Synthesis of Amino Acid Derived β-Cyclodextrins Used in Chiral Separation by Capillary Electrophoresis

Six new kinds of amino acid derived β-cyclodextrins were synthesized to improve their water solubility and chiral separation properties. They are heptakis{2,6-di-O-[3-L-(1-isopropyl carboxyl methyl amino)-2-(hydroxy) propyl]}-β-cyclodextrin (i.e. L-Val-β-CD), heptakis{2,6-di-O-[3-L-(1-benzyl carboxyl methyl amino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Phe-β-CD), heptakis{2,6-di-O-[3-(D, L-1-benzyl carboxyl methyl amino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. D,L-Phe-β-CD), heptakis{2,6-di-O-[3-(L-1-hydroxymethyl carboxyl methyl amino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Ser-β-CD), heptakis{2,6-di-O-[3-(L-1-carboxylmethyl carboxyl methyl amino)- 2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Asp-β-CD), heptakis{2,6-di-O-[3-(L-2-carboxyl tetramethylene amino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Pro-β-CD). Their chemical structures were certified using FTIR and ()~1H NMR. Except for L-Phe-β-CD and D,L-Phe-β-CD, that are in soluble in water, the other amino acid derived β-CDs all have good water solubility. D,L-tyrosine and promethazine were baselinely separated by L-Val-β-CD in capillary electrophoresis.

Carboxymethyl-β-cyclodextrin for Chiral Separation of Amino Acids Derivatized with Fluorescene-5-isothiocyanate by Capillary Electrophoresis and Laser-induced Fluorescence Detection

A method using carboxymethyl-b-cyclodextrin (CM-b-CD) as selector for chiral separation of amino acids by capillary electrophoresis and laser-induced fluorescence detection was studied. Resolution was better than that obtained by b-CD or HP-b-CD.

Synthesis and Characterisation of Water-Soluble Carboxymethyl-Cyclodextrin Polymer as Capillary Electrophoresis Chiral Selector

The water-soluble carboxymethyl-cyclodextrin polymer (CM-CD polymer) was synthesized and used as capillary electrophoresis chiral selector. Verrapamil and thiopentorusodium were well separated using CM-CD polymer as chiral selector.

6-O-(Hydroxypropyltrimethylammonia)-β-cyclodextrin with Low Degree of Substitution: Convenient Preparation and its Application as a Chiral Selector in Capillary Electrophoresis

A cationic cyclodextrin derivative 6-O-（hydroxypropyltrimethylammonia）-β-cyclodextrin （GTA-β-CD） with low degree of substitution was prepared through a convenient method in solid phase. The product could be used as a valuable chiral selector in the capillary electrophoresis （CE） separation of some acidic drug enantiomers such as naproxen, ofloxacin, ibuprofen and warfarin.

Carboxymethyl-β-Cyclodextrin for Chiral Separation of Basic Drugs by Capillary Elcctrophoresis

Four basic drugs were separated by capillary electrophoresis (CE) usingcarboxymethyl-β-yclodextrin (CM-0-CD) as chiral selector. The effects of CM-β-CDconmptration, applied voltage. operation temperature were investigated. Under the selectedconditions. norephedrine. ofloxacin. terbutaline and chlorpheniramine were enantiomerallybaieline-separated using H3PO4-triethanolamine buffer at PH 3 containing 10, 5.5, 2. 2mmol/LCM-β-CD respectively.

Method Development of Enantiomer Separations by Affinity Capillary Electrophoresis,Cyclodextrin Electrokinetic Chromatography and Capillary Electrophoresis-Mass Spectrometry

Capillary electrophoresis (CE) has become a powerful tool for enantiomer separations during the last decade. Since 1993, the author has investigated enantiomer separations by affinity capillary electrophoresis (affinity CE) with some proteins and by cyclodextrin electrokinetic chromatography (CDEKC) with some charged cyclodextrins (CDs). Many successful enantiomer separations are demonstrated from our study in this review article. In the enantiomer separations by affinity CE, the deterioration of detection sensitivity was observed under high concentration of the protein in running solutions. The partial filling technique was practically useful to solve the serious problem. It allowed operation at high protein concentrations, such as 500 μmol/L, without the detection problem. Charged CDs had several advantages for the enantiomer separations over neutral ones. Strong electrostatic interactions between a charged CD and oppositely charged analytes should be effective for the formation of the complex. A large difference in electrophoretic mobility between the free analyte and the inclusion complex should also enhance the enantiomeric resolution. In CE mass spectrometry (CE MS), the partial filling technique was applied to avoid the introduction of nonvolatile chiral selectors into the CE MS interface. By replacing the nonvolatile electrolytes in the running buffer by volatile ones, the separation conditions employed in CE with the UV detection method could be transferred to CE MS.

Investigation of Mixed Chiral Selectors of Different Metal Ion-L-Alanine Complex and β-Cyclodextrin on the Chiral Separation of Dansyl Amino Acids with Capillary Electrophoresis

Chiral separation of dansyl amino acids by capillary electrophoresis using mixed selectors of Mn(II)- L -alanine complex and β -cyclodextrin ( β -CD) was studied. Resolution was considerably superior to that obtained by using either Mn(II)- L -alanine complex or β -CD alone. The effects of separation parameters,such as pH value of buffer solution,capillary temperature,the concentration of Mn(II)- L -alanine complex,the types of CD and ligand on the migration times and resolutions were investigated. Six different transition metal complexes, Cu(II), Zn(II),Co(II),Ni(II),Hg(II) and Cd(II)- L -alanine complexes have been employed and compared with Mn(II) complex. Differences in retention and selectivity were found. The substitution of Cu(II),Zn(II),Co(II) and Ni(II) for Mn(II) resulted in a better chiral resolution while Hg(II) and Cd(II) showed poorer resolution abilities. The chiral separation mechanism was also discussed briefly.

Separation of chiral drugs with sulfobutylether-β-cyclodextrin bycapillary zone electrophoresis

Sulfobutylether－β－cyclodextrin（SBE－β－CD）was used as a chiral selector tor separatingten chlral drugs with resolution 1．2 by capillary zone electrophoresls（CZE）， The backgroundelectrolylc solution comprised of 120 mmol／L Britton－Robinson buffer（BRB） containing1 ～10mmol／L SBE－β－CD with the pH value adjusted from 5．0－6．8． Five of the drugs were better resolvedthan those previously reported with neutral CDs．

Chiral Separation of Esmolol and Terazosin by Cyclodextrinmodified Capillary Zone Electrophoresis

Cyclodextrin-modified CZE was applied to the chiral separation of two basic drugs, i.e., esmolol and terazosin. Selector screening and concentration optimization experiments were performed. Resolution 3.1 for esmolol, 1.2 for terazosin were achieved when using 60 mmol/L gamma-CD and 60 mmoL/L DM-P-CD, respectively, in 50 mmol/L pH 2.5 sodium phosphate buffer.

Chiral Separation of Chlorpheniramine by Capillary Electrophoresis *L

Aim To study the chiral separation of chlorpheniramine(Chp) by using a mixture of β CD and glutamate β CD as the chiral additive in CE. Methods Mixture of β cyclodextrin and glutamate β cyclodextrin was used as a chiral selector to the separation of chlorpheniramine. The effects of the concentrations of β cyclodextrin and glutamate β cyclodextrin, the voltage and the pH of buffers on the separation of chlorpheniramine were studied. Results The chiral recognization of the mixed chiral selector was better than that of a single selector. At pH below 4, the pH of buffers did not affect the separation and the separation of chlorpheniramine had good reproducibility. Conclusion Using a mixture of β CD and Glu β CD as chiral selector is useful for the enantioseparation of Chp in CE.

Separation of chiral drugs with β-CD phosphate by capillary electrophoresis

β-Cyclodextrin phosphate (β-CD-phosphate) was used as a selector for separating chiral drugs by capillary electrophoresis (CE). A solution comprising of 120 mmol/L Britton Robinson buffer (BRB) containing 10 mmol/L 0-CD phosphate with the pH adjusted to 7.0 was used as the background electrolyte (BGE), and a small amount of analyte was injected (600v/1s). Triethylamine, diethylamine, triethanolamine, diethanolamine, Tris added as modifier were compared. Isoprenaline, methoxamine, oxprenolol, practolol were successfully resolved.

Chiral Separation of N-Benzoyl Phenylalanine Methyl Ester by Nonaqueous Capillary Electrophoresis

A successful chiral separation of N-benzoyl phenylalanine methyl ester has been achieved by nonaqueous capillary electrophoresis (NACE) using P-CD as chiral selector in formamide (FA). Some experimental parameters influencing the chiral separation such as concentration of P-CD, ionic strength and apparent pH (pH*) are discussed.

Preparation of β-Cyclodextrin Modified FusedSilica Capillary and Its Application inCapillary Electrophoresis Enantiom eric Separation

A simple type of chiral selector immobilized capillaries was prepared and applied to the separation of some enantiomers by capillary electrophoresis(CE) without chiral selective reagents in a buffer solution. β Cyclodextrin (CD) was bonded to the inner wall of fused silica capillary with the aid of 3 (2 cyclooxypropoxyl) propyl trimethoxy silane or 3 aminopropyltriethoxyl silane as bridge. The synthesis conditions such as reaction temperature, reaction ratios, solvents were optimized. The stability and reproducibility of the CD modified capillaries were studied under different operation conditions. It is satisfactory to apply the capillary to the chiral separation of d,l adrenaline and the atracurium besilate diastereoisomers under the optimized conditions.

The Synthesis and Characterization of β-cyclodextrin Derivated Pancreatin Used as Chiral Selector in Capillary Electrochromatography

The preparation of capillary electrochromatography column for chiral separation with β-cyclodextrin derivatized Pancreatin was imvestigated, which had three steps, synthesis of β-cyclodextrin derivated pancreatin, the modification of the capillary internal surface and the covalent binding of β-cyclodextrin derivated pancreatin on the capillary internal wall. β-cyclodextrin derivated pancreatin was synthesized using β-cyclodextrin and protein in the presence of ethylene glycol diglycidyl ether （EGDE） in boric acid buffer at pH = 8.7. Amino group was coated on the internal surface of the silica capillary by sot-gel technology using triethoxylmethylsiloxane and （ 3-aminopropyl ） trimethoxysiloxane. Covalent binding of β-cyclodextrin derivated pancreatin was performed by glataraldehyde. Chlorpheniramine, phenylalanine and troopine were separated baseline by β-cyclodetrin derivated pancreatin in capillary electrochromatography.

Preparation and Characterization of β-Cyclodextrin Derivatized Ovalbumin Used as Chiral Selector in Pressure Capillary Electrochromatography

Synthesis and properties of β-cyclodextrin derivatized ovalbumin used as chiral selector were investigated, β-cyclodextrin derivatized ovalbumin was synthesized using β-cyclodextrin and ovalbumin in the presence of ethylene glycol diglycidyl ether in boric acid buffer at pH value 8.7 at 37℃. Amino group was coated on the internal surface of the silica capillary by sol-gel technology with triethoxylmethylsiloxane and （3-aminopropyl）trimethoxysiloxane. Covalent binding of g-cyclodextrin derivatized ovalbumin was performed by glutaraldehyde. Enantiomers of chlorpheniramine, phenylalanine and atropine were separated by pressure capillary electrochromatography column coated with β-cyclodextrin derivatized ovalbumin.

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).

Separation of Chiral Isomers of Chloramphenicol Metabolite by Capillary Zone Electrophoresis Using Cyclodextrin as Chiral Selector

In recent years capillary zone electrophoresis (CZE) has become a powerful technique to separate a variety of complex mixtures.Because CZE possesses the advantages of high efficiency, easily operating for separation of biological molecules, it is a more powerful separating tool and cannot be replaced by HPLC, GC or SFC.

A Novel Polybrene/Chondroitin Sulfate C Double Coated Capillary and Its Application in Capillary Electrophoresis

A new capillary coated by double polymer, polybrene/chondroitin sulfate C (P/CC), was developed using a simple procedure. The P/CC double coated capillary showed long lifetime, strong chemical stability and good reproducibility. It endured during more than 100 replicated analyses and was also tolerant to HCl (1 mol/L), NaOH (0.01 mol/L), CH3OH and CH3CN. The P/CC double coated capillary can be applied to basic drug analyses. The adsorption of basic drugs to the capillary wall was suppressed and the peak tailing greatly decreased. The use of the P/CC double coated capillary allowed excellent separation of the enantiomers of some basic drugs by using chondroitin sulfate C as the chiral selector, and the peak symmetry of basic drugs was further improved under these conditions.

深共晶溶剂协同羧甲基-β-环糊精促进美托洛尔的毛细管电泳手性分离

手性药物的对映体理化性质极其相似,而药理、毒理作用常常存在显著差异,因此探索提高对映体分离性能的创新策略对手性分离具有重要意义。以往关于毛细管电泳(CE)中β-受体阻断药美托洛尔(MET)对映体分离的研究主要集中在仅添加手性选择剂环糊精(CD)及其衍生物,而对于在CD的基础上添加辅助添加剂的研究较少。本研究将3种深共晶溶剂(DESs)氯化胆碱-葡萄糖、氯化胆碱-果糖和乳酸-葡萄糖作为辅助添加剂,用于MET的CE手性分离,推测了DES对基于CD的毛细管电泳分离MET对映体的协同作用。首先考察了CD种类、CD浓度、缓冲液pH值和缓冲液浓度对MET分离的影响,优化得到了最优条件(15 mmol/L羧甲基-β-环糊精、pH=3.0、40 mmol/L磷酸盐缓冲液)。其次制备了3种DESs作为添加剂,研究不同DESs及其质量分数对手性分离的作用,最终确定了最佳条件:采用质量分数1.5%的氯化胆碱-果糖型DES,此时MET的分离度从不添加DES时的1.30提升至2.61,实现了基线分离。最后对分离效果以及机理进行了推测。本文所建立的MET对映体手性分离分析方法不仅对提高手性药物质量、保证临床用药安全有效具有重要意义,还有助于将DES协同用于CD衍生物毛细管电泳手性分离的进一步研究与发展。

含有氨基和羧基的β-环糊精衍生物合成及性能测试

目的合成含有氨基和羧基的水溶性β－环糊精衍生物并测试其性能，这些化合物用作毛细管电泳添加剂．方法将β－环糊精与含有氨基的化合物在碱性条件下用环氧氯丙烷连接起来．结果合成了七（２，６－二－Ｏ－羧甲基）－β－环糊精（羧甲基－β－ＣＤ）、七｛２，６－二－Ｏ－［３－（２－氨基乙氨基）－２－羟丙基］｝－β－环糊精（乙二胺－β－ＣＤ）、七｛２，６－二－Ｏ－［３－（１，３－二羧基丙氨基）－２－羟丙基］｝－β－环糊精（谷氨酸－β－ＣＤ）、七｛２，６－二－Ｏ－［３－羧甲基氨基）－２－羟丙基〗｝－β－环糊精（甘氨酸－β－ＣＤ）、七｛２，６－二－Ｏ－［３－（１，２－二羧基乙氨基）－２－羟丙基］｝－β－环糊精（天冬氨酸－β－ＣＤ）、七｛２，６－二－Ｏ－［３－氨基－２－羟丙基）ｑ－β－环糊精（氨基－β－ＣＤ）、七｛２，６－二－Ｏ－［３－（２－羟基乙氨基）－２－羟丙基］｝－β－环糊精（乙醇氨－β－ＣＤ）等七种含有氨基和羧基的β－环糊精衍生物，结果表明它们具有良好的水溶性．将羧甲基－β－ＣＤ和谷氨酸－β－ＣＤ用作毛细管电泳添加剂分离了异丙嗪和扑尔敏两种手性异构体，得到了较好的分离结果．结论将氨基和羧基引入环糊精后可极大改善β－环糊精的水?