用于分子识别的分子印迹聚合物固定相

着重介绍了分子印迹聚合物（MIP）作为一种分离介质在手性化合物拆分方面的应用,系统总结了分子印迹的原理和MIP的4种合成方法,初步探讨了MIP的分子识别机理,并阐述了它的应用以及优点和缺点。     

介孔二氧化硅对映选择性吸附的手性印迹调控

使用手性阴离子表面活性剂作为超分子模板, 采用共结构导向法制备手性介孔二氧化硅(CMS), 并运用圆二色谱(CD)对CMS对映选择性吸附结果进行检测, 比较了有无共结构导向剂(CSDA)在介孔表面的排列对吸附选择性的影响. 结果表明, 当使用构型相反的手性超分子模板剂对原合成CMS材料的介孔内表面进行修饰时, 可诱导结构共导向剂N?三甲氧基硅基丙基?N, N, N?三甲基氯化铵(TMAPS)发生手性相反的排列进而导致完全相反的对映选择性吸附. 实验证明此方法合成的CMS的对映选择性吸附及分离能力主要是由修饰在介孔表面的TMAPS螺旋排列形成的手性印迹所导致. 此手性超分子模板诱导TMAPS手性印迹的策略具有一定的普适性, 可对原合成介孔材料对映选择性吸附进行原位调控, 对于拓展其在立体选择性识别、 不对称催化及药物输送等方面的应用具有一定的指导意义.     

A molecularly imprinted monolith for the fast chiral separation of antiparasitic drugs by pressurized CEC

Molecularly imprinted polymer (MIP) monoliths with (S)‐ornidazole ((S)‐ONZ) as the template molecule have been designed and prepared by the simple thermal polymerization of methacrylic acid, 4‐vinylpyridine, and ethylene dimethacrylate in the presence of a binary porogenic mixture of toluene and dodecanol. The influences of polymerization mixture composition on the chiral recognition of ONZ have been evaluated, and the imprint effect in the optimized MIP monolith has been clearly demonstrated. The new monolithic stationary phase with optimized porous property and good selectivity was used for the chiral separation of ONZ by pressurized CEC. The pressurized CEC conditions were also optimized to obtain the good chiral separation. The enantiomers were rapidly separated within 9 min on the MIP‐based chiral stationary phase, whereas the chiral separation was not obtained on the nonimprinted polymer. Additionally, the proposed method has been successfully applied to the chiral separation of ONZ in tablet samples by injection of the crude sample. The cross‐selectivity for similar antiparasitic drug was investigated. The results indicated that the chiral separation of secnidazole could also be obtained on the optimized MIP monolith within 14 min.     

Facile enantioseparation and recognition of mandelic acid and its derivatives in self‐assembly interaction with chiral ionic liquids

Mandelic acid and its derivatives are important medical intermediates in the pharmaceutical industry. Different stereoisomers exhibited distinct biological properties to human bodies. Given that, enantioselective recognition and separation of mandelic acid are of great importance. In this study, four novel different types of chiral ionic liquids bearing designed functional groups were synthesized and successful enantioselective precipitation with mandelic acid and its derivatives. That is, (R, R)‐chiral ionic liquid 1 can coprecipitated with S‐mandelic acid and its derivatives was observed. In addition, good correlation coefficient is achieved by using electrospray mass spectrum at negative ion pattern for quick analysis of the enantioselective precipitation, which could be served as a method of enantioselective recognition. The possible intermolecular interactions are established after systematical studies by NMR spectroscopy and DFT calculations.     

Synthesis and Applications of Functionalized Magnetic Nanomaterials in Enantioseparation

Efficient enantioselective separation is a challenging task due to the identical physical and chemical properties of enantiomers. Functionalized magnetic nanomaterials modified with chiral ligands on their surface possess both magnetic property and chiral recognition ability, and have demonstrated great potential in chiral discrimination. This review summarizes the applications of magnetic nanomaterials modified with various chiral selectors (e.g., β-cyclodextrins, polymers, proteins, amino acids and cellulose) in enantioselective separation. After proper preparation and modification, these functionalized magnetic nanomaterials are effective for enantioseparation. Therefore, enantioseparations based on functionalized magnetic nanomaterials are convenient, economical and effective.     

Encoding Chiral Molecular Information in Metal Structures

The concept of encoding molecular information in bulk metals has been proposed over the past decade. The structure of various types of molecules, including enantiomers, can be imprinted in achiral substrates. Typically, to encode metals with chiral information, several approaches, based on chemical and electrochemical concepts, can be used. In this Minireview, recent achievements with respect to the development of such materials are discussed, including the entrapment of chiral biomolecules in metals, the chiral imprinting of metals, as well as the combination of imprinting with nanostructuring. The features and potential applications of these designer materials, such as chirooptical properties, enantioselective adsorption and separation, as well as their use for asymmetric synthesis will be presented. This will illustrate that the development of molecularly encoded metal structures opens up very interesting perspectives, especially in the frame of chiral technologies.     

Recent advances of application of porous molecular cages for enantioselective recognition and separation

Porous materials with well‐defined pore structures have received considerable attention in the past decades due to their unique structures and wide applications. Most porous materials such as zeolites, metal‐organic frameworks, covalent organic frameworks, and porous organic polymers are extended to infinite frameworks or networks by robust covalent or coordination bonds. Porous molecular cages composed of discrete molecules with permanent cavities are an emerging class of porous material and the discrete molecules assemble into solids by weak intermolecular interaction. In comparison to porous extended solids such as metal‐organic frameworks and covalent organic frameworks, porous molecular cage solids are generally soluble in organic solvents thus allowing solution processing, making them more convenient to apply in many fields. This review mainly focuses on the recent advances of application of porous molecular cages (porous organic cages and metal‐organic cages) for enantioselective recognition and separation from 2010 to present, including gas chromatography, capillary electrochromatography, chiral fluorescent recognition, chiral potentiometric sensing, and enantioselective adsorption. Furthermore, the two important family members of porous molecular cages, porous organic cages and metal‐organic cages, are also discussed.     

Chiral separations by capillary electromigration techniques in nonaqueous media. I. Enantioselective nonaqueous capillary electrophoresis

Enantiomer separations by CE employing nonaqueous conditions are reviewed. The general focus of this article is directed towards solvent effects on chiral recognition and the separation mechanism. After a general discussion of solvent effects on the individual processes involved in CE enantiomer separation, specifics for various selector classes are discussed together with a few applications of enantioselective nonaqueous CE.     

Examination of Template Structural Effects on CEC Chiral Separation Performance of Molecule Imprinted Polymers Made by a Generalized Preparation Protocol

Some acidic chiral templates were used to prepare open tubular (OT) molecule imprinted polymer (MIP) capillary columns to explore the effects of molecular structures of templates on chiral recognition capabilities and to verify the feasibility of the general MIP preparation protocol introduced in the previous study. The templates are phenyl carboxylic acids and their derivatives. Optimization was carried out for chiral separation of template enantiomers for each MIP column through varying pH and composition of eluent. It was found that the preparation protocol can be successfully applied for the appropriate templates with functional groups fulfilling the three-points interaction rule. The chiral separation performances were quite satisfactory for MIPs of such templates although they are yet inferior to the separation performances of the MIP columns fabricated with the templates of profen drugs (2-arylpropionic acids with a large substituent on the phenyl ring). Subtle variations of the template molecular structures have been found to be critical to enhance chiral recognition ability of the resultant MIP column.     

手性杯芳烃的合成及性质

手性杯芳烃是一类重要的主体化合物，在手性识别、对映体分离、不对称催化 等方面有潜在的用途、综述了手性杯芳烃的合成及其在手性识别、对映体分离方面 的性能。     

Open tubular capillary columns with basic templates made by the generalized preparation protocol in capillary electrochromatography chiral separation and template structural effects on chiral separation capability

Some open tubular (OT) molecule imprinted polymer (MIP) silica capillary columns have been prepared using atenolol, sulpiride, methyl benzylamine (MBA) and (1-naphthyl)-ethylamine (NEA) as templates by the pre-established generalized preparation protocol. The four MIP thin layers of different templates showed quite different morphologies. The racemic selectivity of each MIP column for the template enantiomers was optimized by changing eluent composition and pH. The template structural effects on chiral separation performance have been examined. This work verifies the versatility of the generalized preparation protocol for OT-MIP silica capillary columns by extending its boundary toward templates with basic functional group moieties. This study is the very first report to demonstrate a generalized MIP preparation protocol that is valid for both acidic and basic templates. The chiral separation performances of atenolol and sulpiride by the MIPs of this study were found better than or comparable to those of atenolol and sulpiride obtained by non-MIP separation techniques and those of some basic template enantiomers obtained by MIP based techniques.     

手性多孔材料在色谱分离分析中的应用

手性多孔有机骨架材料(Chiral porous organic frameworks,CPOFs)具有孔性质优异、比表面积高、稳定性好以及易功能化等诸多优点,已经在手性催化、识别和分离等领域中得到应用。手性多孔有机骨架材料主要有手性金属-有机骨架材料(Chiral metal-organic frameworks,CMOFs)和手性共价有机骨架材料(Chiral covalent organic frameworks,CCOFs)及其他材料,这类材料具有特殊的手性识别、吸附作用,在色谱分离分析领域中已成为研究热点之一。该文综述了手性多孔材料的合成及其在色谱分离和选择性吸附中的应用,展望了未来CPOFs材料可能的应用与发展方向。     

涂层技术在毛细管电泳手性分离中的应用

手性是自然界的本质属性之一。手性分离分析技术对生命科学、环境科学、生物工程和药物工程等许多学科都具有十分重要的意义。当前,对不同种类手性化合物进行拆分已成为毛细管电泳技术最具特色的研究和应用领域之一。然而,被分析物(或拆分剂)在毛细管内壁的吸附是毛细管电泳手性分离中的常见问题。涂层技术就是采用不同的方法对毛细管内壁进行改性,是抑制非特异性吸附、提高分离效率及分离重现性最简便和最有效的方法。本文主要综述了近十几年来各种涂层技术在毛细管电泳手性分离领域的应用现状,并对毛细管涂层技术今后的发展进行了展望。     

Aryl Crown Ethers Based on d-Glucose Scaffold – Highly Selective Receptors of Amino Acid Ester Hydrochlorides

Amino acids are important biomolecules with a broad scope of applications in chemical and biological sciences. Their functions and properties depend on their absolute configuration. Therefore, methods for chiral recognition and separation of amino acids are highly sought after. For the purposes of diagnostic and medicinal applications chiral recognition of amino acids in water is particularly relevant. However synthetic receptors for enantioselective binding of amino acids in aqueous media are rare. Recently we reported a d -glucose-based crown ether for chiral recognition of amino acid esters in water. We achieved enantioselectivities towards amino acids with hydrophobic sidechains which were among the highest ever reported for a small molecule receptor. The binding affinities were however moderate. Herein we disclose analogs of that receptor, containing aryl functionalities in the crown ether fragment. The new receptors show considerably improved binding affinities for amino acid ester hydrochlorides in water, while retaining high enantio- or chemoselectivities.     

Chromatographic Separation of the Enantiomers of a Series of C2-Asymmetric Bi-Naphthyl Compounds by Molecularly Imprinted Polymers

The aim of this study was to observe the chiral separation of a series of C₂-asymmetric bi-naphthyl compounds on molecularly imprinted polymers (MIPs) using 1,1′-bi-2-naphthol (BINOL) as template. MIP prepared using 4-vinylpyridine as the functional monomer showed better chiral recognition for the template than the MIPs prepared using acrylamide, 2-(diethylamino)ethylmethacrylate and 2-vinylpyridine, respectively. ¹H-NMR was used for comparison of the interactions between template and functional monomers. For chromatographic analysis the effects of mobile phase and temperature on the chiral separation were investigated. When 4-vinylpyridine was employed as the functional monomer, chiral separation of 1,1′-bi-2-naphthol and its analogues were studied. The MIP also demonstrated an ability to discriminate between enantiomers of structurally related compounds that had not been imprinted. The thermodynamic parameters of interactions between substrates and MIP in acetonitrile based mobile phase were investigated by the Van’t Hoff equation. In this study, the specific hydrogen-bonding interactions seemed to be the key factor to achieve chiral separation.     

Preparation and characterization of grafted imprinted monolith for capillary electrochromatography

In this paper, a molecularly imprinted polymer (MIP) coating grafted to a trimethylolpropane trimethacrylate (TRIM) core material for CEC was reported. The core monolith was prepared with a solution of 20% (w/w) TRIM in a mixture of porogen and a polymerization precursor, which can generate a stable electroosmotic flow due to the formation of ionizable groups after postpolymerization hydrolization. Graft polymerization took place on the resultant TRIM monolith with a mixture of template, methacrylic acid, and ethylene glycol dimethacrylate. Strong recognition ability (selectivity factor was 5.83) for S‐amlodipine and resolution of enatiomers separation (up to 7.99) were obtained on the resulting grafted imprinted monolith in CEC mode. The influence of CEC conditions on chiral separation, including the composition of mobile phase, pH value, and the operating voltages was studied. These results suggest that the method of grafted polymerization reported here allows a rapid development of MIP monolith once core materials with desired properties are available, and is a good alternative to prepare CEC‐based monolithic MIPs.     

Open tubular layer of S‐ofloxacin imprinted polymer fabricated in silica capillary for chiral CEC separation

An open tubular molecule imprinted polymer (OT‐MIP) capillary column has been prepared for chiral separation of ofloxacin enantiomers in CEC. The S‐ofloxacin imprinted OT column was fabricated by thermally initiated non‐covalent polymerization procedure inside a pretreated and silanized fused silica capillary. The template molecule was incorporated with methacrylic acid (MAA), ethylene glycol dimethacrylate (EDMA) and 4‐styrenesulfonic acid (4‐SSA) and dissolved in a porogen mixture of ACN/2‐propanol (9:1). The separation efficiency of the 4‐SSA MIP column was found quite better than that of the MIP column without 4‐SSA. It has been demonstrated that our OT‐MIP column can separate ofloxacin enantiomers with excellent chiral separation efficiency after tuning the various chromatographic conditions. The optimized chromatographic eluent was 85:15, v/v%, ACN/60 mM sodium acetate at pH 7. The separation efficiency and selectivity of chiral separation of this study were far better than those obtained by previous methods for chiral separation of R‐ and S‐ofloxacin.     

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.     

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。     

Bile Salts in Chiral Micellar Electrokinetic Chromatography: 2000–2020

Bile salts are naturally occurring chiral surfactants that are able to solubilize hydrophobic compounds. Because of this ability, bile salts were exploited as chiral selectors added to the background solution (BGS) in the chiral micellar electrokinetic chromatography (MEKC) of various small molecules. In this review, we aimed to examine the developments in research on chiral MEKC using bile salts as chiral selectors over the past 20 years. The review begins with a discussion of the aggregation of bile salts in chiral recognition and separation, followed by the use of single bile salts and bile salts with other chiral selectors (i.e., cyclodextrins, proteins and single-stranded DNA aptamers). Advanced techniques such as partial-filling MEKC, stacking and single-drop microextraction were considered. Potential applications to real samples, including enantiomeric impurity analysis, were also discussed.