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Recently, ionic liquids have been widely used for chiral separation. However, several papers have reported the use of ionic liquids as the sole chiral selector. In this work, a novel capillary electrophoresis method using the ionic liquid 3-methyl-1-(3-sulfopropyl)-1H-imidazol-3-ium lactobionate (MSI-LA) as a chiral selector was developed for the enantioseparation of propranolol, metoprolol, bisoprolol, esmolol, atenolol, sotalol, terbutaline and clenbuterol. Method optimization was conducted and the optimized method (40 mM borax buffer, v/v 30% methanol, pH 8.5, 160 mM MSI-LA; +10 kV voltage; capillary temperature, 15 °C; 50 mbar/5 s injection; detection wavelength, 230 nm) was successful for the baseline separation of the eight basic drugs. The LA (lactobionic acid) system was compared. The possible mechanisms of enantioseparation were investigated using molecular modeling. Both the cation and anion of MSI-LA provided interactions between the chiral selector and analytes, and finally enhanced chiral recognition capability compared with LA.

A monolithic capillary column was prepared by single-step copolymerization of the ionic liquid 1-vinyl-3-octylimidazolium bromide (VOI) and styrene. The VOI and styrene monomers were introduced to provide multiple interaction sites and increase hydrophobicity and aromaticity of the monolithic column, respectively. The effect of porogen ratio, monomer ratio and reaction temperature on permeability was investigated. The resulting column was characterized by scanning electron microscopy, and the results suggest that the column possesses high porosity and good homogeneity. A relatively strong anodic electroosmotic flow was generated over a wide range of pH values (pH 2.0–10.0), and this facilitates the rapid separation of analytes within 12 min. Alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs), proteins and amino acids were used to evaluate the performance of the monolithic column under capillary electrochromatography mode by UV detection. Mixed-mode retention mechanisms including hydrophobic interaction, π-stacking, ion-exclusion interaction were observed. The monolithic column exhibits high column efficiency (8.72 × 104 plates∙m−1) and satisfying separation capability (the resolution of four alkylbenzenes: 2.54, 2.86 and 4.62, four PAHs: 2.79, 4.83 and 4.77, three proteins: 4.35 and 2.86, two amino acids: 3.34).

A new bilayer chiral stationary phase for use in open tubular capillary electrochromatography (OT-CEC) system is described. Gold nanoparticles were modified with L-cysteine, with a tetramethylammonium lactobionate ionic liquid that acts as the chiral selector. The gold nanoparticle-coated column provides good enantioseparation and favorable reproducibility. Compared with an uncoated separation system, the column developed displays improved separation of the racemic β-blockers propranolol, esmolol, bisoprolol and sotalol (resolutions of enotiomers are 6.29, 6.11, 6.12 and 6.02, respectively). The materials and coatings were characterized by scanning electron microscopy and transmission electron microscopy. The main driving forces (CEC and electro-osmotic flow) were studied to evaluate the variation of the immobilized columns. The effects of buffer pH value, concentration of chiral selector, type of organic modifier and applied voltage were optimized. Satisfactory relative standard deviations were achieved in run-to-run, day-to-day and column-to-column experiments. Graphical abstractSchematic preparation of a capillary column with bilayer chiral selectors coated gold nanoparticles. This novel OT-CEC system was applied for separation of four basic racemic β-blockers.

Discovering more superior performance of ionic liquids for the separation science has triggered increasing interest. In this work, two new Hydroxy acid-based chiral ionic liquids (CILs) (tertramethylammonium-d-pantothenate (TMA-d-PAN), tertramethylammonium-d-quinate (TMA-d-QUI)) were designed and first used as additives to establish the maltodextrin-based synergistic systems for enantioseparation in capillary electrophoresis (CE). Compared to traditional single maltodextrin chiral separation system, significantly improved separations of all tested drugs in the CIL/Maltodextrin synergistic systems were obtained. Some parameters (CIL concentration, maltodextrin concentration, buffer pH, and applied voltage) in the TMA-d-PAN/Maltodextrin synergistic system have been examined and optimized for analytes. The molecular docking software AutoDock was applied to simulate the recognition process and surmise feasible resolution mechanism in the Maltodextrin/CILs synergistic systems, which has certain guiding value.

As a novel separation mode of capillary electrophoresis (CE), liposome electrokinetic capillary chromatography (LEKC) has aroused considerable attention in recent years; however, the enantioseparation based on this new system has not been previously investigated. In this study, we proposed a brand-new LEKC chiral separation approach using liposomes comprised of phosphatidylcholine (PC) and cholesterol as pseudo-stationary phase and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as chiral selector. Compared with the single CD system and CD-SDS-MEKC system, this LEKC method presented an obviously preferable enantioseparation of four model drugs (naproxen, warfarin, ketoprofen and amlodipine). In this new established system, all the enantiomers represented baseline separations with the resolution and selectivity respectively achieving 1.584/1.067 (for naproxen), 2.226/1.045 (for warfarin), 1.537/1.038 (for ketoprofen) and 2.592/1.097 (for amlodipine), while other two comparative systems demonstrated no separation or a poor separation. Several important parameters affecting the enantioseparation, such as buffer pH, concentration of liposomes, phosphate buffer solution (PBS) and chiral selector (SBE-β-CD), and applied voltage were systematically investigated. Satisfactory repeatability was achieved through intra-day, inter-day and batch-to-batch investigations with relative standard deviations less than 3.40%. Furthermore, the established method was successfully applied to test the chiral impurity of naproxen sample.

The authors describe the fabrication of a stationary phase for use in enantioseparation in capillary electrochromatography (CEC). The stationary phase was obtained by covalent immobilization of graphene oxide (GO) on the inner walls of a fused-silica capillary. Methyl-β-cyclodextrin was used as the chiral selector, and the enantiomers were detected by UV absorptiometry. Compared with uncoated fused-silica capillary, obviously improved separation of three tested drug enantiomers was obtained in the GO-polymer coated capillary column (the resolution of Naproxen: 0 → 1.56, Warfarin: 0 → 1.89 and Pranoprofen:0 → 1.51). The effects of buffer pH, type and proportion of organic modifier, concentration of chiral selector and applied voltage were optimized. Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results.

This study deals with the nonaqueous capillary electrophoretic enantioseparation of twenty-two amino alcohol drugs with a maltobionic acid (MA)-based ionic liquid (tetramethylammonium maltobionic acid, TMA-MA) as the novel chiral selector. In consideration of the poor solubility of MA in organic solvents, we managed to transform MA into ionic liquids (ILs) for the first time. Interestingly, this chiral selector exhibited powerful enantioselectivity towards the model analytes in company with boric acid. Systematical experiments were carried out to investigate the influence of concentration of TMA-MA, boric acid and tris (hydroxymethyl) aminomethane (Tris) as well as applied voltage on the enantioseparation. A great majority of enantiomers (except labetalol) were baseline separated under the optimized conditions and the effect of the molecular structure of amino alcohol drugs on the chiral separation was discussed. In addition, electrophoretic experiments, nuclear magnetic resonance (NMR), mass spectrometry (MS) and molecular modeling with the Gaussian program were employed to demonstrate the mechanism of chiral recognition. Based on the formation of an ionic liquid-boric acid-analyte complex, hydrogen binding was mainly responsible for enantioseparation.

Recently, in separation science, ionic liquids (ILs) have been commonly used as modifiers for buffer solutions, dynamic coating solutions, or coating solutions on carriers in capillary electrophoresis. However, only several papers have reported the use of chiral ILs as the sole chiral selector. In this paper, a chiral ionic liquid, cholinium-clindamycin phosphate (Ch-CP), was synthesized and employed as a sole chiral selector in capillary electrophoresis (CE). A series of parameters affecting the separation were optimized, including chiral selector concentration, buffer pH, proportion of organic modifier, as well as the applied voltage. Under the optimal conditions, compared to clindamycin phosphate (CP), the IL selector showed better enantioseparation capability and improved peak shapes for five racemic drugs. In addition, Molecular docking program Autodock was employed to elucidate the chiral recognition mechanism of Ch-CP, the computing results conformed to the experimental results.

Transfersomes were a special kind of nanomaterials with higher deformability and flexibility. A rapid method for coated-column preparation using anionic transfersomes as a coating material by electrostatic adsorption was developed. With carboxymethyl-β-cyclodextrin added in running buffer as the chiral selector, the capillary electrochromatography enantioseparation system based on the transfersomes-coated column modified by electrostatic adsorption was established for the first time. Propranolol and metoprolol acted as model drugs to evaluate the enantioseparation performance, these two basic drugs achieved baseline separation with satisfactory resolution and selection factor in this transfersomes-electrochromatography system but only partial separation in bare column system. In order to get the optimal separation condition, concentration of chiral selector, buffer pH, and applied voltage were systematically investigated. A rapid and efficient enantioseparation electrochromatography system was established and showed that transfersomes as the stationary phase could efficiently improve chiral separation effect.

Recently, increasing attention has been given to the research on chiral ionic liquids (CILs) in chiral separation field; however, only a few literatures focus on the exploration of CILs as the sole chiral selector. In this study, an ionic liquid chiral selector based on antibiotic, namely tetramethylammonium clindamycin phosphate (TMA-CP), was originally synthesized and subsequently utilized for enantioseparation in capillary electrophoresis (CE). Remarkably improved separations of eight racemic analytes were achieved in TMA-CP system in contrast to the clindamycin phosphate (CP) system. The optimal separation conditions were determinated by systematic experiments on several crucial parameters including the type and proportion of organic modifier, CIL concentration, buffer pH, and applied voltage. Additionally, molecular modeling with AutoDock was applied to probe into the chiral recognition mechanism of the ionic liquid chiral selectors, which well corresponded with the experimental results. It is the first time that antibiotic-based ionic liquid was exploited as favorable sole chiral selector in CE, and this strategy has paved a new way for development of novel ionic liquids chiral selectors based on antibiotics. Graphical abstract.

The inner wall of a capillary was coated with glycidyl methacrylate (GMA) to form tentacle-type coating, and poly(glycidyl methacrylate) nanoparticles (PGMA NPs) were then immobilized on the film. Ethanediamine-β-cyclodextrin as chiral selector was covalently bonded into the PGMA NPs through the ring-open reaction. The materials were characterized by SEM, TEM and FT-IR. The modified column was applied to the enantioseparation of the racemates of propranolol, amlodipine and metoprolol. Compared to a capillary with a single layer of CD-PGMA (without GMA coating) and to a CD-GMA system (without PGMA nanoparticles), the performance of the capillary is strongly improved. The effects of buffer pH value and applied voltage were optimized. Best resolutions (propranolol: 1.27, metoprolol: 1.01 and amlodipine: 2.93) were obtained when using the PGMA-coated capillary system. The run-to-run, day-to-day and column-to-column reproducibility were tested and found to be highly attractive. The new stationary phase is likely to have a large potential and scope in that it may also be applied to chiral separations of other enantiomers, such as amino acids and biogenic amines. Graphical abstract Schematic presentation of the preparation of a capillary column with glycidyl methacrylate (GMA) coating which was then immobilized with poly(glycidyl methacrylate) nanoparticles and ethanediamine-β-cyclodextrin. This novel open tubular column was applied to construct capillary electrochromatography system for separation of basic racemic drugs.

In recent years, ionic liquid-based surfactants have drawn more and more attention. As a new promising brand of surfactants, ionic liquid-based surfactants have their unique properties and superior aggregation behavior, which can be introduced as micellar pseudostationary in MEKC mode. In this paper, a novel ionic liquid-based surfactant, 1-butyl-3-methylimidazolum dodecyl sulfate [C4MIm][C12SO4], was synthesized through ion exchange reaction and applied for the first time to form micellar as pseudostationary phase for chiral separation with clindamycin phosphate as chiral selector. As observed, compared with conventional non-ionic liquid anionic surfactant, improved separation of tested drug enantiomers was obtained in the established MEKC system with ionic liquid-based surfactant. Parameters such as concentration of ionic liquid-based surfactants, type and proportion of organic modifier, concentration of chiral selector, and pH of buffer solution were systematically investigated to optimize the ionic liquid-based surfactant MEKC system.

In this paper, a chiral selector, N-(4-H-1, 2, 4-triazolium)-lactobionamides (LA-ATM), was synthesized and applied for enantioseparation in capillary electrophoresis (CE) for the first time. Compared with lactobionic acid (LA) separation system, enhanced enantioseparation of five tested drugs was achieved in this modification system. In order to achieve good chiral separation, several parameters such as chiral selector concentration, buffer pH, applied voltage as well as the type and proportion of organic modifier were systematically investigated. Molecular modeling was applied to demonstrate the chiral recognition mechanism of the LA-ATM, which well supported the experimental results. Furthermore, a mathematical equation built up based on the molecular mechanics calculations was used in predicting resolution of tested drugs using LA or LA-ATM mediated CE, the predicted result was well correlated with the experimental result.

Magnetic nanoparticles (MNPs) modified with β-cyclodextrin and mono-6-deoxy-6-(1-methylimidazolium)-β-cyclodextrin tosylate (an ionic liquid), which called MNP-β-CD and MNP-β-CD-IL, were coated into the capillary inner wall. Compared to an uncoated capillary, the new systems show good reproducibility and durability. The systems based on the use of MNP-β-CD or MNP-β-CD-IL as stationary phases were established for enantioseparation of Dns-modified amino acids. Improved resolutions were obtained for both CEC systems. Primary parameters such as running buffer pH value and applied voltage were systematically optimized in order to obtain optimal enantioseparations. Under the optimized conditions, the capillaries exhibited excellent chiral recognition ability for six Dns-amino acids (the DL-forms of alanine, leucine, lsoleucine, valine, methionine, glutamic acid) and provided a promising way for the preparation of chiral column. Graphical Abstract Schematic presentation of the open-tubular capillary electrochromatography systems with MNP-β-CD and MNP-β-CD-IL as stationary phases for enantioseparation of dansylated amino acids.

In this paper, two spiral structure CILs, 1-butyl-3-methylimidazolium(T-4)-bis[(2S)-2-(hydroxy-κO)-3-methyl-butanoato-κO]borate(BMIm+BLHvB-) and 1-butyl-3-methylimidazolium (T-4)-bis[(αS)-α-(hydroxy-κO)-4-methyl-benzeneacetato-κO]borate (BMIm+BSMB-)were applied to evaluate their potential synergistic effect with dextrin for CE enantiomeric separation. The established dextrin-based synergistic system with CILs as additives showed good separation performance towards four tested drugs, including duloxetine, ketoconazole, sulconazole and citalopram. It was also observed that significantly improved separation and selectivity for tested analytes were achieved in CILs/dextrin synergistic system compared to single dextrin system. Primary parameters, such as the concentration of CIL, dextrin concentration, buffer pH and applied voltage, were systematically investigated to optimize the enantiomeric separation with BMIm+BLHvB-/dextrin as model system. Finally, the method of Statistical Product and Service Solutions (SPSS) was exploited to further elucidate the influence of experimental parameters on the synergistic effect.

In this paper, the use of clarithromycin lactobionate, a kind of antibiotic chiral selector, in combination with four neutral cyclodextrin derivatives (glucose-β-cyclodextrin, hydroxyethyl-β-cyclodextrin, methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin) was reported for the first time. As a result, these dual systems gave much better resolution of nefopam (the Rs increased to 3.58, 2.72, 1.49 and 1.42, respectively) compared to the single systems. The effects of buffer pH and selector concentration on the separation of nefopam were also investigated. Additionally, some other basic drugs including metoprolol, atenolol, propranolol, bisoprolol, esmolol and ritodrine were tested for the investigation and evaluation of the enantiorecognition capability of the four dual systems. As expected, the synergistic effect was observed in four systems. Different results of these dual systems were also summarized.

Much attention has been paid to chiral ionic liquids (ILs) in analytical chemistry, especially its application in capillary electrophoresis (CE) enantioseparation. However, the investigation of chiral ionic liquids synergistic systems based on antibiotic chiral selectors has been reported in only one article. In this work, a novel chiral ionic liquid, tetramethylammonium-L-hydroxyproline (TMA-L-Hyp), was applied for the first time in CE chiral separation to evaluate its potential synergistic effect with clindamycin phosphate (CP) as the chiral selector. As observed, significantly improved separation was obtained in this TMA-L-Hyp/CP synergistic system compared to TMA-L-Hyp or a CP single system. Several primary factors that might influence the separation were investigated, including CP concentration, TMA-L-Hyp concentration, buffer pH, types and concentrations of organic modifier, applied voltage, and capillary temperature. The best results were obtained with a 40 mM borax buffer (pH 7.6) containing 30 mM TMA-L-Hyp, 80 mM CP, and 20% (v/v) methanol, while the applied voltage and temperature were set at 20 kV and 20°C, respectively. Chirality 27:598–604, 2015. © 2015 Wiley Periodicals, Inc.

Recently,ionic liquids (ILs) functionalized cyclodextrins (CDs) have attracted more and more attention in the fields of enantioseparation. In this study, a novel IL amino triazolium functionalized β-CD derivative, mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-β-cyclodextrin chloride (4-ATMCDCl), was synthesized for the first time and managed to separate dansyl amino acids and naproxen by capillary electrophoresis (CE). Compared with native β-CD, the new selector exhibited good water solubility and enhanced enantioselectivity. Several crucial parameters such as selector concentration, buffer pH, and applied voltage were systematically investigated. The molecular docking program Autodock was applied to further demonstrate the mechanism of chiral recognition and the enhanced enantioselectivity of 4-ATMCDCl, which showed good agreement with our experimental results.

Chiral ionic liquids (ILs) have aroused widespread interest in separation science; however, only a few papers have reported the application of chiral ILs in CE for enantioseparation, and the use of chiral ILs as the sole chiral selector in an electrophoretic or a chromatographic system was reported in only three papers. In this study, we designed a lactobionic acid LA-based IL, tetramethylammonium-lactobionate (TMA-LA), and it is very interesting to find that the chiral separation capability can be remarkably improved when a conventional saccharide chiral selector evolved into an IL chiral selector. A comparative study of the enantiorecognition capability of three separation systems (single LA system, LA + TMA-chloride (TMA-Cl) system, and TMA-LA IL system) was also conducted, and the results showed that the use of TMA-LA IL as the sole chiral selector exhibited a remarkable superiority. A series of parameters affecting the enantioseparation, such as the type and proportion of organic modifier, buffer composition and pH, chiral selector concentration, as well as applied voltage were systematically investigated. The best enantioseparation was obtained at pH 7.6 using a 40 mM borax buffer with 40% v/v methanol, 200 mM TMA-LA, and 20 kV applied voltage. It is the first time that a saccharide-based IL is evaluated as a sole chiral selector in CE, and we hope this study would provide a new direction for the development of novel ILs chiral selectors based on conventional chiral selectors.