石英晶体微天平L-半胱氨酸修饰电极手性识别扁桃酸的研究

扁桃酸(MA)是一种重要的手性药物中间体,非对映体盐结晶分离法是目前工业上获得手性扁桃酸的主要方法,该方法的关键在于选择高性能的拆分试剂~([1]).然而迄今为止,拆分试剂的选择仍然主要是凭经验和试错法来获得.本实验提出了一种基于石英晶体微天平(QCM)检测的手性识别扁桃酸的新方法,考察了L-半胱氨酸(L-Cys)对手性扁桃酸的选择性识别能力.     

二(2-乙基己基)磷酸与酒石酸衍生物复合萃取拆分扁桃酸外消旋体

本文研究了扁桃酸对映体在含二(2-乙基己基)磷酸(D2EHPA)与酒石酸衍生物复合手性选择剂的正辛醇-水两相体系中的萃取分配行为,考察了酒石酸衍生物的种类和初始浓度、D2EHPA的初始浓度、扁桃酸的初始浓度、萃取温度对分配系数和分离因子的影响.结果显示,复合手性选择剂能提高分配系数和分离因子,D2EHPA与D-酒石酸衍生物的复合手性选择剂与L-扁桃酸对映体比与D-扁桃酸对映体形成更稳定的非对映体复合物;且D2EHPA与二对甲基苯甲酰酒石酸(DTTA)的复合手性选择剂的手性选择性大于D2EHPA与二苯甲酰酒石酸(DBTA)的复合手性选择剂;同时,扁桃酸的初始浓度、萃取温度对分配系数和分离因子的影响较大.     

Chiralpak AD-H和Chiralcel OJ-H手性固定相拆分扁桃酸系列化合物

对比了商品化的淀粉型手性固定相Chiralcel OJ-H和纤维素型手性固定相Chiralpak AD-H柱在正相条件下对扁桃酸系列8个化合物的拆分,结果表明Chiralcel OJ-H柱对扁桃酸系列化合物具有更强的手性识别能力,8个外消旋扁桃酸化合物在36 min内都得到了基线分离。研究发现,扁桃酸苯环上的取代基对其拆分的难易程度影响很大,其电子诱导效应影响扁桃酸类化合物在固定相上的保留时间,其空间位阻效应是扁桃酸在固定相上被拆分成败的决定因素。通过对比分析扁桃酸和手性柱的结构,探讨了可能的手性拆分机理是基于Chiralpak AD-H(Chiralcel OJ-H)手性固定相和扁桃酸系列化合物之间的氢键-氢键、偶极-偶极、π-π电子相互作用以及空间适应性等诸多因素的综合影响,其中空间适应性起到至关重要的作用。本研究可为一些实际光学活性扁桃酸及其类似物的对映体纯度测定与拆分研究提供参考。     

手性配体立体选择性萃取拆分对映体动力学研究

建立了一些手性配体立体选择性萃取拆分对映体的动力学方程,并以过渡金属Cu2 与手性配体Nn十二烷基L羟基脯氨酸所形成的二元配合物配位萃取拆分扁桃酸对映体的实验对动力学方程进行了验证,在本实验条件下计算得到D扁桃酸和L扁桃酸总的传质系数分别为:kovD=8.33×10-5ms,kovL=7.75×10-5ms。实验结果表明有关动力学参数对萃取拆分过程可以进行预测和有效控制。     

双水相手性萃取拆分扁桃酸外消旋体

研究了扁桃酸(MA)对映体在含β-环糊精(β-CD)手性选择剂的聚乙二醇(PEG)/(NH_4)_2SO_4双水相体系中的萃取分配行为.考察了pH、PEG和(NH_4)_2SO_4的质量分数、β-CD的浓度、MA的浓度与萃取温度等因素对拆分效果的影响.实验结果表明:双水相手性萃取具有很强的手性分离能力,β-CD对L-MA对映体的识别能力大于对D-MA对映体的识别能力;当温度为30℃、pH=1.0、PEG2000质量分数为30%、(NH_4)_2SO_4质量分数为20%、β-CD的浓度为0.008 mol/L、扁桃酸的浓度为0.05 mol/L时,分离因子(α)达到2.46,上、下相对映体过剩值(e.e.%)分别为42.13%和40.43%.     

手性离子液体配体交换色谱拆分扁桃酸对映体的研究

本文基于配体交换的机理,研究了以脯氨酸手性离子液体作为手性配体拆分扁桃酸(MA)对映体的方法及热力学过程。详细考察了手性离子液体的烷基链长、铜离子的浓度、离子液体的浓度和pH等因素对MA对映体分离的影响。研究发现,不同烷基链长的手性离子液体中,以1-丁基-3-甲基咪唑L-脯氨酸为配体时,MA对映体的拆分效果最好;随着铜离子浓度的增加,MA对映体的保留时间和分离度先增大再减小;而随着1-丁基-3-甲基咪唑L-脯氨酸离子液体的浓度和流动相pH的增大,保留时间和分离度均增大。本文还测定了拆分过程中的一些热力学参数,结果表明,MA对映体的拆分过程是一个焓控的过程,L-MA较D-MA与固定相有更强的相互作用,保留时间更长。     

手性配体高效液相色谱法拆分扁桃酸对映体的热力学性质

手性配体;扁桃酸;对映体拆分;热力学性质     

扁桃酸甲酯对映体的毛细管电泳手性拆分

采用β-环糊精及其衍生物作为手性选择剂，对扁桃酸甲酯对映体进行毛细管电泳分离，考察了不同环糊精种类和浓度、背景电解质类型及pH对分离效果的影响；实验结果表明，pH6．0、50g／L磺酸化环糊精(Su-β-CD)、20mmol/L Tris的磷酸缓冲液，可以使扁桃酸甲酯对映体得到基线分离。     

双相(O/W)识别手性萃取分离α-环己基扁桃酸对映体

提出一种新的手性分离技术双相(O/W)识别手性萃取. 研究了α-环己基扁桃酸对映体在D(L)-酒石酸异丁酯1,2-二氯乙烷有机相和β-环糊精衍生物水相萃取体系中的分配行为; 考察了β-环糊精衍生物种类和浓度、酒石酸酯构型和浓度、水相pH 值等因素对萃取性能的影响. 实验结果表明, 双相(O/W)识别手性萃取具有很强的手性分离能力, 羟丙基β-环糊精、羟乙基β-环糊精、甲基β-环糊精均对S-α-环己基扁桃酸对映体的识别能力大于对R-α-环己基扁桃酸对映体的识别能力, 其中以羟丙基β-环糊精的识别能力最强; 而D-酒石酸异丁酯的识别能力刚好相反; 在羟丙基β-环糊精和D-酒石酸异丁酯萃取体系中, α-环己基扁桃酸外消旋体一次萃取分离后, 水相中S-对映体e.e.%达到27.6%, R-和S-对映体的分配系数(k_R和k_S)分别为2.44和0.98, 分离因子(α)达2.49; 同时pH值和萃取剂浓度对手性分离能力有显著影响. 双相(O/W)识别手性萃取对外消旋体化合物的制备性分离有着十分重要的意义.     

高效液相色谱手性流动相添加剂法分离扁桃酸和邻氯扁桃酸对映体

扁桃酸和邻氯扁桃酸是医药生产中的重要中间体。以氨基酸和金属离子作为手性流动相添加剂的配体交换色谱已被广泛应用于手性物质分离，但用于拆分扁桃酸较难，因其紫外吸收波长短，而使用最常用的Cu^2 作为配合离子时有很强的紫外吸收。本实验采用Zn^2 作配合离子，避开了检测方面的难题，直接拆分了扁桃酸和邻氯扁桃酸对映体。     

Chiral discrimination of limonene by use of beta-cyclodextrin-coated quartz-crystal-microbalances (QCMs) and data evaluation by artificial neuronal networks

The enantiomeric composition of the chiral flavoring agent limonene was analyzed by means of a quartz-crystal microbalance (QCM) sensor. As chiral selectors three different modified beta-cyclodextrins were investigated. The selector molecules were applied as mixtures in different polysiloxane matrices. The chiral separation factors alpha for limonene obtained at 30 degrees C by gas chromatography and by use of the QCM sensor were comparable. Evaluation of sensor data was performed by use of an artificial neuronal network (ANN); this enabled prediction of the enantiomeric composition of the gas mixtures.     

石英晶体微天平在手性识别中的应用

石英晶体微天平(QCM)是一类重要的质量型检测器,因具有灵敏度高、分析速度快、检测成本低等优点而具有极好的应用前景,现已广泛应用于环境监测、药物分析、食品质量控制等诸多领域。手性工程的崛起对简单、快速、在线的手性检测技术提出了挑战,QCM手性传感器就是其中一个重要的发展分支。该文简要介绍了QCM的典型实验装置和基本传感原理,详细综述了近年来QCM在手性识别领域的研究进展,包括以环糊精衍生物、分子印迹聚合物、氨基酸衍生物等为手性主体的QCM在手性识别中的应用,并对其今后的发展进行了展望。     

对巯基苯硼酸修饰石英晶体微天平传感器用于测定唾液酸

硼酸与二醇的脱水缩合反应已被广泛用于检测或富集顺式邻位多羟基化合物. 本文以对巯基苯硼酸(MPBA)自组装修饰石英晶体微天平(QCM)芯片, 基于硼酸根对唾液酸的特殊反应, 建立了检测唾液酸(SA)的新方法. 采用扫描电子显微镜表征了对巯基苯硼酸对石英晶体微天平的功能化修饰过程, 并研究了溶液pH值对芯片表面亲和力的影响. 实验结果表明, 随着pH值的降低, 修饰芯片对唾液酸的结合能力增强, 而对参照物葡萄糖的结合能力则降低. 在pH=4.0的条件下, 该传感器在0.50~5.0 mmol/L范围内对唾液酸有很好的线性响应, 相关系数为0.9950, 检出限为0.15 mmol/L. 此传感器提供了一种简易的唾液酸检测方法, 为实际样品的测定奠定了基础.     

Functional amino acid ionic liquids as solvent and selector in chiral extraction

Amino acid ionic liquids (AAILs) have received great attention due to their potentials in catalysis and separations. In this work, functional AAILs were used as solvent and selector in chiral liquid–liquid extraction for the first time. The AAILs have shown distinct enantioselectivity in amino acid extraction. Using these functional AAILs as acceptor phase and ethylacetate as donor phase, more L-enantiomer of amino acid was extracted into the ionic liquid phase than that of D-enantiomer. The influencing factors, including AAILs structure, copper ion concentration, organic phase and amino acid concentration, were investigated. We found that the enantioselective enrichment of racemic amino acids was achieved through a chiral ligand-exchange mechanism. The enantioselectivity of single-step extraction was up to enantiomeric excess value of 50.6%. Moreover, the functional AAILs were found to be efficient extraction solvents for amino acids. The logarithm of distribution coefficient for L-Phe was in the range of 3.4–3.6 in the ionic liquid–ethylacetate two-phase system. This liquid–liquid extraction approach may extend the application of ionic liquids in chiral separations.     

On the use of dispersed nanoparticles modified with single layer beta-cyclodextrin as chiral selecor to enhance enantioseparation of clenbuterol with capillary electrophoresis

A new strategy for chiral separation by capillary electrophoresis employing modified-nanoparticles as chiral selector is described for clenbuterol analysis. Nanoparticles modified with β-cyclodextrin (β-CD) form a large surface area platform to serve as a pseudostationary chiral phase, which can be applied for the enhancement of the enantioseparation. The application of four kinds of nanoparticles was investigated (multi-walled nanotubes (MWNTs), polystyrene (PS), TiO₂ and Al₂O₃) modified with single layer β-CD as chiral selector in the enantioseparation of clenbuterol by capillary electrophoresis (CE). Successful clenbuterol enantioseparation could be achieved with the β-CD-modified MWNTs as chiral selector. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) confirmed the β-CD modification of the nanoparticles. The effects of nanoparticles, surfactant, chiral selector (β-CD) and run buffer were studied in relation to the enantiomeric separation of clenbuterol. This study opens attractive perspectives for the use of modified nanoparticles for chiral separational purposes in CE.     

手性选择体的固定量对固定相手性分离的影响

为研究手性选择体的固定量对固定相对映体分离能力的影响,将L-(-)-二苯甲酰酒石酸与苯甲醇反应,制备出单苄酯,再将此单苄酯的另一羧基转化为酰氯,得到手性选择体,将此选择体固定在氨丙基硅胶上,制备出选择体固定量较高的固定相,比较了此固定相与前期工作中选择体相同但选择体固定量较低的固定相在手性分离能力方面的差异,此外讨论了...     

Evaluation of balhimycin as a chiral selector for enantioresolution by capillary electrophoresis

The glycopeptide antibiotic balhimycin and its haloanalogue bromobalhimycin were evaluated as chiral selectors for enantioresolution by capillary electrophoresis. In order (i) to eliminate the adsorption of the glycopeptide antibiotics on the capillary wall, (ii) to shorten the separation time and (iii) to improve the detection sensitivity, a combined approach of the dynamic surface coating technique, the co-electroosmotic flow electrophoresis technique and the partial filling technique was employed for the enantioresolution of 16 acidic racemates. The effect of experimental parameters (plug length of the partial filling solution containing the chiral selector, selector concentration and buffer pH) on enantiorecognition was investigated. Furthermore, the enantiorecognition ability imparted by balhimycin, bromobalhimycin and vancomycin were compared. For most tested compounds, the highest enantiorecognition was obtained with balhimycin as chiral selector. Only in the case of the enantioresolution of tiaprofenic acid, vancomycin showed a superior enantiorecognition.     

Durable chiral sensor based on quartz crystal microbalance using self-assembled monolayer of permethylated β-cyclodextrin

A novel chiral sensor based on quartz crystal microbalance (QCM) with a self-assembled monolayer of permethylated β-cyclodextrin as the enantioselective coating has been derived which exhibit improved enantioselectivity and excellent long-term environmental stability when used in gas phase sensing.     

A novel quartz crystal microbalance gas sensor based on porous film coatings. A high sensitivity porous poly(methylmethacrylate) water vapor sensor

We describe a novel and generally applicable approach for creating voids in films deposited on the surface of solid substrates. Such films are advantageous when a quartz crystal microbalance (QCM) is the basis of a sensor. We show that films with large void volumes produce more sensitive sensors than with the original film. Poly(methylmethacrylate) (PMMA) was used as the polymer layer deposited on a quartz crystal microbalance (QCM) to demonstrate our technique for the model system of water vapor analysis in flowing nitrogen gas. A film of pure PMMA on a QCM is a sensor for water vapor in a gas phase. A more sensitive sensor was created by dip coating QCM crystals into solutions containing mixtures of PMMA and poly(d,l-lactide) (PDLL) and then evaporating the solution films on the QCM crystals to form mixed polymer films of varying PDLL content. The PDLL was then removed from the mixed polymer films by exposure to a NaOH solution to form pure PMMA films having various void volumes. A leached PMMA film that originally contained 50% by weight PDLL had a 3.7 times larger QCM sensitivity for water vapor than a pure PMMA film.     

Enantioselective Discrimination of Alcohols by Hydrogen Bonding: A SERS Study

Efficient and generic enantioselective discrimination of various chiral alcohols is achieved by using surface‐enhanced Raman scattering (SERS) spectroscopy through charge–transfer (CT) contributions. The relative intensities of the peaks in the SERS spectra of a chiral selector are strongly dependent on the chirality of its surroundings. This highly distinct spectral discrepancy may be due to the tendency of chiral isomers to form intermolecular hydrogen‐bonding complexes with the chiral selector in different molecular orientations, resulting in different CT states and SERS intensities of the adsorbates in the system. This study opens a new avenue leading to the development of novel enantiosensing strategies. A particular advantage of this approach is that it is label‐free and does not employ any chiral reagents, including chiral light.