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).

Three Cinnamyl β-Cyclodextrins Used as GC Stationary Phases

Aim To study the chromatographis beheviors of three new cinnamyl cyclodextrin derivative stationary phases. Mehtods Three new cinnamyl β-cyclodextrins, heptakis-(2, 6-di-O-cinnamyl-3-O-methyl)-β-CD, heptakis-(2, 6-di-O-cinnamyl-3-O-acetyl-)-β-CD and heptakis-2, 6-di-O-cirinamyl-3-O-trifluoroacetyl)-β-CD were synthesized and coatal on fused-silica capillary columns . Results The new stationary phases have better thermal stability, good column efficiency and excellent mpaxation power for some sutstituted benzene positional isomers. It was found that the introduction of cinnamyl groups has a significant effect on these stationary phases. Conclusion There new subetituted β-CD compounds are very suitable to be ed as gas chromatographic stationary phases.

Retention behaviors of novel ionic liquid stationary phases and their selectivity for capillary gas chromatography

One chloride-terminated ionic liquid（CTIL） and two hydroxyl-terminated ionic liquids（HTILs） were synthesized and used as stationary phases for capillary gas chromatography（CGC）.Molecular interactions of these stationary phases were evaluated by Abraham solvation parameter model,indicating that the CTIL exhibits remarkably strong H-bond basicity and the HTILs possess both H-bond basicity and acidity.The molecular interactions were further confirmed by separation of a complex mixture consisting of ketones,aldehydes,esters,alcohols and aromatic compounds.It was found that the obtained solvation parameters correlate well with the chromatographic performances of the analytes in terms of elution order and resolution.The well correlated relationship between the solvation parameters and the selectivity of the CTIL and HTILs stationary phases is quite helpful in predicting and understanding the retention behaviors of different types of analytes on these stationary phases.

AN EASY-TO-MAKE OZONE GENERATOR FOR THE IMMOBILIZATION OF STATIONARY PHASES IN GC CAPILLARY COLUMNS

An easy-to-make ozone generator which can be made with readily available materials is proposed. Concentration of the ozone prepared with this generator could reach that of ozone in equilibrium with oxygen. Cured with the ozone thus prepared, GC capillary columns with immobilized SE-54 phase and excellent chromatographic performance were successfully prepared.

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.

Novel guanidinium-based ionic liquids as stationary phases for capillary gas chromatography

The present study describes guanidinium-based ionic liquids（GBILs） as stationary phases for capillary gas chromatography （CGC） and to the best of our knowledge,no related reports are available up to now.In this study,a hexaalkylguanidinium ionic liquid（DOTMG-NTf;） was synthesized and coated statically onto capillary columns.Selectivity of the stationary phase was evaluated by separating Grob test mixture,test mixture,alcohols mixture,and fatty acid methyl esters mixture,and thermal stability was investigated as well.The present study demonstrates that GBILs as CGC stationary phases exhibit satisfactory selectivity and thermal stability and have a great potential as new candidates for CGC stationary phases.

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.

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.

Selectivity of New β-Cyclodextrin Derivatives as CGC Stationary Phases and Application for the Analysis of Volatile Compounds in Traditional Chinese Medicines

New cyclodextrin derivatives （CDs）, heptakis（2, 6-di- O-methyl-3- O-methoxymethyl）-β-CD （ Ⅰ ） and heptakis（2, 3, 6-tri-O-methoxymethyl）-β-CD （ Ⅱ ）, were investigated for their chromatographic performance as stationary phases for capillary gas chromatography （CGC）. Both of the CDs exhibited good selectivity and satisfactory separation for test mixtures and aromatic positional isomers, and volatile compounds from Ligusticurn chuanxiong Hort. Additionally, the selectivity and elution orders of major compounds were compared with a well-recognized commercial column on the basis of the results by gas chromatography-mass spectrometry （GC-MS）. The present work demonstrates the good selectivity of the two new CDs and can be used as GC stationary phases for the separation of positional isomers and analytes in complex samples.

Comparison of different polysaccharide-based chiral stationary phases for enantioselective resolution of Naftopidil and its derivatives by HPLC

Effective enantioseparation of Naftopidil and its derivatives by HPLC was accomplished using several different polysaccharide-based chiral stationary phases（CSPs）.In normal-phase mode,the compounds were eluted on four coated-and two immobilized-columns with the mixture of n-hexane,isopropanol and diethylamine（DEA）.Polysaccharide tris（3,5- dimethylphenyl carbamate） was shown to be the best enantiomer selector.In addition,the immobilized column packed with Chiralpak IA or IB was applied under polar-organic and reversed-phase conditions,both of which exhibited excellent enantioselectivity for Naftopidil and its derivatives.Furthermore,the underlying possible chiral recognition mechanisms were discussed.

Separation of substituted phenylpiperazine derivatives with immobilized polysaccharide-based chiral stationary phases by supercritical and subcritical fluid chromatography

Six newly synthesized racemic 1-（substituted phenyl）-4-[3-（indole-4-yl-oxy）-2-hydroxypropyl]-piperazine 1-6 were successfully resolved by carbon dioxide supercritical fluid chromatography （SFC） on an analytical scale column packed with immobilized polysaccharide-based chiral stationary phases （CSPs）. We found that separation on the Chiralpak IA CSP was superior to the other two immobilized CSPs （Chiralpak IB and Chiralpak IC）, and isopropanol （IPA） was a superior modifier compared to the other five solvents including ethanol, methanol, tetrahydrofuran, acetonitrile and dichloromethane. The effects of organic modifier composition, back pressure, and column temperature for enantioseparation of all six compounds were studied. Of the physical parameters studied, modifier composition had the greatest impact on retention. Changing temperature generally had less impact on retention but produced the greatest selectivity changes. The optimum condition was found as follows： Chiralpak IA column, column temperature 35 ~C, back pressure 120 bar, 35% IPA containing 0.1% diethylamine （v/v） in mobile phase, flow rate of mobile phase 3.0 mL/min, UV detection 283 nm. Separation of all six racemic compounds was completed within 10 rain and excellent resolution was obtained. Thus, SFC was found to be the methodology of choice for resolving the enantiomers of this class of compounds.

Enantiomer Separation of α-Dimethyl Dicarboxylate Biphenyl and Related Biphenyl Compounds by Normal Phase HPLC on Polysaccharide Based Chiral Stationary Phases

Cellulose tris(4-methylphenylcarbamate), amylosetris(3,5-di-methylphenylcarbamate) and amylose tris (phenylcarbamate) were prepared by the methodreported by Okamoto and were coated onto an aminopropylated mesoporous spherical silica gel. Thesefinal products were used as chiral stationary phases of high performance liquid chromatography forthe eighteen structurally related biphenyl compounds. The resolution was made using normal-phasemethodology with a mobile phase consisting of n-hexane-alcohol (ethanol, 1-propanol, 2-pro-panol or1-butanol). The effects of various aliphatic alcohols in the mobile phase were studied. Thestructural features of the solutes that influence then- k′ were discussed. A dominant effect oftrifluoroacetic acid on chiral separation of acidic solutes was noted.

Preparation and Enantioseparation Property of Chiral Stationary Phases Based on Cellulose Tris(3,5-dimethylbenzoate)——A New Way to Prepare Polysaccharide-coating Type Chiral Stationary Phases

A new method to prepare polysaccharide-coating type chiral stationary phases （CSPs） was developed in this work. As a typical example, naked silica gel was coated by cellulose, which was then derivatized with 3,5-dimethylbenzoyl chloride to afford cellulose tris（3,5-dimethylbenzoate）-silica gel （CTDBS） complex. The silanols on CTDBS were end-capped with 3- aminopropyltriethoxysilane to obtain CSP 1. The amino groups on CSP 1 were further end-capped with 3,5-dimethylbenzoyl chloride to give CSP 2. The silanols on CTDBS were end-capped with methyltrimethoxysilane to yield CSP 3. CSPs 1-3 were characterized by FTIR, solid-state 13C-NMR and elemental analysis. The enantioseparation abilities of CSPs 1-3 were evaluated with structurally various chiral analytes. The enantioseparation results demonstrated that the end-capping moieties on CSPs 1 and 2 significantly affected enantioseparation. In addition, the effect of the structures of chiral analytes and end- capping moieties on the retention factors and the resolutions was discussed.

Preparation and Chiral Recognition of New Chiral Stationary Phases Derived from Cellulose Microspheres

A new way to prepare cellulose-type chiral stationary phases （CSPs） has been established in the present work.Cellulose microspheres with a volume-average diameter of 11.5 m were prepared by an emulsion-solidification method.Three new CSPs were obtained by crosslinking the cellulose microspheres with terephthaloyl chloride （TPC）,and then modifying the crosslinked microspheres with 4-methylbenzoyl chloride,3,5-dimethylbenzoyl chloride and 3,5-dichlorobenzoyl chloride,respectively.The microspheres and the CSPs were characterized by FT-IR,element analysis and scanning electronic microscopy （SEM）.The chiral recognition ability of the CSPs was evaluated with high-performance liquid chromatography （HPLC）.The chromatographic results demonstrate that the CSP prepared from 3,5-dichlorobenzoyl chloride possesses better chiral recognition ability compared with two other CSPs.

Triptycene-derived heterocalixarene:A new type of macrocycle-based stationary phases for gas chromatography

This work reports the investigation of a new triptycene-derived oxacalixarene(TDOC)as the stationary phase for gas chromatography(GC)with high-resolution performance for a wide range of analytes and isomers.The TDOC scaffold is composed of triptycene and 1,8-naphthyridine moieties,inherently differing from the conventional calixarenes in structures and properties.As a result,the TDOC column exhibited outstanding column efficiency of 5679 plates/m by n-dodecane at 120℃.It showed advantageous performance for separations of the mixtures with various analytes and achieved high resolution of diverse isomers(skeletal,positional and cis-/trans-isomers)from apolar to polar nature.Moreover,the TDOC column exhibited high thermal stability up to 310℃.To date,the TDOC-based materials have not been reported in chromatography.This work demonstrates the good potential of the triptycene-derived heterocalixarenes as a new class of stationary phases for chromatographic analyses.

Investigation of Peptoid Chiral Stationary Phases Terminated with N＇-Substituted PhenyI-L-proline/leucine Amide

Eight peptoid chiral stationary phases （CSPs） terminated with N＇substituted phenyl-L-proline or L-leucine amide were prepared and evaluated under normal phase mode. With 59 racemic analytes, we compared the enantio- meric separations on CSPs terminated with p-methylphenyl, p-chlorophenyl and unsubstituted phenyl. For short peptoid selectors containing only one S-N-（1-phenylethyl） glycine （Nspe） unit, the terminal p-methyl substituent did not affect chiral recognition abilities significantly. In L-proline amide terminated CSPs, p-chloro substituent resulted in obviously inferior selectivity while in L-leucine amide terminated CSPs, it worked much better. Longer peptoid selectors containing two more Nspe units generally performed much better than the shorter ones, due to the great contributions of peptoid chain to chiral recognition. Meanwhile, the effects of the terminal substituent on selectivity were found changed on these CSPs. For CSPs terminated with L-leucine amide, the terminal p-chloro substituent in longer selector no longer produced the best recognition ability; the CSP with unsubstituted phenyl instead performed best. Comparison of these peptoid CSPs varied in terminal substituents and chain length was conducted to gain a better understanding of the chiral recognition mechanism of this type CSP and promote the development of more useful CSPs.

Investigation on Two Novel Substituted β-Cyclodextrins Used as GC Stationary

Aim To study the chromatographic behaviors of two dipentyl cyclodextrin derivative stationary phases. Methods Two new β-cyclodextrin derivatives, heptakis-[2, 6-di-O-pentyl-3-O-(4-nitrobenzyl)] -β-CD and heptakis-[2, 6-di-O-pentyl-3 -O-(5 -hexenyl)]-β-CD, were synthesized and coatal on fed-silica capillary columns. The chromatographic behaviors of the columns were characterized . Results It was found that the she, polarity, and aromatic property of the substituted group at the 3-position of heptakis-(2, 6 - di - O - pentyl) - β - cyclodextrins greatly influenced their chromatographic properties and separation ability. The introduction of aromatic group or a group containing a double-bond may bring π-π interactions between the host and guest molecules, and therefore increases the separation ability of the β-CDs for substituted benzene isomers. Conclusion The new substituted β-CD compounds are very suitable for being used as gas chromatogaphic stationary phases.

Separation Properties of a New Polysiloxane-Anchored β-Cyclodextrin Derivative as Gas Chromatography Stationary Phase

A new capillary gas chromatography stationary phase, monokis (2,6 di O benzyl 3 O propyl (3’)) hexakis(2,6 di O benzyl 3 O methyl) β CD bonded polysiloxane, was synthesized. It exhibited separation abilities to disubstituted benzene isomers and some chiral solutes. It was also found that the polarity of CD derivatives can be lowered both by chemically bonding it to polysiloxane and by diluting it in polysiloxane. The separation abilities of the polysiloxane anchored CDs (SP CD) are higher than that of the unbonded CDs (S CD) and the diluted S CD at lower column temperature. Hydrosilylation reaction is one of the best methods to lower the operating temperature of CDs.