Recent applications and chiral separation development based on stationary phases in open tubular capillary electrochromatography(2019–2022)

Capillary electrochromatography(CEC)plays a significant role in chiral separation via the double separation principle,partition coefficient difference between the two phases,and electroosmotic flow-driven separation.Given the distinct properties of the inner wall stationary phase(SP),the separation ability of each SP differs from one another.Particularly,it provides large room for promising applications of open tubular capillary electrochromatography(OT-CEC).We divided the OT-CEC SPs developed over the past four years into six types:ionic liquids,nanoparticle materials,microporous materials,biomaterials,non-nanopolymers,and others,to mainly introduce their characteristics in chiral drug separation.There also added a few classic SPs that occurred within ten years as supplements to enrich the features of each SP.Additionally,we discuss their applications in metabolomics,food,cosmetics,environment,and biology as analytes in addition to chiral drugs.OT-CEC plays an increasingly significant role in chiral separation and may promote the development of capillary electrophoresis(CE)combined with other instruments in recent years,such as CE with mass spectrometry(CE/MS)and CE with ultraviolet light detector(CE/UV).

Effect of Single-walled Carbon Nanotubes on Cellulose Phenylcarbamate Chiral Stationary Phases

Single-walled carbon nanotubes（SWNTs） have a high adsorption ability and nanoscale interactions. Cellulose trisphenylcarbamates possess high enantioseparation ability in high-performance liquid chromatography（HPLC）. Single-walled carbon nanotubes mixed with cellulose trisphenylcarbamate are coated on the silica gel as chiral stationary phases and higher enantioseparation factors are obtained. After a single-walled carbon nanotube is linked to the 6-pesition of cellulose 2,3-bisphenylcarbamate, its enantioseparation resolution increases compared to that of the cellulose trisphenylcarbamate. It is the first time that SWNTs have been applied to enantioseparation. The results indicate that the single-walled carbon nanotubes are good promoters of chiral recognition. This method can be used to improve the enantioseparation efficiency of the polysaccharide chiral stationary phases.

Glucose,cellobiose,lactose and raffinose used as chiral stationary phases in HPLC

This paper presents the enantioseparation using glucose, cellobiose, lactose and raffinose as chiral selector bonded to silica gel via an arm in HPLC. Surprisingly, they also possess high enantioseparation selectivity, may be used in normal-phase and reversed- phase mode, and there is a big chiral discriminating complementary. This work indicates that oligosaccharides could soon become very attractive as a new class of chiral stationary phase for HPLC.

Synthesis of novel chiral stationary phases for high-performance liquid chromatography

Three novel chiral selectors 4a-c were synthesized from （S）-amino acids and （R）-1-phenyl-2-（4-methylphenyl）ethylamine. 4a-c were connected to 3-aminopropylsilanized silica gel to be used as the chiral stationary phase for HPLC. Five amino acid derivatives and two pyrethroid insecticides were fairly resolved on these three new chiral stationary phases under normal phase condition.

Preparation of new hybrid organic/inorganic polymeric chiral stationary phases for ligand-exchange chromatography

Three new hybrid organic/inorganic polymeric ligand-exchange chiral stationary phases were developed by radical chain transfer reaction and surface grafting on silica gel, and successfully used for the enantioseparations of DL-amino acids and DL-hydroxyl adds. The resolutions were achieved by using water containing 2.0 × 10^-4 mol/L of CuAc2 as a mobile phase, column temperature of 40 ℃, flow rate of 1.0 mL/min and detection at UV 254 nm. The elution order of D-isomer before L-isomer was observed for all DL-amino acids resolved except DL-Pro.

Separation of Enantiomers of Clopidogrel on Chiral Stationary Phases by Packed Column Supercritical Fluid Chromatography

A packed column supercritical fluid chromatography (SFC) method for the separation of clopidogrel enantiomers on a chiral stationary phase and CO2 with modifier as mobile phase has been developed at an analytical scale. Among 11 different 2 stationary phases the Chiral cel OD-H column showed by far the best separation properties. The influence of different modifiers, injection solvents, temperature, and pressure, and density of the fluid, respectively, on the separation behaviour has been studied. It was found that the separation behaviour strongly depends on the type of modifier and the modifier content. Temperature and pressure are of less influence.

Modification of Chiral Stationary Phases with L-Proline as a Selector for Ligand-exchange Chromatography via Introducing Hydrophobic Groups

Three chiral stationary phases（CSPl, CSP2 and CSP3） for ligand-exchange chromatography were prepared by firstly using dimethylchlorosilane as an endcapping reagent for decreasing residual silanol groups on the surface of silica gel, and then modifying the surface of silica gel with allyl glycidyl ether and alkenes through the hydrosilation reaction, and lastly introducing L-proline as a chiral selector. The enantiomer resolutions of 14 amino acids and 2 hydroxyl acids were completed on the CSPs by using an aqueous solution of Cu（Ac）2 as mobile phase at a flow rate of 1.0 mL/min and column temperature of 40 ℃ with detection at UV 254 nm. In terms of enantioseleetivity a, column efficiency and resolution Rs, the chromatographic behaviors of the analytes on the CSPs were discussed via comparing them to those on the CSP4 prepared via the reference method. The results show that enantioselectivity a, column efficiency and resolution Rs of the analytes on the CSPs could be improved by using the above modifying method.

High performance liquid chromatographic separation of thirteen drugs collected in Chinese Pharmacopoeia 2010(Ch.P2010) on cellulose ramification chiral stationary phase

The enantiomers separation of thirteen drugs collected in Ch.P2010 was performed on chiral stationary phase of cellulose ramification (chiralpak OD and chiralpak OJ) by high performance liquid chromatographic (HPLC) methods, which included ibuprofen (C1), ketoprofen (C2), nitrendipine (C3), nimodipine (C4), felodipine (C5), omeprazole (C6), praziquantel (C7), propranolol hydrochloride (C8), atenolol (C9), sulpiride (C10), clenbuterol hydrochloride (C11), verapamil hydrochloride (C12), and chlorphenamine maleate (C13). The mobile phase consisted of isopropanol and n-hexane. The detection wavelength was set at 254 nm and the fiow rate was 0.7 mL/min. The enantiomers separation of these thirteen racemates on chiralpak OD column and chiralpak OJ column was studied, while the effects of proportion of organic additives, alcohol displacer and temperature on the separation were studied. And the mechanism of some of racemates was discussed. The results indicated that thirteen chiral drugs could be separated onchiral stationary phase of cellulose ramification in normal phase chromatographic system. The chromatographic retention and resolution of enantiomers could be adjusted by factors including column temperature and the concentration of alcohol displacer and organic alkaline modifier in mobile phase. It was shown that the resolution was improved with reducing concentration of alcohol displacer. When concentration of organic alkaline modifier was 0.2% (v/v), the resolution and the peak shape were fairly good. Most racemates mentioned above had better resolution at column temperature of 25 1C. When racemates were separated, the temperature should be kept so as to obtain stable separation results.

COVALENTLY BONDING CHIRAL POLYURETHANE ON AMINATED SILICA GEL:A NEW STRATEGY TO PREPARE CHIRAL STATIONARY PHASE FOR HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Two polyurethanes of different molecular weights were prepared by the copolymerization of phenyl diisocyanate and diisopropyl tartrate. The polyurethanes having terminal isocyanate groups were reacted with 3-aminopropyl silica gel to afford two chiral stationary phases. The M^- n of the two polyurethanes were 4057 g/mol and 6442 g/mol. The polyurethanes and the corresponding chiral stationary phases were characterized by FT-IR,^1 H NMR and elemental analysis. The loading capacities of the polyurethanes on silica gel were 0.68 mmol units/g and 0.61 mmol units/g, respectively. The separation performance and the influence of additives, triethylamine and trichloroacetic acid, on the separation of chiral compounds were investigated by HPLC. The chiral stationary phase prepared from polyurethane with M^- n of 4057 g/mol demonstrated better enantioseparation capability than that with M^- n of 6442 g/mol. Additionally, it was found that the addition of triethylamine and trichloroacetic acid in the mobile phases significantly improved the enantioseparation for these two chiral stationary phases.

Preparation and chiral recognitio of a novel chiral stationary phase for HPLC,based on mono(6~A-N-1-(2-hydroxyl)-phenylethylimino-6~A-deoxy)-β-cyclodextrin and covalently bonded silica gel

A novel chiral stationary phase （CSP） was prepared by immobilizing mono（6A-N-1-（2-hydroxyl）-phenylethylimino-6A- deoxy）-β-cyclodextrin onto the surface of silica gel via a longer spacer. This chiral stationary phase exhibited good enantioselectivity for a variety of chiral compounds under reversed-phase conditions.

The Optical Resolution of Chiral Tetrahedrone-type Clusters Contai- ning SCoFeM (M=Mo or W) Using High Performance Liquid Chromatography Chiral Stationary Phase

Amylose tris (phenylcarbamate) chiral stationary phase (ATPC-CSP) was prepared and used for optical resolution of clusters 1 and 2. n-Hexane/2-propanol ( 99/1; v/v) were found to be the most suitable mobile phase on ATPC-CSP.

Preparation of novel chiral stationary phase based on click chemistry for ligand exchange chromatography

Click chemistry was applied to immobilize L-proline derivative onto azide-modified silica gel to give a novel chiral stationary phase （denoted as click-CSP） for ligand exchange chromatography. The developed protocol combines the benefits of operational simplicity, exceptionally mild conditions and high surface loadings. The enantioselectivity α of some DL-arnino acids on the click- CSP were found to be in the range from 1.13 to 3.46. The chromatographic resolutions of some DL-amino acids and the stability study firmly illustrate the potential of click chemistry for preparation chiral stationary phase for ligand exchange chromatography.

MIL-53-based homochiral metal-organic framework as a stationary phase for open-tubular capillary electrochromatography

Homochiral metal-organic frameworks(MOFs)have attracted considerable attention in many fields of research,such as chiral catalysis and chiral chromatography.However,only few homochiral MOFs can be effectively used in capillary electrochromatography(CEC)and their performances are far from adequate.In this study,we successfully synthesized achiral nanocrystalline MIL-53.A facile post-synthetic modification strategy was then implemented to functionalize the product,yielding a homochiral MOF:L-His-NH-MIL-53.This MOF was then employed as a chiral coating in open-tubular CEC mode(OT-CEC),and,as such,it exhibited high enantioselectivities for several racemic drugs.The homochiral MOF and the fabricated capillary coating were systematically characterized using transmission electron microscopy,scanning electron microscopy(with energy-dispersive X-ray spectrometry),Fourier-transform infrared spectroscopy,X-ray diffractometry,thermogravimetric analysis,circular dichroism spectroscopy,Brunauer-Emmett-Teller surface area measurements,and X-ray photoelectron spectroscopy.This study is expected to provide a new strategy for the design and establishment of MOF-based chiral OT-CEC systems.

Molecular Imprinting of (R)-(+)-α-Methylbenzylamine for Chiral Stationary Phase

A new type of molecular imprinting stationary phase was prepared by using R- (+)-α -methylbenzy lamine as the print molecule. Experiments of high performance liquid chromatography show that the new stationary phase has high enantio-selectivity and discriminates (R, S) -(± )- α -methylbenzylamine successful ly with α value of 1. 67

Two Side Chain β-CD Polysiloxanes Used as New Stationary Phase for Chiral Separation by HRGC

Two new stationary phases : (Ⅰ) [bikis(2,6-di-O-pentyl-3-O-hex-6O-pentyl-3-O-methyl)-β-CD-polysiloxane] and (Ⅱ) [heptkis(2,6-di-O-methyl-3-O-hex-6-enyl)-β-CD-polysiloxane] were synthesized and successfully used for GC separation of chiral isomers.The possess high column efficiency and exhibit fine chiral separation ability.

Enantioseparation of some Racemic Compounds on Cellulose Tris (3,5-dimethylphenylcarbamate) Chiral Stationary Phase

Seven chiral compounds were resolved on cellulose tris (3,5-dimethylphenylcarbamate) chiral stationary phase (CDMPC-CSP) using n-hexane/alcohol as mobile phase. Solvent strength and structural characteristics of the compounds effecting on the retention and resolution were discussed. Satisfactory separation was obtained.

A chiral stationary phase with special hydrophobic framework for ligand-exchange chromatography

A novel chiral stationary phase （CSP1） for ligand-exchange chromatography （CLEC） was prepared by firstly using dimethylchlorosilane as an endcapping reagent for decreasing residual silanol group on the surface of silica gel, and then introducing L-Pro as a chiral selector and hydrophobic octyl group to the silica gel surface simultaneously. The enantioseparations of 14 DL-amino acids on CSP1 were achieved with the enantioselectivity α ranging from 1.09 to 2.44 and the resolution Rs being between 0.8 and 6.3. The chromatographic performances of CSP1 with the bonded phase （CSP2） prepared using reference method were compared. The results showed that the column efficiency and resolution Rs of chiral stationary phase could be improved by using the above modifying method.

Enantioseparation of Racemic Naproxen Esters on Cellulose Tris (4-methylbenzoate) Chiral Stationary Phase

Several kinds of racemic naproxen ester were successfully separated on CTMB chiral stationary phase with hexane-ethanol (98:2, vol./vol.) as the mobile phase. The influence of mobile phase composition and structure of racemic naproxen ester on chiral separation was studied and the chiral recognition mechanism of CTMB was discussed.

Liquid Chromatographic Resolution of Racemic 2-Phenyl-1,1-cyclopropanedicarbonitrile and its Analogues on Chiral Stationary Phase

Excellent resolution of racemic 2-phenyl-1,1-cyclopropanedicarbonitrile and its nine analogues was accomplished using 100-5CH1-TBB chiral stationary phase under normal-phase HPLC conditions. The influence of mobile phase and the optimum conditions for the resolution of optically active enantiomers were investigated.

The Synthesis of A New Cyclodextrin-Crown Ether Chiral Stationary Phase and Application in Gas Chromatography

A new compound of mono 6 (1' benzo aza 15 crown 5) 2,3,6 permethyl β cyclodextrin (BA 15C5 PM CD) was synthesized. The structure was determined to be coincide with our anticipation by spectroscopy. As a stationary phase for capillary gas chromatography, excellent separation for enantiomers and positional isomers was achieved.