Development and evaluation of spherical molecularly imprinted polymer beads

The majority of studies on molecularly imprinted polymers has until now been carried out on irregularly shaped particles prepared by grinding of polymer monoliths. The preparation procedures are time- and labor-consuming and produce particles of wide size distributions. To answer the need for fast and straightforward routes to spherical molecularly imprinted polymer beads, we have developed a method comprising the formation of droplets of pre-polymerization solution directly in mineral oil by vigorous mixing followed by transformation of the droplets into solid spherical beads by photoinduced free-radical polymerization. No detergents or stabilizers were required for the droplet formation. Factors influencing the bead synthesis have been investigated and are detailed here. The beads were evaluated in parallel with corresponding irregularly shaped particles prepared from polymer monoliths. Conditions for the synthesis of propranolol-imprinted poly(methacrylic acid-co-trimethylolpropane trimethacrylate) beads in the size range of 1-100 microm in almost quantitative yield are described. The beads were applied as the recognition element in a 96-well plate format radioligand assay of propranolol in human serum.     

Protein recognition via surface molecularly imprinted polymer nanowires

In this paper, we present a technique for the preparation of polymer nanowires with the protein molecule imprinted and binding sites at surface. These surface imprinting nanowires exhibit highly selective recognition for a variety of template proteins, including albumin, hemoglobin, and cytochrome c. This recognition may be through a multistep adsorption, with the specificity conferred by hydrogen bonding and shape selectivity. Due to the protein imprinted sites are located at, or close to, the surface; these imprinted nanowires have a good site accessibility toward the target protein molecules. Furthermore, the large surface area of the nanowires results in large protein molecule binding capacity of the imprinted nanowires.     

分子印迹聚合物膜的制备及其应用

分子印迹膜兼具分子印迹与膜技术的优点,近年来已成为分子印迹技术领域研究的热点之一.首先对分子印迹技术及分子印迹膜进行了简介,继而重点对分子印迹膜的主要制备方法,包括原位聚合法、相转化法、表面修饰法和电化学聚合法等进行了评述,对现有分子印迹膜的分离性能进行了总结和分析.最后对分子印迹膜在手性物质拆分、固相萃取、农药残留检测及仿生传感等领域的应用及其研究方向进行了介绍和展望.     

单步溶胀聚合法制备单分散分子印迹聚合物微球:孔结构及其吸附与识别性能

采用单步溶胀聚合法在水溶液中制得了单分散的S-萘普生分子印迹聚合物微球。利用扫描电镜及氮气吸附试验分析了微球的形态及孔结构,并考察了微球的吸附与识别性能。研究结果表明,通过单步溶胀聚合法制得的分子印迹聚合物微球具有较窄的粒径分布（ε〈2．0％）,氯仿及交联剂的用量对微球的表面形态、孔径大小及分布、比表面积等都有明显的影响。Scatchard分析表明分子印迹聚合物微球在识别S-萘普生分子过程中存在两类结合位点,高亲和力的结合位点的离解常数为Kd1=2.13mmol/L,Qmax1=36.46μmolg/g,低亲和力的结合位点的离解常数为Kd2=31．55mmol／L,Qmax2=389．99μmol／g。     

磁性分子印迹聚合物微球的应用研究进展

将磁性分离技术与分子印迹技术相结合,制备磁性分子印迹聚合物(MMIPMs),该复合材料兼具良好的超顺磁性和高选择吸附性两大优点,具有广阔的应用前景。文章重点综述了磁性分子印迹聚合物微球在食品检测、医药领域、手性药物拆分、生物分离和环境检测方面的应用进展,并指出未来发展方向。     

Application of a molecularly imprinted polymer for the effective recognition of different anti-epidermal growth factor receptor inhibitors

A molecularly imprinted polymer (MIP) was prepared using (E)-piceatannol, a natural potential anti-epidermal growth factor receptor (EGFR) inhibitor, as the template and 4-vinylpyridine as the functional monomer. The template was isolated from a Chinese traditional Tibetan medicinal herb, Caragana jubata, by a solid-phase extraction procedure. The crude extract of this herb was loaded on the MIP column for the binding test, and two different compounds besides the template itself were specifically recognized by the polymer, which were identified to be butein and quercetin possessing potent anti-EGFR tyrosine kinase activities with IC(50) values of 10 and 15 microM, respectively. Affinity and selectivity for these inhibitors and another three compounds coexisting with the template in this herb were evaluated in the chromatographic mode. For the first time, the affinity of a molecularly imprinted polymer was investigated to be correlative to the bioactivities of the analytes. The chromatographic behavior of the analytes was consistent with their activity values: the more active inhibitor was retained longer on the MIP. This research work afforded us a new approach for the effective recognition of novel anti-EGFR inhibitors from herbs by using the MIP as the receptor mimic to assay the bioactivities of reserved components, which will be very helpful in the direct separation of lead candidates for anticancer drugs.     

Surface-grafted molecularly imprinted polymers for protein recognition.

A technique for coating microplate wells with molecularly imprinted polymers (MIPs) specific for proteins is presented. 3-Aminophenylboronic acid was polymerized in the presence of the following templates: microperoxidase, horseradish peroxidase, lactoperoxidase, and hemoglobin, via oxidation of the monomer by ammonium persulfate. This process resulted in the grafting of a thin polymer layer to the polystyrene surface of the microplates. Imprinting resulted in an increased affinity of the polymer toward the corresponding templates. The influence of the washing procedure, template concentration, and buffer pH on the polymer affinity was analyzed. It was shown that the stabilizing function of the support and spatial orientation of the polymer chains and template functional groups are the major factors affecting the imprint formation and template recognition. Easy preparation of the MIPs, their high stability, and their ability to recognize small and large proteins, as well as to discriminate molecules with small variations in charge, make this approach attractive and broadly applicable in biotechnology, assays and sensors.     

Data on the structure and recognition properties of the template-selective binding sites in semi-IPN-based molecularly imprinted polymer membranes

Data on the structure and recognition properties of the template-selective binding sites in molecularly imprinted polymer membranes are presented. Porous molecularly imprinted polymer membranes based on semi-interpenetrating polymer networks (semi-IPN) were synthesized using the method of molecular imprinting in a combination with the method of computational modeling. Methacrylic acid, itaconic acid, and acrylamide were identified as optimal functional monomers for a model template — atrazine. Optimal ratios between atrazine and functional monomers as well as their binding energies were determined using the method of computational modeling and compared with the experimental data on the adsorbtion capability of porous molecularly imprinted polymer membranes. The factors influencing quality of the template-binding sites in MIP membranes (binding energy template-functional monomer and the number of functional groups taking part in the recognition of the template molecule) were revealed. The computational atrazine-selective membranes were capable of highly-selective and effective adsorbtion of atrazine from its 10^− 9–10^− 4 M aqueous solutions, and were characterized by high stability during prolonged storage. The apparent structure of the synthetic mimics of biological receptors to triazine herbicides was compared with the structure of their natural counterparts.     

分子印迹聚合物微球合成方法研究进展

对近年来发展起来的分子印迹聚合物微球(MIPMs)合成方法的研究进展进行了综述。重点介绍了表面分子印迹聚合物合成法、核-壳型分子印迹聚合物合成法、基于β-环糊精分子印迹聚合物的合成法3种新型MIPMs制备方法。阐述了常用的沉淀聚合法、种子溶胀聚合法、悬浮聚合法合成MIPMs的发展现状。最后对MIPMs的发展趋势提出了展望。     

Assay system for the herbicide 2,4-dichlorophenoxyacetic Acid using a molecularly imprinted polymer as an artificial recognition element

Noncovalent molecular imprinting of a synthetic polymer with the herbicide 2,4-dichlorophenoxyacetic acid has been achieved in the presence of the polar solvents methanol and water. Formation of the prearranged complex relied on hydrophobic and ionic interactions between the template and the functional monomer 4-vinylpyridine. The polymer obtained binds the original template with an appreciable selectivity over structurally related compounds. The potential use of micrometer-sized imprinted polymer particles as the recognition element in a radioligand binding assay for 2,4-dichlorophenoxyacetic acid is demonstrated.     

Monoclonal behavior of molecularly imprinted polymer nanoparticles in capillary electrochromatography

A new approach based on miniemulsion polymerization is demonstrated for synthesis of molecularly imprinted nanoparticles (MIP-NP; 30-150 nm) with "monoclonal" binding behavior. The performance of the MIP nanoparticles is characterized with partial filling capillary electrochromatography, for the analysis of rac-propranolol, where (S)-propranolol is used as a template. In contrast to previous HPLC and CEC methods based on the use of MIPs, there is no apparent tailing for the enantiomer peaks, and baseline separation with 25,000-60,000 plate number is achieved. These effects are attributed to reduction of the MIP site heterogeneity by means of peripheral location of the core cross-linked NP and to MIP-binding sites with the same ordered radial orientation. This new MIP approach is based on the substitution of the functional monomers with a surfactant monomer, sodium N-undecenoyl glycinate (SUG) for improved inclusion in the MIP-NP structure and to the use of a miniemulsion in the MIP-NP synthesis. The feasibility of working primarily with aqueous electrolytes (10 mM phosphate with a 20% acetonitrile at pH 7) is attributable to the micellar character of the MIP-NPs, provided by the inclusion of the SUG monomers in the structure. To our knowledge this is the first example of "monoclonal" MIP-NPs incorporated in CEC separations of drug enantiomers.     

Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays

The interaction of seven novel fluorescent labeled beta-lactams with a library of six polymer materials molecularly imprinted (MI) with penicillin G (PenG) has been evaluated using both radioactive and fluorescence competitive assays. The highly fluorescent competitors (emission quantum yields of 0.4-0.95) have been molecularly engineered to contain pyrene or dansyl labels while keeping intact the 6-aminopenicillanic acid moiety for efficient recognition by the cross-linked polymers. Pyrenemethylacetamidopenicillanic acid (PAAP) is the tagged antibiotic that provides the highest selectivity when competing with PenG for the specific binding sites in a MI polymer prepared with methacrylic acid and trimethylolpropane trimethacrylate (10:15 molar ratio) in acetonitrile in the presence of PenG. Molecular modeling shows that recognition of the fluorescent analogues of PenG by the MI material is due to a combination of size and shape selectivity and demonstrates how critical the choice of label and tether chain is. PAAP has been applied to the development of a fluorescence competitive assay for PenG analysis with a dynamic range of 3-890 muM in 99:1 acetonitrile-water solution. Competitive binding studies demonstrate various degrees of cross-reactivity for some antibiotics derived from 6-aminopenicillanic acid, particularly amoxicillin, ampicillin, and penicillin V (but not oxacillin, cloxacillin, dicloxacillin, or nafcillin). Other antibiotics, such as chloramphenicol, tetracycline, or cephapirin, do not compete with PAAP for binding to the imprinted polymer. The MI assay has successfully been tested for PenG analysis in a pharmaceutical formulation.     

利用辐射聚合方法制备黄芩素分子印迹聚合物

首次采用电子加速器高能电子束辐射聚合的方法制备黄芩素分子印迹聚合物。该方法与传统的聚合方式相比,具有无需添加引发剂、反应速度快、生成产物稳定等特点。只需以中药活性成分黄芩素为模板分子,α-甲基丙烯酸为功能单体,就可以制备具有特异选择吸附性的黄芩素分子印迹聚合物。并运用红外光谱分析、透射电子显微镜、扫描电镜研究了黄芩素分子印迹聚合物的结构。     

Design of size-tunable molecularly imprinted polymer for selective adsorption of acetaminophen

Pharmaceutical and personal care products are a broad and diverse group of biologically active compounds which are widely used and unregulated suspected carcinogens. In this study, the fabrication of molecularly imprinting polymer (MIP) particles by precipitation polymerisation were developed to selectively and rapidly capture acetaminophen, a commonly used analgesic and antipyretic drug, by hydrogen and hydrophobic bondings. Methacrylic acid, 3-(trimethoxysilyl) propyl methacrylate and 2, 2′-azobis-isobutyronitrile were utilised as the functional monomer, cross-linker and initiator. Acetonitrile was found to be the optimised porogen to obtain imprinted polymers with surface area and pore size of 447.2 m²/g and 3.35 nm. By adjusting the ratio of cross-linker and functional monomer, the particle size of MIPs changed from 177 to 2782 nm when the ratio increased from 0.43 to 12.8. In addition, the adsorption equilibrium of acetaminophen by MIPs can be reached within the first 30 min because of the surface imprinting characteristics and small particle sizes. In addition, the maximum adsorption capacity of acetaminophen and the adsorption constant, well fitted by Langmuir equation, were 0.35 mg/g and 0.045 L/mg. In addition, the MIPs exhibited the excellent selectivity to acetaminophen. The high surface area and adsorption capacity and excellent selectivity make MIPs an ideal tailor-made green material and can open the door to develop the novel technology for adsorption and removal of pharmaceutical and personal care products in the environment.     

具有辅助性能的红霉素分子印迹聚合物的制备及性能

分别制备了磁性Fe3O4@聚丙烯酸(Fe3O4@PAA)红霉素分子印迹聚合物(ERYMIP)和光降解TiO2@PAAERYMIP,以期更好地分离或降解红霉素,从而提高处理残留红霉素的能力.采用SEM、XRD、FTIR、TG和磁滞回线(MHL)等对两种印迹聚合物的形貌、结构和性能进行了表征.实验表明Fe3O4@PAA E...     

L-色氨酸分子印迹膜的表征、识别性能及识别机理

以L-色氨酸为模板分子,甲基丙烯酸为功能单体,聚砜为基膜,采用紫外光接枝法制备L-色氨酸手性分子印迹固膜.用扫描电镜和原子力电子显微镜对固膜的形貌进行表征,并对其特异性吸附性能及识别机理进行研究.固膜的手性分离因子高达4.1,由Scatchard模型分析分子印迹固膜与模板分子之间的结合作用力以氢键作用为主.     

Dipyridamole recognition and controlled release by uniformly sized molecularly imprinted nanospheres

We used novel synthetic conditions of precipitation polymerization to obtain uniformly sized molecularly imprinted nanospheres of dipyridamole for application in the design of new drug delivery systems. In addition, the morphology, drug release, and binding properties of molecularly imprinted polymers (MIPs) were studied, and the effects of morphology on other properties were investigated. The MIPs prepared by acetonitrile/chloroform (19:1, v/v) were uniformly sized nanospheres with an average mean diameter of approximately 88 nm at a wetted state, 50 nm at a dry state, and a polydispersity index of 0.062. The imprinted nanospheres showed excellent binding properties and had 62.7% of template binding compared with 17.1% of its blank polymer. The imprinted nanospheres with 67.5 (mg template/of polymer) of binding capacity had better imprinting efficiency than the 50.5% of binding capacity shown by irregularly shaped MIP particles that were prepared by chloroform. The molecular binding abilities of imprinted nanospheres in human serum were evaluated by HPLC analysis (binding about 77% of dipyridamole). Results from release experiments of MIPs showed a very slow, controlled, and satisfactory release of dipyridamole. The loaded drug was released up to 99% in 17 days for nanospheres and 22 days for irregularly shaped particles.     

氧化乐果分子印迹微球的制备及其性能研究

以氧化乐果为模板分子,甲基丙烯酸（MAA）为功能单体,利用悬浮聚合法制备了粒径分布范围较窄的氧化乐果分子印迹微球（MIPMs）和空白对照微球（NMIPMs）。通过紫外光谱及红外光谱说明了MAA与氧化乐果之间的结合作用,并利用扫描电子显微镜（SEM）观察了所制微球的外观形态和粒径分布。静态吸附实验证明MIPMs对氧化乐果的吸附量明显大于NMIPMs。Scatchard分析表明,MIPMs在识别氧化乐果过程中存在两类结合位点：高亲和位点的解离常数KD1=0.131mmol/L,最大表观结合量Qmax1=3.890μmol/g,低亲合位点解离常数为KD2=5.178mmol/L,最大表观结合量Qmax2=62.232μmol/g。选择性吸附实验结果表明MIPMs对氧化乐果的吸附量最大,具有很好的选择性能。     

Composite of Au nanoparticles and molecularly imprinted polymer as a sensing material

A molecularly imprinted polymer with immobilized Au nanoparticles (Au-MIP) is reported as a novel type of sensing material. The sensing mechanism is based upon the variable proximity of the Au nanoparticles immobilized in the imprinted polymer, which exhibits selective binding of a given analyte accompanied by swelling that causes a blue-shift in the plasmon absorption band of the immobilized Au nanoparticles. Using adrenaline as the model analyte, it was shown that molecular imprinting effectively enhanced the sensitivity and selectivity, and accordingly, Au-MIP selectively detects the analyte at 5 microM. The combination of molecular imprinting and the Au nanoparticle-based sensing system was shown to be a general strategy for constructing sensing materials in a tailor-made fashion due to wide applicability of the imprinting technique and the independence of the sensing mechanism from the analyte recognition system.     

Characterization of swellable molecularly imprinted polymer particles by surface plasmon resonance spectroscopy

Surface plasmon resonance (SPR) has been used to investigate template binding at sites in theophylline-imprinted poly-[N-(N-propyl) acrylamide] particles. At concentrations as low as 10(-6) M theophylline, particle swelling is detected as a shift in the angle of minimum reflectance. The binding constant of theophylline estimated from the inflection point of the theophylline calibration curve is approximately 10,000. The imprinted polymer particles do not respond to caffeine or theobromine (which differs from theophylline by a single methyl group) at concentrations as high as 10(-2) M. Full-scale response of the imprinted polymer particles to theophylline (template) occurs in less than 15 minutes, and swelling is reversible. The immobilized imprinted polymer particles can undergo approximately 20 to 25 swelling and shrinking cycles before there is significant loss in functionality. A unique aspect of these imprinted polymer particles is that template binding causes the angle of minimum reflectance to decrease, not increase, in magnitude. Adsorption, which causes an increase in the angle of minimum reflectance, can be readily discriminated from template binding.