分子印迹聚合物微球的制备及应用研究进展

球形分子印迹聚合物具有制备简单、使用方便；分子识别效率高且便于功能设计等优点，近年来成为分子印迹技术领域研究的热点之一。对球形分子印迹聚合物微球的制备及其应用研究进展作了较为详细的介绍。     

Label‐Free Colorimetric Detection of Trace Atrazine in Aqueous Solution by Using Molecularly Imprinted Photonic Polymers

Based on the combination of colloidal‐crystal templating and a molecular imprinting technique, a sensor platform for efficient detection of atrazine in aqueous solution has been developed. The sensor is characterized by a 3D‐ordered interconnected macroporous structure in which numerous nanocavities derived from atrazine imprinting are distributed in the thin wall of the formed inverse polymer opal. Owing to the special hierarchical porous structure, the molecularly imprinted polymer opals (or molecularly imprinted photonic polymer; MIPP) allow rapid and ultrasensitive detection of the target analyte. The interconnected macropores are favorable for the rapid transport of atrazine in polymer films, whereas the inherent high affinity of nanocavites distributed in thin polymer walls allows MIPP to recognize atrazine with high specificity. More importantly, the atrazine recognition events of the created nanocavities can be directly transferred (label‐free) into a readable optical signal through a change in Bragg diffraction of the ordered macropores array of MIPP and thereby induce color changes that can be detected by the naked eye. With this novel sensory system, direct, ultrasensitive (as low as 10^?8 ng mL^?1), rapid (less than 30 s) and selective detection of atrazine with a broad concentration range varying from 10^?16 M to 10^?6 M in aqueous media is achieved without the use of label techniques and expensive instruments.     

Molecularly Imprinted Polymers: Compromise between Flexibility and Rigidity for Improving Capture of Template Analogues

New synthetic strategies for molecularly imprinted polymers (MIPs) were developed to mimic the flexibility and mobility exhibited by receptor/enzyme binding pockets. The MIPs were prepared by bulk polymerization with quercetin as template molecule, acrylamide as functional monomer, ethylene glycol dimethacrylate as cross‐linker, and THF as porogen. The innovative grafting of specific oligoethylene glycol units onto the imprinted cavities allowed MIPs to be obtained that exhibit extended selectivity towards template analogues. This synthetic strategy gives promising perspectives for the design of molecular recognition of molecules based on a congruent pharmacophore, which should be of interest for drug development.     

芦丁-槲皮素双模板印迹聚合物的制备、表征及识别

以芦丁(RT)-槲皮素(QT)为混合模板分子制备了芦丁-槲皮素复合模板分子印迹聚合物。 优化了制备条件,研究了模板用量比、功能单体及交联剂用量对印迹聚合物吸附性能的影响。 用傅里叶红外光谱和扫描电镜对分子印迹聚合物进行结构表征。 探讨了分子印迹聚合物的吸附动力学、等温吸附及键合位点特征,考察了其选择识别性能,并以分子印迹聚合物为吸附介质,萃取分离芦丁粗提液中的目标化合物。 结果表明,当槲皮素与芦丁的摩尔比为3:2,且模板总量与功能单体及交联剂用量摩尔比为1:8:10时,所得分子印迹聚合物的吸附性能最好,对槲皮素和芦丁的吸附量分别达47.86和60.97 mg/g。 吸附可在3.5 h内达到平衡,显示了较快的吸附动力学。 Scatchard分析表明,分子印迹聚合物基体中存在四类不同性能的键合位点,分别为芦丁和槲皮素的高亲和键合位点及非选择键合位点。 相对分布系数(k=K_d(RT)/K_d(QT),K_d=q_e/ρ_e,K_d为分布系数,q_e为平衡吸附量,ρ_e为平衡质量浓度)大于1,表明了分子印迹聚合物对芦丁具有更高的选择键合作用,当模拟混合物中芦丁和槲皮素浓度分别为0.07和0.03 mmol/L时,相对分布系数和分离因子(α=q_e(RT)/q_e(QT))分别达6.669和25.02。 另外,以乙腈、甲醇及甲醇-醋酸混合物依次为洗脱剂,通过分子印迹固相萃取可从槐米提取物中分离芦丁和槲皮素两种黄酮类化合物,总回收率分别为96.70%和94.67%。     

Molecularly Imprinted Photonic Polymers as Sensing Elements for the Creation of Cross‐Reactive Sensor Arrays

By combining molecular imprinting and colloidal crystal templating, molecularly imprinted inverse‐opal photonic polymers (MIPPs) acting as sensing elements have been exploited to create sensor arrays for the first time. With this new strategy, abundant sensing elements with differential sensing abilities were easily accessible. Because of the unique hierarchical porous structure integrated in each sensing element, high sensitivity and selectivity, fast response and self‐reporting (label‐free) detection could be simultaneously achieved. All these fascinating features indicate that MIPPs are ideal sensing elements for creating sensor arrays. By integrating the individual sensing elements on a substrate, the formed array chip delivers better portability and high‐throughput capability. As a demonstration, six kinds of contaminants were selected as analytes. The detection and discrimination of these analytes and even their mixtures in a wide range of concentrations, particularly trace amounts of analyte against a high background of other components, could be achieved, indicating the powerful capability of MIPPs‐based sensor array for sensing. These results suggest that the described strategy opens a new route for sensor array creation and should find important applications in a wide range of areas.     

Molecularly Imprinted Multi‐Layer Core‐Shell Nanoparticles – A Surface Grafting Approach

Surface initiated living‐radical polymerization (SIP) based on dithiocarbamate iniferters has been used to create molecularly imprinted core‐shell (CS) nanoparticles. Using this approach, propranolol, morphine and naproxen have been successfully imprinted in particle shells (the latter could not be imprinted using conventional aqueous‐based CS methods). Rebinding properties of the imprinted particles appear to be similar to those made by alternative methods. The living radical initiation mechanism makes it possible to build complex multi‐layer particles sequentially. As a demonstration, multi‐layer propranolol‐imprinted particles were generated. Two additional functional shells were grown over the imprinted shell, while the propranolol binding was retained, albeit at a reduced level.

     

Molecularly Imprinted Polymer Nanomaterials and Nanocomposites: Atom‐Transfer Radical Polymerization with Acidic Monomers

Molecularly imprinted polymers (MIPs) are artificial receptors which can be tailored to bind target molecules specifically. A new method, using photoinitiated atom‐transfer radical polymerization (ATRP) for their synthesis as monoliths, thin films and nanoparticles is described. The synthesis takes place at room temperature and is compatible with acidic monomers, two major limitations for the use of ATRP with MIPs. The method has been validated with MIPs specific for the drugs testosterone and S‐propranolol. This study considerably widens the range of functional monomers and thus molecular templates which can be used when MIPs are synthesized by ATRP, as well as the range of physical forms of these antibody mimics, in particular films and lithographic patterns, and their post‐functionalization from living chain‐ends.     

Molecularly imprinted polymers bearing spiropyran‐based photoresponsive binding sites capable of photo‐triggered switching for molecular recognition activity

Photoresponsive molecularly imprinted nanocavities were prepared using a newly designed functional monomer bearing a photoresponsive spiropyran moiety with a carboxy group that can interact with atrazine (the template molecule), in which the spiropyran moiety was incorporated into the binding cavities. Spectrophotometric analysis confirmed that the spiropyran moiety was photoresponsive even after polymerization. The selectivity of the EDMA‐based molecularly imprinted polymer (MIP_EDMA) was tested to examine the binding behavior of atrazine and other agrochemicals, revealing that the atrazine‐imprinted polymer can bind selectively to triazine herbicides. Photo‐triggered switching of the binding activity in MIP_EDMA was investigated, and the binding activity was found to decrease dramatically after UV light irradiation, suggesting that the spiropyran moiety in the binding cavities was transformed to the merocyanine form, resulting in unfavorable translocation of the carboxy group for atrazine binding. Consequently, the spiropyran‐based MIP_EDMA demonstrated in this study could open a way to realizing reliable photoresponsive smart materials. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1637–1644     

没食子酸磁性表面分子印迹聚合物的制备与选择性识别性能

羟基苯甲酸类化合物用途广泛,极性较强,在复杂水溶液体系中这些类似物的分离纯化与分析非常困难。 本文以磁性Fe₃O₄纳米颗粒为载体,没食子酸(GA)为模板分子,制备了磁性表面分子印迹聚合物(MIP)。 利用透射电子显微镜、红外光谱、磁强测定等检测手段对MIP进行了结构表征。 并对其吸附性能进行研究,比较了该MIP对GA及其它3种结构类似物的吸附性能差异。 结果表明,制备的以GA为模板的磁性分子印迹聚合物为核壳球形结构,键合牢固,对GA的吸附动力学符合准二级动力学方程模型,吸附过程属于Langmuir单分子层吸附。 该聚合物对GA表现出优异的选择性识别能力,其吸附量(318 K时37.736 mg/g)远远高于结构类似物。 该磁性分子印迹聚合物对模板分子不仅具有特异识别能力,而且能够磁控分离,分离效率高,可用于固相萃取。     

Electrochemical Sensor for trans‐Resveratrol Determination Based on Indium Tin Oxide Electrode Modified with Molecularly Imprinted Self‐Assembled Films

A voltammetric sensor for sensitive and specific determination of trans‐resveratrol (RES) were prepared based on immobilization of an RES‐imprinted film on the surface of functionalized Indium Tin Oxide (ITO) electrode, which was modified with γ‐methacyloxypropyl trimethoxysilane (γ‐MPS). Cyclic Voltammetry (CV) was presented to extract RES from the molecularly imprinted polymer film and RES were extracted rapidly and completely. The binding performance of the imprinted electrode with the template RES were investigated using differential pulse voltammetry (DPV). The results showed that the imprinted ITO film can give selective recognition to the template RES over that of structurally analogous molecules. A linear response to RES in the concentration range of 2.0×10^?6 M to 2.0×10^?5 M was observed with a correlation coefficient of 0.992, and the detection limit of the electrochemical sensor was 8.0×10^?7 M. Whereas, binding to the reference nonimprinted electrode, made in the same way but without the addition of template RES, there was almost no response to RES.     

A Programmable Signaling Molecular Recognition Nanocavity Prepared by Molecular Imprinting and Post‐Imprinting Modifications

Inspired by biosystems, a process is proposed for preparing next‐generation artificial polymer receptors with molecular recognition abilities capable of programmable site‐directed modification following construction of nanocavities to provide multi‐functionality. The proposed strategy involves strictly regulated multi‐step chemical modifications: 1) fabrication of scaffolds by molecular imprinting for use as molecular recognition fields possessing reactive sites for further modifications at pre‐determined positions, and 2) conjugation of appropriate functional groups with the reactive sites by post‐imprinting modifications to develop programmed functionalizations designed prior to polymerization, allowing independent introduction of multiple functional groups. The proposed strategy holds promise as a reliable, affordable, and versatile approach, facilitating the emergence of polymer‐based artificial antibodies bearing desirable functions that are beyond those of natural antibodies.     

Stereoselective and Chiroselective Surface Plasmon Resonance (SPR) Analysis of Amino Acids by Molecularly Imprinted Au‐Nanoparticle Composites

Au nanoparticles (NPs) functionalized with thioaniline and cysteine are used to assemble bis‐aniline‐bridged Au‐NP composites on Au surfaces using an electropolymerization process. During the polymerization of the functionalized Au NPs in the presence of different amino acids, for example, L ‐glutamic acid, L ‐aspartic acid, L ‐histidine, and L ‐phenylalanine, zwitterionic interactions between the amino acids and the cysteine units linked to the particles lead to the formation of molecularly imprinted sites in the electropolymerized Au‐NP composites. Following the elimination of the template amino acid molecules, the electropolymerized matrices reveal selective recognition and binding capabilities toward the imprinted amino acid. Furthermore, by imprinting of L ‐glutamic or D ‐glutamic acids, chiroselective imprinted sites are generated in the Au‐NP composites. The binding of amino acids to the imprinted recognition sites was followed by surface plasmon resonance spectroscopy. The refractive index changes occurring upon the binding of the amino acids to the imprinted sites are amplified by the coupling between the localized plasmon associated with the Au NPs and the surface plasmon wave.     

Employment of Molecularly Imprinted Polymers to High‐Throughput Screen nNOS‐PSD‐95 Interruptions: Structure and Dynamics Investigations on Monomer–Template Complexation

Molecularly imprinted polymers (MIPs) are employed to screen nNOS‐PSD‐95 (neuronal nitric oxide synthase post‐synaptic density protein‐95) interruptions. 5‐(3,5‐Dichloro‐2‐hydroxybenzylamino)‐2‐hydroxybenzoic acid (ZL006; a potential drug candidate for the treatment of stroke, depression, and pain) is employed as a template. Four kinds of functional monomers (2‐VP: 2‐vinylpyridine; 4‐VP: 4‐vinylpyridine; MMA: methyl methacrylate; and MAAM: methacrylamide) are designed, and their complexation with ZL006 in various solvents (methanol, acetonitrile, toluene, chloroform) is investigated by molecular dynamics simulations and quantum mechanics calculations. Both 4‐VP and MAAM have stronger interactions with ZL006 than those of 2‐VP and MMA. The appropriate ratio of monomer to template is 3:1. Intermolecular hydrogen bonds play a dominant role in monomer–template complexation. Ideal solvents are toluene and chloroform, and the solvation effect on monomer–template complexation is revealed. Both molecular modeling and adsorption experiments demonstrate that as‐synthesized ZL006‐MIP with 4‐VP as a monomer has better selectivity than that employing MAAM to screen for nNOS‐PSD‐95 interruptions.     

Synthesis of thermo‐responsive bovine hemoglobin imprinted nanoparticles by combining ionic liquid immobilization with aqueous precipitation polymerization

Surface molecular imprinting over functionalized nanoparticles has proved to be an effective approach for construction of artificial nanomaterials for protein recognition. Herein, we report a strategy for synthesis of core–shell protein‐imprinted nanoparticles by the functionalization of nano‐cores with ionic liquids followed by aqueous precipitation polymerization to build thermo‐responsive imprinted polymer nano‐shells. The immobilized ionic liquids can form multiple interactions with the protein template. The polymerization process can produce thermo‐reversible physical crosslinks, which are advantageous to enhancing imprinting and facilitating template removal. With bovine hemoglobin as a model template, the imprinted nanoparticles showed temperature‐sensitivity in both dispersion behaviors and rebinding capacities. Compared with the ionic‐liquid‐modified core nanoparticles, the imprinted particles exhibited greatly increased selectivity and two orders of magnitude higher binding affinity for the template protein. The imprinted nanoparticles achieved relatively high imprinting factor up to 5.0 and specific rebinding capacity of 67.7 mg/g, respectively. These nanoparticles also demonstrated rapid rebinding kinetics and good reproducibility after five cycles of adsorption–regeneration. Therefore, the presented approach may be viable for the fabrication of high‐performance protein‐imprinted nanoparticles with temperature sensitivity.     

A novel ion‐imprinted hydrogel for recognition of potassium ions with rapid response

A novel ion‐imprinted strategy is developed for synthesizing responsive hydrogels with rapid response to potassium ions. With potassium ions as templates, ion‐imprinted poly(N‐isopropylacrylamide‐co‐benzo‐15‐crown‐5‐acrylamide) (P(NIPAM‐co‐B15C5Am)) hydrogels are synthesized with 15‐crown‐5 crown ethers mounted on the polymer networks in pairs; therefore, it is very easy and fast for the crown ethers to capture potassium ions again by their Venus flytrap action and form stable 2:1 “host–guest” complexes with potassium ions in the ion‐recognition process. As a result, the response rate of the ion‐imprinted hydrogels to potassium ions is significantly faster than that of normal P(NIPAM‐co‐B15C5Am) hydrogels in which 15‐crown‐5 crown ethers are randomly pendent on the polymeric networks. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and Conformational Analysis of (α‐D‐Galactosyl)phenylmethane and α‐,β‐Difluoromethane Analogues: Interactions with the Plant Lectin Viscumin

To bend about : The conformations of three phenyl‐C‐galactosides in solution were evaluated by using theoretical calculations and NMR spectroscopic studies. The α‐CF₂ derivative (see scheme) showed significant flexibility of the pyranose ring and around the pseudoanomeric center, whereas the other two analogues more closely resemble the natural galactosides. Regardless, all three compounds bind to a plant lectin.

     

Complexation and Catenation in Aqueous Media Using a Self‐Assembled PdII Metallacyclic Receptor

A M₂L₂ rectangular‐shaped metallacycle, obtained by metal‐directed self‐assembly of a 2‐(pyridin‐4‐ylmethyl)‐2,7‐diazapyrenium salt and [(en)Pd (NO₃)₂] (en=ethylenediamine), has been investigated as a molecular receptor for a wide range of aromatic substrates in water. Complexation and catenation of the receptor with selected mono‐ and polycyclic aromatic substrates produced 1:1 inclusion complexes and [2]catenanes in a highly efficient fashion, as determined by NMR and UV/Vis spectroscopic techniques, as well as single‐crystal X‐ray crystallography. Furthermore, the thermodynamic and kinetic features of the complexation processes have been analyzed for selected model guests.     

Determination of Acrolein‐Derived 3‐Hydroxypropylmercapturic Acid in Human Urine Using Solid‐phase Extraction Combined with Molecularly Imprinted Mesoporous Silica and LC‐MS/MS Detection

A novel method for the analysis of (3‐hydroxypropyl)mercapturic acid (HPMA), a major acrolein metabolite in human urine incorporating a molecularly imprinted solid‐phase extraction (MISPE) process using N‐acetylcysteine ‐imprinted mesoporous silica particles coupled with LC‐MS/MS detection was developed. The molecularly imprinted mesoporous silica particles were synthesized based on the supported material of ordered mesoporous silica SBA‐15 with N‐acetylcysteine (NAC) as template using surface molecular imprinting technology. The condition of MISPE procedures was optimized. The use of MISPE improved the accuracy and precision of the LC‐MS method and lowered the limit of detection (0.23 ng/mL). The recoveries at three spiked levels ranged between 88.5% to 108.6%. The developed MISPE method enabled the selective extraction of HPMA successfully in human urine and could be used as an effective approach for the determination of ultra‐trace HPMA in complex biological matrices. The results in real samples showed that median levels of HPMA were significantly higher (1922.0 ng/mg of creatinine, N = 75) in smokers than in nonsmokers (759.1 ng/mg of creatinine, N = 5), demonstrating the higher acrolein uptake in smokers than in nonsmokers.