introduced. Meanwhile, several kinds of surfactants have been applied as the micelle-forming agents in the CLE micellar electrokinetic chromatography mode. The highlight of recent research of CLE-CEC is the exploitation of novel columns for chiral separation. Then, two kinds of capillary columns, packed capillary and monolithic capillary column, have been briefly described. Finally, the effective application of these chiral separation methods has been presented, including the application in life science and food analysis area.     

Mechanism of enantioseparation of DL-pantothenic acid in ligand exchange capillary electrophoresis using a diol-borate system

Borate complexes formed in the ternary system at pH 9.2 containing borate, (S)-3-amino-1,2-propanediol (SAP), and DL-pantothenic acid (DL-PTA) were identified by 13C and 11B NMR, and it is confirmed that the binary complexes, [B(OH)2(SAP)], [B(SAP)2]+ [B(OH)2(D- or L-PTA)]2-, and [B(D- or L-PTA)2]3- (including [B(D-PTA)(L-PTA)]3-), and the ternary complexes, [B(SAP)(D- or L-PTA)]-, coexist at equilibrium in the ternary system. Thermodynamic experiments by variable-temperature 11B NMR revealed that the ternary complex, [B(SAP)(D-PTA)]-, is entropically more stable than [B(SAP)(L-PTA)]-. Because two geometrical isomers are possible for the respective ternary complexes, semi-empirical molecular orbital calculations were performed by PM5, PM3, and AM1 methods in order to obtain the optimized structures. It is indicated from the calculated heats of formation and experimentally obtained thermodynamic parameters that the (S)-isomer is more probable for the respective ternary complexes with D- and L-PTA. In the optimized structure of (S)-[B(SAP)(D-PTA)]- in water, the SAP and D-PTA ligands were oppositely oriented to form a rather linear structure, while the diastereomer, (S)-[B(SAP)(L-PTA)]-, had a folded structure. Because such a difference in the solvated structure of the ternary complexes can give a different electrophoretic velocity in CE, the enantioseparation of DL-PTA in CE is reasonably attributed to a difference in the observed electrophoretic mobility for the equilibrated ternary systems containing the respective ternary complexes.     

Mass spectrometry detection as an innovative and advantageous tool in ligand exchange capillary electrophoresis

The copper(II) complex of a modified cyclodextrin, namely 6-mono-deoxy-6-[4-(2-aminoethyl)imidazolyl]-β-CD (CDmh), previously synthesized and characterized in our laboratory and already used as chiral selector for ligand exchange capillary electrophoresis (LECE) with optical detection, is investigated here in LECE using electrospray-mass spectrometry (ESI-MS) as the detection device. The potential of this hyphenated method is compared with the results previously obtained with optical detection by studying the chiral resolution of tryptophan racemate. Chiral separation conditions compatible with LECE-ESI-MS could be achieved based on the figures of merit obtained by LECE-UV. Interestingly, the values of LOD obtained by LECE-ESI-MS were significantly better than those obtained by LECE-UV and thus, ESI-MS detection seems to open new perspectives in chiral separations by LECE.     

Fast ion chromatography using short anion exchange columns

A fast ion chromatographic system is described which uses shorter column lengths and compares various eluent profiles in order to maximise the performance without sacrificing the chromatographic resolution. Both isocratic and gradient elution profiles were considered to find the most efficient mode of separation. The separation and determination of seven target anions (chloride, chlorate, nitrate, chromate, sulfate, thiocyanate and perchlorate) was achieved using a short (4 mm ID, 50 mm long) column packed with Dionex AS20 high-capacity anion exchange material. A hydroxide eluent was used at an initial concentration of 25 mM (at a flow-rate of 1.0 mL/min) and two performance maxima were found. The maximum efficiency occurred at a normalised gradient ramp rate of 5 mM/t₀, resulting in a peak capacity of 16, while the fastest separation (<3 min) occurred at a normalised ramp rate of 30 mM/t₀. The retention time, peak width and resolution using the different eluent profiles on varying column lengths is also compared. Further investigations in this study determined that the highest peak capacity separation under gradient conditions could be approximated using an isocratic separation. The advantage of using this novel approach to approximate the maximum efficiency separation removes the need for column re-equilibration that is required for gradient elution resulting in faster analyses and enhanced sample throughput, with benefits in particular for multidimensional chromatography.     

Chiral separation of ephedrine isomers by capillary electrophoresis using bovine serum albumin as a buffer additive

A method utilizing bovine serum albumin (BSA) as buffer additive for chiral separation by means of capillary electrophoresis is described. Parameters that affect chiral separation, such as buffer pH, buffer concentration, BSA concentration, and organic modifier, are investigated. Baseline resolution of ephedrine-pseudoephedrine and norephedrine-norpseudoephedrine isomers are achieved in an uncoated capillary with a 20 mmol/L phosphate buffer at pH 9.0 in the presence of 10 micromol/L BSA and 15% (v/v) 2-propanol at 25 degrees C. The developed method can be applied for the analysis of ephedra plant extracts that contain the four test drugs.     

Environmental monitoring of wastewater using capillary ion electrophoresis

Capillary ion electrophoresis (CIE) is a capillary electrophoretic technique which has been developed for the rapid analysis of low-molecular-mass inorganic and organic ions. Anion and cation analysis of wastewater samples from a meat processing plant will be discussed. The wastewater samples were collected above, at point of discharge, and at various points downstream from the plant. The purpose of the analysis was to investigate dilution effects of the wastewater as it mixes with the stream water. CIE allows for rapid analysis times (typically less than 5 min) with little sample preparation required.     

Enantioseparation of underivatised amino acids by ligand exchange capillary electrophoresis in a counter-electroosmotic mode

Enantiomer separations of underivatised amino acids were carried out by using ligand exchange capillary electrophoresis (LECE). Chiral discrimination is based on the formation of ternary complexes between copper(II), a chiral selector (L-proline or trans-4-hydroxy-L-proline) and an amino acid. All amino acids containing aromatic moieties or not were detected at 214 nm because of their interactions with copper(II). In order to reduce copper(II) adsorption onto capillary walls, we used hexadimethrine bromide to reverse the electroosmotic flow. Using this original strategy, the studied enantiomers migrated in the opposite direction of the anodic electroosmosis. After optimising the analytical conditions taking into account the chiral resolution and the detection sensitivity, we performed very satisfactory enantioseparations not only of aromatic amino acids (tryptophan, tyrosine, phenylalanine and histidine) but also of aliphatic amino acids (threonine, serine, isoleucine and valine). These enantioseparations were performed in a short analysis time at 35 °C. In order to rationalise the obtained results, we evaluated the complexation constants corresponding to the formed ternary complexes by capillary electrophoresis and we used molecular mechanics modelling.     

离子液体作为添加剂的毛细管电泳法拆分盐酸金刚乙胺

将新离子液体[EIMCH2CONHBu]BF4用于毛细管电泳法拆分手性药物,建立了以β-环糊精为手性选择剂拆分盐酸金刚乙胺对映体的毛细管电泳方法。分别考察了离子液体浓度,手性选择剂浓度,缓冲溶液种类、浓度及pH值,分离电压等参数对分离度的影响,从而确定了盐酸金刚乙胺对映体的最佳拆分条件:[EIMCH2CONHBu]BF4溶液体积分数3.2%,β-环糊精18 mmol/L,NaH2PO4 15 mmol/L,缓冲液pH 3.03,分离电压15 kV。在优化的实验条件下,盐酸金刚乙胺对映体得到基线分离,分离度可达1.51。实验结果表明[EIMCH2CONHBu]BF4能够增强β-环糊精的手性拆分能力,对手性拆分有协同作用。     

Chiral separation of four fluoroquinolone compounds using capillary electrophoresis with hydroxypropyl-beta-cyclodextrin as chiral selector

A capillary zone electrophoresis (CZE) investigation on the enantiomeric separation of lomefloxacin, gatifloxacin, pazufloxacin and ofloxacin was undertaken. Resolution of the enantiomers was achieved using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as the chiral selector. Parameters influencing separation include cyclodextrin concentration, separational potential, pH and organic additive are discussed. A buffer consisting of 70 mM phosphate and 40 mM HP-beta-CD at pH 3.96 was found to be highly efficient for the separation of lomefloxacin, at pH 3.90 for gatifloxacin, at pH 5.04 for pazufloxacin and at pH 2.16 for ofloxacin. To the best of our knowledge, this is the first report on the enantiomeric resolution of lomefloxacin and gatifloxacin applying CE.     

Chiral separation of synthetic vicinal diol compounds by capillary zone electrophoresis with borate buffer and beta-cyclodextrin as buffer additive.

The investigation on capillary electrophoretic enantioseparation of six synthetic compounds containing vicinal diol groups has been undertaken to acquire the optimum conditions using native beta-cyclodextrin (beta-CD) as chiral selector and borate as a background electrolyte. The separation was carried out in an uncoated capillary (58.5 cm x 75 microm i.d., effective length 48.5 cm) and the effects of several important factors were investigated in detail. The results showed that beta-CD as a chiral selector exhibited good enantioselectivity and that the enantioseparation was greatly influenced by the structure of the diols, the borate concentration and the buffer pH. The optimum performance was obtained for the chiral vicinal diols under the conditions of 200 mM borate buffer of pH 9.8 containing 1.7% beta-CD at an applied voltage of 15 kV and a capillary temperature of 20 degrees C. Under the conditions, four diols were baseline separated with fast analysis time and the good theoretical plate numbers (above 10 x 10(4)) and favorable migration-time reproducibilities (RSDs below 3.0%) were obtained. The separation results were satisfactory.     

Chiral analysis of amphetamine-type stimulants using reversed-polarity capillary electrophoresis/positive ion electrospray ionization tandem mass spectrometry

Reversed-polarity (RP) capillary electrophoresis/positive ion electrospray ionization mass spectrometry (CE-ESI+ MS) and tandem mass spectrometry (MS/MS) were utilized for simultaneous chiral separation of nine amphetamine-type stimulants (ATS) (dl-norephedrine, dl-norpseudoephedrine, dl-ephedrine, dl-pseudoephedrine, dl-amphetamine, dl-methamphetamine, dl-methylenedioxyamphetamine, dl-methylenedioxymethamphetamine, and dl-methylenedioxyethylamphetamine). Using highly sulfated gamma-cyclodextrin (SU(XIII)-gamma-CD) as a chiral selector, the nine ATS were completely separated within 50 min. The migrated ATS-CD complex was dissociated at the ESI interface, and only ATS molecules went into the MS detector so that all 18 individual enantiomers were identified by their mass spectra. The detection limit of MS/MS was 10 times more sensitive than those for single MS. Seized d-methamphetamine hydrochloride samples dissolved at high concentration (20 mg/mL) were analyzed. Impurities originating in the precursor such as l-ephedrine and d-pseudoephedrine were detected and identified by tandem mass spectra.     

毛细管电泳的手性拆分(文献综述)

 根据最近文献,对毛细管电泳在手性拆分领域中的应用和发展进行了评述,包括各种操作模式和各类手性选择剂,进一步评述了手性拆分机理的研究,显示出毛细管电泳是手性拆分的一种高效、快速、简便的分离手段。     

Chiral separations in capillary electrophoresis.

The marked increase in the number of communications on the utilization of electrophoresis for practical chiral separations within the last three years is the most evident, and the most important fact. It reveals that the basic period of intensive research in the field is finished. The search for chiral selectors discriminating racemates in a reasonably analytical manner and the study of both the mechanism and physicochemical aspects of the chiral discrimination process were the main features of that period. Here, we review the state of the art in the field and state the references of the related literature up to the end of 1998.     

Chiral separation of hydroxyflavanones in cyclodextrin-modified capillary zone electrophoresis using sulfated cyclodextrins as chiral selectors

Chiral separations of three hydroxyflavanone aglycones, including 2'-, 3'-, and 4'-hydroxyflavanone, in capillary zone electrophoresis (CZE) using randomly sulfate-substituted beta-cyclodextrin (S-beta-CD) or dual cyclodextrin (CD) systems consisting of S-beta-CD and a neutral CD at low pH were investigated. The results indicate that S-beta-CD is an excellent chiral selector for enantioseparation of 2'-hydroxyflavanone and is a good chiral selector for 3'-hydroxyflavanone. Depending on the concentration of S-beta-CD ranging from 2.0 to 0.75% (w/v), the enantioresolution values were 10.5-19.5 and 1.8-3.4 for 2'- and 3'-hydroxyflavanone, respectively. The enantiomers of 4'-hydroxyflavanone could be effectively separated with S-beta-CD at a concentration of 2.0% (w/v) within 20 min. The enantioselectivity and enantioresolution follow the order 2'-hydroxyflavanone>3'-hydroxyflavanone>4'-hydroxyflavanone. Alternatively, with the addition of sodium dodecyl sulfate (SDS) monomers at low concentrations in the electrophoretic system, enantioselectivity of these hydroxyflavanone aglycones could be enhanced with dual CD systems. In this case, SDS monomer acted as a complexing agent probably first with S-beta-CD and then subsequently with the analytes for increasing the effective electrophoretic mobility of the analytes towards the anode and as a selectivity controller for affecting the selectivity of hydroxyflavanones. Better enantioseparation between 2'-hydroxyflavanone and 3'-hydroxyflavanone could be achieved with a dual CD system consisting of S-beta-CD and gamma-CD than that with S-beta-CD and beta-CD. In addition, possible chiral recognition mechanisms of hydroxyflavanones are discussed.     

Rapid inorganic ion analysis using quantitative microchip capillary electrophoresis

Rapid quantitative microchip capillary electrophoresis (CE) for online monitoring of drinking water enabling inorganic ion separation in less than 15 s is presented. Comparing cationic and anionic standards at different concentrations the analysis of cationic species resulted in non-linear calibration curves. We interpret this effect as a variation in the volume of the injected sample plug caused by changes of the electroosmotic flow (EOF) due to the strong interaction of bivalent cations with the glass surface. This explanation is supported by the observation of severe peak tailing. Conducting microchip CE analysis in a glass microchannel, optimized conditions are received for the cationic species K+, Na+, Ca2+, Mg2+ using a background electrolyte consisting of 30 mmol/L histidine and 2-(N-morpholino)ethanesulfonic acid, containing 0.5 mmol/L potassium chloride to reduce surface interaction and 4 mmol/L tartaric acid as a complexing agent resulting in a pH-value of 5.8. Applying reversed EOF co-migration for the anionic species Cl-, SO42- and HCO3- optimized separation occurs in a background electrolyte consisting of 10 mmol/L 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and 10 mmol/L HEPES sodium salt, containing 0.05 mmol/L CTAB (cetyltrimethylammonium bromide) resulting in a pH-value of 7.5. The detection limits are 20 micromol/L for the monovalent cationic and anionic species and 10 micromol/L for the divalent species. These values make the method very suitable for many applications including the analysis of abundant ions in tap water as demonstrated in this paper.