Multilayer coatings based on gold nanoparticles and polymers with bovine serum albumin as a functional layer for the chiral separation in capillary electrochromatography.

In this study, we developed physically adsorbed multi-layer coatings using poly-l-lysine or poly(diallyldimethylammonium chloride) and gold nanoparticles, which were functionalized with bovine serum albumin for the chiral separation in electrochromatography. The approach involves sequentially depositing positively charged polymers and negatively charged citrate-stabilized gold nanoparticles. By repeating this modification cycle, we created two- and four-layer coatings, which were sequentially functionalized with albumin forming three- and five-layer coatings that were finally applied for the separation of enantiomers of dl-tryptophan. The formed coatings exhibit stability across a pH range of 2-10 and feature a dense, uniform surface, as confirmed by scanning electron microscope images. The number of layers impacted nanoparticle deposition density, with five-layer coatings being denser than three-layer ones. Five-layer coatings enable baseline separation of dl-tryptophan enantiomers, whereas three-layer coatings require the presence of albumin in the background electrolyte for separation. Therefore, increasing the number of layers and gold nanoparticles density enhances albumin active center concentration on capillary walls, improving the separation of dl-tryptophan enantiomers. The five-layer coatings can be easily fabricated and possess good repeatability of analytes migration time.

Preparation and study of a capillary electrochromatographic column prepared by conjugating ß-CD COFs and gold-poly glycidyl methacrylate nanoparticles.

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing ß-cyclodextrin covalent organic frameworks (ß-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10 min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26% RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.

Enantiomeric analysis of drugs in water samples by using liquid-liquid microextraction and nano-liquid chromatography.

The nano-LC technique is increasingly used for both fast studies on enantiomeric analysis and test beds of novel stationary phases due to the small volumes involved and the short conditioning and analysis times. In this study, the enantioseparation of 10 drugs from different families was carried out by nano-LC, utilizing silica with immobilized amylose tris(3-chloro-5-methylphenylcarbamate) column. The effect on chiral separation caused by the addition of different salts to the mobile phase was evaluated. To simultaneously separate as many enantiomers as possible, the effect of buffer concentration in the mobile phase was studied, and, to increase the sensitivity, a liquid-liquid microextraction based on the use of isoamyl acetate as sustainable extraction solvent was applied to pre-concentrate four chiral drugs from tap and environmental waters, achieving satisfactory recoveries (>70%).

Quantitation of tryptophan and kynurenine in human plasma using 4-vinylphenylboronic acid column by capillary electrochromatography coupled with mass spectrometry.

Tryptophan (TRP) is an essential amino acid catabolized mainly through the kynurenine pathway, and part of it is catabolized in the brain. The abnormal depletion of TRP and production of kynurenine (KYN) by two enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), have been linked to various neurological diseases. The ratio of TRP/KYN in plasma is a valuable measure for IDO/TDO activity and the prognosis of disease conditions. The 4-vinylphenylboronic acid (4-VPBA) was evaluated as a novel stationary phase for OT-CEC-MS/MS. TRP, KYN, and 3-hydroxykynurenine were separated using optimum conditions of 15 mM (NH4 )2 CO3 at pH 8 as a background electrolyte and 25 kV separation voltage on a 90 cm column. The usefulness of the 4-VPBA column for simple, fast, repeatable, and sensitive CEC-ESI-MS/MS application was demonstrated for the quantitation of TRP and KYN in the plasma of healthy human subjects and neuroinflammation subjects. The plasma sample was extracted on a zirconia-based ion-exchange cartridge for simultaneous protein precipitation and phospholipid removal. The method of standard addition, in combination with the internal standards approach, was used to prepare the calibration curve to overcome matrix matching and eliminate procedural errors. The developed quantitation method was validated according to FDA guidelines for sensitivity, accuracy, precision, and extraction recovery. The measured plasma level of TRP and KYN in healthy humans is aligned with the human metabolome database for the same two metabolites.

Preparation of open tubular capillary column covalently coated with polystyrene sulfonate with 4,4'-Azobis(4-cyanopentanoyl chloride) as polymerization initiator for electrochromatographic separation of alkaloids, sulfonamides, and peptides.

An open tubular capillary electrochromatography column covalently bonded with polystyrene sulfonate was prepared via in situ polymerization using functionalized Azo-initiator 4,4'-Azobis(4-cyanopentanoyl chloride). Scanning electron, fluorescence, and atomic force microscopy techniques showed the formation of a relatively rough layer of polymer. In addition, -CN and C = O stretching vibrations from infrared spectroscopy proved the successful immobilization of the azo-initiator through covalent bonding and X-ray photoelectron spectroscopy confirmed the elemental composition of the formed polymer layer. The prepared column was found to be appropriate for small and medium-sized molecules separation. Compared to bare fused silica capillary column higher selectivity and resolution were obtained for the separation of alkaloids, sulfonamides, and peptides as a result of the electrostatic and pi-pi stacking interactions between the small organic molecules and the coated column without compromising the electroosmotic flow mobility. Separation efficiency was also increased compared to the bare capillary for the separation of alkaloids (about 1.5 times). Moreover, intraday, inter-day, intra-batch, and inter-batch relative standard deviation values of retention time and peak area of peptides were within 2% and 10%, respectively, indicating good repeatability of the column preparation procedure. The developed method for the covalent bonding of polymers through a functionalized azo-initiator could represent a promising stable method for the preparation of an open tubular column.

Lipase-based MIL-100(Fe) biocomposites as chiral stationary phase for high-efficiency capillary electrochromatographic enantioseparation.

A novel chiral porous column was fabricated by lipase immobilized MIL-100(Fe) biocomposites as chiral stationary phase through covalent coupling and applied to capillary electrochromatographic enantioseparation. MOF-based lipase biocomposites not only enhance stereoselective activities but also improve the stability and applicability of the enzyme. The functionalized porous columns were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and powder X-ray diffraction. The performance of the porous column was evaluated by enantioseparating amino acid enantiomers, affording high resolution over 2.0. Besides, the enantio-resolutions of phenylephrine, phenylsuccinic acid, chloroquine, and zopiclone were also greater than 2.0. The relative standard deviations of run-to-run, intra-, and inter-day repeatability were within 4.0% in terms of resolution and retention time, exhibiting excellent stability of the column. Conceivably, the results show that MOF-based lipase composites as chiral stationary phase offer a highly efficient means for enantioseparation in capillary electrochromatography, attributing to the enhanced enantioselective activities of lipase by highly ordered frameworks.

One-step synthesis of chiral molecularly imprinted polymer TiO2 nanoparticles for enantioseparation of phenylalanine in coated capillary electrochromatography.

A novel chiral molecularly imprinted polymer TiO2 nanoparticle was synthesized in one step for the enantioseparation of phenylalanine in coated capillary electrochromatography. To the author's knowledge, the chiral molecularly imprinted nanomaterials have still not been reported, to date. Chiral molecularly imprinted TiO2 nanomaterials (L-PHE@MIP(APTES-TEOS)@TiO2) were used as a chiral stationary phase to separate the phenylalanine enantiomers in coated capillary electrochromatography (CEC). The imprinted coating was prepared from L-phenylalanine (L-PHE) as the template, TiO2 nanoparticles (NPs) as the support substrate, 3-aminopropyltriethoxysilane (APTES) as the functional monomer, and tetraethyl silicate (TEOS) as the cross-linker. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used for the characterization of the L-PHE@MIP(APTES-TEOS)@TiO2@capillary. Fourier transform infrared spectra (FT-IR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA) were employed for the characterization of the L-PHE@MIP(APTES-TEOS)@TiO2. The effects of the applied voltage, pH value, buffer concentration, and acetonitrile content were investigated  experimentally to determine the optimum conditions for CEC. The best resolution for  phenylalanine enantiomers by CEC reached a value of 3.48. In addition, the specific recognition effect of L-PHE@MIP(APTES-TEOS)@TiO2 on PHE enantiomers was studied by selective experiment. Finally, adsorption kinetic research, adsorption equilibrium isotherm study, and adsorption thermodynamic experiment were carried out to investigate the separation mechanism of PHE enantiomers with the L-PHE@MIP (APTES-TEOS)@TiO2@capillary, and the results were consistent with those of CEC experiments.

Construction of chiral capillary electrochromatography microsystems based on Aspergillus sp. CM96.

Novel chiral capillary electrochromatography (CEC) microsystems were constructed based on Aspergillus sp. CM96. As a newly discovered intrinsic characteristic of the cell, cell chirality occupies an essential position in life evolution. Aspergillus sp. CM96 spore (CM96s) was chosen as a proof of concept to develop chiral capillary columns. Interestingly, various types of amino acid (AA) enantiomers were baseline separated under the optimized conditions. Furthermore, the time-dependent chiral interactions between AAs and CM96s were explored in a wider space. Pectinases generated from Aspergillus sp. CM96 fermentation were immobilized onto graphene oxide-functionalized capillary silica monoliths for separating AA enantiomers. Molecular docking simulations were performed to explore chiral separation mechanisms of pectinase for AA enantiomers. These results indicated that Aspergillus sp. CM96-based CEC microsystems have a significant advantage for chiral separation.

Emerging Developments in Separation Techniques and Analysis of Chiral Pharmaceuticals.

Chiral separation, the process of isolating enantiomers from a racemic mixture, holds paramount importance in diverse scientific disciplines. Using chiral separation methods like chromatography and electrophoresis, enantiomers can be isolated and characterized. This study emphasizes the significance of chiral separation in drug development, quality control, environmental analysis, and chemical synthesis, facilitating improved therapeutic outcomes, regulatory compliance, and enhanced industrial processes. Capillary electrophoresis (CE) has emerged as a powerful technique for the analysis of chiral drugs. This review also highlights the significance of CE in chiral drug analysis, emphasizing its high separation efficiency, rapid analysis times, and compatibility with other detection techniques. High-performance liquid chromatography (HPLC) has become a vital technique for chiral drugs analysis. Through the utilization of a chiral stationary phase, HPLC separates enantiomers based on their differential interactions, allowing for the quantification of individual enantiomeric concentrations. This study also emphasizes the significance of HPLC in chiral drug analysis, highlighting its excellent resolution, sensitivity, and applicability. The resolution and enantiomeric analysis of nonsteroidal anti-inflammatory drugs (NSAIDs) hold great importance due to their chiral nature and potential variations in pharmacological effects. Several studies have emphasized the significance of resolving and analyzing the enantiomers of NSAIDs. Enantiomeric analysis provides critical insights into the pharmacokinetics, pharmacodynamics, and potential interactions of NSAIDs, aiding in drug design, optimization, and personalized medicine for improved therapeutic outcomes and patient safety. Microfluidics systems have revolutionized chiral separation, offering miniaturization, precise fluid control, and high throughput. Integration of microscale channels and techniques provides a promising platform for on-chip chiral analysis in pharmaceuticals and analytical chemistry. Their applications in techniques such as high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC) offer improved resolution and faster analysis times, making them valuable tools for enantiomeric analysis in pharmaceutical, environmental, and biomedical research.

Homomesoporous Metal-Organic Framework for High-Performance Electrochromatographic Separation.

Metal-organic frameworks (MOFs) have exhibited tremendous potential in the area of separation science. However, most of the developed MOF-based stationary phases contained only microporous structures and suffer from limited separation performance. Herein, homomesoporous MOFs with excellent mass transfer capability and strong thermodynamic interactions are first explored as the novel stationary phase for high-performance capillary electrochromatographic separations. As a proof of concept, noninterpenetrated mesoMOF-1 with uniform mesopore sizes (22.5 × 26.1 Å) and good stability was facilely grown on the inner surface of capillaries and applied as a homomesoporous MOF coating-based stationary phase for high-efficiency electrochromatographic separation. Seven types of analytes with different molecular dimensions were all baseline separated on a mesoMOF-1 coated column with high theoretical plate numbers and excellent repeatability, exhibiting significantly improved separation selectivity and column efficiency in comparison to a microporous HKUST-1 coated column. The maximum column efficiencies of the mesoMOF-1 coated column for substituted benzenes and halobenzenes reached up to 1.4 × 105 plates/m, and its mass loadability was also much higher than that of the HKUST-1 coated column. In addition, based on the analysis of adsorption kinetics and chromatographic retention behaviors, the interaction and retention mechanisms of different molecular-weight analytes on mesoMOF-1 coated stationary phases were systematically explored and disclosed in detail. These results indicate that the homomesoporous MOF-based stationary phase can effectively balance the kinetic diffusion (mass transfer capability) and thermodynamic interactions (the strength of adsorption interaction), having great potential for high-performance chromatographic separation.

Open Tubular Capillary Electrochromatography-Mass Spectrometry for Analysis of Underivatized Amino Acid Enantiomers with a Porous Layer-Gold Nanoparticle-Modified Chiral Column.

By developing a novel chiral column, we integrate open tubular capillary electrochromatography into sheathless mass spectrometry (MS) for efficient analysis of underivatized amino acid enantiomers. The chiral column is easily fabricated by modifying the inner surface of a capillary with a three-dimensional porous layer (PL, thickness ∼ 90 nm, pore size ∼ 30 nm) and gold nanoparticles and by introducing a chiral selector, thiol ß-cyclodextrin (SH-ß-CD), onto the modified surface via Au-S bonds. This approach greatly enhances the specific surface area and thus the ratio of the stationary phase to mobile phase and interaction between the stationary phase and analytes. The proposed PLOT@Au@CD column is coupled to the sheathless CE-ESI-MS system for chiral analysis of amino acid enantiomers. No derivatization of amino acids is required for chiral analysis, and baseline separation of a total of 15 pairs of amino acid enantiomers is achieved within 17 min with high column efficiencies of 5.60 × 104 to 1.82 × 106 N/m, high resolutions of 1.51-10.0, and low limits of detection between 0.02 and 0.09 µg/mL. The separation efficiency and MS intensity are only slightly decreased over 60 runs or after usage for 15 days, showing excellent repeatability and stability of the PLOT@Au@CD column. The proposed method is successfully applied to the determination of amino acid enantiomers in vinegar samples with satisfactory accuracy. Our study provides a new approach for developing a chiral stationary phase in the chromatographic separation technique, which can be easily coupled to sensitive MS detection, thus it would be of value for various applications in the fields of chiral analysis.

Metal-Organic Frameworks-Based Immobilized Enzyme Microreactors Integrated with Capillary Electrochromatography for High-Efficiency Enzyme Assay.

Enzyme assays are important for studying enzyme-mediated biochemical reactions and for clinical diagnosis and drug development. The technique of an immobilized enzyme microreactor (IMER) integrated with capillary electrophoresis (CE) has been frequently utilized in online enzyme assays. However, the traditional approaches for IMER-CE enzyme analysis have some defects such as low loading capacity and poor stability. Herein, metal-organic frameworks (MOFs), which have enormous potential in the fields of enzyme immobilization and capillary electrochromatographic (CEC) separation, were first explored as novel support materials with good enzyme immobilization performance and stationary phases with excellent separation abilities to construct an integrated MOFs-IMER-CEC microanalysis system for a high-efficiency online enzyme assay. As a proof-of-concept demonstration, acetylcholinesterase (AChE) was immobilized on a densely packed UiO-66-NH2 nanocrystal coating on a capillary inner surface with abundant intercrystalline mesoporosity and was employed as a highly effective and robust IMER for CEC-integrated online enzyme analysis. The excellent separation performance of the UiO-66-NH2-modified capillary was verified by high-efficiency separation of three types of neutral, acidic, and basic compounds. The Michaelis-Menten constant and enzyme inhibition kinetics of UiO-66-NH2-IMER were systematically assessed, exhibiting distinct advantages such as remarkably increased enzyme loadability, superior affinity for substrates, and greatly improved stability and repeatability compared to CE-integrated IMERs prepared by the traditional covalent bonding method. Furthermore, the developed method was successfully utilized for detecting organophosphorus pesticides in leguminous vegetable samples, demonstrating its strong practicality. The study not only proposed a novel support material and construction strategy for a high-performance microchannel-based IMER but also can be widely used in bioanalysis and biosensing research.

ß-Cyclodextrin covalent organic framework supported by polydopamine as stationary phases for electrochromatographic enantioseparation.

In this work, a new open-tubular capillary electrochromatography (OT-CEC) column was prepared using ß-cyclodextrin covalent organic framework (ß-CD COF) as a stationary phase. Polydopamine was used to assist fabrication of ß-CD COF on an inner wall of a fused-silica capillary. The coating layer on the capillary was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electroosmotic flow (EOF) was also studied to evaluate the variation of the inner wall of immobilized columns. Furthermore, the chiral separation effectiveness of the fabricated capillary column was evaluated by CEC using enantiomers of several related proton pump inhibitors as model analytes, including omeprazole, lansoprazole, pantoprazole and tenatoprazole. The effects of bonding time and concentration of ß-CD COF, the type, concentration and pH of buffer, applied voltage were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of four analytes were resolved within 15 min with resolutions of 1.63-2.62. The relative standard deviation values for migration times and resolutions of the analytes representing intraday and interday were less than 6.75% and 4.24%, respectively. The results reveal that ß-CD COF has great potential as chiral-stationary phases for enantioseparation in CEC.

Zeolitic imidazolate framework-67-modified open-tubular column with cyclodextrin for enantioseparation in capillary electrochromatography.

The histidine-modified zeolitic imidazolate framework [His-ZIF-67] was prepared with the histidine, 2-methylimidazole, and Co2+ under ambient temperature. His-ZIF-67 was bonded via a glycidyl methacrylate copolymer to the internal surface of capillary and then functionalized with the NH2 -ß-cyclodextrin (NH2 -ß-CD). The materials were characterized by field emission scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, N2 adsorption-desorption isotherm, X-ray diffraction, and X-ray photoelectron spectroscopy. In comparison with the NH2 -ß-CD@capillary, the NH2 -ß-CD@His-ZIF-67@capillary-coated column shows significantly enhanced resolution for chiral molecules. The NH2 -ß-CD@His-ZIF-67@capillary column achieved the baseline separation of amlodipine and metoprolol (the resolution of amlodipine: 1.70; metoprolol: 1.50) and the partial separation of atenolol and propranolol (the resolution of atenolol: 1.03; propranolol: 0.60). These were attributed to the histidine modification and the features of ZIF-67, including an excellent surface area and the abundant porosity. The pH and proportion of organic modifier in the buffer were crucial for enantioseparation performance and were evaluated in detail. The fabricated NH2 -ß-CD@His-ZIF-67@capillary-coated column showed good stability and repeatability (relative standard deviation <6.3%). The molecular modeling with AutoDock and grand canonical ensemble was carried out to evaluate the interactions between chiral stationary phase and racemic drugs.

One-pot synthesis of a novel chiral Zr-based metal-organic framework for capillary electrochromatographic enantioseparation.

A novel chiral stationary phase (CSP) of Zr-based metal-organic framework, l-Cys-PCN-224, was prepared by one-pot method and applied for the enantioseparation by capillary electrochromatography. The CSP was characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, Fourier-transform infrared spectra, nitrogen adsorption/desorption, circular dichroism spectrum, zeta-potential, and so on. The results revealed that the CSP had good crystallinity, high specific surface area (2580 m2 /g), and good thermal stability. Meanwhile, the cross-section of l-Cys-PCN-224-bonded open-tubular (OT) column was observed by a scanning electron microscope, which proved the successful bonding of l-Cys-PCN-224 particles to the inner wall. Relative standard deviations of the column efficiencies were 3.87%-9.14%, and not obviously changed after 200 runs, which indicated that l-Cys-PCN-224-bonded OT column had the better stability and reproducibility. Excellent chiral separation performance was verified with nine kinds of natural amino acids including acidic, neutral, and basic as the analytes. All amino acids studied achieved good separation with the resolution of 1.38-13.9 and selector factor of 1.11-3.71. These results demonstrated that the CSP had an excellent potential in the chiral separation field.

Preparation of a zeolite imidazole skeleton-silica hybrid monolithic column for amino acid analysis via capillary electrochromatography.

We developed a novel, convenient and low-cost one-pot strategy for preparing a zeolitic imidazolate framework-8 (ZIF-8)-silica hybrid monolithic column by adding ZIF-8 directly to a polymer solution of the silica matrix. The simulated stationary phase and monolithic column prepared under optimal conditions were characterized using X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis nitrogen physisorption and zeta potential. The results obtained confirmed the successful introduction of ZIF-8 into the silica monolithic column, and the prepared monolithic column exhibited good permeability and physicochemical stability. A capillary electrochromatography method was developed based on a ZIF-8-silica hybrid monolithic column through which 15 mixed amino acids, 4 neutral compounds, 4 nipagin esters and 2 chlorinated fungicides were separated in 14, 5, 7 and 6 min, respectively, under optimal conditions. The relative standard deviations retention times and column efficiencies in run-to-run, day-to-day and column-to-column varied in the ranges of 1.90%-2.21%, 2.13%-2.51% and 3.08%-6.65%, respectively, which demonstrated that ZIF-8-silica hybrid monolithic column exhibited satisfactory reproducibility and stability. The incorporation of ZIF-8 into a silica monolithic column is a promising method for preparing novel monolithic columns composed of a metal-organic framework.

In situ photoinitiated fabrication of phosphorylcholine-functionalized polyhedral oligomeric silsesquioxane hybrid monolithic column for mixed-mode capillary electrochromatography.

A monolithic-based mixed-mode stationary phase was prepared for capillary electrochromatography via the fast photoinitiated polymerization of 2-methacryloyloxyethyl phosphorylcholine and polyhedral oligomeric silsesquioxane methacrylate (POSS-MA) monomers in the presence of crosslinker pentaerythritol triacrylate (PETA). Several copolymerization parameters, including the composition of monomers or porogens, ratio of crosslinkers to monomers, and polymerization time, were systematically optimized to tune the permeability and efficiency of monolithic columns. The morphologies and structures of the as-prepared monoliths were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, thermogravimetry and nitrogen adsorption/desorption analysis, indicating a typical POSS skeleton morphology with numerous mesopores on the monolith. Owing to the incorporation of zwitterionic functional groups and rigid POSS skeleton on the hybrid monolith, the resulting stationary phase exhibited both hydrophilic and electrostatic interactions, as well as good mechanical stability. Pressurized CEC separation of various kinds of polar compounds such as amides, nucleobases, nucleosides and benzoic acids, and polypeptide antibiotics was achieved by mixed-mode retention mechanisms including hydrophilic interaction chromatography (HILIC) and weak cation exchange chromatography (WCX) with a high column efficiency up to 93 500 plates per m (thiourea).

Our research cooperation with Professor Yoshio Okamoto.

This article summarizes our cooperation with the research group of Prof. Yoshio Okamoto at Nagoya University during the period of time between 1992 and 2005. Although the text deals entirely with enantioseparations in high-performance liquid chromatography, capillary electrophoresis, and capillary electrochromatography, this is not a detailed review in any of these areas. The text highlights selected aspects of these techniques, which have been the subject of our joint research and in part their reflection in follow-up research by our and other research groups. Together with more systematically studied topics, aspects such as ultrafast separation of enantiomers, uncommonly high separation factor of enantiomers and other related issues are also addressed.

Carboxymethyl-ß-cyclodextrin and histidine-zeolitic imidazolate framework-8 used for enantioseparation of three basic drugs in open-tubular capillary electrochromatography.

Metal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine-zeolitic imidazolate framework-8 (His-ZIF-8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl-ß-cyclodextrin (CM-ß-CD) as the chiral selector was chemically bonded to the His-ZIF-8@capillary column. The prepared CM-ß-CD@His-ZIF-8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM-ß-CD@capillary column without His-ZIF-8, the CM-ß-CD@His-ZIF-8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (Rs : 0 → 2.29), propranolol (Rs : 0 → 1.69), and atenolol (Rs : 0 → 0.79). His-ZIF-8 concentration, buffer pH, buffer concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The repeatability of intraday, day-to-day, and column-to-column have been discussed; the result was preferable, and the relative standard deviation (RSD) of separation parameters was <6.7%.

A covalent organic framework for chiral capillary electrochromatography using a cyclodextrin mobile phase additive.

Covalent organic frameworks (COFs) have been recognized as promising solid phases in capillary electrochromatography (CEC). Imine-based COF-coated open-tubular CEC column (COF TpBD-coated OT column) was prepared and characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectra, thermogravimetric analysis (TGA), nitrogen adsorption/desorption (Brunauer-Emmett-Teller [BET]), and scanning electron microscopy (SEM). The results showed that the column efficiency was up to 26,776 plate/m, and the thickness of stationary phase was about 6.00 µm for the column prepared under the optimal conditions. Enantioseparation of 15 kinds of the single chiral compounds (histidine, arginine, lysine, leucine, threonine, methionine, valine, aspartic acid and glutamic acid, fipronil, diclofop, imazamox, quizalofop-p, imazethapyr, and acephate) and 3 kinds of mixed amino acids racemaces (valine, methionine, and glutamic acid) were performed with three methods: capillary electrochromatography with COF TpBD-coated OT column (Method 1), CEC with COF TpBD-coated OT column as the separation channels, and capillary electrophoresis (CE) with HP-ß-CD as the chiral mobile phase additive (Method 2) and CE with HP-ß-CD as the chiral mobile phase additive (Method 3). Separation efficiency and chiral selectivity of Method 2 was best among the three methods. Under the optimal separation conditions of Method 2, all the enantiomers reached the baseline separation regardless of the single chiral compounds or the mixed amino acids. Relative standard deviation (RSDs) of the mean column efficiency for reproducibility and stability was in the range of 0.46-1.49%. This combination of CEC and CE has great potential for use in chiral separation.