Chiral separation of α-cyclohexylmandelic acid enantiomers using ionic liquid/salt aqueous two-phase system

In this paper, an ionic liquid-based aqueous two-phase system (ILATPS) was applied to the chiral separation of α-cyclohexylmandelic acid (α-CHMA) enantiomers with hydroxypropyl-β-cyclodextrin (HP-β-CD) as the chiral selector. Several influencing parameters were investigated including the types and concentration of ionic liquids, the amount of phase-forming salt, temperature, mixing time, pH, and the content of HP-β-CD. The results showed that not all ILATPS had the ability to chirally recognise the selected enantiomers and that [C₄mim]BF₄/(NH₄)₂SO₄-based ATPS possessed the best enantioseparation ability of the investigated ILATPSs. Under optimal conditions, the separation factor (α) attained 1.59 in a single-step extraction. ILATPS is much “greener” than other liquid-liquid extraction systems, showing its potential for application to the chiral separation.     

全衍生化羟丙基-β-环糊精固定相的制备及应用

研究了3, 5-二甲基苯基异氰酸酯对羟丙基-β-环糊精固定相的手性识别影响.通过异氰酸丙基三乙氧基硅烷作偶联剂,将羟丙基-β-环糊精键合到3-氨丙基硅烷化硅胶上,再用3, 5-二甲基苯基异氰酸酯对β-环糊精和硅胶其余羟基进行衍生化,制得一种新型的3, 5-二甲基苯基氨基甲酸酯全衍生化羟丙基-β-环糊精键合硅胶手性固定相.在反相色谱条件下,对9种手性药物进行了拆分,结果表明,3, 5-二甲基苯基氨基全衍生化固定相较之羟丙基-β-环糊精固定相有更好的分离效果.     

Enantioseparation of mandelic acid enantiomers in ionic liquid aqueous two-phase extraction systems

In the past decade, ionic liquids have received great attention owing to their potential as green solvent alternatives to conventional organic solvents. In this work, hydrophobic achiral ionic liquids (1-butyl-3-methylimidazolium-hexafluorophosphate([bmim][PF₆]), 1-octyl-3-methylimidazolium tetrafluoroborate([omim][BF₄])) were used as solvents in chiral liquid-liquid extraction separation of mandelic acid (MA) enantiomers with β-cyclodextrin (β-CD) derivatives as hydrophilic chiral selectors preferentially forming complexes with (R)-enantiomers. Factors affecting the separation efficiency were optimised, namely the type of the extraction solvents and β-CD derivatives, concentrations of the β-CD derivatives and MA enantiomers, pH, and temperature. Excellent enantioseparation of MA enantiomers was achieved in the ionic liquid aqueous two-phase extraction systems under the optimal conditions of pH 2.5 and temperature of 5°C with the maximum enantioselectivity (α) of 1.74. The experimental results demonstrated that the ionic liquid aqueous two-phase extraction systems with a β-CD derivative as the chiral selector have a strong chiral recognition ability, which might extend the application of ionic liquids in chiral separation.     

Optimized Conditions of Enantioseparation of β-Blockers by CZE Using Carboxymethyl-β-Cyclodextrin as Chiral Selector

Capillary zone electrophoresis was used for the enantiomeric separation of six β-blocking drug substances with β-cyclodextrin (β-CD) and its derivatives as chiral selectors employing an uncoated capillary. The effects of pH value and composition of the background electrolyte (BGE), the capillary temperature and running voltage have been investigated. The results showed that β-CD type, concentration and pH value have a strong influence on the efficiency of the chiral separation. Carboxymethyl-β-cyclodextrin (CM-β-CD) gave a baseline enantiomeric separation for six β-blocking drug substances under optimal conditions, whereas the β-CD, hydroxypropyl-β-cyclodextrin (HP-β-CD) showed no chiral recognition. The potential and capillary temperature did not have a great effect on enantiomer resolution.     

β-环糊精类液相色谱固定相及其手性拆分应用研究进展

β-环糊精是以1,4-糖苷键首尾相连的环状低聚糖,具有手性识别功能,特别是衍生化的β-环糊精键合固定相,对手性化合物具有良好的拆分能力。本文介绍了β-环糊精的结构和性质,综述了各种衍生化的β-环糊精液相色谱键合固定相及其在手性化合物拆分中的应用。     

Enantiomeric separation of racemic clenbuterol by capillary zone electrophoresis

A method for capillary electrophoretic enantiomeric separation of a racemic clenbuterol has been established with hydroxypropyl-β-cyclodextrin as the chiral selector. General equations and data analysis are presented to relate mobility to the equilibrium constants in simple binding equilibria and used to determine binding constants and thermodynamic parameters for host-guest complexation of clenbuterol enantiomers with hydroxypropyl-β-cyclodextrin as a selector. The effects of β-cyclodextrin type and concentration, buffer type, concentration and pH, as well as separation voltage and capillary temperature were investigated in detail. A maximal resolution of 6.78 was obtained. The binding constants of the host-guest complex of clenbuterol enantiomers with hydroxypropyl-β-cyclodextrin, K _R-CD and K _S-CD are 22.50 and 43.09 l mol^-1, respectively.     

Influence of the Buffer Organic Cation on the Chiral Separation of Some Basic Drugs by Capillary Zone Electrophoresis

This paper addresses the influence of small organic cations in the background electrolyte (BGE) on chiral separation by capillary zone electrophoresis (CZE). Seven basic drugs, viz. alprenolol, amphetamine, anisodamine, isoprenaline, pinacidil, synephrine, and verapamil were used as test compounds with hydroxylpropyl-β-cyclodextrin (HP-β-CD) as the chiral selector. Resolution of the chiral test compounds was studied at pH 2.5 in the presence of Tris, ethanolamine, diethanolamine, triethanolamine, diethylamine, and triethylamine, which exist in their cationic forms at this pH value. Among the six cationic additives studied, triethylamine is most effective in enhancing resolution. A tentative mechanism of the effect is proposed.     

Preparation of polar group derivative β-cyclodextrin bonded hydride silica chiral stationary phases and their chromatography separation performances

Three new polar group-substituted β-cyclodextrin derivatives were synthetized and they covalent bonded to hydride silica to obtain chiral stationary phases. Their separation results of 35 chiral pyrrolidine compounds were also presented and discussed.     

烯丙基-β-环糊精基手性毛细管电色谱整体柱的一步法制备及其性能

以烯丙基-β-环糊精、甲基丙烯酸缩水甘油酯和乙二醇二甲基丙烯酸酯为功能单体,一步键合制备了环糊精聚合物毛细管整体柱.在电色谱模式下18种氨基酸对映体得到成功分离.研究发现,将修饰的环糊精衍生物作为功能单体制备出的毛细管整体柱对疏水性,含氨基和苯环的手性化合物具有良好的保留行为,并具有良好的稳定性和重现性.新型电色谱柱也被应用于手性药物的分离.     

Enantioseparation of novel psychoactive chiral amines and their mixture by capillary electrophoresis using cyclodextrins as chiral selectors

The prevalence of new psychoactive substances (NPS) has been increasing during the last decade as well as their constant growth of availability across the whole world. Regardless of the potential health hazard, NPS (often racemic compounds) are frequently sought after and abused for their psychoactive effects that may differ for individual enantiomers. In this work, capillary electrophoresis was used for the chiral separation of a mixture of eleven psychoactive chiral amines using β-cyclodextrin and carboxymethyl-β-cyclodextrin as chiral selectors at various concentrations. Chiral separation was successful for all the analytes studied. A mixture of these analytes was subsequently analyzed under optimal conditions, i.e., when using 20 mmol/L carboxymethyl-β-cyclodextrin in 50 mmol/L sodium phosphate buffer, pH 2.5. In this case, chiral separation occurred in nine out of eleven analytes. To our best knowledge, we achieved enantioseparations of seven analyzed compounds by CE for the first time.     

β-环糊精及其衍生物对维生素分子的识别作用

以乙基紫(EV)为光谱探针,采用紫外-可见光谱法测定了两种维生素(V)与β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)和磺丁醚-β-环糊精(SBE-β-CD)的包合特性.结果表明,多种弱相互作用力协同作用于环糊精的包合过程,主-客体间的尺寸匹配影响了包合物的稳定性.包合能力β-CDHP-β-CDSBE-β-CD.     

Solvation and rotational dynamics of coumarin 153 in ionic liquids: comparisons to conventional solvents

Steady-state and time-resolved emission spectroscopy with 25 ps resolution are used to measure equilibrium and dynamic aspects of the solvation of coumarin 153 (C153) in a diverse collection of 21 room-temperature ionic liquids. The ionic liquids studied here include several phosphonium and imidazolium liquids previously reported as well as 12 new ionic liquids that incorporate two homologous series of ammonium and pyrrolidinium cations. Steady-state absorption and emission spectra are used to extract solvation free energies and reorganization energies associated with the S0 <--> S1 transition of C153. These quantities, especially the solvation free energy, vary relatively little in ionic liquids compared to conventional solvents. Some correlation is found between these quantities and the mean separation between ions (or molar volume). Time-resolved anisotropies are used to observe solute rotation. Rotation times measured in ionic liquids correlate with solvent viscosity in much the same way that they do in conventional polar solvents. No special frictional coupling between the C153 and the ionic liquid solvents is indicated by these times. But, in contrast to what is observed in most low-viscosity conventional solvents, rotational correlation functions in ionic liquids are nonexponential. Time-resolved Stokes shift measurements are used to characterize solvation dynamics. The solvation response functions in ionic liquids are also nonexponential and can be reasonably represented by stretched-exponential functions of time. The solvation times observed are correlated with the solvent viscosity, and the much slower solvation in ionic liquids compared to dipolar solvents can be attributed to their much larger viscosities. Solvation times of the majority of ionic liquids studied appear to follow a single correlation with solvent viscosity. Only liquids incorporating the largest phosphonium cation appear to follow a distinctly different correlation.     

3-位烯丙基及甲基衍生的β-环糊精固定相的合成及气相色谱性能研究

制备了一种新的β-环糊精衍生物固定相2,6-二-O-戊基-3-O-[(甲基)5(烯丙基)2]-β-CD,并对其气相色谱分离性能进行研究。实验显示,该固定相具有良好的柱表面性能和较强的色谱分离能力,对一些芳香族位置异构体的分离能力优于2,6-二-O-戊基-3-O-烯丙基-β-CD衍生物,对10余种手性物质显示出较好的选择性能,且对α-位取代的丙酸酯类手性分离效果明显优于杂环类β-CD衍生物。与2,6-二-O-戊基-3-O-烯丙基-β-CD固定相的分离性能比较表明,β-CD 3位羟基部分甲基基团的引入能增强对芳香族位置异构体的选择能力,但不能明显改变烯丙基衍生物的手性分离能力。     

Enantiomeric resolution of chiral imidazole derivatives using capillary electrophoresis with cyclodextrin-type buffer modifiers

Enantiomeric resolutions of some chiral pharmaceuticals containing the imidazole (1,3-diazole) moiety were carried out using capillary electrophoresis. Various native cyclodextrins (ga-, β- and γ-cyclodextrin) and derivatized cyclodextrins (hydroxypropyl-, and sulfobutyl ether-β-cyclodextrin) were used as chiral buffer modifiers. The effects of the cavity size, the structure and the charge of the selectors on the chiral recognition ability were evaluated. The influence of the type and concentration of the organic modifier on the separation of miconazole enantiomers and the pH of the run buffer on the separation of enilconazole enantiomers was also studied.     

Preparation and application of rifamycin-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography

Rifamycin-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (RCD-HPS), a new type of substituted β-cyclodextrin-bonded chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been synthesized by the treatment of bromoacetate-substituted-(3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (BACD-HPS) with rifamycin SV in anhydrous acetonitrile. The stationary phase is characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. This new CSP has a chiral selector with two recognition sites: rifamycin and β-cyclodextrin (β-CD). The chromatographic behavior of RCD-HPS was studied with several disubstituted benzenes and some chiral drug compounds under reversed-phase HPLC mobile phase conditions. The results show that RCD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds due to the cooperative functioning of rifamycin and β-CD.     

丙烯酰胺-β-环糊精毛细管电色谱手性整体柱的制备及应用

以丙烯酰胺-β-环糊精和聚甲基丙烯酸缩水甘油酯为功能单体,乙二醇二甲基丙烯酸酯为交联剂,采用原位聚合法制备了聚丙烯酸酯-β-环糊精手性毛细管整体柱。 通过红外和扫描电子显微镜表征了整体柱固定相的结构和形貌。 并以苯丙氨酸为考察物考察了柱子的稳定性和重现性,柱效达到47701 plates/m,获得了良好的分离效果。 在毛细管电色谱模式下,采用丙烯酰胺-β-环糊精整体柱首次拆分盐酸依替福林对映体,结果使盐酸依替福林对映体达到了基线分离。     

Development of Vancomycin-Capped β-CD-Bonded Silica Particles as Chiral Stationary Phase for LC

Vancomycin-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (VCD-HPS), a new type of substituted β-cyclodextrin-bonded chiral stationary phase (CSP) for liquid chromatography (LC), have been synthesized by treatment of bromoacetate-substituted-(3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (BACD-HPS) with vancomycin in anhydrous methanol. The stationary phase is characterized by elemental analysis. This new CSP has a chiral selector with two recognition sites: vancomycin and β-cyclodextrin (β-CD), which can provide multiple interactions with the solutes. The chromatographic performance of VCD-HPS was studied with several disubstituted benzenes and some chiral drug compounds as solutes in reversed-phase LC. The results show that VCD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds.     

Equilibrium studies on reactive extraction of naproxen enantiomers using hydrophilic ��-cyclodetrin derivatives extractants

A simple and low-cost method using liquid?Cliquid extraction coupled with complexation reactive technique has been developed for enantioselective separation of naproxen enantiomers. Three kinds of modified ??-cyclodextrins including methyl-??-cyclodextrin (Me-??-CD), hydroxyethyl-??-cyclodextrin (HE-??-CD) and hydroxypropyl-??-cyclodextrin (HP-??-CD), were selected as hydrophilic chiral selectors for extraction naproxen from organic phase to aqueous phase. A systematic study of the factors affecting chiral separation performance were investigated. The experiment results obtained show that, HP-??-CD, HE-??-CD and Me-??-CD has stronger recognition abilities for S-naproxen than those for R-naproxen. Among the ??-CD derivatives studied, HP-??-CD has the strongest ability for chiral recognition and separation. Excellent enantioselectivity (a) of 1.59 is obtained under the optimal conditions of pH of 2.5 and temperature of 5 °C.     

Preparation and characteristics of hydroxypropyl-β-cyclodextrin polymeric nanocapsules loading nimodipine

Nimodipine loaded hydroxypropyl-β-cyclodextrin polymeric nanocapsules were prepared by interfacial polyaddition of hydroxypropyl-β-cyclodextrin and isophorone diisocyante in a miniemulsion system. The effects of ultrasonicate times on the preparation of miniemulsion, the total amount of hydroxypropyl-β-cyclodextrin and isophorone diisocyante, and the molar ratio of isophorone diisocyante to hydroxypropyl-β-cyclodextrin on the capsule size and drug release behavior from capsule were investigated. The chitosan based polymeric nanocapsules were prepared as a control to study the effect of hydroxypropyl-β-cyclodextrin molecules in capsule matrix on the drug release. The results indicated that the droplet size of miniemulsion and capsule size decreased with increasing sonicate times. When the total amount of hydroxypropyl-β-cyclodextrin and isophorone diisocyante, and the molar ratio of isophorone diisocyante to hydroxypropyl-β-cyclodextrin were increased, the capsule as well, but the drug release rates from capsules became slower. The drug release behaviors from hydroxypropyl-β-cyclodextrin polymeric nanocapsules were affected by the drug diffusion through the polymer matrix and the formation of inclusion complex between drug and hydroxypropyl-β-cyclodextrin.     

Multiple Ether-Functionalized Phosphonium Ionic Liquids as Highly Fluid Electrolytes

Ionic liquids (ILs) are promising electrolytes, although their often high viscosity remains a serious drawback. The latter can be addressed by the introduction of multiple ether functionalization. Based on the highly atom efficient synthesis of tris(2-ethoxyethyl) phosphine, several new phosphonium ionic liquids were prepared, which allows studying the influence of the ether side chains. Their most important physicochemical properties have been determined and will be interpreted using established approaches like ionicity, hole theory, and the Walden plot. There is striking evidence that the properties of phosphonium ionic liquids with the methanesulfonate anion are dominated by aggregation, whereas the two triple ether functionalized ILs with the highest fluidity show almost ideal behavior with other factors being dominant. It is furthermore found that the deviation from ideality is not significantly changed upon introduction of the ether side chains, although a very beneficial impact on the fluidity of ILs is observed. Multiple ether functionalization therefore proves as a powerful tool to overcome the disadvantages of phosphonium ionic liquids with large cations.