MIP Synthesis Research Articles

Synthesis of Boronate Affinity-Based Oriented Dummy Template-Imprinted Magnetic Nanomaterials for Rapid and Efficient Solid-Phase Extraction of Ellagic Acid from Food.

Ellagic acid (EA) is a natural polyphenol and possesses excellent in vivo bioactivity and antioxidant behaviors, which play an important role in the treatment of oxidative stress-related diseases, such as cancer. Additionally, EA is also known as a skin-whitening ingredient. The content of EA would determine its efficacy. Therefore, the accurate analysis of EA content can provide more information for the scientific consumption of EA-rich foods and cosmetics. Nevertheless, the analysis of EA in these samples is challenging due to the low concentration level and the presence of interfering components with high abundance. Molecularly imprinted polymers are highly efficient pretreatment materials in achieving specific recognition of target molecules. However, the traditional template molecule (EA) could not be absolutely removed. Hence, template leakage continues to occur during the sample preparation process, leading to a lack of accuracy in the quantification of EA in actual samples, particularly for trace analytes. In addition, another drawback of EA as an imprinting template is that EA possesses poor solubility and a high price. Gallic acid (GA), called dummy templates, was employed for the synthesis of MIPs as a solution to these challenges. The approach used in this study was boronate affinity-based oriented surface imprinting. The prepared dummy-imprinted nanoparticles exhibited several significant advantages, such as good specificity, high binding affinity ((4.89 ± 0.46) × 10-5 M), high binding capacity (6.56 ± 0.35 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward EA. The reproducibility of the dummy-imprinted nanoparticles was satisfactory. The dummy-imprinted nanoparticles could still be reused even after six adsorption-desorption cycles. In addition, the recoveries of the proposed method for EA at three spiked levels of analysis in strawberry and pineapple were 91.0-106.8% and 93.8-104.0%, respectively, which indicated the successful application to real samples.

Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer

Abstract Kaempferia galanga L. extract contains ethyl p-methoxycinnamate (EPMC) and ethyl cinnamate (EC), which have several pharmacological activities. EPMC and EC have been successfully isolated, but the %yield was low. Therefore, developing an isolation method to increase the %yield result of EPMC and EC is essential. The molecularly imprinted polymers have been applied to separate lot of active compounds from natural products with excellent results. MIP synthesis is usually performed using a single template with high selectivity for the target analyte but only detect single chemical compounds. Hence, this study synthesized multi-template molecularly imprinted polymers (MT-MIPs) for isolating EPMC and EC simultaneously using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate or trimethyl propane trimethacrylate (TRIM) as a crosslinker. The study results indicate that MT-MIP produced with TRIM is more effective in separating EPMC and EC simultaneously in K. galanga L. extracts. However, the yields of EPMC and EC were still low. The yields of EPMC and EC in n-hexane extracts were 1.557 and 1.929%, with purity of 66.330 and 61.510%, respectively. Further research is necessary to determine the ideal functional monomer and its ratio to template molecules to obtain the excellent selectivity of the MT-MIPs used for simultaneously isolating EPMC and EC.

Greenness of dispersive microextraction using molecularly imprinted polymers

Abstract Molecularly imprinted polymers (MIPs) as materials with determined levels of selectivity and specificity for designated analytes have recently gained much attention in various application fields. However, with the growing adoption of green analytical chemistry (GAC) principles, it is essential to investigate the greenness of MIP synthesis and its subsequent application in sample preparation, as well as to evaluate the “green” nature of the developed analytical methodologies, such as dispersive solid-phase microextraction (DSPME). Accordingly, the main objective of this research was to evaluate the greenness of MIP-based glycidyl methacrylate synthesis and MIP use as a DSPME sorbent prior to high-performance liquid chromatography with mass spectrometry (HPLC-MS). The green perspective of MIP-DSPME prior to HPLC-MS was investigated using various analytical metric tools such as the Analytical Eco-Scale, the Green Analytical Procedure Index, and Analytical GREEnness (AGREE). Since these analytical tools are not fully implementable for the assessment of the greenness of the MIP synthesis, some alternative approaches were used to optimize the synthesis parameters to make the MIP DSPME sorbent as close as possible to the GAC principles. The calculated AGREE score (0.62) and 91 points in the Analytical Eco-Scale for the proposed DSPME technique using MIP indicated a high level of greenness.

Electrochemical sensing of monoterpene phenols in plant essential oils using a molecularly imprinted polymer dual-template sensor

Monoterpene phenols are naturally occurring aromatic compounds found in plant essential oils, contributing to their distinct flavors, fragrances, and medicinal properties. Thymol and carvacrol, major constituents of thyme and oregano essential oils, have garnered significant attention due to their diverse biological activities. Here, we propose the development of a novel double template molecular imprinted electrochemical sensor (DT-MIP sensor) for the selective and simultaneous detection of thymol and carvacrol. The sensor's performance was optimized by varying the quantity of functional monomer, cross-linker, and template molecules during MIP synthesis. The DT-MIP sensor demonstrated superior recognition properties and high sensitivity, with detection limits of 0.11 μM for carvacrol and 0.24 μM for thymol. Selectivity tests confirmed minimal interference from potential interfering agents. GC-MS analysis validated the sensor's accuracy in detecting thymol and carvacrol concentrations in thyme and oregano essential oils. The simplicity, cost-effectiveness, and portability of the DT-MIP sensor offer promising applications in food quality control, environmental monitoring, and medical diagnostics.

Next generation biosensors employing molecularly imprinted polymers as sensing elements for in vitro diagnostics

Biosensors for in vitro diagnostics (IVD) have huge potential and are likely to play a significant role in advanced as well as in the low resource healthcare setups. With time, these devices are gaining traction in cardiac diagnosis, cancer, autoimmune diseases and pathogenic microbial infections. Periodical advancements in nanomaterials employed in biosensors have led to miniaturization and improved characteristics of both plasmonic and electrical sensors. Mostly antibodies are employed in the development of IVD however, there are challenges due to the fragile nature of these biological molecules that adversely affects the storage and shelf life of biosensors. Ongoing developments in the synthesis of artificial antibodies or MIPs that offer improved stability, selectivity and multiplexing ability facilitates their application in biosensors for IVD. In addition, versatility and facile synthesis protocols of MIPs enable their rapid integration into mass manufacturing systems. Here, we discuss the changing dynamics of IVD enabled by MIP based biosensors. We will mainly focus on microbes and clinically relevant biomarkers that have been targeted for infectious disease detection and different imprinting strategies relevant to them. The biosensor platforms employing MIPs for their POC and IVD potential for biological samples have been discussed. The commercial potential of MIPs which has translated into 8 commercial platforms so far including IVD have been delineated. To improve the performance of MIPs in general, the computationally aided MIP design that is actively focused to address some of the challenges associated with the translation of MIPs for various applications including IVD have been discussed.

Полианилин в молекулярном импринтинге: синтез, свойства, применение. Обзор

Molecular imprinting is a rapidly developing and promising approach for the selective recognition for target molecules of different nature. In this review, we have collected works devoted to synthesis and application of polyaniline-based molecularly imprinted polymers (MIPANI) over the last 5 years. The manuscript provides brief descriptions of the main approaches to the synthesis of PANI MIPs and the advantages and disadvantages of each technique. We also discuss the effect of various factors on the process of MI-PANI synthesis, including polymerization methods, molecular weight of template molecules and the types of scaffolds. The analytical characteristics of the resulting sensors are also provided. Thus, it can be concluded that polyaniline is a very promising material for MIPs synthesis.

An Update on the Use of Molecularly Imprinted Polymers in Beta-Blocker Drug Analysis as a Selective Separation Method in Biological and Environmental Analysis.

Beta-blockers are antihypertensive drugs and can be abused by athletes in some sport competitions; it is therefore necessary to monitor beta-blocker levels in biological samples. In addition, beta-blocker levels in environmental samples need to be monitored to determine whether there are contaminants from the activities of the pharmaceutical industry. Several extraction methods have been developed to separate beta-blocker drugs in a sample, one of which is molecularly imprinted polymer solid-phase extraction (MIP-SPE). MIPs have some advantages, including good selectivity, high affinity, ease of synthesis, and low cost. This review provides an overview of the polymerization methods for synthesizing MIPs of beta-blocker groups. The methods that are still widely used to synthesize MIPs for beta-blockers are the bulk polymerization method and the precipitation polymerization method. MIPs for beta-blockers still need further development, especially since many types of beta-blockers have not been used as templates in the MIP synthesis process and modification of the MIP sorbent is required, to obtain high throughput analysis.

Molecularly Imprinted Polymers Coupled with Surface-Enhanced Raman Spectroscopy to Detect Chemical Hazards in Foods.

Preparation of molecularly imprinted polymers coupled with surface-enhanced Raman spectroscopy (MIP-SERS) sensor and its application in detecting chemical hazards in food matrices are described. Sample cleaning is achieved by molecularly imprinted solid-phase extraction (MISPE), and target molecules are detected by SERS. Procedures of MIP synthesis, MISPE preparation, SERS substrate preparation, spectral collection, data analysis, and food analysis application are described.

A NEW MIP EMBEDDED CRYOGEL FOR SELECTIVE PRE-CONCENTRATION AND REMOVAL OF PROPACHLOR

Propachlor is a pesticide commonly used in the chloroacetanilide herbicide group. Propachlor contamination occurs in groundwater resources and soil sources. Therefore removal and also the determination of trace amounts of propachlor is a very important issue. Molecularly imprinted polymers (MIPS) are preferred for their advantages such as high affinity, strength, and selectivity in pesticide removal and determination. In this study, MIP embedded cryogel was synthesized for selective adsorption and removal of propachlor. MIP synthesis was performed using the template molecule propachlor, functional monomer methacrylic acid, crosslinker ethylene glycol dimethacrylate (EDGMA), solvent hexadecane and 2,2-azo-bis-isobutyronitrile (AIBN) as the initiator. Cryogels are a good alternative for separation and purification because of their advantageous properties such as short diffusion, low pressure and adsorption and elution in a short time. The structure of MIP was determined using scanning electron microscopy (SEM), Elemental analyze and Fourier transform infrared spectroscopy (FT-IR), and the structure of MIP embedded cryogel was determined using scanning electron microscopy (SEM). The highest adsorption capacity for MIP was 5.58 mg g-1 at pH 5. The highest adsorption capacity for MIP embedded cryogel was found to be 14.38 mg g-1. MIP embedded cryogel were used for selective adsorption and desorption of propachlor in environmental samples. The concentration of propachlor in environmental samples was analyzed by high-performance liquid chromatography (HPLC).

Magnetic ferroferric oxide and polydopamine molecularly imprinted polymer nanocomposites based electrochemical impedance sensor for the selective separation and sensitive determination of dichlorodiphenyltrichloroethane (DDT)

Dichlorodiphenyltrichloroethane (DDT) is a kind of broad-spectrum insecticides, which is potentially toxic and persistently threatens the safety of environment and food, due to their stability in nature and difficulty to degrade. For the first time, a novel impedance chemical sensor based on magnetic Fe3O4 and polydopamine molecularly imprinted polymer magnetic nanoparticles (PDA@Fe3O4 MIP MNPs) was designed. Bisphenol A (BPA) and dopamine were used as virtual template molecules and functional monomer for MIP synthesis, respectively. Recognition cavities formed in PDA layers could specifically recognize and effectively adsorb DDT molecules, with the help of virtual templates that had similar molecular structure to DDTs. The as-prepared PDA@Fe3O4-MIP MNPs could be used for specific adsorption and efficient extraction of target molecules 4,4′-DDT from food samples. The electrochemical impedance of the PDA@Fe3O4-MIP MNPs increased sensitively with the adsorption of 4,4′-DDT, the correlationship between of the electrochemical impedance response and the concentration of 4,4′-DDT were applied in the construction of electrochemical impedance sensors for the determination of 4,4′-DDT. The sensor showed a good linear relationship between the charge transfer resistance (Rct) and the 4,4′-DDT concentration over a range from 1 × 10−11 to 1 × 10−3 mol L−1 with a detection limit of 6 × 10−12 mol L−1. The sensor also exhibited excellent sensitivity and selectivity as well as high stability for the detection of pesticide residues and other environmentally harmful chemicals in various food samples.

Computational study on acetamiprid-molecular imprinted polymer.

In the present work we investigate, through DFT calculations, the mechanism of formation of a molecular imprinted polymer for the acetamiprid (ACT) insecticide, using four different functional monomers, four molar ratios attempts, and considering eight distinct solvents. As the main result we obtain the following theoretical protocol for the MIP synthesis: methacrylic acid (MMA) as functional monomer, 1:4M ratio, i.e., one ACT to four MMAs, and chloroform as solvent. This DFT calculated condition shows more favorable energies for the formed complexes. We consider this work quite relevant since it can be used by experimentalists in order to reach an efficient MIP synthesis for ACT, avoiding wasted time and laboratory resources. Graphical abstract Best MIP Synthesis Protocol for Acetamiprid.

Molecular imprinting for protein recognition: Current status, challenges and applications

Molecular recognition plays a critical role in numerous living systems. Over the past several decades, considerable attempts have been made to create synthetic recognition systems with high specifity and selectivity for a certain molecue by utilizing natural receptors such as antibodies, receptors, enzymes and aptamers. Despite their high selectivity and broad range of applications, these biomolecules always suffer from some drawbacks, for example, instablity in harsh condition, high production cost. In response to these limitations, the alternative molecular imprinting technique has attracted a number of researchers sustain interests, shows a promising potential in the creation of synthetic recognition systems. Molecular imprinting, a synthetic Lock to Key technique that uses molecular templates to create selective binding sites in cross-linked polymers, has become one of the most efficient methods for preparation of selective recognition materials. To date, a wide range sizes of template including inorganic ions, drugs, nucleic acids, peptides, proteins, viruses, and whole cells have been extensively applied in the synthesis of various specific molecularly imprinted polymers. Among them, the majority of the publications and successful applications in molecular imprinting are aimed at recognition and separation of small molecules. Molecular imprinting of biomacromolecules, especially proteins, still remains great challenges. Due to its large size, environmentally instability, chemical and structural complexity, traditional imprinting methods were limited and not suitable for proteins. Since 2011, protein imprinting has acheived some significant breakthroughs in imprinting methods and applications. On one hand, some novel and special protein imprinting methods have been developed, such as nanomaterial-based imprinting, boronate affinity-based surface imprinting, epitope imprinting, solid-phase synthesis and post-imprinting modification. These newly emerging methods effectively solved some key issues in protein imprinting and were applied for synthesis of MIPs with special properties that were not well demonstrated before. In this paper, we have analyzed the merits and problems of these methods in detail. On the other hand, based on the novel protein imprinting materials with special properties, some new advanced applications, such as disease diagnosis, proteomics and bioimaging, have well been demonstrated and showed great potentials. In addition, the future challenges and opportunities in protein imprinting were also discussed. Despite the tremendous interest in protein imprinting, related research studies were still behind compared to the progress made in molecular imprinting of small molecules. Particularly, the design of universal protein imprinting materials with desirabe properties still remains great challenges. As to future development, developing facile and versatile protein imprinting methods is still of significant importance. Meanwhile, as a multidisciplinary technology, protein imprinting should develop rapidly along with the advances in polymer technology, nanotechnology, analytical chemistry, biotechnology and so on. We forsee that, in a long period of time, creating new protein imprinting strategies, developing desirable protein imprinting materials with special properties based on borrowing and integration of related technologies/strategies, and thereby enable potential important applications are still the main direction of protein imprinting.

Efficient molecularly imprinted polymer as a pipette-tip solid-phase sorbent for determination of carvedilol enantiomers in human urine.

In this work, an efficient pipette tip based on molecularly imprinted polymers solid-phase extraction (PT-MIP-SPE) method was developed for carvedilol (CAR) analysis. This compound is available in clinical practice as a racemic mixture, in which (-)-(S)-CAR is a β- and α1-adrenergic antagonist, while (+)-(R)-CAR only acts as an α1-adrenergic antagonist. Enantioseparation of CAR presented satisfactory retention times (5.85 and 14.84min), acceptable theoretical plates (N=2048 and 2018) and good resolution (Rs=9.27). The separation was performed using a Chiralpak® IA column (100mm×4.6mm, 3μm), a mixture of methanol:ethanol:water (64:15:21, v/v/v) plus 0.3% diethylamine as mobile phase, temperature of 35°C and flow rate of 1.5mLmin-1. After density functional theory calculations based on prepolymerization complexes, the best protocol for the MIP synthesis was chosen. Then, some parameters that affect the PT-MIP-SPE technique were investigated. After optimization, the best conditions were 300μL of water as washing solvent, 500μL of acetonitrile:acetic acid (7:3, v/v) as eluting solvent, 20mg of MIP, 500μL of urine sample (pH 12.5) and no addition of NaCl. Recoveries±relative standard deviation (RSD%) for (+)-(R)-CAR and (-)-(S)-CAR were 101.9±4.8% and 104.6±2.1%, respectively. The method was linear over the concentration range from 20 to 1280ngmL-1 for each enantiomer, with correlation coefficients larger than 0.99 for both enantiomers. The method was applied successfully in a preliminary study of urinary excretion after administration of CAR racemate to a healthy volunteer.

Enzyme‐Initiated Free‐Radical Polymerization of Molecularly Imprinted Polymer Nanogels on a Solid Phase with an Immobilized Radical Source

AbstractAn enzyme‐mediated synthetic approach is described for the preparation of molecularly imprinted polymer nanoparticles (MIP‐NPs) in aqueous media. Horseradish peroxidase (HRP) was used to initiate the polymerization of methacrylate or vinyl monomers and cross‐linkers by catalyzing the generation of free radicals. To prevent entrapment of the enzyme in the cross‐linked polymer, and to enable it to be reused, HRP was immobilized on a solid support. MIPs based on 4‐vinylpyridine and 1,4‐bis(acryloyl)piperazine for the recognition of 2,4‐dichlorophenoxyacetic acid (2,4‐D) and salicylic acid were synthesized in an aqueous medium. MIPs for the protein trypsin were also synthesized. MIP nanoparticles with sizes between 50 and 300 nm were obtained with good binding properties, a good imprinting effect, and high selectivity for the target molecule. The reusability of immobilized HRP for MIP synthesis was shown for several batches.

Enzyme-Initiated Free-Radical Polymerization of Molecularly Imprinted Polymer Nanogels on a Solid Phase with an Immobilized Radical Source.

An enzyme-mediated synthetic approach is described for the preparation of molecularly imprinted polymer nanoparticles (MIP-NPs) in aqueous media. Horseradish peroxidase (HRP) was used to initiate the polymerization of methacrylate or vinyl monomers and cross-linkers by catalyzing the generation of free radicals. To prevent entrapment of the enzyme in the cross-linked polymer, and to enable it to be reused, HRP was immobilized on a solid support. MIPs based on 4-vinylpyridine and 1,4-bis(acryloyl)piperazine for the recognition of 2,4-dichlorophenoxyacetic acid (2,4-D) and salicylic acid were synthesized in an aqueous medium. MIPs for the protein trypsin were also synthesized. MIP nanoparticles with sizes between 50 and 300 nm were obtained with good binding properties, a good imprinting effect, and high selectivity for the target molecule. The reusability of immobilized HRP for MIP synthesis was shown for several batches.

Modeling prepolymerization step of a serotonin imprinted polymer.

Studies on generating artificial macromolecular receptors by molecular imprinting of synthetic polymers significantly emerged in the literature during last decades. The non-covalent approach, one of the three methods used in MIP synthesis, is more flexible for the choice of functional monomers, possible target molecules, and use of the imprinted materials. This study aims to investigate a serotonin imprinted polymer prepared by non-covalent approach using molecular modeling. The calculations were carried out by using density functional theory at ωB97XD/6-31++G(d,p) level and the polarizable continuum model was used for solvent calculations. Computational results showed that DMSO plays an important role in the MIP formation as it seems to control the size and the shape of the cavity. DMSO performs these tasks through hydrogen bonding and dispersive interactions. Although experimental IR could not verify the specific interaction modes because of broadband structure, computational IR results showed these modes clearly indicating the interactions leading to MIP formation. This model is specific to the studied serotonin-acrylamide-DMSO system but further studies may reveal a general computational protocol for other MIP systems.

Study on the cross-linked molecularly imprinted poly(methacrylic acid) and poly(acrylic acid) towards selective adsorption of diuron

In the present study new molecularly imprinted adsorbents based on poly(methacrylic acid) and poly(acrylic acid) have been synthesized, characterized and evaluated as selective materials for the adsorption of diuron. Morphological, textural data and the presence of functional groups in the polymer have been evaluated by means of SEM, nitrogen adsorption–desorption assays and FT-IR, respectively. Two functional monomers were evaluated for the MIP synthesis, methacrylic acid (MIPMAA) and acrylic acid (MIPAA), and the first one showed higher selectivity and better adsorption towards diuron in the presence of competitor molecules, carbofuran and 2,4-D. The experimental adsorption isotherm of diuron has been obtained at pH7.0 in phosphate buffer (0.05molL−1):acetonitrile (1:2, v/v) medium and equilibrium time of 180min. The respective maximum adsorption capacities (MAC) of MIPMAA and MIPAA were found to be 14.58 and 7.32mgg−1. One should note that MAC of MIPAA and its respective blank polymer (NIPAA) was very similar to each other, while for the MIPMAA its MAC was significantly higher (14.58mgg−1) than the MAC of NIPMAA (6.12mgg−1). Such result demonstrates the great influence of monomer on the adsorption and selectivity of MIP. Adsorption kinetic data were well fitted to pseudo-first-order and intraparticle diffusion models, while the adsorption isotherms showed good fit to the isotherm of Langmuir–Freundlich for two sites (LF-2) and one site (LF-1), but the former one allowed insight into the adsorption mechanism with more details.

Microwave Assisted Synthesis of Quercetin-Selective MIPs Grafted on Silica Gel Surface

The silica gel surface was alkylated by silane coupling agent KH-570 under the microwave assisted and orthogonal experiment was adopted to optimize the silica gel surface silanized experimental conditions with synthetic yield as index. With quercetin as the template molecule, 4 - vinyl pyridine as the functional monomer, ethylene glycol dimethyl acrylate as the cross linking agent, azodiisobutyronitrile as initiator, under the microwave assisted in silane silicone surface quercetin molecularly imprinted polymer was successfully synthesized. Take selected quercetin as index, another orthogonal experiment was implemented to optimize the quercetin-selective MIPs synthesis experiment on silica gel surface. What is more, the adsorptive property of quercetin-selective MIPs which was grafted on silica gel surface has been inspected. We have extracted of quercetin in the ethyl acetate from raspberry with quercetin-selective MIPs grafted on silica gel surface. Synthetic time have been shortened more than a dozen times, the efficiency of preparation of MIPs have been greatly improved.

Molecularly imprinted polymers coated on carbon nanotubes for matrix solid phase dispersion extraction of camptothecin from Camptotheca acuminate

The protocol for the synthesis of MIPs.

Selective extraction of dimethoate from cucumber samples by use of molecularly imprinted microspheres

Molecularly imprinted polymers for dimethoate recognition were synthesized by the precipitation polymerization technique using methyl methacrylate (MMA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The morphology, adsorption and recognition properties were investigated by scanning electron microscopy (SEM), static adsorption test, and competitive adsorption test. To obtain the best selectivity and binding performance, the synthesis and adsorption conditions of MIPs were optimized through single factor experiments. Under the optimized conditions, the resultant polymers exhibited uniform size, satisfactory binding capacity and significant selectivity. Furthermore, the imprinted polymers were successfully applied as a specific solid-phase extractants combined with high performance liquid chromatography (HPLC) for determination of dimethoate residues in the cucumber samples. The average recoveries of three spiked samples ranged from 78.5% to 87.9% with the relative standard deviations (RSDs) less than 4.4% and the limit of detection (LOD) obtained for dimethoate as low as 2.3μg/mL.