Molecularly Imprinted Polymers Specific towards 4-Borono-L-phenylalanine-Synthesis Optimization, Theoretical Analysis, Morphology Investigation, Cytotoxicity, and Release Studies.

The aim of this study was to create molecularly imprinted polymers (MIPs) that are specific towards 4-borono-L-phenylalanine (BPA) to serve as boron compound carriers. The honeycomb-like MIPs were characterized in the matter of adsorption properties, morphology, structure, and cytotoxicity towards A549 and V79-4 cell lines. The honeycomb-like MIP composed from methacrylic acid and ethylene glycol dimethacrylate was characterized by a binding capacity of 330.4 ± 4.6 ng g-1 and an imprinting factor of 2.04, and its ordered, porous morphology was confirmed with scanning electron microscopy. The theoretical analysis revealed that the coexistence of different anionic forms of the analyte in basic solution might lower the binding capacity of the MIP towards BPA. The release profiles from the model phosphate buffer saline showed that only 0 to 4.81% of BPA was released from the MIP within the time frame of two hours, furthermore, the obtained material was considered non-cytotoxic towards tested cell lines. The results prove that MIPs can be considered as effective BPA delivery systems for biomedical applications and should be investigated in further studies.

Molecularly Imprinted Carriers for Diagnostics and Therapy-A Critical Appraisal.

Simultaneous diagnostics and targeted therapy provide a theranostic approach, an instrument of personalized medicine-one of the most-promising trends in current medicine. Except for the appropriate drug used during the treatment, a strong focus is put on the development of effective drug carriers. Among the various materials applied in the production of drug carriers, molecularly imprinted polymers (MIPs) are one of the candidates with great potential for use in theranostics. MIP properties such as chemical and thermal stability, together with capability to integrate with other materials are important in the case of diagnostics and therapy. Moreover, the MIP specificity, which is important for targeted drug delivery and bioimaging of particular cells, is a result of the preparation process, conducted in the presence of the template molecule, which often is the same as the target compound. This review focused on the application of MIPs in theranostics. As a an introduction, the current trends in theranostics are described prior to the characterization of the concept of molecular imprinting technology. Next, a detailed discussion of the construction strategies of MIPs for diagnostics and therapy according to targeting and theranostic approaches is provided. Finally, frontiers and future prospects are presented, stating the direction for further development of this class of materials.

A Fusion of Molecular Imprinting Technology and Siloxane Chemistry: A Way to Advanced Hybrid Nanomaterials.

Molecular imprinting technology is a well-known strategy to synthesize materials with a predetermined specificity. For fifty years, the "classical" approach assumed the creation of "memory sites" in the organic polymer matrix by a template molecule that interacts with the functional monomer prior to the polymerization and template removal. However, the phenomenon of a material's "memory" provided by the "footprint" of the chemical entity was first observed on silica-based materials nearly a century ago. Through the years, molecular imprinting technology has attracted the attention of many scientists. Different forms of molecularly imprinted materials, even on the nanoscale, were elaborated, predominantly using organic polymers to induce the "memory". This field has expanded quickly in recent years, providing versatile tools for the separation or detection of numerous chemical compounds or even macromolecules. In this review, we would like to emphasize the role of the molecular imprinting process in the formation of highly specific siloxane-based nanomaterials. The distinct chemistry of siloxanes provides an opportunity for the facile functionalization of the surfaces of nanomaterials, enabling us to introduce additional properties and providing a way for vast applications such as detectors or separators. It also allows for catalyzing chemical reactions providing microreactors to facilitate organic synthesis. Finally, it determines the properties of siloxanes such as biocompatibility, which opens the way to applications in drug delivery and nanomedicine. Thus, a brief outlook on the chemistry of siloxanes prior to the discussion of the current state of the art of siloxane-based imprinted nanomaterials will be provided. Those aspects will be presented in the context of practical applications in various areas of chemistry and medicine. Finally, a brief outlook of future perspectives for the field will be pointed out.

N-(2-Arylethyl)-2-methylprop-2-enamides as Versatile Reagents for Synthesis of Molecularly Imprinted Polymers.

The paper describes the formation of six aromatic N-(2-arylethyl)-2-methylprop-2-enamides with various substituents in benzene ring, viz., 4-F, 4-Cl, 2,4-Cl2, 4-Br, 4-OMe, and 3,4-(OMe)2 from 2-arylethylamines and methacryloyl chloride in ethylene dichloride with high yields (46-94%). The structure of the compounds was confirmed by 1H NMR, 13C NMR, IR, and HR-MS. Those compounds were obtained to serve as functionalized templates for the fabrication of molecularly imprinted polymers followed by the hydrolysis of an amide linkage. In an exemplary experiment, the imprinted polymer was produced from N-(2-(4-bromophenyl)ethyl)-2-methylprop-2-enamide and divinylbenzene, acting as cross-linker. The hydrolysis of 2-(4-bromophenyl)ethyl residue proceeded and the characterization of material including SEM, EDS, 13C CP MAS NMR, and BET on various steps of preparation was carried out. The adsorption studies proved that there was a high affinity towards the target biomolecules tyramine and L-norepinephrine, with imprinting factors equal to 2.47 and 2.50, respectively, when compared to non-imprinted polymer synthesized from methacrylic acid and divinylbenzene only.

Magnetic Molecularly Imprinted Nano-Conjugates for Effective Extraction of Food Components-A Model Study of Tyramine Determination in Craft Beers.

In this paper, magnetic molecularly imprinted nano-conjugates were synthesized to serve as selective sorbents in a model study of tyramine determination in craft beer samples. The molecularly imprinted sorbent was characterized in terms of morphology, structure, and composition. The magnetic dispersive solid phase extraction protocol was developed and combined with liquid chromatography coupled with mass spectrometry to determine tyramine. Ten samples of craft beers were analyzed using a validated method, revealing tyramine concentrations in the range between 0.303 and 126.5 mg L-1. Tyramine limits of detection and quantification were 0.033 mg L-1 and 0.075 mg L-1, respectively. Therefore, the fabricated molecularly imprinted magnetic nano-conjugates with a fast magnetic responsivity and desirable adsorption performance could be an effective tool for monitoring tyramine levels in beverages.

Magnetic Core-Shell Molecularly Imprinted Nano-Conjugates for Extraction of Antazoline and Hydroxyantazoline from Human Plasma-Material Characterization, Theoretical Analysis and Pharmacokinetics.

The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its metabolite, hydroxyantazoline (ANT-OH) in analytical method employing liquid chromatography coupled with mass spectrometry method. The core-shell material was characterized in terms of adsorption properties, morphology and structure. The heterogeneous population of adsorption sites towards ANT-OH was characterized by two Kd and two Bmax values: Kd (1) = 0.319 µg L-1 and Bmax (1) = 0.240 µg g-1, and Kd (2) = 34.6 µg L-1 and Bmax (2) = 5.82 µg g-1. The elemental composition of magnetic sorbent was as follows: 17.55, 37.33, 9.14, 34.94 wt% for Si, C, Fe and O, respectively. The extraction protocol was optimized, and the obtained results were explained using theoretical analysis. Finally, the analytical method was validated prior to application to pharmacokinetic study in which the ANT was administrated intravenously to three healthy volunteers. The results prove that the novel sorbent could be useful in extraction of ANT and ANT-OH from human plasma and that the analytical strategy could be a versatile tool to explain a potential and pharmacological activity of ANT and ANT-OH.

Imprinting Technology for Effective Sorbent Fabrication: Current State-of-Art and Future Prospects.

In the last 10 years, we have witnessed an extensive development of instrumental techniques in analytical methods for determination of various molecules and ions at very low concentrations. Nevertheless, the presence of interfering components of complex samples hampered the applicability of new analytical strategies. Thus, additional sample pre-treatment steps were proposed to overcome the problem. Solid sorbents were used for clean-up samples but insufficient selectivity of commercial materials limited their utility. Here, the application of molecularly imprinted polymers (MIPs) or ion-imprinted polymers (IIPs) in the separation processes have recently attracted attention due to their many advantages, such as high selectivity, robustness, and low costs of the fabrication process. Bulk or monoliths, microspheres and core-shell materials, magnetically susceptible and stir-bar imprinted materials are applicable to different modes of solid-phase extraction to determine target analytes and ions in a very complex environment such as blood, urine, soil, or food. The capability to perform a specific separation of enantiomers is a substantial advantage in clinical analysis. The ion-imprinted sorbents gained interest in trace analysis of pollutants in environmental samples. In this review, the current synthetic approaches for the preparation of MIPs and IIPs are comprehensively discussed together with a detailed characterization of respective materials. Furthermore, the use of sorbents in environmental, food, and biomedical analyses will be emphasized to point out current limits and highlight the future prospects for further development in the field.

Application of Magnetic Core-Shell Imprinted Nanoconjugates for the Analysis of Hordenine in Human Plasma-Preliminary Data on Pharmacokinetic Study after Oral Administration.

In this paper, we developed and validated a new analytical method to determine the pharmacokinetic profile of hordenine in plasma samples of human volunteers after oral administration of hordenine-rich dietary supplements. For this purpose, a magnetic molecularly imprinted sorbent was fabricated and characterized. The application of a magnetic susceptible material facilitates pretreatment step while working with a highly complex sample, reducing time and costs. An optimized, fast, and reliable separation step was combined with liquid chromatography tandem mass spectrometry, providing an analytical method for analysis of hordenine in human plasma after dietary supplement intake. The method was validated (lower limit of quantification of 0.05 µg/L), enabling the pharmacokinetic profile of hordenine to be determined. The highest concentration of hordenine was noted after 65 ± 14 min, reaching the value of 16.4 ± 7.8 µg/L. The average t1/2 was 54 ± 19 min. The apparent volume of distribution was 6000 ± 2600 L (66 ± 24 L/kg when adjusted for weight).

Theoretical and experimental proof for selective response of imprinted sorbent - analysis of hordenine in human urine.

The objective of this paper was to extend comprehensive theoretical and experimental investigations at the molecular level to identify factors responsible for the high selectivity of imprinted sorbents. This knowledge was utilized in a new analytical strategy devoted to the analysis of hordenine in human urine after beer consumption. Among the various polymeric compositions tested, the most effective material was built up from methacrylic acid and ethylene glycol dimethacrylate (MIP1), showing a satisfactory binding capacity (4.44 ±â€¯0.15 µmol g-1) and high specificity towards hordenine (AF = 5.90). The comprehensive analyses of porosity data and surface measurements revealed differences between imprinted polymers. The characterization of binding sites of MIP1 revealed a heterogeneous population with two values of Kd (2.75 and 370 µmol L-1) and two values of Bmax (1.82 and 99 µmol g-1) for higher and lower affinity respectively. The extensive theoretical analyses of interactions between various analytes and the MIP model cavity showed the highest binding energy for hordenine (ΔEB1 = -175.17 kcal mol-1). The method was validated for selectivity, lowest limit of quantification, calibration curve performance, precision, accuracy, matrix effect, carry-over and stability in urine. Extracts were prepared according to guidelines of the European Medicines Agency. The validation criteria were fulfilled, and the method was satisfactorily applied to urine samples collected prior to, and 2 h after, consumption of 2 L of beer, revealing the presence of hordenine at the mean level of 129 ±â€¯27 ng mL-1. Additionally, ability of the sorbent to purify the urine sample was assessed using flow injection analysis tandem mass spectrometry, for comparison with other extraction techniques.

Semiconductor nanocrystal-polymer hybrid nanomaterials and their application in molecular imprinting.

Quantum dots (QDs) are attractive semiconductor fluorescent nanomaterials with remarkable optical and electrical properties. The broad absorption spectra and high stability of QD transducers are advantageous for sensing and bioimaging. Molecular imprinting is a technique for manufacturing synthetic polymeric materials with a high recognition ability towards a target analyte. The high selectivity of the molecularly imprinted polymers (MIPs) is a result of the fabrication process based on the template-tailored polymerization of functional monomers. The three-dimensional cavities formed in the polymer network can serve as the recognition elements of sensors because of their specificity and stability. Appending specific molecularly imprinted layers to QDs is a promising strategy to enhance the stability, sensitivity, and selective fluorescence response of the resulting sensors. By merging the benefits of MIPs and QDs, inventive optical sensors are constructed. In this review, the recent synthetic strategies used for the fabrication of QD nanocrystals emphasizing various approaches to effective functionalization in aqueous environments are discussed followed by a detailed presentation of current advances in QD conjugated MIPs (MIP-QDs). Frontiers in manufacturing of specific imprinted layers of these nanomaterials are presented and factors affecting the specific behaviour of an MIP shell are identified. Finally, current limitations of MIP-QDs are defined and prospects are outlined to amplify the capability of MIP-QDs in future sensing.

Theoretical and experimental approach to hydrophilic interaction dispersive solid-phase extraction of 2-aminothiazoline-4-carboxylic acid from human post-mortem blood.

In this paper, we proposed an innovative hydrophilic interaction dispersive solid-phase extraction (HI-d-SPE) protocol suitable for the isolation of the potential cyanide intoxication marker, 2-aminothiazoline-4-carboxylic acid (ATCA), from such complicated matrix as post-mortem blood. To create an optimal HI-d-SPE protocol, two sorbents were used: a molecularly imprinted polymer (MIP) and commercially available Oasis-MCX®. The latter sorbent was identified as more recovery-efficient with higher clean-up abilities in a carefully optimized process. Computational analysis was employed to provide insight into the adsorption mechanism of the two selected sorbents. The theoretical results were in agreement with the experiment regarding the efficiency of the sorbent. HI-d-SPE was successfully applied to the analysis of ATCA in 20 post-mortem blood samples using LC-MS/MS. The analytical performance of the method was finally compared to prior existing methods, in turn revealing its superiority.

Separation of octopamine racemate on (R,S)-2-amino-1-phenylethanol imprinted polymer--Experimental and computational studies.

Ten molecularly imprinted polymers coded as MIP1-MIP10 were prepared by the radical bulk polymerization using (R,S)-(±)-2-amino-1-phenylethanol as the structural analog of the target analyte (R,S)-octopamine. The functional monomers, 4-vinylbenzoic acid (1), methacrylic acid (2), acrylic acid (3), trifluoromethacrylic acid (4), itaconic acid (5), acrylamide (6), isopropenylbenzene (7), 2-hydroxyethyl methacrylate (8), 2-(diethylamino)ethyl methacrylate (9), allylamine (10) were polymerized consecutively with the ethylene glycol dimethacrylate cross-linker in methanol as the porogen. On the basis of the binding capacity of (R,S)-octopamine MIP1 with affinity factor equal to 6.37 was selected for further analysis. The affinity of polymer matrix MIP1 was tested by the non-competitive binding experiments of eight structurally related analytes. Finally, molecularly imprinted solid phase extraction (MISPE) of (R,S)-octopamine from spiked human serum albumin was carried out in order to verify the applicability of novel sorbent. The molecular modeling was employed to rationalize the stereodifferentiation of the analytes by the stereospecific sites formed in the polymer matrix.

A separation of tyramine on a 2-(4-methoxyphenyl)ethylamine imprinted polymer: an answer from theoretical and experimental studies.

A 2-(4-methoxyphenyl)ethylamine imprinted polymer (MIP) was successfully applied for the selective separation of tyramine. A computational analysis was used to predict the affinity of the polymer matrix towards tyramine and a preliminary experimental evaluation was made for the target analyte. Then the experimental analysis of polymer towards tyramine was continued. The binding sites were characterized with employment of the Langmuir and Freudlich models. After the optimization of solid phase extraction towards tyramine, the most appropriate systems for the extraction steps were chosen: methanol-water 85:15 v/v for the loading and the washing as well as 0.04 M aq. ammonium acetate-methanol 30:70 v/v for the elution steps. The biogenic compounds as tryptamine, serotonin, octopamine, synephrine, and l-tyrosine were used for the selectivity study on the basis of binding capacities of the analytes on the imprinted and the non-imprinted polymers. The theoretical approach to obtained results allowed to explain the adsorption selectivity of the tested polymer. Finally, the complex matrix of bovine serum albumin was used to show the usefulness of imprinted material for bioanalysis. The obtained recoveries showed the superiority of MIP over the commercial sorbent C18. Total recoveries of tyramine from spiked bovine serum albumin sample were determined as: 95±2%, 14±3%, and 1.9±0.4% for the imprinted, non-imprinted, and commercial C18 sorbents, respectively.