Molecularly imprinted polymer microspheres prepared by precipitation polymerization using a sacrificial covalent bond

Molecularly imprinted polymer microspheres were prepared by precipitation polymerization using a sacrificial covalent bond. In the present model, cholesteryl (4‐vinyl)phenyl carbonate was used as a template monomer. The imprinted microspheres were prepared using ethylene glycol dimethacrylate (EDMA) and divinylbenzene (DVB) as crosslinker. The base‐labile carbonate ester bond was easily hydrolyzed to leave imprinted cavities in the resulting polymers. Radioligand binding analysis, elemental analysis, and scanning electron microscopy were used to characterize the imprinted materials. Imprinted microspheres prepared from DVB crosslinker had larger and more defined spherical shape, and displayed better imprinting effect than did the EDMA‐based microparticles. For comparison, imprinted bulk polymers were also prepared in the same reaction solvent as that used in precipitation polymerization. Elemental analysis results indicated that imprinted microspheres contained more template monomer units than bulk materials. The efficiency of template removal by hydrolysis treatment for microspheres was also higher than that for bulk polymers. For DVB‐based polymers, imprinted microspheres displayed higher specific cholesterol uptake than did the corresponding bulk polymer. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1390–1398, 2006     

Imprinted β‐cyclodextrin polymers using naringin as template

The objective of this study was to identify a kind of molecular imprinting polymer (MIP) which was suitable for recognizing naringin (NG) in aqueous medium. Based on two crosslinkers (hexamethylene diisocyanate and epichlorohydrin) and two polymerization methods (solution polymerization and emulsion polymerization), four non‐covalent naringin‐β‐cyclodextrine (NG‐β‐CD) imprinted polymers were prepared by using β‐CD as a functional monomer and NG as a template molecule. The binding property and selectivity were evaluated by equilibrium binding experiments. These demonstrated that all the sites in the MIPs show good selective binding ability for NG from naringin dihydrochalcone, a structurally similar molecule. Of the four MIPs, rod‐like 3# MIP which was prepared by emulsion polymerization using hexamethylene diisocyanate as crosslinker exhibited the highest selectivity, its imprinting factor α being 1.53. Scatchard analysis of 3# MIP suggests that there are two classes of binding sites during the MIP's recognition of NG. Additionally, the 3# MIP could be used at least five times without any loss in sorption capacity. Copyright © 2011 Society of Chemical Industry     

Cholesterol interaction with recombinant human sterol carrier protein-2

The interaction of human recombinant sterol carrier protein-2 (SCP-2) with sterols was examined. Two independent ligand binding methods, Lipidex 1000 binding of [³H]cholesterol and a fluorescent dehydroergosterol binding assay, were used to determine the affinity of SCP-2 for sterols. Binding analysis indicated SCP-2 bound [³H]cholesterol and dehydroergosterol with aK _d of 0.3 and 1.7 μM, respectively, and suggested the presence of a single binding site. Phase fluorometry and circular dichroism were used to characterize the SCP-2 sterol binding site. Alterations in dehydroergosterol lifetime, SCP-2 tryptophan lifetime, and SCP-2 tryptophan quenching by acrylamide upon cholesterol binding demonstrated a shielding of the SCP-2 tryptophan from the aqueous solvent by bound sterol. Differential polarized phase fluorometry revealed decreased SCP-2 tryptophan rotational correlation time upon cholesterol binding. Circular dichroism of SCP-2 indicated that cholesterol elicited a small decrease in SCP-2 alpha helical content. The data suggest that SCP-2 binds sterols with affinity consistent with a lipid transfer protein that may act either as an aqueous carrier or at a membrane surface to enhance sterol desorption.     

分子印迹技术及应用

分子印迹技术作为一种新型高效分离技术,具有空间专一识别特性。本文综述了共价法与非共价法分子印迹技术的基本原理,采用传统方法、扩散聚合、悬浮聚合和表面印迹等制备分子印迹聚合物的方法,以及分子印迹技术在色谱分离、抗体和受体模拟物、固相萃取、生物传感器等领域的应用。最后指出分子印迹技术目前存在的问题。     

Preparation of molecularly imprinted polymer microspheres via reversible addition-fragmentation chain transfer precipitation polymerization

The first combined use of reversible addition-fragmentation chain transfer (RAFT) polymerization and precipitation polymerization in the molecular imprinting field is described. The new polymerization technique, namely RAFT precipitation polymerization (RAFTPP), provides MIP microspheres with obvious molecular imprinting effects towards the template, fast template binding process and an appreciable selectivity over structurally related compounds, while only irregular MIP aggregates were obtained via traditional radical precipitation polymerization (TRPP) under similar reaction conditions. The MIP microspheres prepared via RAFTPP have proven to show improved binding capacity, larger binding constant and apparent maximum number for high-affinity sites, and significantly higher high-affinity binding site density in comparison with the MIP prepared via TRPP.     

醋酸甲基环己酯在双氧水生产中的应用

叙述了双氧水生产中的新型溶剂醋酸甲基环己酯对于2-乙基蒽醌的溶解情况,并对其配制成工作液在300t／a双氧水中试装置进行应用评价试验。试验结果表明,2-乙基蒽醌的溶解能力提高30％,应用于双氧水的生产,可相应提高双氧水装置生产能力30％。     

Preparation of molecularly imprinted polymers in supercritical carbon dioxide

Molecularly imprinted polymer nanoparticles were prepared in supercritical carbon dioxide using a noncovalent imprinting approach. In the present work, propranolol was used as a model template, methacrylic acid as a functional monomer, and divinylbenzene as a crosslinker. Under a high dilution condition, the heterogeneous polymerization resulted in discrete crosslinked polymer nanoparticles. Compared with the nonimprinted polymers, the imprinted nanoparticles displayed much higher propranolol uptake in a low polarity organic solvent. The use of a single enantiomer (S)‐propranolol as the template clearly demonstrated that the imprinted binding sites are chiral‐selective, with a cross‐reactivity towards (R)‐propranolol of less than 5%. The overall binding performance of the imprinted nanoparticles was comparable to imprinted polymers prepared in conventional organic solvents. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 2863–2867, 2006     

Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.     

Preparation and recognition performance of cholic acid-imprinted material prepared with novel surface-imprinting technique

Acrylamide (AM) was first graft-polymerized on the surface of crosslinked polyvinyl alcohol (CPVA) microspheres by initiating of cerium salt, and then the grafted polyacrylamide (PAM) was transformed to polyvinylamine (PVAm) via Hofmann degradation reaction, resulting in the grafted microspheres PVAm/CPVA. By adopting the novel surface molecular imprinting technique put forward by us, cholic acid molecule-imprinted material MIP-PVAm/CPVA was prepared with glutaraldehyde as crosslinking agent The binding character of MIP-PVAm/CPVA towards cholic acid molecules was studied in depth with both batch and column methods and using cholesterol as a contrast compound whose chemical structure is similar with cholic acid to a certain extent. The experimental results show that the surface-imprinted material MIP-PVAm/CPVA has excellent binding affinity and recognition selectivity for the template molecule, cholic acid. The selectivity coefficient of PVAm/CPVA microspheres (non-imprinting material) for cholic acid relative to cholesterol is only 1.314, displaying very poor recognition selectivity for cholic acid. However, after imprinting, the selectivity coefficient of MIP-PVAm/CPVA for cholic acid in respect to cholesterol is remarkably enhanced to 11.231, displaying the excellent recognition selectivity and binding affinity towards cholic acid molecules. Besides, MIP-PVAm/CPVA microspheres have fine desorption property, and by using a mixture of ethanol and NaOH aqueous solution as an eluent, the desorption ratios can reach 99.73% as the effluent amount gets up to 20 bed volumes (BV).     

溶剂对分子印迹聚合物分子识别能力的影响：实验研究与计算量子化学分析

以茶碱为印迹分子，甲基丙烯酸为功能单体，二甲基丙烯酸乙二醇酯为交联剂，以氯仿、二甲基亚砜和四氢呋喃为溶剂，合成了分子印迹聚合物并测定了其对茶碱分子的识别能力，实验结果显示，在氯仿中合成的MIPs的分子识别性能最佳.综合Scatchard分析吸附行为、¹H NMR测定氢键以及量子化学中的密度泛函计算印迹分子和单体分子的溶剂化能等方法，研究聚合反应的溶剂体系对于印迹聚合物分子识别能力的影响及其作用机制.计算结果显示：采用与印迹分子和单体相互作用力较弱的溶剂体系所合成的印迹聚合物具有较高的分子识别性能.这与¹H NMR分析结果和吸附测定实验结果具有一致性.上述结果表明，溶剂对于分子印迹聚合物的分子识别性能具有重要的影响，而计算量子化学分析对于分子印迹介质合成时的溶剂体系选取和优化具有很好的指导作用.     

Controlled release of prednisolone acetate from molecularly imprinted hydrogel contact lenses

The aim of this work was to study the influence of methacrylic acid (MAA) as a comonomer and the application of a molecular imprinting technique on the loading and release properties of weakly crosslinked 2‐hydroxyethyl methacrylate (HEMA) hydrogels, with a view toward their use as reloadable soft contact lenses for the administration of prednisolone acetate (PA). The hydrogels were prepared with HEMA (95.90–98.30 mol %) as a backbone monomer, ethylene glycol dimethacrylate (140 mM) as a crosslinker, and MAA (0, 50, 100, or 200 mM) as a functional monomer. Different PA/MAA molar ratios (0, 1 : 8, 1 : 6, and 1 : 4) in the feed composition of the hydrogels were also applied to study the influence of the molecular imprinting technique on their binding properties. The hydrogels (0.4 mm thick) were synthesized by thermal polymerization at 60°C for 24 h in a polypropylene mold. The hydrogels were then characterized by the determination of their swelling and binding properties in water. Their loading and release properties were also studied in 0.9% NaCl and artificial lachrymal fluid. Increasing the MAA content of the hydrogel and applying the molecular imprinting technique led to an increase in the loading capacity of the hydrogel. The optimized imprinted hydrogel showed the highest affinity for PA and the greatest ability to control the release process, sustaining it for 48 h. The results obtained clearly indicate that the incorporation of MAA as a comonomer increased the PA loading capacity of hydrogel. Our data showed that the molecular imprinting technique also had a significant effect on the loading and release properties of the hydrogels. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Comparative analysis of atrazine molecularly imprinted polymers using acetonitrile and toluene as solvents

Acetonitrile and toluene are solvents commonly used for the synthesis of atrazine molecularly imprinted polymers (MIPs), but their effects have seldom been compared in the same imprinting system. In this paper, effects of the two solvents in an atrazine molecular imprinting system were evaluated theoretically and experimentally. A polarizable continuum model was adopted, and it was found that using the two solvents, the energy difference for the atrazine–methacrylic acid complex between vacuum and solution was not the same. The two types of MIPs prepared using different solvents vary in morphology, porosity, binding capacity, and specificity. All of these results suggest that the abilities of the solvents used to form hydrogen bonds with other compounds in the system are different. The porogen imprinting effect of the solvents also has an influence on binding capacity. Compared to MIPs synthesized using acetonitrile as solvent (MIPs-ACN), MIPs synthesized using toluene as solvent (MIPs-PhMe) have fewer but larger pores and exhibit much higher adsorption capability but less rigorous specificity. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47190.     

Tocopherol‐targeted membrane adsorbents prepared by hybrid molecular imprinting

A hybrid molecular imprinting technique for a tocopherol target enabled the preparation of novel membrane adsorbents. α‐Tocopherol methacrylate was used as a functional monomer, and molecular imprinted polymer (MIP) was prepared by copolymerization with divinylbenzene. After the copolymer was granulated, several hybrid molecular imprinted membranes (HMIP) containing the polymer powders were prepared by using polymer scaffolds such as polysulfone (PSf), cellulose acetate (CA), and nylon (Ny). All HMIP membranes prepared by the phase inversion technique showed selective binding of α‐tocopherol (α‐Toc) over its derivative, δ‐tocopherol (δ‐Toc). The imprint efficiencies were 0.49 for the MIP powder and 0.60, 0.64, and 0.53 for the PSf, Ny, and CA‐HMIP systems, respectively. These HMIP membranes retained their binding capacity without losing significant selectivity relative to the MIP powder. Our results demonstrated that the α‐Toc‐imprinted sites were responsible for the selective binding of the target molecules by the HMIP membranes. The membranes' binding behavior was analyzed using Scatchard plots; a heterogeneous distribution of binding sites was observed in both the MIP polymer and HMIP membranes. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers     

豆甾醇和β-谷甾醇在环己酮和正戊醇中的溶解特性研究

实验测定了豆甾醇和β-谷甾醇在环己酮和正戊醇为溶剂中不同温度下的溶解特性以及豆甾醇，β-谷甾醇，环己酮(正戊醇)三组分体系相图。实验结果表明，在相同条件下，β-谷甾醇在上述两种溶剂中的溶解度比豆甾醇的大，且在环己酮中溶解度随温度的变化比豆甾醇的变化大。同时探讨了以正戊醇和环己酮为溶剂，用重结晶法从精制植物甾醇中分离豆甾醇和β-谷甾醇的方法，并用红外和紫外光谱法定量分析了提纯产物中豆甾醇和β-谷甾醇的含量。     

Synthesis of the artemisinin‐imprinting polymers on silica surface and its adsorption behavior in supercritical CO2 fluid

Molecular imprinting polymers (MIPs) for artemisinin were prepared by using 3‐aminopropyltriethoxysilane and calix[4]arene bonded on silica particle surface as the functional monomers, tetraethoxysilicane as cross‐linker, and artemisinin as template. The MIPs were characterized by Fourier Transform Infrared Spectroscope and SEM. Their adsorption capacities were evaluated by static adsorption experiments. The MIPs showed high adsorption capacity and good selectivity for artemisinin. The maximum adsorption capacity of MIPs for artemisinin was 40.0 mg/g. The imprinting factor and the selective factor of the artemisinin‐imprinting polymers was 2.0 and 1.5, respectively. The imprinted film coating onto the silica surface showed a fast kinetics for recognizing and binding templates. Especially, mass transfer reaches the equilibrium within 3.5 h and the adsorption capacity of MIPs for artemisinin reached 120.0 mg/g in supercritical CO₂ fluid. © 2011 American Institute of Chemical Engineers AIChE J, 2011     

Enhancing therapeutic loading and delaying transport via molecular imprinting and living/controlled polymerization

This work demonstrates for the first time molecular imprinting using a “living/controlled” polymerization (LCP) strategy to enhance template loading/affinity and delay release in weakly crosslinked gels. Two gel systems were studied: poly(DEAEM‐co‐HEMA‐co‐PEG200DMA) gels imprinted for diclofenac sodium and poly(MAA‐co‐EGDMA) gels imprinted for ethyl adenine‐9‐acetate. Experimental evidence confirms that template diffusion coefficients within imprinted gels can be heavily influenced by template binding affinity. Recognition studies revealed significant increases in template loading/affinity with large increases in loading for LCP, and dynamic template release studies showed that imprinting via LCP extends the template release profile by twofold over that of imprinting via conventional free‐radical polymerization techniques and fourfold over the control network (less Fickian and toward zero‐order release with a profile coefficient of 0.70). Analysis of reaction kinetics indicated that LCP with reversible termination events increases the chemically controlled chain propagation mechanism, and that binding sites are formed during this phase of the polymerization. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

Evaluation of aminoquinoline‐imprinted polymers and the recognition mechanism

Three molecularly imprinted polymers P(2‐AQ), P(3‐AQ), and P(8‐AQ) based on methacrylic acid (MAA)–ethylene glycol dimethacrylate were prepared using isomers 2‐aminoquinoline (2‐AQ), 3‐aminoquinoline (3‐AQ), and 8‐aminoquinoline (8‐AQ) as template, respectively, by non‐covalent bulk polymerization technique. Neither P(3‐AQ) nor P(8‐AQ) exhibited imprinting effect for 3‐AQ or 8‐AQ, whereas P(2‐AQ) showed significant imprinting effect for 2‐AQ. This indicates that the position of amino group on the quinoline ring has crucial influence on imprinting effect. The recognition mechanism of P(2‐AQ) was investigated extensively by such methods as selective experiments, comparative study with 2‐aminopyridine‐imprinted polymer, and effect of different kinds of mobile phases. It is confirmed that there are complementary cavities in P(2‐AQ) both in size and in the arrangement of functional groups to 2‐AQ, and MAA binds 2‐AQ via cyclic hydrogen bond. Furthermore, the influence of synthetic conditions on 2‐AQ‐imprinted polymers was explored. We found 2‐AQ‐imprinted polymer synthesized in acetonitrile porogen showed higher imprinting effect for 2‐AQ than that prepared in chloroform. It is deduced that the morphology of the former might be more favorable to 2‐AQ binding, which is also supported indirectly by the fluorimetric experiments estimating the interaction of 2‐AQ with MAA in these two porogens. Additionally, 2‐AQ‐imprinted polymers prepared using two different amounts of acetonitrile exhibited very different imprinting effects, which suggested that porogen amount used in the imprinting process exerted significant influence. In addition to the in‐depth elucidation of the recognition mechanism of 2‐AQ‐imprinted polymer, this article provides the basis for the separation and enrichment of bioactive 2‐AQ. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Imparting Cholesterol Recognition Sites in Radiation Polymerised Poly(2-hydroxyethyl methacrylate) by Molecular Imprinting

The technique of molecular imprinting has been used for inducing affinity sites towards specific molecules in synthetic polymers. We have used the method for creating recognition sites for cholesterol in poly(2-hydroxyethyl methacrylate) which was polymerised by γ-irradiation. Our preliminary studies using a mixture of cholesterol and testosterone demonstrated the high degree of selectivity of the polymer towards cholesterol. © of SCI.     

Molecularly Imprinted Ion-Exchange Resin for Fe3+

Abstract

Ion exchange resins selective for the sequestration of Fe³⁺ from aqueous solutions containing citrate were prepared by the molecular imprinting technique. Sorption characteristics of imprinted resins prepared with high (85 mole%) and low (3 mole%) amounts of covalent cross‐linking were examined. Experiments to determine loading capacity and selectivity, relative to several metal ions of physiological significance, were performed. The Fe³⁺ capacity of the highly cross‐linked resin was larger but the selectivity was lower.     

Library screening studies to investigate substrate specificity in the reaction catalyzed by cholesterol oxidase

We tested whether it is possible to alter the substrate specificity of cholesterol oxidase for similarly sized sterols, i.e. cholesterol, beta-sitosterol and stigmasterol. Using existing X-ray crystal structures, we made a model of the predicted Michaelis complex of cholesterol and cholesterol oxidase. Based on this model, we identified five residues that are in direct contact with the steroid tail, Met58, Leu82, Val85, Met365 and Phe433. We prepared seven mutant libraries that contained the codon NYS (N = A, C, G, T; Y = C, Y; S = C, G) at one, two or three of the targeted positions by cassette mutagenesis. The libraries were screened for catalytic activity against three different sterols under k(cat)(*)/K(m)(*) conditions with 25 mol% sterol/DOPC unilamellar vesicles. The results of our screens suggest that specific packing interactions are not realized in the transition state of binding and that loss of active site water may be the predominant source of binding energy.