Recent advances and future trends in molecularly imprinted polymers-based sample preparation

Molecular imprinting technology is a well-established technique for the obtainment of tailor-made polymers, so-called molecularly imprinted polymers, with a predetermined selectivity towards a target analyte or structurally related compounds. Accordingly, molecularly imprinted polymers are considered excellent materials for sample preparation providing unprecedented selectivity to analytical methods. However, the use of molecularly imprinted polymers in sample preparation still presents some shortcomings derived from the synthesis procedure itself limiting its general applicability. In this regard, molecularly imprinted polymers use to display binding sites heterogeneity and slow diffusion mass transfer of analytes to the imprinted sites affecting their overall performance. Besides, the performance of molecularly imprinted polymers in organic solvents is excellent, but their selective binding ability in aqueous media is considerably reduced. Accordingly, the present review pretends to provide an updated overview of the recent advances and trends of molecularly imprinted polymers-based extraction, focusing on those strategies proposed for the improvement of mass transfer and selective recognition in aqueous media. Besides, with the progressive implementation of Green Chemistry principles, the different steps and strategies for the preparation of molecularly imprinted polymers are reviewed from a green perspective.     

Magnetic molecularly imprinted polymers synthesized by surface‐initiated reversible addition‐fragmentation chain transfer polymerization for the enrichment and determination of synthetic estrogens in aqueous solution

Magnetic molecularly imprinted polymers have attracted significant interest because of their multifunctionality of selective recognition of target molecules and rapid magnetic response. In this contribution, magnetic molecularly imprinted polymers were synthesized via surface‐initiated reversible addition addition‐fragmentation chain transfer polymerization using diethylstilbestrol as the template for the enrichment of synthetic estrogens. The uniform imprinted surface layer and the magnetic property of the magnetic molecularly imprinted polymers favored a fast binding kinetics and rapid analysis of target molecules. The static and selective binding experiments demonstrated a desirable adsorption capacity and good selectivity of the magnetic molecularly imprinted polymers in comparison to magnetic non‐molecularly imprinted polymers. Accordingly, a corresponding analytical method was developed in which magnetic molecularly imprinted polymers were employed as magnetic solid‐phase extraction materials for the concentration and determination of four synthetic estrogens (diethylstilbestrol, hexestrol, dienestrol, and bisphenol A) in fish pond water. The recoveries of these synthetic estrogens in spiked fish pond water samples ranged from 61.2 to 99.1% with a relative standard deviation of lower than 6.3%. This study provides a versatile approach to prepare well‐defined magnetic molecularly imprinted polymers sorbents for the analysis of synthetic estrogens in water solution.     

金属卟啉分子印迹聚合物的合成与性能研究

以5-(4-羟基苯基)-10,15,20-三苯基卟啉锌为印迹分子,4-乙烯基吡啶为功能单体,乙二醇二甲基丙烯酸酯为交联剂,合成了具有金属卟啉识别能力的分子印迹聚合物.紫外可见滴定光谱研究表明,功能单体与印迹分子在聚合前形成1:1的配合物.通过吸附试验、荧光光谱及斯卡查特分析法,考察了分子印迹聚合物对锌卟啉化合物的识别性能.结果表明,印迹聚合物对结构类似的卟啉化合物具有良好的识别能力,对印迹分子荧光性能的影响远大于其对应的非印迹聚合物.在浓度较低时,印迹聚合物对印迹分子的结合常数和最大结合量分别为:1.61×106L/mol和3.22×10-5mol/g.     

Efficient synthesis of molecularly imprinted polymers with bio‐recognition sites for the selective separation of bovine hemoglobin

We developed a facile approach to the construction of bio‐recognition sites in silica nanoparticles for efficient separation of bovine hemoglobin based on amino‐functionalized silica nanoparticles grafting by 3‐aminopropyltriethoxylsilane providing hydrogen bonds with bovine hemoglobin through surface molecularly imprinting technology. The resulting amino‐functionalized silica surface molecularly imprinted polymers were characterized using scanning electron microscope, transmission electronic microscopy, Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, and thermogravimetric analysis. Results showed that the as‐synthesized imprinted polymers exhibited spherical morphology and favorable thermal stability. The binding adsorption experiments showed that the imprinted polymers can reach equilibrium within 1 h. The Langmuir isotherm and pseudo‐second‐order kinetic model fitted the adsorption data well. Meanwhile, the imprinted polymers possessed a maximum binding capacity up to 90.3 mg/g and highly selectivity for the recognition of bovine hemoglobin. Moreover, such high binding capacity and selectivity retained after eight cycles, indicating the good stability and reusability of the imprinted polymers. Finally, successful application in the selective recognition of bovine hemoglobin from a real bovine blood sample indicated that the imprinted polymers displayed great potentials in efficient purification and separation of target proteins.     

水相识别分子印迹技术

在各种基于超分子方法的仿生识别体系中,分子印迹聚合物已经证明是一种有潜力的合成受体,受到了广泛的关注。传统的分子印迹技术通常是在有机溶剂中制备对小分子具有选择性的印迹聚合物,而在水相中制备及识别生物大分子的研究仍具有相当的挑战性。从小分子到生物大分子、从有机相到水相,反映了分子印迹技术的发展趋势。本文对最近几年分子印迹在水相制备与识别方面的最新进展进行了总结与评述,探讨了水相识别印迹聚合物的设计策略与制备方法;着重介绍了水相识别技术在固相萃取、色谱固定相、药物控释、中药有效成份提取以及生物分子识别等方面的应用;指出了提高水相识别选择性的途径并对其将来的发展进行了建议与展望。     

基于β-环糊精的分子印迹聚合物在环境和食品样品前处理中的应用进展

β-环糊精（β-CD）及其衍生物作为一种新兴的功能单体在分子印迹技术中得到了越来越多的应用。β-CD及其衍生物能够与许多分子形成主-客体包合物,基于这一包合作用制备的分子印迹聚合物具有稳定性好和选择性高等优点,因此在具有复杂基质的环境和食品样品中目标化合物的选择性分离和富集中得到了重视和发展。该综述主要回顾了2013年以来文献中报道的一些基于β-CD及其衍生物作为功能单体的分子印迹聚合物在环境水和食品样品前处理方面的最新应用,揭示这一分子印迹聚合物在复杂样品前处理中的优势。     

1-乙烯基-3-甲基咪唑离子液体/分子印迹材料用于牛血红蛋白的识别

分子印迹聚合物是一类对目标分子具备特异性辨别能力的高分子吸附剂材料.运用本体聚合法,以牛血红蛋白(BHb)为模板分子,丙烯酰胺(AAM)和碘化1-乙烯基-3-甲基咪唑离子液体在交联剂、引发剂和加速剂的作用下进行聚合,制备的分子印迹材料对牛血红蛋白(BHb)具备特异性识别功能.同时,对识别条件进行了优化和讨论.     

Discrimination of peptides by using a molecularly imprinted piezoelectric biosensor

Based on the direct formation of a molecularly imprinted polymer on gold electrodes, we have developed a peptide sensor for the detection of low-molecular-weight peptides. A new cross-linking monomer, (N-Acr-L-Cys-NHBn)(2), was employed to attach the surface of the chip and to copolymerize with other monomers. Interestingly, N-benzylacrylamide participates in the polymerization and recognition is carried out in an aqueous environment. By using quartz crystal microbalance detection, short peptides can be monitored by their interaction with plastic antibodies specific for the target peptides. The selectivity of molecularly imprinted polymers and the sensitivity of such artificial biosensors have been combined to differentiate between traces of oxytocin and vasopressin to the ng mL(-1) scale.     

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.     

Determination of Chlorogenic Acid and Rutinum in Herba Artemisiae Scopariae with Multitemplate Molecularly Imprinted Polymers for Solid-phase Extraction with High-performance Liquid Chromatography

Novel multitemplate molecularly imprinted polymers were prepared using mixtures of chlorogenic acid and rutinum as molecular templates, acrylamide as a functional monomer, divinylbenzene as the cross-linker, and 20:80 methanol:acetone as the porogen. The polymers were assessed for solid-phase extraction (SPE) for the purification of two compounds from Herba Artemisiae Scopariae. The synthesized molecularly imprinted polymers were identified by infrared spectroscopy and scanning electron microscopy. Systematic characterization of the functional monomer and porogens on the recognition properties of the molecularly imprinted polymers were carried out. Comparison with single-template molecularly imprinted polymers showed that the multitemplate molecular polymers exhibited higher selectivity and adsorption capacity for multiple analytes. The optimization of washing solvent as 1:9 acetone:water and the elution solvent as 9:1 acetonitrile:acetic acid provided a reliable analytical method with strong recognition toward multiple analytes in Herba Artemisiae Scopariae extracts with satisfactory recoveries of 89.6% for chlorogenic acid and 93.8% for rutinum. These results demonstrate that the multitemplate molecularly imprinted polymers coupled with SPE are effective for the selective purification of bioactive compounds in complex samples.     

Synthesis and chromatographic evaluation of molecularly imprinted polymers prepared by the substructure approach for the class-selective recognition of glucuronides

Two series of molecularly imprinted polymers (MIPs) for the class-selective recognition of glucuronides have been prepared by using lipophilic substructures of the target analyte as template molecule and potent host monomers against oxyanions, that are expected to establish a strong stoichiometric interaction with the single carboxylic group of the template. The polymers were tested as stationary phases in liquid chromatography for specific recognition. A preliminary investigation of the imprinting properties of eleven MIPs was carried out, by comparing the retention time of the template and of structurally related compounds on the MIP column with that on the corresponding non-imprinted polymer (NIP). The two polymers showing the best performance were selected to further test cotinine, mycophenolic acid, testosterone and their respective glucuronides as model compounds. The high specificity obtained against glucuronides and the different chemical structure of the parent drug make the two MIPs class-selective imprinted receptors, also suitable for SPE application.     

Synthesis of stationary phases that provide group recognition for polychlorinated biphenyls by porogenic fragment template imprinting

Molecular recognition based on imprinted polymers results from the polymerization of functional monomers and cross‐linkers in the presence of a target analyte (i.e. template), with subsequent removal of the template to create synthetic binding sites. However, complete removal of the template is difficult to achieve, thereby leading to template leaching, which adversely affects real‐world analytical applications. To overcome this challenge, the present study utilizes porogenic fragment template imprinting techniques to provide an alternative synthetic strategy to generate molecularly imprinted polymers with molecular recognition toward polychlorinated biphenyls. Thereafter, thus‐generated imprinted polymers have been applied as stationary phases in molecularly imprinted solid‐phase extraction for preconcentrating six “indicator polychlorinated biphenyls” in both organic and aqueous media. Recoveries of up to 98.9% (imprinted polymers) versus 73.0% (conventional C₁₈) in an organic phase, and up to 97.4% (imprinted polymers) versus 89.4% (C₁₈) in an aqueous phase have been achieved corroborating the utility of this advanced sorbent material. Finally, porogenic fragment template imprinting strategies have yielded molecularly imprinted polymers that are useful for the quantitative determination of polychlorinated biphenyls in environmental matrices, which provides a low‐cost strategy for tailoring stationary phases that avoid template leaching in applications in solid‐phase extraction as well as liquid chromatography.     

Chemosensory performance of molecularly imprinted fluorescent conjugated polymer materials

Fluorescent conjugated polymers are an attractive basis for the design of low detection limit sensing devices owing to their intrinsic signal amplification capability. A simple and universal method to rationally control or fine-tune the chemodetection selectivity of conjugated polymer materials toward a desired analytical target would further benefit their applications. In a quest of such a method we investigated a general approach to cross-linked molecularly imprinted fluorescent conjugated polymer (MICP) materials that possess an intrinsic capability for signal transduction and have potential to enhance selectivity and sensitivity of sensor devices based on conjugated polymers. To study these capabilities, we prepared an MICP material for the detection of 2,4,6-trinitrotoluene and related nitroaromatic compounds. We found the imprinting effect in this material to be based on analyte shape/size recognition being substantial and generally overcoming other competing thermodynamically determined trends. The described molecularly imprinted fluorescent conjugated polymers show remarkable air stability and photostability, high fluorescence quantum yield, and reversible analyte binding and therefore are advantageous for sensing applications due to the ability to "preprogram" their detection selectivity through a choice of an imprinted template.     

Role of molecularly imprinted polymers for selective determination of environmental pollutants--a review

The molecularly imprinted polymers (MIPs) are synthetic polymers possessing specific cavities designed for a target molecule. By a mechanism of molecular recognition, the MIPs are used as selective tools for the development of various analytical techniques such as liquid chromatography, capillary electrochromatography, solid-phase extraction (SPE), binding assays and biosensors. This review describes the application of MIPs to the determination of environmental pollutants in these different analytical approaches with a special emphasis on their potential as selective SPE sorbent for the selective extraction of target analytes from complex matrices.     

溶胶-凝胶法制备的罗丹明B/二氧化钛分子印迹聚合物的结构与吸附性能

以罗丹明B为模板分子,以钛酸丁酯为交联剂,采用溶胶-凝胶法在酸性条件下制备了罗丹明B二氧化钛溶胶-凝胶分子印迹聚合物;利用傅立叶变换红外光谱和透射电镜分析了分子印迹聚合物的结构,使用热重分析测定了其热稳定性,采用静态吸附和动态吸附方法考察了其吸附性能,并与非印迹聚合物进行了对比.结果表明,与非印迹聚合物相比,印迹聚合物具有网络状多孔隙凝胶微结构及对模板分子的特异性识别结合位点,因而对模板分子具有更好的吸附性能和特异选择性.其原因可能在于,模板分子上的羰基与钛酸丁酯水解产生的羟基产生氢键作用,使钛酸围绕于模板分子周围,并通过缩聚形成凝胶;当模板分子洗脱后,孔隙得到保留并形成网络状凝胶,从而能够吸附更多的模板分子.     

Ternary choline chloride/caffeic acid/ethylene glycol deep eutectic solvent as both a monomer and template in a molecularly imprinted polymer

A molecularly imprinted polymer based on a ternary deep eutectic solvent comprised of choline chloride/caffeic acid/ethylene glycol was prepared. The caffeic acid in the ternary deep eutectic solvent was used as both a monomer and template. The molecularly imprinted polymer based on the ternary deep eutectic solvent was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, field‐emission scanning electron microscopy, Brunauer–Emmett–Teller surface area analysis, atomic force microscopy, and elemental analysis. A series of molecularly imprinted polymers based on choline chloride/caffeic acid/ethylene glycol with different molar ratios was prepared and applied to the molecular recognition of polyphenols. A comparison of the recognition ability of molecularly imprinted polymers to polyphenols revealed that the choline chloride/caffeic acid/ethylene glycol (1:0.4:1, molar ratio) molecularly imprinted polymer had the best molecular recognition effect with 132 μg/g of protocatechuic acid, 104 μg/g of catechins, 80 μg/g of epicatechin, and 123 μg/g of caffeic acid in 6 h, as well as good molecular recognition ability for polyphenols from a Radix Asteris sample. These results show that the ternary deep eutectic solvent based molecularly imprinted polymer is a potential medium that can be applied to drug purification, drug delivery, and drug analysis.     

Imprinted polymers-tailor-made mimics of antibodies and receptors

The technique of molecular imprinting allows the formation of specific recognition sites in synthetic polymers through the use of templates or imprint molecules. These recognition sites mimic the binding sites of antibodies and other biological receptor molecules. Molecularly imprinted polymers can therefore be used in applications relying on specific molecular binding events. The stability, ease of preparation and low cost of these materials make them particularly attractive. This review focuses on recent developments and advances in the field of molecularly imprinted materials, with special emphasis on applications in immunoassays and sensors recently developed by our group and by others.     

模板结构与分子印迹效果间关系的研究

以一些分子量和体积都较小的简单化合物作为模板分子,合成分子印迹聚合物 。通过总结43种化合物的分子印迹聚合物的色谱数据,来研究模板分子的分子量、 作用位点数目、分子刚性等因素与印迹效果的关系。根据免疫学中免疫原性的定义 ,我们提出“印迹原性”的概念,即,化合物能够产生印迹效应的性质称为印迹原 性;具有印迹原必的化合物称为印迹原;并讨论了具有较强选择性的印迹原的化学 基础。所得到的结论将有助于对分子印迹聚合物的识别机理的进一步理解,并且对 于根据模板分子性质预测MIP分子识别能力将具有一定的指导意义。