Water-compatible Molecularly Imprinted Polymers Research Articles

Facile construction of magnetic hydrophilic molecularly imprinted polymers with enhanced selectivity based on dynamic non-covalent bonds for detecting tetracycline

While a number of methods towards water-compatible molecularly imprinted polymers (MIPs) have been reported, new strategies affording simple preparation process and enhanced adsorption selectivity towards templates are needed to promote the further development of MIPs. Herein, we propose a novel method for preparing water-compatible MIPs (Cu-CMMIPs) with enhanced selectivity for tetracycline (TC) based on the dynamic physically cross-linking. The as-synthesized styrene-methacrylic acid copolymer was introduced as hydrophilic cross-linking functional monomers instead of conventional functional monomers and cross-linkers, thus eliminating the need of optimizing the cross-linkers/functional monomers ratio. The copper ions served as cross-linker, and in view of increased adsorption capacity and enhanced selectivity of the prepared MIPs, it was hypothesized that the introduction of copper ions would result in the strong interaction between the polymer network and TC. The imprinting process of TC is carried out by direct physical cross-linking of active groups of TC with functional groups of the polymeric network. The resultant Cu-CMMIPs exhibited excellent hydrophilicity, outstanding adsorption capacity and selectivity towards TC in water. Finally, the developed Cu-CMMIPs were applied as magnetic solid phase extraction adsorbents for the specific recognition of TC in environmental water combined with HPLC-DAD detection (LOD is 3.75 μg/L and the recoveries ranging from 91.2 % to 101.3 %). The proposed concept in this work for fabrication of MIPs with facile preparation process, enhanced selectivity and satisfactory hydrophilicity would inspire more ideas to implement in cost-effective adsorbents construction.

Synthesis and Application of Zwitterionic Magnetic Molecularly Imprinted Polymer for Selective Removal of Fluoroquinolones from Aqueous Solution

Background: Although molecularly imprinted polymers (MIPs) have now been widely utilized for the sample pretreatment, chromatography separation and removal of pollutants, conventional MIPs are still lack of satisfactory compatibility with water, thus leading to poor molecular recognition for target analytes in aqueous solutions. This aim of study was to prepare the watercompatible MIPs. Methods: The zwitterionic MMIPs were synthesized on vinyltrimethoxysilane-coated Fe3O4 (Fe3O4-VTMS) through a surface imprinting process by using levofloxacin (LEV) as a template, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SPE) as a functional monomer, N, N-methylene-bis-acrylamide (MBA) as a crosslinker and potassium persulfate as an initiator. Results: The prepared zwitterionic LEV-MMIPs were characterized by Fourier transform infrared spectrometry, X-ray diffraction, vibrating sample magnetometry, scanning electron microscopy and water contact angle test. The characterization results showed that zwitterionic LEV-MMIPs exhibited good magnetic responsiveness and super-hydrophilicity (the contact angle is 0°). The optimum pH for binding LEV was found to be 6.0 and the binding isotherm followed the Langmuir isotherm model of monolayer adsorption. The binding process was very fast and the pseudo-second-order model fitted well with the kinetic data. The adsorption capacity of these zwitterionic MMIPs was 54.30 mg g-1 with a selectivity factor of 1.6 compared to the magnetic non-imprinted polymers (MNIPs). Their feasibility for removing fluoroquinolones (FQs) from the environmental sample was demonstrated using pearl river water spiked with LEV, gatifloxacin, ciprofloxacin and lomefloxacin. The zwitterionic LEV-MMIPs could be reused at least five times with a removal efficiency of more than 80% for the selected FQs. Conclusion: The prepared zwitterionic LEV-MMIP is a promising sorbent for rapid, selective and efficient removal of fluoroquinolones from aqueous medium.

Water-Compatible Fluorescent Molecularly Imprinted Polymers.

Preparation of molecularly imprinted polymers (MIPs) capable of directly and selectively recognizing small organic analytes in aqueous samples (particularly in the undiluted complex biological samples) is described. Such water-compatible MIPs can be readily obtained by the controlled grafting of appropriate hydrophilic polymer brushes onto the MIP particle surfaces. Two types of synthetic approaches (i.e., "two-step approach" and "one-step approach") for preparing complex biological sample-compatible hydrophilic fluorescent MIP nanoparticles and their applications for direct, selective, sensitive, and accurate optosensing of an antibiotic (i.e., tetracycline (Tc)) in the undiluted pure bovine/porcine serums are presented.

Pickering emulsion-based molecular imprinting

Due to the specific recognition ability of the target molecules, molecularly imprinted polymers (MIPs) have been widely used in many fields. So far, the research in molecular imprinting mainly focused on two aspects: (1) synthesis of MIPs with more functions; (2) expanding applications of the traditional MIPs, especially for MIPs synthesized by precipitation polymerization. To address these points, our group recently introduced a new insight in molecular imprinting based on Pickering emulsion: (1) Pickering emulsion polymerization could be used to the synthesize water-compatible MIP spheres with well-controlled structures; (2) MIP nano/microparticles stabilized emulsions were introduced to molecular imprinting to endow the MIP particles with more functions, or to create new interfacial binding or catalytic systems for MIP nano/microparticles. It is noted that, although the first molecular imprinting in Pickering emulsion has been presented for only a few years, the publications in this field increased very fast. In this review, we summarized the synthesis of MIP spheres via Pickering emulsion polymerization, and discussed the advantages and limitations of this synthesis method. Due to the unique properties of the particle stabilized emulsion, the imprinted systems offered several advantages to the resulted MIP spheres, and which could be further utilized to solve the long-tern challenges in imprinting of small molecules: (1) well-designed hierarchical structures (surface nano-pores from the particle stabilizers and accessible molecular binding cavities from the templates); (2) group recognition of a series of chemicals with a similar moiety (epitope imprinting); and (3) specific recognition capability in aqueous conditions because of the hydrophilic surface of the MIPs. Moreover, for imprinting biomacromolecules and other large templates (virus particles, bacteria and animal cells), Pickering emulsion was also particularly interesting, because the templates themselves could be directly used as solid stabilizers to synthesis Pickering emulsion, and thus created accessible surface imprinted sites for the recognition. In this review, we also demonstrated that MIP nano/microparticles stabilized emulsions were promising interfacial systems in molecular imprinting. On one hand, this emulsion could be utilized for the fabrication of functional materials with pre-designed recognition ability towards the target molecules. As examples, the Janus MIP particles, which displayed attractive abilities as self-propelled transporters for controlled drug delivery, could be prepared via a wax-water Pickering emulsion. Multifunctional colloidosomes, which showed both specific molecular recognition of the MIP nanoparticles and dose-dependent fluorescence response to fructose, could be synthesized by using W/O Pickering emulsions stabilized by clickable nanoparticles: Alkyne-coated MIP nanoparticles and azide-modified nanoparticles, followed by an interfacial click reaction. On the other hand, the introduction of Pickering emulsion expanded tha application environment of the traditional MIP nano/microparticles to a oil-water interface. For example, MIP microgel stabilized Pickering emulsions with the capability to catalyze the formation of disulfide bonds in peptides at the O/W interface has been reported recently. These works system will greatly promote the application of molecular imprinting in various fields such as organic synthesis, disease diagnosis, proteomics and bio-imaging Moreover, we discussed the prospects of the applications of molecular imprinting in Pickering emulsion in a near future, (1) uniform MIP spheres should be fabricated by optimizing the emulsion systems and choosing suitable reactors; (2) stable Pickering emulsion systems should be developed for biomacromolecular imprinting, such as proteins, micro organisms and human cells; (3) MIP nano/microparticles prepared by Pickering emulsion should be designed for immunoassay, biomedicine, environmental governance and chemical catalysis. As a summary, we believed that molecular imprinting in Pickering emulsion provided a facile synthetic approach for producing new functional materials, as well as an interfacial binding or catalytic environment for appilication of the traditional MIP nano/microparticles. All these works show great potential in clinical pathogenic screening, noninvasive detection and drug delivery.

Molecularly Imprinted Polymers: Novel Discovery for Drug Delivery.

Molecularly imprinted polymers (MIP) are novel carriers synthesized by imprinting of a template over a polymer. This paper presents the recent application of MIP for diagnostic and therapeutic drug delivery. MIP owing to their 3D polymeric structures and due to bond formation with the template serves as a reservoir of active causing stimuli sensitive, enantioselective, targetted and/or controlled release. The review elaborates about key factors for optimization of MIP, controlled release by MIP for various administration routes various forms like patches, contact lenses, nanowires along with illustrations. To overcome the limitation of organic solvent usage causing increased cost, water compatible MIP and use of supercritical fluid technology for molecular imprinting were developed. Novel methods for developing water compatible MIP like pickering emulsion polymerization, co-precipitation method, cyclodextrin imprinting, surface grafting, controlled/living radical chain polymerization methods are described with illustration in this review. Various protein imprinting methods like bulk, epitope and surface imprinting are described along with illustrations. Further, application of MIP in microdevices as biomimetic sensing element for personalized therapy is elaborated. Although development and application of MIP in drug delivery is still at its infancy, constant efforts of researchers will lead to a novel intelligent drug delivery with commercial value. Efforts should be directed in developing solid oral dosage forms consisting of MIP for therapeutic protein and peptide delivery and targeted release of potent drugs addressing life threatening disease like cancer. Amalgamation of bio-engineering and pharmaceutical techniques can make these future prospects into reality.

MIPs in Aqueous Environments.

When organic solvent-compatible molecularly imprinted polymers (MIPs) are used in aqueous environment, how to reduce nonspecific binding is a major challenge. By modifying the binding solvents and introducing appropriate washing and elution steps, even relatively hydrophobic MIPs can gain optimal rebinding selectivity in aqueous conditions. Furthermore, water-compatible MIPs that can be used to treat aqueous samples directly have been prepared. The use of hydrophilic co-monomers, the controlled surface modification through controlled radical polymerization, and the new interfacial molecular imprinting methods are different strategies to prepare water-compatible MIPs. By combining MIPs with other techniques, both organic solvent-compatible and water-compatible MIPs can display better functional performances in aqueous conditions. Intensive studies on MIPs in aqueous conditions can provide new MIPs with much-improved compatibilities that will lead to more interesting applications in biomedicine and biotechnology.

Molecularly Imprinted Polymers for Clean Water: Analysis and Purification

Because of their predetermined selectivity, molecularly imprinted polymers (MIPs) have been extensively investigated to offer efficient separation of organic pollutants for water analysis and purification. In this review, we first describe the current development of water-compatible MIPs, and the physical encapsulation and chemical immobilization of MIP particles for practical applications related to water analysis and purification. We summarize the challenges in understanding the mechanisms in molecular imprinting, with a special emphasis on the use of nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and synchronous fluorescence spectroscopy to gain theoretical insights into the molecular imprinting process. The highlighted synthetic methods and the mechanistic investigations discussed in this review should facilitate the identification of the most crucial factors affecting the applications of MIPs for clean water.

Towards water compatible MIPs for sensing in aqueous media

When synthesizing molecularly imprinted polymers (MIPs), a few fundamental principles should be kept in mind. There is a strong correlation between porogen polarity, MIP microenvironment polarity and the imprinting effect itself. The combination of these parameters eventually determines the overall binding behavior of a MIP in a given solvent. In addition, it is shown that MIP binding is strongly influenced by the polarity of the rebinding solvent. Because the use of MIPs in biomedical environments is of considerable interest, it is important that these MIPs perform well in aqueous media. In this article, various approaches are explored towards a water compatible MIP for the target molecule l-nicotine. To this end, the imprinting effect together with the MIP matrix polarity is fine-tuned during MIP synthesis. The binding behavior of the resulting MIPs is evaluated by performing batch rebinding experiments that makes it possible to select the most suitable MIP/non-imprinted polymer couple for future application in aqueous environments. One method to achieve improved compatibility with water is referred to as porogen tuning, in which porogens of varying polarities are used. It is demonstrated that, especially when multiple porogens are mixed, this approach can lead to superior performance in aqueous environments. Another method involves the incorporation of polar or non-polar comonomers in the MIP matrix. It is shown that by carefully selecting these monomers, it is also possible to obtain MIPs, which can selectively bind their target in water.

Efficient One‐Pot Synthesis of Water‐Compatible Molecularly Imprinted Polymer Microspheres by Facile RAFT Precipitation Polymerization

Molecular imprinting is a versatile and straightforward method for the preparation of polymer receptors with tailor-made recognition sites. Despite the tremendous progress made in this field, many challenges still remain to be addressed. In particular, it has been shown that the presently developed molecularly imprinted polymers (MIPs) are normally only organic solvent compatible and they mostly fail to show specific template bindings in pure aqueous solutions, thus significantly limiting their practical applications in the field of biotechnology. Although some approaches, which either use specifically designed functional monomers or apply the conventional imprinting protocol, have been developed for the preparation of MIPs with molecular recognition ability under aqueous conditions, versatile approaches for the preparation of MIPs that are applicable in pure aqueous environments are still rare. Herein, we report a new and efficient one-pot approach to obtain pure-water-compatible and narrowly dispersed MIP microspheres with surface-grafted hydrophilic polymer brushes by facile reversible addition/fragmentation chaintransfer (RAFT) precipitation polymerization (RAFTPP), mediated by hydrophilic macromolecular chain-transfer agents (Macro-CTAs; Scheme 1). The presence of hydrophilic polymer brushes on MIP microspheres significantly improved their surface hydrophilicity and dramatically reduced their hydrophobic interactions with template molecules in pure aqueous media, thus leading to their water compatibility. The easy availability of many different hydrophilic Macro-CTAs (by either RAFT polymerization of hydrophilic monomers or hydrophilic polymer end group modification), together with the versatility of RAFTPP for the controlled preparation of MIP microspheres, makes this strategy highly applicable for the design of hydrophilic and water-compatible MIPs. Two strategies have been developed for the synthesis of water-compatibleMIPs by improving their surface hydrophilicity; these strategies involve the use of a hydrophilic comonomer, functional monomer, or crosslinker in the molecular imprinting process, and the postmodification of the preformed MIPs. Although simple in principle, the former strategy either requires time-consuming optimization of MIP formulation components or can only be applied in some special systems. In comparison, the latter strategy, which involves the surface grafting of hydrophilic polymer layers, has proven highly attractive because it not only significantly improves the MIPs surface hydrophilicity, but also provides a protective layer to prevent protein molecules from blocking their imprinting sites in biological solutions. Very recently, we have successfully prepared pure-water-compatible MIP microspheres by the controlled grafting of hydrophilic polymer layers onto the preformed MIP particles. Compared with this two-step approach, the new strategy presented herein allows the more efficient controlled synthesis of pure-water-compatible MIP microspheres with surface-grafted hydrophilic polymer brushes by a one-pot RAFTPP method. To show proof-of-principle for our strategy, a model noncovalent molecular imprinting system was chosen because Scheme 1. Chemical structures of the utilized RAFT agents (including hydrophilic Macro-CTAs and CDB) and the schematic protocol for the one-pot preparation of water-compatible MIP microspheres by RAFT precipitation polymerization.

Metal ion mediated synthesis of molecularly imprinted polymers targeting tetracyclines in aqueous samples

Molecularly imprinted polymers (MIPs) prepared in water-containing systems are more appropriate as adsorption materials in analyte extraction from biological samples. However, water as a polar solvent involved in the synthesis of MIPs frequently disrupts non-covalent interactions, and causes non-specific binding. In this study Fe 2+ was used as mediator to prepare MIPs, targeting tetracyclines (TCs) of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC), with TC as template molecule and methacrylic acid (MAA) as functional monomer. The subsequent binding assay indicated that Fe 2+ was responsible for substantially improved specific binding in recognition of TCs by decreasing the non-specific binding. Spectrophotometric analysis suggested the existence of the strong interactions among TC, metal ions and MAA in the mixture of methanol and water. Moreover, mass spectrometric measurements verified that Fe 2+ could bridge between TC and MAA to form a ternary complex of one TC, one Fe 2+ and four MAAs with a mass of 844.857. Furthermore, combined with molecularly imprinted solid-phase extraction (MISPE) for sample pretreatment, HPLC–UV analysis data revealed good performance of the obtained MIPs as adsorbents. The recoveries of TC, OTC and CTC in urine samples were 80.1–91.6%, 78.4–89.3% and 78.2–86.2%, respectively. This research strategy provides an example for preparation of desirable water-compatible MIPs extracting target drugs from aqueous samples by introducing metal ion as mediator into conventional polymerization system.

Recognition mechanism of water-compatible molecularly imprinted solid-phase extraction and determination of nine quinolones in urine by high performance liquid chromatography

Novel water-compatible molecularly imprinted polymers (MIPs) were synthesized in methanol–water systems with ofloxacin as templates and methacryclic acid as functional monomers. The MIPs were used as a special sorbent for the selective solid-phase extraction (SPE) of nine quinolones from urine samples, showing high affinity to the quinolones in aqueous environment. Its molecular recognition mechanisms were investigated by the molecular simulation and the experimental validation with UV and infrared spectrogram as well as 1H NMR. Binding capability and chromatographic characteristic were also evaluated. By using the water-compatible MIPs as SPE sorbents, the nine quinolones can be selectively extracted and enriched, while all matrices interferences were eliminated simultaneously. Under the optimal conditions of SPE and high performance liquid chromatography (HPLC), the good linearity of the method was obtained in a range of 0.05–30 μg/mL with the correlation coefficient of >0.999 and the relative standard division of 2.0–7.4%. The detection limits (s/n = 3) were in a range of 0.036–0.10 μg/mL. The proposed method was successfully applied for the selective extraction and separation of the studied quinolones in urine samples.