Synthesis and characterization of photo‐responsive magnetic molecularly imprinted microspheres for the detection of sulfonamides in aqueous solution

A dual responsive molecularly imprinted polymer sensitive to both photonic and magnetic stimuli was successfully prepared for the detection of four sulfonamides in aqueous media. The photoresponsive magnetic molecularly imprinted polymer was prepared by surface imprinting polymerization using superparamagnetic Fe₃O₄ nanoparticles functionalized with a silica layer as a support, water‐soluble 4‐[(4‐methacryloyloxy)phenylazo]benzenesulfonic acid as the functional monomer, and sulfadiazine as the template. The magnetic molecularly imprinted polymers showed specific affinity to sulfadiazine and its structural analogs in aqueous media. Upon alternate irradiation at 365 and 440 nm, the quantitative bind and release of the four sulfonamides by magnetic molecularly imprinted polymers occurred. Furthermore, the prepared magnetic molecularly imprinted polymers were used as solid‐phase extraction material selectively extracted the four sulfonamides from water samples with good recoveries. Thus, a simple, convenient, and reliable detection method for sulfonamides in the environment based on responsive magnetic molecularly imprinted polymers was successfully established.     

Ordered macroporous quercetin molecularly imprinted polymers: Preparation,characterization, and separation performance

Ordered macroporous molecularly imprinted polymers were prepared by a combination of the colloidal crystal templating method and the molecular imprinting technique by using SiO₂ colloidal crystal as the macroporogen, quercetin as the imprinting template, acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross‐linker and tetrahydrofuran as the solvent. Scanning electron microscopy and Brunauer–Emmett–Teller measurements show that the ordered macroporous molecularly imprinted polymers have a more regular macroporous structure, a narrower pore distribution and a greater porosity compared with the traditional bulk molecularly imprinted polymers. The kinetic and isothermal adsorption behaviors of the polymers were investigated. The results indicate that the ordered macroporous molecularly imprinted polymers have a faster intraparticle mass transfer process and a higher adsorption capacity than the traditional bulk molecularly imprinted polymers. The ordered macroporous molecularly imprinted polymers were further employed as a sorbent for a solid‐phase extraction. The results show that the ordered macroporous molecularly imprinted polymers can effectively separate quercetin from the Gingko hydrolysate.     

Preconcentration of indapamide from human urine using molecularly imprinted solid‐phase extraction

A simple, sensitive, and selective molecularly imprinted solid‐phase extraction and spectrophotometric method has been developed for the clean‐up and preconcentration of indapamide from human urine. Molecularly imprinted polymers were prepared by a non‐covalent imprinting approach using indapamide as a template molecule, 2‐(trifluoromethyl) acrylic acid as a functional monomer, ethylene glycol dimethacrylate as a crosslinker, N,N‐azobisisobutyronitrile as a thermal initiator and acetonitrile as a porogenic solvent. A non‐imprinted polymer was also prepared in the same way, but in the absence of template. Molecularly imprinted polymer and non‐imprinted polymer sorbents were dry‐packed into solid‐phase extraction cartridges. Eluates from cartridges were analyzed using a spectrophotometer for the determination of indapamide by referring to the calibration curve in the range 0.14–1.50 μg/mL. Preconcentration factor, limit of detection, and limit of quantification were 16.30, 0.025 μg/mL, and 0.075 μg/mL, respectively. A relatively high imprinting factor (9.3) was also achieved and recovery values for the indapamide spiked into human urine were in the range of 80.1–81.2%. In addition, relatively low within‐day (0.17–0.42%) and between‐day (1.1–1.4%) precision values were obtained as well. The proposed molecularly imprinted solid‐phase extraction and spectrophotometric method was successfully applied to selective extraction, preconcentration, and determination of indapamide from human urine samples.     

Molecularly imprinted monolithic stationary phases for liquid chromatographic separation of enantiomers and diastereomers

The method for preparation of molecularly imprinted monolithic stationary phase has been improved to achieve liquid chromatographic separation of enantiomers and diastereomers. By adopting low polar porogenic solvents of toluene and dodecanol and optimal polymerization conditions, the molecularly imprinted monolithic stationary phases with good flow-through properties and high resolution were prepared. Enantiomers of amino acid derivatives and diastereomers of cinchona alkaloids were completely resolved using the monolithic stationary phases. The influence of porogenic composition, monomer-template ratio and polymerization conditions on the chromatographic performance was investigated. Some chromatographic conditions such as the composition of the mobile phase and the temperature were characterized. Scanning electron microscopy showed that the molecularly imprinted monolithic stationary phase has a large through-pore structure to allow the mobile phase to flow through the column at very low backpressure. Accelerated separations of enantiomers and diastereomers were therefore achieved at elevated flow rates. Finally, the chiral recognition performance of the prepared stationary phase in aqueous media was investigated. Hydrophobic interaction, and ionic and/or hydrogen bonding interactions were proposed to be responsible for the recognition mechanism.     

Cost‐effective imprinting combining macromolecular crowding and a dummy template for the fast purification of punicalagin from pomegranate husk extract

The combination of molecular crowding and virtual imprinting was employed to develop a cost‐effective method to prepare molecularly imprinted polymers. By using linear polymer polystyrene as a macromolecular crowding agent, an imprinted polymer recognizable to punicalagin had been successfully synthesized with punicalin as the dummy template. The resulting punicalin‐imprinted polymer presented a remarkable selectivity to punicalagin with an imprinting factor of 3.17 even at extremely low consumption of the template (template/monomer ratio of 1:782). In contrast, the imprinted polymer synthesized without crowding agent, did not show any imprinting effect at so low template amount. The imprinted polymers made by combination of molecular crowding and virtual imprinting can be utilized for the fast separation of punicalagin from pomegranate husk extract after optimizing the protocol of solid‐phase extraction with the recovery of 85.3 ± 1.2%.     

Preparation and evaluation of the highly cross‐linked poly(1‐hexadecane‐co‐trimethylolpropane trimethacrylate) monolithic column for capillary electrochromatography

In this paper, a novel highly cross‐linked porous monolithic stationary phase having a long alkyl chain ligand (C16) was introduced and evaluated in CEC. The monolithic stationary phase was prepared by in situ copolymerization of 1‐hexadecene, trimethylolpropane trimethacrylate, and 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid (AMPS) in the presence of ternary porogenic solvent (cyclohexanol/1,4‐butanediol/water). In preparing monoliths, the ternary cross‐linker trimethylolpropane trimethacrylate was usually applied to preparing molecularly imprinted polymers or molecularly imprinted solid‐phase extraction, instead of binary cross‐linker ethylene dimethacrylate. 1‐Hexadecene was introduced to provide the non‐polar sites (C16) for chromatographic retention, while AMPS was used to generate the EOF for transporting the mobile phase through the monolithic capillary. Monolithic columns were prepared by optimizing proportion of porogenic solvent and AMPS content in the polymerization solution as well as the cross‐linkers. The monolithic stationary phases could generate a strong and stable EOF in various pH values and exhibit an RP‐chromatographic behavior for neutral compounds. For charged compounds, the separation was mainly based on the association of hydrophobic, electrostatic and electrophoretic interaction.     

Preparation of l‐phenylalanine‐imprinted solid‐phase extraction sorbent by Pickering emulsion polymerization and the selective enrichment of l‐phenylalanine from human urine

A novel l‐ phenylalanine molecularly imprinted solid‐phase extraction sorbent was synthesized by the combination of Pickering emulsion polymerization and ion‐pair dummy template imprinting. Compared to other polymerization methods, the molecularly imprinted polymers thus prepared exhibit a high specific surface, large pore diameter, and appropriate particle size. The key parameters for solid‐phase extraction were optimized, and the result indicated that the molecularly imprinted polymer thus prepared exhibits a good recovery of 98.9% for l‐ phenylalanine. Under the optimized conditions of the procedure, an analytical method for l‐ phenylalanine was well established. By comparing the performance of the molecularly imprinted polymer and a commercial reverse‐phase silica gel, the obtained molecularly imprinted polymer as an solid‐phase extraction sorbent is more suitable, exhibiting high precision (relative standard deviation 3.2%, n = 4) and a low limit of detection (60.0 ± 1.9 nmol·L^?1) for the isolation of l‐ phenylalanine. Based on these results, the combination of the Pickering emulsion polymerization and ion‐pair dummy template imprinting is effective for preparing selective solid‐phase extraction sorbents for the separation of amino acids and organic acids from complex biological samples.     

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。     

Selective enrichment and separation of phosphotyrosine peptides by thermosensitive molecularly imprinted polymers

Novel thermosensitive molecularly imprinted polymers were successfully prepared using the epitope imprinting approach in the presence of the mimic template phenylphosphonic acid, the functional monomer vinylphosphonic acid‐Ti⁴⁺, the temperature‐sensitive monomer N‐isopropylacrylamide and the crosslinker N,N′‐methylenebisacrylamide. The ratio of the template/thermosensitive monomers/crosslinker was optimized, and when the ratio was 2:2:1, the prepared thermosensitive molecularly imprinted polymers had the highest imprinting factor. The synthetic thermosensitive molecularly imprinted polymers were characterized by Fourier transform infrared spectroscopy to reveal the combination and elution processes of the template. Then, the adsorption capacity and thermosensitivity was measured. When the temperature was 28°C, the imprinting factor was the highest. The selectivity and adsorption capacity of the thermosensitive molecularly imprinted polymers for phosphotyrosine peptides from a mixture of three tailor‐made peptides were measured by high‐performance liquid chromatography. The results showed that the thermosensitive molecularly imprinted polymers have good selectivity for phosphotyrosine peptides. Finally, the imprinted hydrogels were applied to specifically adsorb phosphotyrosine peptides from a sample mixture containing phosphotyrosine and a tryptic digest of β‐casein, which demonstrated high selectivity. After four rebinding cycles, 78.9% adsorption efficiency was still retained.     

Chiral separation of racemic mandelic acids by use of an ionic liquid-mediated imprinted monolith with a metal ion as self-assembly pivot

A new chiral stationary phase based on molecularly imprinted polymers (MIP) was prepared in ionic liquid by use of the metal pivot concept. Imprinted monoliths were synthesized by use of a mixture of R-mandelic acid (template), 4-vinylpyridine, ethylene glycol dimethacrylate, and several metal ions as pivot between the template and functional monomer. A ternary mixture of dimethyl sulfoxide–dimethylformamide–[BMIM]BF₄ containing metal ions was used as the porogenic system. Separation of the enantiomers of rac-mandelic acid was successfully achieved on the MIP thus obtained, with resolution of 1.87, whereas no enantiomer separation was observed on the imprinted monolithic column in the absence of metal ions. The effects of polymerization conditions, including the nature of the metal ion and the ratios of template to metal ions and template to functional monomer, on the chiral separation of mandelic acid were investigated. The results reveal that use of metal ions as a pivot, in combination with ionic liquid, is an effective method for preparation of a highly efficient MIP stationary phase for chiral separation.

Preparation of a stoichiometric molecularly imprinted polymer for auramine O and application in solid‐phase extraction

We describe a stoichiometric approach to the synthesis of molecularly imprinted polymers specific for auramine O. Using the stoichiometric interaction in molecular imprinting, no excess of binding sites is necessary and binding sites are only located inside the imprinted cavities. The free base of the template was obtained to facilitate the interaction with the monomers. Itaconic acid was selected as the functional monomer, and stoichiometric ratio of the interaction with the free base was investigated. The molecularly imprinted polymer preparation conditions such as cross‐linker, molar ratio, porogen were optimized as divinylbenzene, 1:2:20 and chloroform/N,N‐dimethylformamide, respectively. Under the optimum conditions, a good imprinting effect and very high selectivity were achieved. A solid‐phase extraction method was developed using the molecularly imprinted polymers as a sorbent and extraction procedure was optimized. The solid‐phase extraction method showed a high extraction recovery for auramine O in its hydrochloride form and free form compared to its analogues. The results strongly indicated that stoichiometric imprinting is an efficient method for development of high selectivity molecularly imprinted polymers for auramine O.     

Synthesis and evaluation of ginsenosides imprinted polymer-based chromatographic stationary phase

The molecular imprinting technique has aroused great interest in preparing novel stationary phases, and the resulting materials named molecularly imprinted polymers coated silica packing materials exhibit good performance in separating diverse analytes based on their good characteristics (including high selectivity, simple synthesis, and good chemical stability). To date, mono-template is commonly used in synthesizing molecularly imprinted polymers-based stationary phases. The resulting materials always own the disadvantages of low column efficiency and restricted analytes, and the price of ginsenosides with high purity was very high. In this study, to overcome the weaknesses of molecularly imprinted polymers-based stationary phases mentioned above, the multi-templates (total saponins of folium ginseng) strategy was used to prepare ginsenosides imprinted polymer-based stationary phase. The resulting ginsenosides imprinted polymer-coated silica stationary phase has a good spherical shape and suitable pore structures. Additionally, the total saponins of folium ginseng were cheaper than other kinds of ginsenosides. Moreover, the ginsenosides imprinted polymer-coated silica stationary phase-packed column performed well in the separation of ginsenosides, nucleosides, and sulfonamides. The ginsenosides imprinted polymer-coated silica stationary phase possesses good reproducibility, repeatability, and stability for seven days. Therefore, a multi-templates strategy for synthesizing the ginsenosides imprinted polymer-coated silica stationary phase is considered in the future.     

Signaling molecularly imprinted polymers: molecular recognition-based sensing materials

Molecular imprinting is a template polymerization technique that can easily provide synthetic polymers capable of molecular recognition for given target molecules. In addition to their highly specific recognition ability, we are attempting to introduce signaling functions to molecularly imprinted polymers, enabling them to respond according to specific binding events. Some of our work regarding such signaling molecularly imprinted polymers is presented here, including molecularly imprinted polymers that induce spectral shifts of target compounds because of binding. Such compounds include hydrogen-bonding-based fluorescent imprinted polymers and metalloporphyrin-based signaling molecularly imprinted polymers.     

Scalemic and racemic imprinting with a chiral crosslinker

The development of molecularly imprinted chiral stationary phases has traditionally been limited by the need for a chiral pure template. Paradoxically, availability of a chiral pure template largely defeats the purpose of developing a chiral stationary phase. To solve this paradox, imprinting of scalemic and racemic template mixtures was investigated using both chiral (N-α-bismethacryloyl-l-alanine) and achiral (N,O-bisacrylamide ethanolamine) crosslinkers. Imprinting of scalemic mixtures provided polymers capable of partial separation of Boc-tyrosine enantiomers with virtually the same results when using either the chiral or achiral crosslinker. However, the chiral crosslinker was required for chiral differentiation by the racemic imprinted polymers which were evaluated in both batch rebinding and chromatographic modes. Batch rebinding analysis revealed intersecting binding isotherms for the L- and D-Boc-tyrosine, indicating bias for the D or L enantiomer is concentration dependent. Partial chromatographic separation was achieved by the racemic imprinted polymers providing variable D or L bias in equal probability over multiple replicates of polymer synthesis. Correlation of enantiomer bias with the batch rebinding results and optimization of HPLC parameters are discussed.     

Design of molecular imprinted polymers compatible with aqueous environment

The main problem of poor water compatibility of molecularly imprinted polymers (MIPs) was addressed in examples describing design of synthetic receptors with high affinity for drugs of abuse. An extensive potentiometric titration of 10 popular functional monomers and corresponding imprinted and Blank polymers was conducted in order to evaluate the subtleties of functional groups ionisation under aqueous conditions. It was found that polymers prepared using 2-trifluoromethacrylic acid (TFMAA) in combination with toluene as porogen possess superior properties which make them suitable for effective template recognition in water. The potential impact of phase separation during polymerisation on formation of high quality imprints has been discussed. Three drugs of abuse such as cocaine, deoxyephedrine and methadone were used as template models in polymer preparation for the practical validation of obtained results. The polymer testing showed that synthesized molecularly imprinted polymers have high affinity and selectivity for corresponding templates in aqueous environment, with imprinting factors of 2.6 for cocaine and 1.4 for methadone and deoxyephedrine. Corresponding Blank polymers were unable to differentiate between analytes, suggesting that imprinting phenomenon was responsible for the recognition properties.     

Surface molecularly imprinted polymers prepared by two‐step precipitation polymerization for the selective extraction of oleanolic acid from grape pomace extract

Surface molecularly imprinted polymers were successfully prepared by a novel two‐step precipitation polymerization method. The first‐step allowed the formation of 4‐vinylpyridine divinylbenzene and trimethylolpropane trimethacrylate copolymeric microspheres. In the second‐step precipitation polymerization, microspheres were modified with a molecularly imprinting layer of oleanolic acid as template, methacrylic acid as functional monomer, and divinylbenzene/ethylene glycol dimethacrylate as cross‐linker. The obtained polymers had an average diameter of 4.43 μm and a polydispersity index of 1.011; adsorption equilibrium was achieved within 40 min, with adsorption capacity reaching 27.4 mg/g. Subsequently, the polymers were successfully applied as the adsorbents of molecularly imprinted solid‐phase extraction to separate and purify the oleanolic acid from grape pomace. The content of oleanolic acid in the grape pomace extract was enhanced from 13.4 to 93.2% after using the molecularly imprinted solid‐phase extraction process. This work provides an efficient way for effective oleanolic acid separation and enrichment from complex matrices, which is especially valuable in industrial production.     

Development of a molecularly imprinted solid‐phase extraction sorbent for the selective extraction of telmisartan from human urine

A novel molecularly imprinted solid‐phase extraction with spectrofluorimetry method has been developed for the selective extraction of telmisartan from human urine. Molecularly imprinted polymers were prepared by a noncovalent imprinting approach through UV‐radical polymerization using telmisartan as a template molecule, 2‐dimethylamino ethyl methacrylate as a functional monomer, ethylene glycol dimethacrylate as a cross‐linker, N,N‐azobisisobutyronitrile as an initiator, chloroform as a porogen. Molecularly imprinted polymers and nonimprinted control polymer sorbents were dry‐packed into solid‐phase extraction cartridges, and eluates from cartridges were analyzed using a spectrofluorimeter. Limit of detection and limit of quantitation values were 11.0 and 36.0 ng/mL, respectively. A very high imprinting factor (16.1) was achieved and recovery values for the telmisartan spiked in human urine were in the range of 76.1–79.1%. In addition, relatively low within‐day (0.14–1.6%) and between‐day (0.11–1.31%) precision values were obtained. Valsartan was used to evaluate the selectivity of sorbent as well. As a result, a sensitive, selective, and simple molecularly imprinted solid‐phase extraction with spectrofluorimetry method has been developed and successfully applied to the direct determination telmisartan in human urine.     

Preparation of melamine molecularly imprinted polymer by computer‐aided design

Melamine was chosen as template, methacrylic acid was chosen as functional monomer, and divinylbenzene, ethylene glycol dimethacrylate, trimethylolpropane trimethylacrylate were chosen as cross‐linking agents, respectively. The WB97XD/6‐31G(d, p) method was used to calculate the geometry optimization of the different imprinting ratios, the action sites, the bonding situation, and the optimization of the cross‐linking agents. The nature of the imprinting effect was also studied by the atoms in molecules theory. The theoretical results showed that melamine interacts with methacrylic acid by hydrogen bonding, and the melamine molecularly imprinted polymers with a molar ratio of 1:6 have the most hydrogen bonds and the most stable structure. Divinylbenzene is the best cross‐linking agent for the melamine molecularly imprinted polymers. The melamine molecularly imprinted polymers were synthesized by precipitation polymerization. The results showed that the maximum adsorption capacity for molecularly imprinted polymers towards melamine is 19.84 mg/g, and the adsorption quantity of the polymers to melamine is obviously higher than that of cyromazine, cyanuric acid, and trithiocyanuric in milk. This study could provide theoretical and experimental references for the screening of the imprinting ratio and the cross‐linking agent for the given template and monomer system.     

Molecularly imprinted polymer functionalized magnetic Fe3O4 for the highly selective extraction of triclosan

We present a facile strategy to prepare the molecularly imprinted polymers layer on the surface of Fe₃O₄ nanoparticles with core‐shell structure via sol–gel condensation for recognition and enrichment of triclosan. The Fe₃O₄ nanoparticles were first synthesized by a solvothermal method. Then, template triclosan was self‐assembled with the functional monomer 3‐aminopropyltriethoxysilane on the silica‐coated Fe₃O₄ nanoparticles in the presence of ethanol and water. Finally, the molecularly imprinted polymers were formed on the surface of silica‐coated Fe₃O₄ nanoparticles to obtain the product. The morphology, magnetic susceptibility, adsorption, and recognition property of magnetic molecularly imprinted polymers were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffractometry, vibrating sample magnetometry, and re‐binding experiments. The magnetic molecularly imprinted polymers showed binding sites with good accessibility, fast adsorption rate, and high adsorption capacity (218.34 μg/g) to triclosan. The selectivity of magnetic molecularly imprinted polymers was evaluated by the rebinding capability of triclosan and two other structural analogues (phenol and p‐chlorophenol) in a mixed solution and good selectivity with an imprinting factor of 2.46 was obtained. The application of triclosan removal in environmental samples was demonstrated.     

Multi‐walled carbon nanotube modified dummy‐template magnetic molecularly imprinted microspheres as solid‐phase extraction material for the determination of polychlorinated biphenyls in fish

Novel multi‐walled carbon nanotube modified dummy‐template molecularly imprinted microspheres (MWCNTs@DMMIPs) were successfully synthesized as adsorbents for six kinds of polychlorinated biphenyls (PCBs). MWCNTs@DMMIPs were prepared by a surface molecular imprinting technique. Core–shell Fe₃O₄@SiO₂ nanoparticles were employed as magnetic support. 3,4‐Dichlorobenzene acetic acid was used as a dummy template instead of PCBs, methacrylic acid was used as functional monomer and ethylene glycol dimethacrylate was used as the cross‐linker. The resulting absorbent was characterized by various methods. The adsorbent was employed for extracting PCBs and exhibited good selectivity and high adsorption efficiency. Furthermore, it was reusable and capable of magnetic separation. Adsorption kinetics fit well with a pseudo‐second‐order kinetic equation and also exhibited a three‐stage intra‐particle diffusion model. The Freundlich model was used to describe the adsorption isotherms. The materials were successfully applied to the magnetic dispersive solid‐phase extraction of six kinds of PCBs followed by gas chromatography with mass spectrometry determination in fish samples, the limit of detection of six kinds of PCBs were 0.0028–0.0068 μg/L and spiked recoveries ranged between 73.41 and 114.21%. The prepared adsorbent was expected to be a new material for the removal and recovery of PCBs from contaminated foods.