Molecularly imprinted polymers: present and future prospective

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented.     

Behavior of phenols and phenoxyacids on a bisphenol-a imprinted polymer. Application for selective solid-phase extraction from water and urine samples

A molecularly imprinted polymer (MIP), obtained by precipitation polymerisation with 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as cross-linker, and bisphenol-A (BPA) as template, was prepared. The binding site configuration of the BPA-MIP was examined using Scatchard analysis. Moreover, the behaviour of the BPA-MIP for the extraction of several phenolic compounds (bisphenol-A, bisphenol-F, 4-nitrophenol, 3-methyl-4-nitrophenol) and phenoxyacid herbicides such as 2,4-D, 2,4,5-T and 2,4,5-TP has been studied in organic and aqueous media in the presence of other pesticides in common use. It was possible to carry out the selective preconcentration of the target analytes from the organic medium with recoveries of higher than 70%. In an aqueous medium, hydrophobic interactions were found to exert a remarkably non-specific contribution to the overall binding process. Several parameters affecting the extraction efficiency of the BPA-MIP were evaluated to achieve the selective preconcentration of phenols and phenoxyacids from aqueous samples. The possibility of using the BPA-MIP as a selective sorbent to preconcentrate these compounds from other samples such as urine and river water was also explored.     

Synthesis of molecularly imprinted polymers for amino Acid derivates by using different functional monomers

Fmoc-3-nitrotyrosine (Fmoc-3-NT) molecularly imprinted polymers (MIPs) were synthesized to understand the influence of several functional monomers on the efficiency of the molecular imprinting process. Acidic, neutral and basic functional monomers, such as acrylic acid (AA), methacrylic acid (MAA), methacrylamide (MAM), 2-vinylpyridine (2-VP), 4-vinylpyridine (4-VP), have been used to synthesize five different polymers. In this study, the MIPs were tested in batch experiments by UV-visible spectroscopy in order to evaluate their binding properties. The MIP prepared with 2-VP exhibited the highest binding affinity for Fmoc-3NT, for which Scatchard analysis the highest association constant (2.49 × 10(4) M(-1)) was obtained. Furthermore, titration experiments of Fmoc-3NT into acetonitrile solutions of 2-VP revealed a stronger bond to the template, such that a total interaction is observed. Non-imprinted polymers as control were prepared and showed no binding affinities for Fmoc-3NT. The results are indicative of the importance of ionic bonds formed between the -OH residues of the template molecule and the pyridinyl groups of the polymer matrix. In conclusion, 2-VP assists to create a cavity which allows better access to the analytes.     

Polymer composite adsorbents using particles of molecularly imprinted polymers or aluminium oxide nanoparticles for treatment of arsenic contaminated waters

Removal of As(V) by adsorption from water solutions was studied using three different synthetic adsorbents. The adsorbents, (a) aluminium nanoparticles (Alu-NPs, <50 nm) incorporated in amine rich cryogels (Alu-cryo), (b) molecular imprinted polymers (<38 μm) in polyacrylamide cryogels (MIP-cryo) and (c) thiol functionalised cryogels (SH-cryo) were evaluated regarding material characteristics and arsenic removal in batch test and continuous mode. Results revealed that a composite design with particles incorporated in cryogels was a successful means for applying small particles (nano- and micro- scale) in water solutions with maintained adsorption capacity and kinetics. Low capacity was obtained from SH-cryo and this adsorbent was hence excluded from the study. The adsorption capacities for the composites were 20.3 ± 0.8 mg/g adsorbent (Alu-cryo) and 7.9 ± 0.7 mg/g adsorbent (MIP-cryo) respectively. From SEM images it was seen that particles were homogeneously distributed in Alu-cryo and heterogeneously distributed in MIP-cryo. The particle incorporation increased the mechanical stability and the polymer backbones of pure polyacrylamide (MIP-cryo) were of better stability than the amine containing polymer backbone (Alu-cryo). Both composites worked well in the studied pH range of pH 2-8. Adsorption tested in real wastewater spiked with arsenic showed that co-ions (nitrate, sulphate and phosphate) affected arsenic removal for Alu-cryo more than for MIP-cryo. Both composites still adsorbed well in the presence of counter-ions (copper and zinc) present at low concentrations (μg/l). The unchanged and selective adsorption in realistic water observed for MIP-cryo was concluded to be due to a successful imprinting, here controlled using a non-imprinted polymer (NIP). A development of MIP-cryo is needed, considering its low adsorption capacity.     

Molecular Imprinted Solid-Phase Extraction System for the Selective Separation of Oleuropein from Olive Leaf

Oleuropein has many antimicrobial, antiviral, and anticancer features found in olive leaf. Therefore, its isolation from olive leaf is very important in such kinds of applications. In this study, a solid-phase extraction system based on the molecularly imprinted polymer (MIP) was proposed for the selective separation of oleuropein from olive leaf. First, oleuropein imprinted polymer has been prepared by the suspension polymerization using methacrylolamidoantiprine–iron (III) metal-chelate monomers. After that, the oleuropein adsorption capacity and selectivity of the prepared imprinted polymer has been determined. The maximum adsorption capacity of oleuropein has found to be 140 mg g^?1. Finally, MIP has been used as a sorbent in the solid-phase extraction for the separation of oleuropein from crude extract of olive leaves. The oleuropein analyses have been realized by high performance liquid chromatography. The obtained results indicated that the prepared molecularly imprinted sorbent could be used for at least 10 times for purification of oleuropein from olive leaf. The application of the proposed system in the real sample showed that 24.2 mg pure oleuropein could be obtained from 1.0 g of crude olive leaf extract. As a result, the low cost, simple, and selective adsorbent has been developed for oleuropein adsorption. Supplemental materials are available for this article. Go to the publisher's online edition of Separation Science & Technology to view the supplemental file.     

The Preparation of BHb-Molecularly Imprinted Gel Polymers and Its Selectivity Comparison to BHb and BSA

Molecularly imprinted gel polymer (MIP) for the selective imprinting of bovine hemoglobin (BHb) was prepared in aqueous media by bulk polymerization using polyacrylamide matrix. The synthesis conditions of BHb-MIP were investigated, which involved the interaction of functional monomers and template protein in different molar ratio, solution pH, and ionic strength. The adsorption experiments indicated that BHb-MIP had a high affinity for BHb over the non-imprinted polymers. The selectivity of BHb-MIP for BHb and bovine serum albumin (BSA) with similar molecular weight was compared. It was demonstrated that BHb-MIP had better selective adsorption and recognition properties to BHb especially in the presence of BSA as competing protein. It might be helpful for selectively separating template protein with MIP from the proteins mixture with similar molecular weight.     

Sorption of Phthalates on Molecularly Imprinted Polymers

Porous beads of styrene divinylbenzene copolymer, S-co-DVB, imprinted with dimethyl phthalate, DMP, were obtained. Two solvents were applied for the formation of pores: n-hexane and n-octane. The sorbents were prepared by membrane emulsification of monomer mixtures containing DMP followed by suspension polymerization. The average diameters of the synthesized beads were 40 µm for beads obtained from mixtures with n-octane, and 30 µm for preparations with n-hexane as solvent. It was shown that almost all monodispersive sorbents were obtained; their SPAN parameter was as small as 0.7–0.9. Sorption properties of evaluated samples varied in relation to the kind of applied reaction mixture. Generally, imprinted materials showed higher sorption capacity towards DMP than their off-template analogues. For the sorbent obtained in the presence of n-octane and with 3 wt.% of DMP, sorption of dimethyl phthalate took the highest value - 89 mg/g. The sorbents imprinted with DMP were checked for sorption of diethyl phthalate, DEP, and dibuthyl phthalate, DBP also. It was shown that sorbability of synthesized materials towards other phthalates was much smaller than for DMP and was not related to the presence of dimethyl phthalate foot prints.     

Self-assembly of thiourea intercalated graphene oxide based dual IIP for the SPE coupled FAAS method development of Cu(II) and Pb(II) determination

A new dual-template surface imprinted polymer for Cu(II) and Pb(II) was synthesized in one pot. Magnetic graphene oxide was self-assembled with low cost and environmentally benign thiourea. Presence of sulfur and nitrogen donor atoms provide hooks for coordination and partial reduction of graphene oxide matrix. It was used as an solid-phase extraction adsorbent for extraction, preconcentration, and coupled with flame atomic absorption spectrometry to manifest performance comparable with inductively coupled plasma atomic emission spectrometry (ICPAES) both in terms of quantification limit as well as interference. The critical experimental parameters such as pH; 4.6, contact time of 15 min and initial concentration of 777 (Q_e; 227 mg g⁻¹) and 800 μg L⁻¹ (Q_e; 273 mg g⁻¹) for Cu(II) and Pb(II), respectively, were optimized using RSM-CCD and artificial neural network. The adsorption process was kinetically faster (50% adsorption in 5 min), following fractal-like-pseudo-second-order (FLPSO) kinetics and Brouers–Sotolongo isotherm model owing to the heterogenous energy landscape. The imprinting factors were in the range of 4–7 in the presence of all coexisting ions. The proposed method was robust in the determination and removal of Cu(II) and Pb(II) from food, ground water, and industry effluents with low limit of detection (Cu(II); 1.03 μg L⁻¹ & Pb(II); 1.79 μgL⁻¹). Spiking and recovery tests were used to assess the method's accuracy. Cu(II)/Pb(II) loaded dual template IIP (DIIP) was utilized to remove anionic dyes with >95% efficiency. Thorough examination of the method and material selectivity (in binary, ternary, and multielement system), multi fold applications of determination, removal of Cu(II), Pb(II), and removal of anionic dyes makes DIIP a promising candidate for environmental remediation.     

Molecularly imprinted solid-phase extraction of fumonisin B analogues in bell pepper,rice and corn flakes

A molecularly imprinted polymer (MIP) for the recognition of fumonisin B analogues (FB) using 2-(diethylamino) ethyl methacrylate (DEAEM) as functional monomer and trimethylolpropane trimethacrylate (TRIM) as cross-linker was prepared by bulk polymerization in acetonitrile. Fumonisin B₁ (FB₁) was used as a template molecule. A molecularly imprinted solid-phase extraction (MISPE) procedure was developed for further application in the analysis of FB. The performance of the MIP throughout the clean-up of spiked bell pepper, rice and corn flake sample extracts was compared with the results obtained when using non-imprinted polymer, C₁₈, strong anion exchange and immunoaffinity sorbents. Extracts were analysed for FB with liquid chromatography-tandem mass spectrometry (LC-MS/MS) after clean-up. Depending on the food matrix and the concentration range of the fumonisins, recoveries after MISPE varied from 62 to 86%, from 62 to 83%, and from 67 to 81% for fumonisin B₁ (FB₁), fumonisin B₂ (FB₂) and fumonisin B₃ (FB₃), respectively. The selectivity of the synthesized MIP for mycotoxins belonging to the group of FB was confirmed by evaluating cross-reactivity from analogue structures and other mycotoxins. Analysis of 39 naturally contaminated samples (corn flakes) by liquid chromatography tandem mass spectrometry indicated that the synthesized MIP could be an excellent alternative for clean-up and pre-concentration of FB in food samples. Pearson correlations between immunoaffinity clean-up and MISPE were calculated and amounted to 0.923 for FB₁, 0.808 for FB₂, and 0.759 for FB₃. It was shown that the developed MIP could be reused more than 50 times. The synthesis of an FB₁ imprinted polymer and its application in food analysis is reported for the first time.     

Effect of the mimic structure on the molecular recognition properties of molecularly imprinted polymers for ochratoxin A prepared by a fragmental approach

In this work the fragmental approach was used to prepare several molecularly imprinted ethylene dimethacrylate-co-methacrylic acid polymers with molecular recognition towards the mycotoxin ochratoxin A, with the aim of searching for simpler mimic templates than the well-known N-(4-chloro-1-hydroxy-2-naphthoylamido)-(l)-phenylalanine. The screening for binding of two different kinds of ochratoxin-related molecules was performed by HPLC analysis. Ochratoxin A and the mimic templates were eluted in acetonitrile–acetic acid (0.1% v/v) and the imprinting factor was measured for all the ligands on all the columns packed with the imprinted polymers. The experimental results show that changes to the amino acidic sub-structure or the presence/absence of a chlorine atom in position 4 on the naphthalene ring system does not affect the molecular recognition of ochratoxin A by the resulting imprinted polymer. On the contrary, the presence of the bulky naphthalene ring system in the mimic template seems to be necessary to preserve the molecular recognition of ochratoxin. This binding behavior was found to be compatible with in silico simulations of the complexation between some of the mimic templates and molecules of methacrylic acid. The use of the mimic template N-(1-hydroxy-2-naphthoylamido)-(L)-phenylalanine seems to represent a synthetically simple approach to the preparation of imprinted polymers with molecular recognition properties towards ochratoxin A.