Enantiomer analysis of chiral carboxylic acids by AIE molecules bearing optically pure aminol groups

Pure enantiomers of carboxylic acids are a class of important biomolecules, chiral drugs, chiral reagents, etc. Analysis of the enantiomers usually needs expensive instrument or complex chiral receptors. However, to develop simple and reliable methods for the enantiomer analysis of acids is difficult. In this paper, chiral recognition of 2,3-dibenzoyltartaric acid and mandelic acid was first carried out by aggregation-induced emission molecules bearing optically pure aminol group, which was easily synthesized. The chiral recognition is not only seen by naked eyes but also measured by fluorophotometer. The difference of fluorescence intensity between the two enantiomers of the acids aroused by the aggregation-induced emission molecules was up to 598. The chiral recognition could be applied to quantitative analysis of enantiomer content of chiral acids. More chiral AIE amines need to be developed for enantiomer analysis of more carboxylic acids.     

新型手性基团修饰的金属卟啉的合成及性质研究

合成了一种手性基团修饰的金属卟啉化合物[5-对(L-亮氨酰氧乙氧基)苯基-10, 15, 20-三苯基卟啉锌]. 通过元素分析、紫外可见光谱、红外光谱、圆二色光谱及核磁共振波谱对该化合物进行了较详细的表征. 同时, 采用分子力学方法搜索了主体的最低能量构象, 从理论上进一步解释实验结果. 利用Z扫描技术测定了该化合物的三阶非线性光学性质.     

Preparation and chiral resolution properties of bridged bis(cyclodextrin)s hybrid spheres for high performance liquid chromatography

Selenium-bridged bis(β-cyclodextrin)s organic–inorganic hybrid silica material with regular spherical shape as new type of chiral stationary phase was directly synthesized under the one-pot hydrothermal synthesis method, and the chiral stationary phase was further characterized by infrared spectroscopy, scanning electron microscopy, thermogravimetry, and elemental analysis. The results of chiral separation showed that eight chiral compounds including various types of chiral alcohols and flavanone were successfully separated in the reversed-phase separation mode by high performance liquid chromatography, which showed the better chiral resolution effect than that on the C2 position of single β-cyclodextrin. The mechanism of chiral separation was likely due to multiple interactions such as inclusion, hydrogen bonding, electrostatic interaction, dipole–dipole interaction, and the synergistic effect of two cyclodextrins during the chiral resolution process. The synergy of the two cyclodextrins has great potential for development in chiral resolution.     

Enantiomeric separation of chiral peptide nucleic acid monomers by capillary electrophoresis with charged cyclodextrins

Direct chiral separation of chiral peptide nucleic acid (PNA) monomers has been achieved for the first time by capillary electrophoresis (CE) with charged cyclodextrins as chiral selectors added to the electrophoretic buffer. Selectively modified 6-deoxy-6-N-histamino-beta-cyclodextrin and sulfobutyl ether-beta-CD were successfully used as chiral selectors for the enantiomeric separation of chiral monomers based on different aminoethylamino acids bearing thymine or adenine as nucleobases. Chiral separations were obtained at low selector concentrations (1-3 mM) with good enantioselectivity and resolution factors. Separations were optimized as a function of pH in order to exploit the effect of the electrostatic interactions between the oppositely charged selector and selectand. The method has been applied to the analysis of the enantiomeric excess of chiral monomers used for the solid phase synthesis of chiral PNA oligomers. CE chiral analysis showed that a very high enantiomeric purity was generally achieved in the synthesis of all monomers, except for histidine and aspartic acid based monomers in which ca. 10% of the "wrong" enantiomer was always present.     

Multicomponent analyses of chiral samples by use of regression analysis of UV–visible spectra of cyclodextrin guest–host complexes

We report the first combined use of analytical spectroscopy, guest–host chemistry, and multivariate regression analysis for determination of enantiometric composition of multicomponent samples of chiral analytes. Sample solutions containing multicomponent analytes of ephedrine, tryptophan, propranolol, and proline of varying enantiomeric composition with beta-cyclodextrin (BCD) or methyl-beta-cyclodextrin (Me-BCD) as chiral host molecules were investigated using ultraviolet (UV)–visible spectroscopy. The interactions of enantiomers of chiral analytes with chiral hosts resulted in the formation of transient diastereomeric inclusion complexes with varying spectral properties. Multivariate analysis using partial-least-square (PLS) regression was used to correlate subtle changes in the UV–visible spectra of the guest–host complexes with the enantiomeric composition of the calibration samples. These PLS regressions were carefully optimized and then used to predict the enantiomeric composition of multicomponent chiral analytes of validation samples. The results of these validation studies demonstrate the predictive ability of the regression models for determination of future enantiomeric composition of samples. The accuracy of the models to correctly predict the enantiomeric composition of samples, evaluated by use of the root mean square percent relative error (RMS%RE) was analyte and chiral host dependent. In general, better prediction of enantiomeric composition of samples and low RMS%RE values were obtained when Me-BCD was used as the chiral host. The analyses procedure reported here is simple, rapid, and inexpensive. In addition, this approach does not require prior separation of chiral analytes, thus reducing analysis time and eliminating the need for expensive chiral columns.     

Synthesis and helical twisting property of polymerizable chiral dopant with temperature-dependent solubility in liquid crystal

In this study,right-handed dicinnamate isosorbide was synthesized via the esterification reaction between optically active isosorbide and cinnamate.The chiral dopant was characterized by FT-IR,~1H NMR,elemental analysis,SEM,UV absorption spectrum.After dissolving in a nematic liquid crystal mixture,the chiral dopant exhibited a temperature-dependent solubility in the chiral nematic liquid crystal mixture.Meanwhile,a relatively high value of helical twisting power of the polymerizable chiral dopant was de...     

Simultaneous, sequential quantitative achiral-chiral analysis by two-dimensional liquid chromatography

In general, chromatographic analysis of chiral compounds involves a minimum of two methods; a primary achiral method for assay and impurity analysis and a secondary chiral method for assessing chiral purity. Achiral method resolves main enantiomeric pairs of component from potential impurities and degradation products and chiral method resolves enantiomeric pairs of the main component and diastereomer pairs. Reversed-phase chromatographic methods are preferred for assay and impurity analysis (high efficiency and selectivity) whereas chiral separation is performed by reverse phase, normal phase, or polar organic mode. In this work, we have demonstrated the use of heart-cutting (LC-LC) and comprehensive two-dimensional liquid chromatography (LC × LC) in simultaneous, sequential achiral and chiral analysis and quantitation of minor, undesired enantiomer in the presence of major, desired enantiomer using phenylalanine as an example. The results were comparable between LC-LC and LC × LC with former offering better sensitivity and accuracy. The quantitation range was over three orders of magnitude with undesired D-phenylalanine detected at approximately 0.3% in the presence of predominant, desired L-phenylalanine (99.7%). The limit of quantitation was comparable to conventional high-performance liquid chromatography. A reversed-phase C18 achiral column in the primary and reversed-phase Chirobiotic Tag chiral column in the secondary dimension were used with a compatible mobile phase.     

手性有序无机介孔硅用作气相色谱固定相

手性介孔材料在手性分离、不对称催化、手性传感等领域具有广泛的应用价值。手性有序无机介孔硅是一类介孔结构高度有序、不含有机成分的手性材料。该文采用D-苯丙氨酸为手性源合成手性有序无机介孔硅(COIMS),将其用聚硅氧烷(OV-1701)稀释后用作固定相制备毛细管气相色谱手性柱,并对该手性柱的分离性能进行了考察,8种手性化合物在该手性柱上得到了拆分。COIMS柱对直链烷烃、醇的分离也表现出良好的选择性。该柱还具有分析时间短、在较高温度下测定稳定等优点,其具有开发成高温手性固定相的潜力。     

Chiral separation of polychlorinated biphenyls using a combination of hydroxypropyl-gamma-cyclodextrin and a polymeric chiral surfactant

Chiral separation of moderately to highly hydrophobic polychlorinated biphenyls (PCBs) using a conventional chiral micelle or a polymeric chiral surfactant, as the single chiral selector is very difficult since the hydrophobic interactions between the chiral PCB and the monomeric or polymeric surfactant is very strong. Combined use of a polymeric chiral surfactant, polysodium N-undecanoyl-D-valinate (poly-D-SUV) with hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) was successful in cyclodextrin modified electrokinetic chromatography (CD-EKC) enantioseparation of PCB congeners. Addition of HP-gamma-CD to the background electrolyte containing poly-D-SUV functioned to improved chiral resolution for the PCBs and reduce the analysis time for these congeners. In addition, concentration of methanol, concentration of 2-(N-cyclohexylamino) ethanesulfonic acid (CHES) buffer and separation voltage was also varied to optimize multicomponent separation of five chiral PCBs. Simultaneous separation and enantioseparation of all five PCBs was possible in less than 50 min under optimized conditions that requires a 5 mM CHES solution buffered at about pH 10 with 1.5% w/v (ca. 60 mM) poly-D-SUV and 16 mM HP-gamma-CD. In addition, 1 M urea and 20% v/v methanol should be added as organic modifier and the capillary temperature maintained at 45 degrees C. As expected the polymeric surfactant showed improved chiral resolution of PCBs over conventional micelles of SUV. Under optimized conditions, when CD-EKC of chiral PCBs using poly-D-SUV was compared to sodium dodecyl sulfate (SDS), better resolution, higher efficiency and shorter analysis time was achieved with poly-D-SUV.     

Chiral discrimination on the host-guest-complexation of resorc[4]arenes with quarternary amines

The interaction of inherently chiral resorc[4]arenes with different chiral ammonium ions was measured by ESI-MS. For that purpose one enantiomer of the ammonium guests was labeled with deuterium to distinguish the enantiomers by their mass. We synthesized the ammonium salts by reaction of chiral primary amines with either CH3I or CD3I and analyzed the resulting ammonium iodides by NMR and optical rotation. The complexation experiments were performed by mixing the chiral host with various ratios of the unlabeled guest and its labeled enantiomer. By analysis of the integrals of the host-guest complexes we observed a chiral discrimination effect and a secondary isotope effect as well.     

A convenient method for the determination of the absolute configuration of chiral amines

A highly useful methodology that allows the determination of the absolute configuration of aliphatic and aromatic chiral amines based on the rationalization of stereoselective three-point interactions during chromatography on a rationally designed chiral stationary phase and conformational analysis of the elutes was developed. This approach is based on the broadly accepted chiral recognition mechanism of the Whelk-O 1 CSP and requires a facile derivatization of the amine and the determination of the lowest energy conformation of the corresponding t-Boc- or Z-derived carbamates. The absolute configuration determined by employing chiral structure activity relationships in HPLC analysis was verified by single-crystal X-ray analysis or studies with carbamoyl derivatives of amines of known configuration. The general validity and applicability of this methodology was demonstrated by analysis of seven carbamates derived from aliphatic and aromatic amines. Due to its simplicity and time-efficiency, i.e., ease of derivatization of amines and fast HPLC method development, this approach can be considered a useful supplement to established techniques such as NMR spectroscopy.     

Nonenzymatic enantioselective monoacetylation of prochiral 2-protectedamino-2-alkyl-1,3-propanediols utilizing a chiral sulfonamide-Zn complex catalyst

[structure: see text] Treatment of a chiral sulfonamide with Et(2)Zn gave quantitatively its Zn complex and then the structure was determined by X-ray crystallographic analysis. Reaction of prochiral N-Boc-2-amino-2-alkyl-1,3-propanediols with Ac(2)O in the presence of 5 mol % of chiral sulfonamide-Zn complex catalyst afforded the corresponding chiral monoacetyl products in 70-92% yields with 70-88% ee values. The proposed mechanism for the catalytic monoacetylation of a prochiral 1,3-propanediol was presented on the basis of CSI-MS analysis.     

手性有机酸保留指数的手性指数及原子类型电拓扑指数模型

基于手性碳原子的取代基次序规则,提出分子手性指数(wj),结合原子类型电拓扑指数(En)研究18种手性羟基酸和氨基酸的薄层色谱保留指数(RM)的定量关系(QSRR).经最佳变量子集回归建立最佳四元数学模型,传统的相关系数(R2)为0.969,留一法(LOO)的交互验证系数(Q2)为0.943,结果证明具有良好的稳健性及预测能力.根据进入该模型的4个结构参数(wj,E13,E16,E17)可知,影响手性有机酸保留指数的主要因素是分子的二维结构特征(如襒O,—OH,—NH2)和分子的手性特征.综上所述,新建wj及En对手性有机酸的保留指数表征具有合理性与有效性,为预测手性有机酸的保留指数提供一种有效方法.     

Chiral covalent organic framework incorporated organic polymer monolithic capillary column for enantioseparations

A chiral covalent organic framework was synthesized, characterized, and incorporated into organic polymer monolithic capillary columns to provide chiral stationary phases for enantioseparations. The prepared monolithic capillary columns were characterized by scanning electron microscopy and elemental analysis. To obtain better enantioseparations, the columns’ preparation conditions, and enantioseparation conditions were optimized. Baseline resolutions of several chiral compounds were obtained with good reproducibility and stability. Furthermore, the mechanism of chiral recognition was investigated using molecular docking with AutoDock. Docking results showed that the enantioselectivity factor rather than resolution is correlated with the binding free energy difference between enantiomers with the chiral covalent organic framework. And abundant acetoxy and nitrile groups as well as benzene rings in the chiral covalent organic framework are responsible for the enantioseparation ability of the chiral monolithic capillary columns.     

Scalemic and racemic imprinting with a chiral crosslinker

The development of molecularly imprinted chiral stationary phases has traditionally been limited by the need for a chiral pure template. Paradoxically, availability of a chiral pure template largely defeats the purpose of developing a chiral stationary phase. To solve this paradox, imprinting of scalemic and racemic template mixtures was investigated using both chiral (N-α-bismethacryloyl-l-alanine) and achiral (N,O-bisacrylamide ethanolamine) crosslinkers. Imprinting of scalemic mixtures provided polymers capable of partial separation of Boc-tyrosine enantiomers with virtually the same results when using either the chiral or achiral crosslinker. However, the chiral crosslinker was required for chiral differentiation by the racemic imprinted polymers which were evaluated in both batch rebinding and chromatographic modes. Batch rebinding analysis revealed intersecting binding isotherms for the L- and D-Boc-tyrosine, indicating bias for the D or L enantiomer is concentration dependent. Partial chromatographic separation was achieved by the racemic imprinted polymers providing variable D or L bias in equal probability over multiple replicates of polymer synthesis. Correlation of enantiomer bias with the batch rebinding results and optimization of HPLC parameters are discussed.     

两种叶菜中5种典型手性农药对映体的超高效液相色谱-串联质谱(UPLC-MS/MS)分析方法研究

基于手性固定相/超高效液相色谱-串联质谱技术建立了同时拆分2种叶菜类蔬菜(菜心、油麦菜)中5种典型手性农药(多效唑、腈菌唑、甲霜灵、三唑酮和唑菌酮)对映体的分析方法。样品用乙腈提取,N-丙基乙二胺(PSA)粉和石墨化碳黑(GCB)粉净化,经手性色谱柱CHIRALCEL OD-RH拆分后,超高效液相色谱-串联质谱(UPLC-MS/MS)检测。结果表明,5种手性农药在0.005~1.0 mg·L-1范围内均呈良好线性关系;在0.01、0.1、0.5 mg·kg-1加标水平下的平均回收率为68.8%~104%,相对标准偏差(n=6)为1.0%~13.7%。该方法准确、简单、可靠,可以满足叶菜类蔬菜中多种手性农药残留的检测要求,并为这5种手性农药对映体在蔬菜中的残留及消解规律研究提供技术支持。     

Chiral structures of 6,12-dibromochrysene on Au(111) and Cu(111) surfaces

Nanoscale low-dimensional chiral architectures are increasingly receiving scientific interest, because of their potential applications in many fields such as chiral recognition, separation and transformation. Using 6,12-dibromochrysene (DBCh), we successfully constructed and characterized the large-area two-dimensional chiral networks on Au(111) and one-dimensional metal-liganded chiral chains on Cu(111) respectively. The reasons and processes of chiral transformation of chiral networks on Au(111) were analyzed. We used scanning tunneling spectroscopy (STS) to analyze the electronic state information of this chiral structure. This work combines scanning tunneling microscopy (STM) with non-contact atomic force microscopy (nc-AFM) techniques to achieve ultra-high-resolution characterization of chiral structures on low-dimensional surfaces, which may be applied to the bond analysis of functional nanofilms. Density functional theory (DFT) was used to simulate the adsorption behavior of the molecular and energy analysis in order to verify the experimental results.     

Efficient 1H NMR chiral discrimination of sulfoxides caused by the dynamic nature of (R,R)-3′,3″-biBINOL

A chiral BINOL dimer, (R,R)-3′,3″-BiBINOL, which possesses both rigid (atropos) and dynamic (tropos) axial chiralities, was found to work as an effective NMR chiral solvating reagent for the determination of the enantiomeric purities of various chiral sulfoxides. The unique chiral discrimination mechanism was also revealed by using DFT calculations and X-ray crystallographic analysis.     

环境中手性污染物对映体分析方法的研究进展

手性污染物对映体尽管具有相似的物理化学性质,但在环境中的吸附、转移、降解等过程往往存在一定差异。生态安全问题与人类健康密切相关,因此,对手性环境污染物进行对映体水平上的分离分析是十分重要的研究课题。目前,国内外对环境中的手性污染物已开展了相关研究,然而全面评述相关分析测定方法的新进展鲜有报道。本文主要对环境中手性污染物的种类以及近5年环境中手性污染物的分析检测技术如液相色谱-质谱联用法、气相色谱-质谱联用法、毛细管电泳法、超临界流体色谱-质谱联用法等进行了归纳、综述和展望,为后续手性污染物的分析检测提供依据和参考。     

带有酰胺侧基的中空手性高分子微球的合成及其分离性能

合成了带有手性基团的多孔高分子微球, 并将其作为高效液相色谱手性固定相用于分离制备盐酸贝那普利的一个重要中间体(R)-α-羟基苯丁酸乙酯.