Molecular recognition effects in atomistic models of imprinted polymers

In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects.     

硫丹分子印迹聚合物的合成及吸附特性分析

采用分子印迹技术,以α-甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,偶氮二异丁腈为引发剂,乙腈为致孔剂,合成以硫丹为模板的印迹聚合物微球。首先利用紫外光谱方法研究了模板与功能单体相互作用情况,采用平衡吸附试验对印迹聚合物吸附效率进行了表征,与化学组成相同的空白聚合物相比,印迹聚合物微球对模板分子具有更高的吸附效率,按最佳合成条件得到的印迹聚合物最大表观吸附量达42.56 mmol/g。     

单体对分子印迹聚合物分子识别能力的影响：量子化学计算与实验研究

采用密度泛函方法计算功能单体与印迹分子的结合能,以与目标分子结合能最大的单体分子来合成分子印迹聚合物.为此,以茶碱为印迹分子,氯仿为溶剂,首先计算了茶碱与甲基丙烯酸、丙烯酰胺和三氟甲基丙烯酸的结合能,其强度顺序为：三氟甲基丙烯酸 > 甲基丙烯酸 > 丙烯酰胺.然后以茶碱为印迹分子、氯仿为溶剂、二甲基丙烯酸乙二醇酯为交联剂,分别采用上述3种单体合成分子印迹聚合物并测定了其分子识别能力,实验结果和量子化学计算结果具有一致性.最后,采用1H NMR考察了茶碱和上述3种单体之间的氢键作用,揭示出二者相互作用的内在机制.研究结果表明量子计算方法可以应用于合成分子印迹聚合物时单体的选择.     

The influence of polymer morphology on the performance of molecularly imprinted polymers

This is the first in-depth study examining the effect of morphology on the performance of 2-aminopyridine (2-apy) imprinted polymers. A series of polymers were prepared by varying the amount of crosslinking monomer (EGDMA) whilst the other polymer components remained constant. Physical characterisation was carried out using conventional techniques, such as nitrogen sorption porosimetry and solvent swelling studies. The use of a novel thermal desorption GC-MS technique suggested higher levels of polymer degradation with prolonged exposure to elevated temperatures for those polymers formed with lower amounts of EGDMA. The thermal desorption GC-MS profiles obtained correlated with the physical characteristics of the polymers, where higher levels of polymer bleed was found to occur with larger average pore diameters. Polymer physical characteristics were also found to correlate with the binding parameters (number of binding sites and polymer-template association energy) obtained from the Langmuir-Freundlich Isotherm (L-FI) and affinity distribution spectra (AD). The flexibility of the polymers formed from lower amounts of EGDMA combined the swelling effect of the solvents on the polymers resulted in an increase in affinity, which was both specific and non-specific in nature.     

Three-level response surface full-factorial design: advanced chemometric approach for optimizing diclofenac sodium-imprinted polymer

The present research work was undertaken to optimize the template:monomer:cross-linker ratio of the diclofenac sodium block molecularly imprinted polymer with respect to the molecular recognition properties. A three-level full-factorial design was employed. This is of great interest because applying this approach instead of traditional methods would be expected to improve validation of the optimum and consumed time. Imprinted polymers with selected ratios and the control polymers were synthesized by precipitation polymerization method and the values of rebind capacity and imprinting factor calculated after performing batch rebinding experiments. The predicted optimum ratios of (1:8:40) and (1:4:40) were found by applying the three-dimensional surface plots for rebind capacity and imprinting factor. The optimized imprinted polymers and their control polymers were produced. These polymers were evaluated using equilibrium binding experiments and finally the optimum molar ratio of (1:8:40) chosen. Batch rebinding experiments were carried out to evaluate the binding and selectivity properties of the optimized polymer. A heterogeneous nature of the binding sites was found based on the Scatchard plot. The selectivity study of imprinted polymers demonstrated a 24 % cross-reactivity towards meclofenamate sodium, but less than 2 % towards fenoprofen calcium.     

Synthesis and characterization of high selective molecularly imprinted polymers for bisphenol A and 2,4-dichlorophenoxyacetic acid by using supercritical fluid technology

Molecularly imprinted polymers (MIPs) have been extensively used in chemical and biochemical related areas due to their high molecular recognition affinity and selectivity for the target molecule. On the other hand, supercritical polymerization is relatively novel technique, which can be applied in the polymerization without hazard organic solvent. This work introduces a supercritical fluid polymerization technique for preparation of MIP particles. The adsorption properties of prepared MIP particles are also investigated. The MIPs were prepared with methyl methacrylate (MMA) as a third monomer, methacrylic acid (MAA) as a functional monomer, templates (bisphenol A (BPA) and 2,4-dichlorophenoxyacetic acid (2,4-D)), methyl methacrylate (MMA) as a third vinyl monomer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker. Equilibrium binding experiments are conducted to evaluate the binding characteristics of MIPs and templates (BPA and 2,4-D). The Scatchard plot analysis demonstrates that two classes of binding sites are formed with the equilibrium dissociation constants. The adsorption ability of the MIPs was also evaluated by measuring the adsorbed amounts of a similar imprinted template structure, the selectivity factor (α), and the imprinting-induced promotion of binding (IPB).     

Selective removal of ATP degradation products from food matrices I: Design and characterization of a dummy molecularly imprinted specific sorbent for hypoxanthine

Specific molecularly imprinted polymers (MIPs) for hypoxanthine (HYP) recognition in aqueous organic media have been developed based upon UV, FTIR and ¹H NMR prepolymerization studies in conjunction with batch rebinding UPLC analyzes. The MIPs, which used the template mimics caffeine (CAF) and theophylline (TPH), are prepared in CHCl₃ by one step precipitation polymerization from acrylamide (AM), 2-hydroxyethyl-methacrylate (HEMA) and methacrylic acid (MAA) as functional monomers, whereas ethylene glycol dimethacrylate (EGDMA), divinylbenzene (DVB) and trimethylolpropane triacrylate (TMPTA) as cross-linkers. The magnitude of the pre-polymerization binding constants between TPH and AM, MAA and HEMA is consistent with the complex stoichiometry (1:2 and 1:1) and number of interaction points (3-, 2-, 1-hydrogen bonded motif). The strong (1:2) complex between TPH and AM (K₁₁ = 3.36 × 10⁴ M⁻¹ and K₁₂ = 1.33 × 10² M⁻¹) makes the corresponding MIP the most suitable for HYP recognition. The best performance of the TPH:AM:EGDMA (1:4:20) MIP is reflected in the high IF and high weighted average affinity based on the Freundlich isotherm. Further polymer characterization by ATR–FTIR, elemental analysis, surface area analysis (BET), swelling and SEM yield vital information regarding the degree of polymerization, real monomer:crosslinker ratio, morphology, pore size distribution plus conformational changes on exposure to different solvents.     

红霉素分子印迹聚合物纳米微球的制备及其吸附特性

以红霉素为模板分子、甲基丙烯酸为功能单体、乙二醇二甲基丙烯酸酯为交联剂,采用沉淀聚合法制备了粒径均一的红霉素纳米分子印迹聚合物微球,优化了分子印迹聚合物的合成条件,确定了模板分子与功能单体的最佳摩尔比为1:3,对其进行了表征. 结果表明,所制聚合物对红霉素的实际最大吸附量可达202.12 mg/g,吸附约200 min达到平衡,对红霉素具有良好的选择性吸附能力.     

Preparation of core–shell structural surface molecular imprinting microspheres and recognition of l-Asparagine based on [N1111]Asn ionic liquid as template

Core–shell structural surface imprinting microspheres were prepared by a simple and effective method. This method combined reversible addition–fragmentation chain transfer (RAFT) with distillation precipitation polymerization RAFT reagent-containing microspheres on the surface. Tetramethylammonium asparagine ([N₁₁₁₁]Asn) ionic liquid or l-Asn, 4-vinylpyridine (4-VP), ethylene glycol dimethacrylate (EGDMA), and RAFT reagent-containing microspheres on the surface were used as template, functional monomer, cross-linker, and chain transfer agent (CTA), respectively. Two kinds of imprinted polymer were obtained, namely, AsnIL-MIPs and Asn-MIPs. The morphology and structure of the polymers were characterized by scanning electron microscopy and Fourier-transform infrared spectroscopy. The binding and selective recognition properties of l-Asn and its analogs were investigated in aqueous solution. Compared with l-Asn as template molecule, AsnIL-MIPs showed faster binding speed and better selective recognition. The binding reached saturation after 1 h, and the selective recognition factor (α) reached 5.28 and 4.26 for the template against l-Asp and l-Arg, respectively. AsnIL-MIPs showed an improved binding rate, binding affinity, and significantly increased recognition.     

分子印迹功能单体选择方法研究进展

分子印迹技术是以一种化合物作为模板,制备出对该模板分子具有特定＂记忆功能＂的聚合物。在分子印迹技术中,功能单体的选择对分子印迹聚合物的识别性能起着至关重要的作用,总结了近些年关于预测功能单体的分析方法及其分析原理,并做了详细的介绍。     

苯胺绿分子印迹聚合物制备条件对识别能力的影响

本文研究了在以苯胺绿为模板分子,α-甲基丙烯酸( MMA)和2-乙烯基吡啶为功能单体,乙二醇二甲基丙烯酸酯( EGDMA)为交联剂,偶氮二异丁腈为引发剂,乙腈和四氧呋喃为溶剂分别在热引发和光引发的条件下合成以孔雀石绿为模板分子的印迹聚合物的实验过程中,通过选择不同配比的反应物,分析了各种合成条件对印迹聚合物识别能力的影...     

沉淀聚合法制备烟酰胺分子印迹聚合物微球

以烟酰胺为模板分子,甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,偶氮二异丁腈为引发剂,乙腈为溶剂,采用沉淀聚合法制备了烟酰胺分子印迹聚合物,通过静态平衡吸附和色谱分析对印迹聚合物进行表征,结果表明,印迹聚合物对烟酰胺分子具有很好的吸附能力和特异识别性。     

Computer simulation and synthesis of stimuli‐responsive polymer by sol‐gel for selective recognition of (4‐chloro‐2‐methylphenoxy)acetic acid

A novel photoresponsive functional monomer bearing a siloxane polymerizable group and azobenzene moieties was synthesized, and then photoresponsive molecularly imprinted sol‐gel polymers were successfully fabricated from the synthesized functional monomer, using (4‐chloro‐2‐methylphenoxy)acetic acid (MCPA) as a molecular template. The photoisomerization properties of the functional monomer are retained after incorporation into the rigid three‐dimensional crosslinked polymer matrix. The template is then removed from the resulting polymer to generate pores, which are complementary to the template in shape, size and functionality. The substrate affinity of the molecularly imprinted polymer (MIP) receptor sites is photoswitchable. This can be attributed to the photoisomerization of azobenzene chromophores within the MIP receptors, resulting in alteration of their geometry and the spatial arrangement of their binding functionalities. The binding affinity of the imprinted recognition sites was switchable by alternate irradiation with UV and visible light, suggesting that azobenzene groups located inside the binding sites could be used as chemical sensors and the trans–cis isomerization could regulate the affinity for MCPA. To study the hydrogen bond interactions between template molecules and functional monomer, computational molecular modeling was employed. The data indicate that the design of the MIP is rational. Copyright © 2012 Society of Chemical Industry     

不同功能单体制备的S-萘普生印迹聚合物材料的性能

以S-萘普生为模板,分别采用丙烯酰胺(AM)、N-乙烯基吡咯烷酮(NVP)和甲基丙烯酸(MAA)3种功能单体,合成了印迹聚合物P1、P2和P3。用UV和Chem 3D计算模拟,研究了功能单体与模板分子之间的相互作用,经PM3半经验方法计算得到AM、NVP、MAA与模板分子之间的相互作用能分别为-32.06、-21.01和-1.55kJ/mol。平衡结合实验测得当底物浓度为0.1 mmol/L时,P1、P2和P3的吸附量分别为0.360、0.305和0.150μmol;在浓度为0.1~4 mmol/L时,3种分子印迹聚合物对S-萘普生的吸附量大小关系为P1>P2>P3,这与计算出的功能单体与模板分子之间的相互作用能大小关系一致。     

Delaying the onset of macrogelation for the synthesis of branched and star-like polymers via conventional free-radical polymerisation: Binary solvent effects and incorporation of surfmers

It is known that the preferential solvation and conformation of a polymer in a solvent mixture are functions of the polymer's molecular weight and the solvent qualities. This paper demonstrates that these relationships can be exploited to delay the onset of macrogelation for branched poly(methyl methacrylate/ethylene glycol dimethacrylate) (p(MMA/EGDMA)) polymers and star-like poly(methyl acrylate/ethylene glycol dimethacrylate) (p(MA/EGDMA)) polymers synthesised via conventional free-radical polymerisation (CFRP) in a binary solvent mixture (consisting of a good solvent and a precipitant for the polymer). The gelation limits of the MMA/EGDMA and MA/EGDMA polymerisations in a methyl ethyl ketone (MEK)/heptane binary solvent mixture can be extended to regions of higher monomer concentration with increases in polymer yield between 13 and 50 ± 5 w/w% for the p(MMA/EGDMA) system and between 8 and 19 ± 6 w/w% for the p(MA/EGDMA) system across the gelation boundary. Thus, a facile method of increasing the concentration of batch reaction mixtures by the simple addition of small amounts of precipitant into the reaction solutions is presented. Furthermore, the gelation limits of both polymerisation systems in the binary solvent mixtures were further extended with increases in polymer yield between 11 and 17 ± 4%w/w for the p(MMA/ODA/EGDMA) system and between 8 and 20 ± 5%w/w for the p(MA/VS/EGDMA) system by the respective incorporation of octadecyl acrylate (ODA) and vinyl stearate (VS) surfmers into the polymers, demonstrating the application of steric hinderance to shield the propagating polymers from excessive cross-linking reactions.     

Synthesis and Evaluation of a Molecularly Imprinted Polymer for Solid Phase Extraction of Ethopabate from Chicken Tissue

In this paper the development and evaluation of a molecularly imprinted polymer (MIP) for ethopabate is described. Ethopabate (ETP), 4-acetamido-2-ethoxybenzoic acid methyl ester, is one of the antibiotics which is used as coccidiostat in poultry feeds. In the present study, two widely used functional monomers, methacrylic acid (MAA) and 4-vinylpyridine (4-VP) were compared theoretically and experimentally as the candidates for MIP preparation. Hyperchem software was employed to estimate binding energies between ETP and functional monomers and batch rebinding experiments were performed to study the binding characteristics of the polymers. The results showed that MAA is a better functional monomer to prepare MIP. UV/Vis and NMR spectroscopy were used as two common tools to study the interactions between ETP and MAA in the pre-polymerization mixture. Liquid chromatography experiments showed that the prepared MIP has recognition capability toward ETP in comparison with other structurally related compounds. The ETP-imprinted polymer was further applied for selective solid phase extraction (SPE) of ETP from a chicken tissue sample. The extraction yield of ETP was found to be quantitative (87 ± 3%) and the LOD and LOQ based on 3 and 10 times of the noise of HPLC profile were 0.05 and 0.32 ng ml^?1, respectively. It was confirmed that the binding ability of the prepared MIP for ETP was essentially sufficient in the presence of other compounds coexisting in tissue sample. Therefore, as a selective and efficient solid phase material, ETP-imprinted polymer has a high potential application in the analysis of residues of this antibiotic in chicken tissue samples.     

Synthesis and characterization of star-like microgels by one-pot free radical polymerization

A one-pot free radical polymerization process was used to prepare methyl acrylate/ethylene glycol dimethacrylate (MA/EGDMA) and methyl methacrylate/ethylene glycol dimethacrylate (MMA/EGDMA) polymers. The role of monomer and crosslinker reactivity ratios in producing different network structures was demonstrated. While both systems produced branched polymers that exhibited low intrinsic viscosities with little variation across a wide range of molecular weights, the star-like microgels formed between a less reactive monomer (MA) with a more reactive crosslinker (EGDMA) gave lower bulk solution viscosities than the more statistical polymers formed between similarly reactive monomers and crosslinkers (MMA and EGDMA). This paper presented a simple and cost-effective synthetic route for the production of polymers with high molecular weight and low viscosity with considerable potential for industrial-scale processing.     

印迹水凝胶作为氟尿嘧啶载体的药物缓释性能

以氟尿嘧啶为模板药物,以甲基丙烯酸羟乙酯为骨架单体,以甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,偶氮二异丁腈为引发剂合成印迹水凝胶,并通过扫描电镜、红外光谱及差示热量扫描等测试手段对凝胶进行了表征,结果表明：制备的印迹水凝胶表面无孔、光滑,氟尿嘧啶与其中的单体通过氢键结合成了复合物,同时经处理后凝胶中已不再残留未反应的单体。印迹水凝胶的吸水溶胀性能实验结果显示其吸水溶胀性能随制备中模板药物的含量的增加而增强,同时同一凝胶的溶胀速度与溶胀率随体系pH值的升高而增强。在氟尿嘧啶溶液中测定水凝胶的药物负载量,结果显示：印迹水凝胶的药物负载能力明显强于非印迹水凝胶,同时印迹水凝胶（8∶1）对药物的负载能力强于印迹水凝胶（4∶1）,药物负载量高达0.0914 mg/g。在模拟体液中测试水凝胶对药物的释放效果结果显示：印迹水凝胶对药物的缓释作用明显优于非印迹水凝胶,并且印迹水凝胶（8∶1）对药物的缓释效果优于印迹水凝胶（4∶1）,对药物的释放平缓,同时,释放体系pH值的升高不利于印迹水凝胶的药物缓释效果。     

甲基对硫磷分子印迹聚合物制备中溶剂和功能单体的影响

为了有效的分离富集水样中的有机磷农药,以甲基对硫磷为模板、二甲基丙烯酸乙二酯为交联剂,采用传统方法制备了甲基对硫磷分子印迹聚合物(MIPs).考察了三种溶剂和三种功能单体及其用量对MIPs吸附性能的影响.结果表明,以氯仿为溶剂制得的MIP特异性最强,溶剂用量对MIPs比表面积和溶胀比的影响显著.氯仿用量为35 mL时MIP性能最理想;~1H-NMR研究显示,4-乙烯基吡啶(4VP)与模板分子通过π-π堆积作用形成稳定的复合物,按4VP与模板分子摩尔比4:1制得的MIP特异性和亲和性较理想.测定了该MIP的吸附等温线,利用Langmuir等温式分析结果,得出其饱和吸附量为625.5 μmol·g~(-1),明显高于非印迹聚合物的饱和吸附量285.7 μmol·g~(-1).利用该MIP对模拟海水样品进行研究,结果显示,MIP对不同有机磷农药的吸附能力表现出一定的差异.通过进一步优化,提高MIPs的选择性,该材料有望用于水样中甲基对硫磷的分离富集和分析.     

Uniformly sized molecularly imprinted polymers for on‐line concentration,purification, and measurement of nimodipine in plasma

Uniformly sized molecularly imprinted polymers (MIPs) for nimodipine have been prepared in an aqueous system by multi‐step swelling and polymerization method, utilizing 4‐vinylpyridine (4‐VPY) or methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EDMA) as a cross‐linking agent. Scanning electron microscopy was used to identify the structure features of the obtained polymers. Further, the influences of some chromatographic conditions were examined to explore the possible recognition mechanism. The results reveal that stable molecularly imprinted polymeric microspheres with good size monodispersity were obtained, and the polymer beads showed specific recognition for the template molecule and some other dihydropyridine calcium antagonists (DHPs). Besides hydrophobic interaction, the molecular shape complementation of DHPs and the MIPs seems to play an important role in the retention and recognition of DHPs. The Scatchard analysis showed that two kinds of binding sites existed in the MIPs. The MIPs was then used as a high‐performance liquid chromatography (HPLC) separation medium to simultaneously concentrate and purify nimodipine in plasma. The results reveal that the obtained MIPs could be used for on‐line concentration, purification, and measurement of nimodipine in biological samples. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009