分子印迹薄层色谱手性固定相的制备及其色谱性能

分别以右旋扁桃酸、右旋邻氯扁桃酸和右旋对氯扁桃酸为模板,丙烯酰胺、乙二醇二甲基丙烯酸酯为功能单体和交联剂合成分子印迹聚合物,并以此作为薄层色谱手性固定相。研究了模板分子消旋体在手性固定相上的分离情况,并讨论了展开剂中乙酸含量对分离的影响。在乙腈-5%乙酸展开体系中扁桃酸、邻氯扁桃酸和对氯扁桃酸消旋体得到较好的分离,分离因子分别为1.45,1.62和1.56。该手性固定相对模板分子的结构类似物也具有一定的手性交叉分离能力。讨论了分析物的化学结构对该手性固定相识别性能的影响。该方法为快速、灵敏地对手性物质分析、定性提供了一条简便的途径。     

右旋邻氯扁桃酸分子印迹聚合物的制备及结合特性研究

以右旋邻氯扁桃酸为模板分子合成了具有高选择性的分子印迹聚合物作为手性分离材料 .紫外光谱研究说明在聚合开始之前模板分子与功能单体形成了配合物 ,并用Hyperchem软件模拟其分子结构 ,结合能分别为 -1 643 7× 1 0 4 J·mol- 1 和 -4 2 799× 1 0 4 J·mol- 1 .分子印迹聚合物对模板分子的结合量高于其它类似物 ,手性分离因子α达 1 76.Scatchard分析表明分子印迹聚合物在识别右旋邻氯扁桃酸分子过程中存在两类结合位点 ,与配合物模拟结构数目一致     

沉淀聚合法制备右旋邻氯扁桃酸分子印迹聚合物微球

以右旋邻氯扁桃酸为模板,丙烯酰胺、乙二醇二甲基丙烯酸酯分别为功能单体和交联剂,采用沉淀聚合法制备了分子印迹聚合物微球,讨论了反应介质用量、聚合温度、引发剂的种类和用量对印迹微球的影响。实验表明：分子印迹微球与传统本体聚合法制备的聚合物相比具有更高的特异识别能力,通过Scatchard分析研究了聚合物的选择结合性能,结果表明分子印迹聚合物微球在识别右旋邻氯扁桃酸分子的过程中存枉两类结合位点,而空白聚合物微球只存在一类结合位点。     

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。     

光学活性(甲基)丙烯酰胺的立体定向自由基聚合——立体控制机理探讨

利用Lewis酸三氟甲磺酸镱(Yb(OTf)3)调控(S)-N-(2-羟基-1-苯乙基)甲基丙烯酰胺((S)-HPEMA)和(S)-N-(2-羟基-1-苯乙基)丙烯酰胺((S)-HPEA)的自由基聚合,得到相应的光学活性聚合物;研究了反应条件对聚合物立体结构的影响,发现以甲醇和正丁醇为溶剂时,Yb(OTf)3的存在可显著提高聚合物的mm三元组的含量,而以DMSO为溶剂时,Yb(OTf)3对聚合物的立构规整性没有明显改变;通过1H-NMR研究了Yb(OTf)3与单体之间的相互作用,结果表明单体的酰胺基团与Lewis酸的稀土金属离子间的配位以及单体的羟基与Lewis酸的三氟甲磺酸根间的氢键影响了单体的加成方向和聚合物的立体结构.     

咖啡酸分子印迹聚合物的制备及其用于咖啡酸的高效液相色谱分离

以咖啡酸为模板分子,丙烯酰胺为功能单体,在水溶液中合成了咖啡酸分子印迹聚合物,制备了分子印迹聚合物色谱分离柱。试验结果表明:聚合物对印迹分子具有很好的亲和性和特异选择性,以甲醇-水(25+75)混合溶液为流动相,咖啡酸与其相似物绿原酸的分离度达到1.91。     

手性药物(S)-布洛芬氢键自组装印迹聚合物识别机理

以含有单一结合基团的手性药物(S)-布洛芬作为模板分子,制备了系列印迹聚合物.采用紫外-可见光谱和红外光谱对印迹及识别机理进行了研究.结果表明,模板分子与功能单体分别通过形成蓝移氢键和红移氢键完成预组装过程和再识别吸附过程,且形成了主客体配比为1∶1的配合物.等温吸附实验结果表明,印迹聚合物对模板分子表现出明显的选择性吸附,特异性吸附容量为37.92μmol/g,印迹指数为3.06,且印迹聚合物内特定的三维空间结构对其特异性吸附性能具有显著影响.由手性分离实验考察了印迹聚合物的拆分性能,其对(R)-布洛芬的分离因子为1.79.     

聚[(S)-3-乙烯基-2,2'-二羟基-1,1'-联萘]的钛配合物催化三乙基铝对醛的不对称加成反应

通过维蒂希反应合成了(S)-3-乙烯基-2,2'-甲氧甲氧基-1,1'-联萘.将单体(S)-3-乙烯基-2,2'-甲氧甲氧基-1,1'-联萘用偶氮二异丁腈作引发剂进行自由基聚合得到了聚[(S)-3-乙烯基-2,2'-二甲氧基甲氧基-1,1'-联萘].该聚合物上的MOM保护基通过酸脱除获得手性螺旋聚合物聚[(S)-3-乙烯基-2,2'-二羟基-1,1'-联萘].将手性螺旋聚合物聚[(S)-3-乙烯基-2,2'-二羟基-1,1'-联萘]与Ti(O-i-Pr)4形成的配合物应用于三乙基铝与醛的不对称加成反应中,获得了较好的对映选择性,ee值最高为85%.更重要的是,这种聚合物还可以被回收利用多次且催化活性没有明显降低.     

萘普生分子印迹拆分及亲和吸附平衡常数的测定

分子印迹 (Molecular imprinting)是一种新的、很有发展潜力的分离技术 [1～ 3 ] .该技术已成功地用于氨基酸、糖类及其衍生物和药物的手性分离 .萘普生是一种重要的非甾体消炎、解热和镇痛药 ,为了减少给药量和对人体产生的毒副作用 ,必须对其进行手性拆分 . Mosbach等 [4 ] 曾以 4-乙烯基吡啶为功能单体 ,利用分子印迹对外消旋萘普生进行了手性拆分 ,但 4-乙烯基吡啶使用前需经过减压蒸馏 ,使用不便 . Haginaka等 [5～ 7] 也采用 4-乙烯基吡啶为功能单体 ,以 (S) -萘普生为模板制得了均一粒径的分子印迹介质 .尽管分子印迹分离技术发展…     

以分子印迹聚合物为固定相手性拆分1,1′-联-2-萘酚及其衍生物

以(R)-(+)-1,1′-联-2-萘酚为模板分子,4-乙烯基吡啶为功能单体合成了分子印迹聚合物,将其作为高效液相色谱的固定相,研究其手性识别特性。对该固定相的手性拆分的色谱条件进行了优化。实验结果表明,合成的印迹聚合物对(R)-(+)-1,1′-联-2-萘酚具有较强的亲和力和特定的选择性,能有效拆分1,1′-联-2-萘酚对映体,分离因子最高达到12.25。通过优化色谱条件,该分子印迹聚合物还能对与1,1′-联-2-萘酚结构相似的衍生物5,6,7,8,5′,6′,7′,8′-八氢-1,1′-联-2-萘酚和1,1′-联萘-2-氨基-2′-酚进行手性拆分,分离因子分别达到1.51和2.40。     

Uniform-sized molecularly imprinted polymer for (S)-naproxen selectively modified with hydrophilic external layer.

A uniform-sized molecularly imprinted polymer (MIP) for (S)-naproxen selectively modified with hydrophilic external layer has been prepared. First, the molecularly imprinted polymer for (S)-naproxen was prepared using 4-vinylpyridine and ethylene glycol dimethacrylate (EDMA) as a functional monomer and cross-linker, respectively, by a multi-step swelling and thermal polymerization method. Next, a 1:1 mixture of glycerol monomethacrylate (GMMA) and glycerol dimethacrylate (GDMA) was used for hydrophilic surface modification, and it was added directly to the molecularly imprinted polymer for (S)-naproxen 4 h after the start of molecular imprinting. The retention factors of all solutes tested were decreased with the surface modified molecularly imprinted polymer, compared with the unmodified molecularly imprinted polymer. However, chiral recognition of racemic naproxen was attained with the surface modified molecularly imprinted polymer as well as the unmodified molecularly imprinted polymer. Further, bovine serum albumin was completely recovered from the surface modified molecularly imprinted polymer. These results revealed that the chiral recognition sites of (S)-naproxen remained unchanged with hydrophilic surface modification, and that the molecularly imprinted polymer for (S)-naproxen was selectively modified with hydrophilic external layer. Preliminary results reveal that the surface modified molecularly imprinted polymer could be applicable to direct serum injection assays of (S)-naproxen.     

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.     

The application of pseudo template molecularly imprinted polymer to the solid-phase extraction of cyromazine and its metabolic melamine from egg and milk

The combination of molecularly imprinted polymer with high performance liquid chromatography has been developed to determine cyromazine and its metabolic melamine in some samples. However, the potential risk of template leakage used in molecularly imprinted polymer is a major disadvantage. To solve this problem, 2-(4,6-diamino-1,3,5-triazin-2-ylamino) ethanethiol disulfide, a molecule that shares the similar imprinting sites with cyromazine and melamine, was selected as pseudo template to prepare molecularly imprinted polymer. Methacrylic acid, ethylene glycol dimethyl acrylate and toluene were selected as functional monomer, crosslinker and porogen, respectively. The molecular recognition property and binding capability of cyromazine and melamine were evaluated by adsorption test and Scatchard analysis. The results showed that the molecularly imprinted polymer based on pseudo template had more excellent affinity and selectivity for cyromazine and melamine. The resulting molecularly imprinted polymer was used as a solid-phase extraction material to enrich cyromazine and melamine in egg and milk samples for high performance liquid chromatography analysis. The solid-phase extraction process was carefully optimized. It was found that when different concentration of cyromazine and melamine standards were spiked into samples, satisfactory recovery rate of cyromazine and melamine were obtained as 85.6-98.8% with relative standard deviation <5.5%.     

Investigation of enantiomer recognition of molecularly imprinted polymeric monoliths in pressurized capillary electrochromatography screening the amino acids and their derivatives

Molecularly imprinted monolithic columns were prepared for chiral separation of tyrosine and its amino acid derivatives by in situ therm-initiated copolymerization of methacrylic acid, 4-vinylpyridine and ethylene glycol dimethacrylate. The enantiomers were rapidly separated on monolithic columns in less than 10 min by pressurized capillary electrochromatography (pCEC). The influences of several parameters such as the content of cross-linking monomer on the composition of the pre-polymerization mixture were systematically investigated. The influence of the pCEC conditions including the composition of the mobile phase was also optimized to obtain the good enantioseparation. It was found that in addition to molecularly imprinted recognition, chromatographic retention and electrophoretic migration play important roles in the retention and chiral recognition of molecularly imprinted polymer (MIP) columns. The cross-selectivity for similar amino acids and its derivatives were systematical investigated for understanding the recognition mechanism on the MIP monolithic columns. The results indicated that molecularly imprinted polymer recognizes the template molecule by its molecular shape defined binding cavity.     

Fabrication of molecularly imprinted hybrid monoliths via a room temperature ionic liquid-mediated nonhydrolytic sol-gel route for chiral separation of zolmitriptan by capillary electrochromatography

A room temperature ionic liquid (RTIL)-mediated nonhydrolytic sol-gel (NHSG) protocol was explored for the fabrication of new molecularly imprinted silica-based hybrid monoliths for chiral separation of a basic template zolmitriptan by CEC. The RTIL-mediated NHSG protocol involved free-radical copolymerization and NHSG process. Three carboxylic acids (trifluoromethyl acrylic acid, cinnamic acid, and methacrylic acid (MAA)) were examined as both the functional monomers and the catalysts for the NHSG condensation of methacryloxypropyltrimethoxysilane (MPTMS) to form silica-based framework. RTIL was incorporated to reduce gel shrinkage and also to act as the pore template. The effects of carboxylic acids and RTIL on the performance of the silica-based hybrid molecularly imprinted polymer (MIP) monoliths were investigated in detail to realize excellent chiral recognition and to give new insights into the mechanism of the RTIL-mediated NHSG strategy. Excellent chiral separation of (R)/(S)-zolmitriptan was achieved when the molar ratio of MAA to MPTMS was 1:4 and 1:2 with RTIL involved. The synergism of the free-radical copolymerization of the C=C bond of carboxylic acids and MPTMS with the NHSG condensation of MPTMS catalyzed by the carboxylic acids was demonstrated. The incorporation of RTIL increased porosity, and hence improved selectivity of the prepared hybrid monoliths.     

电子束辐射聚合制备槲皮素-镍(Ⅱ)金属配位分子印迹聚合物及其识别性能研究

以电子束为辐照射线源,采用辐射聚合法成功制备了槲皮素-Ni(Ⅱ)金属配位分子印迹聚合物.通过紫外光谱研究了槲皮素与Ni(Ⅱ)之间的配位结构、配位作用方式及配位比,并按照1∶2的比例形成稳定配合物,同时也验证了槲皮素、Ni(Ⅱ)及功能单体甲基丙烯酸三者发生了金属配位印迹作用.利用红外光谱对产物的结构进行了表征.透射电镜、扫描电镜、吸附动力学实验分别考察辐射剂量对聚合物的微观形貌、吸附动力学性能的影响,结果表明辐射剂量对印迹聚合物的吸附性能有显著影响.同时选择性吸附实验结果显示该印迹聚合物对槲皮素-Ni(Ⅱ)配合物表现出明显的吸附选择性和特异性,最大结合量可达82.22μmol/g.对黄芩素和柚皮素的吸附选择性较差,分离因子分别为3.915和5.443.     

槲皮素-铜(Ⅱ)配位分子印迹聚合物的制备及其结合特性研究

以槲皮素-铜(Ⅱ)配合物(Qu-Cu)为模板分子、α-甲基丙烯酸为功能单体在强极性溶剂甲醇中合成了一种新型的配位分子印迹聚合物.紫外-可见光谱研究表明槲皮素与铜(Ⅱ)形成1:2配合物,槲皮素、铜(Ⅱ)和功能单体α-甲基丙烯酸三者发生了络合作用.利用透射电镜及平衡结合实验研究了溶剂用量对配位分子印迹聚合物形貌及其吸附性能...     

表面接枝分子印迹聚合物微球的合成及评价

将聚苯乙烯-二乙烯苯微球表面功能基化, 引入引发转移终止剂(initiator-transfer-terminator agent, iniferter), 以活性自由基聚合方式研究了球形树脂表面合成印迹聚合物的方法. 在紫外光引发下, 以左旋麻黄碱为印迹分子, 甲基丙烯酸为功能单体, 在接枝Iniferter后的微球表面进行分子印迹聚合物接枝实验, 并使用不同的反应条件, 探讨了表面接枝印迹层微球制备条件对于识别能力的影响. 平衡吸附的结果表明, 表面接枝聚苯乙烯-二乙烯苯微球对于印迹分子具有亲和能力及选择性, 其识别能力来自于印迹得到的识别位点.