Molecular imprinting leads to functional polymers that are capable to incorporate the template used and thus lead to selective chemical sensor systems when combined with a suitable transducer. Benzene and xylene can e.g. be distinguished with a selectivity factor of nearly ten using mass-sensitive devices such as QCM and SAW, although they both contain an aromatic system and differ only by the methyl groups. Sensing materials are further tuned by using binary mixtures as templates. When analyzing polycyclic aromatic hydrocarbons (PAH) by fluorescence and QCM measurements, the sensitivity is substantially increased if a second template molecule is applied as a porogen. Capacitive sensor measurements on polymers imprinted with microorganisms, such as yeasts, show substantial sensor responses due to highly selective inclusion compared with a non-functionalised surface yielding only negligible effects.

The technology of molecular imprinting permits recognition sites to be inserted into a polymeric material through the polymerisation of a monomer in the presence of a template, or through the dissolution of a preformed polymer in a solution containing the template and then crosslinking or phase inversion so as to obtain the matrix-template complex. This paper will focus on the application of both techniques in the realisation of polymeric membranes with molecular recognition properties in aqueous environments.

Novel bile acid sequestrants based on a polyammonium backbone were synthesized using molecular imprinting technique. These imprinted polymer networks were prepared by crosslinking different polymeric amines with crosslinking agents in the presence of sodium cholate as the template. The template molecules were completely removed from the polymer matrices by repeated washings. The bile acid sequestration properties of these polymeric resins were evaluated under both in vitro and in vivo conditions. Adsorption isotherms performed in physiologically relevant media revealed that molecular imprinting led to improvement in bile acid sequestration with about a twofold increase in the Ka (association constant). More importantly, hamsters fed with imprinted polymers in their diet excreted more bile acids than the non-imprinted control polymer. These results suggest that molecular imprinting may be potentially an interesting approach to prepare novel polymer therapeutics.

Development of a sensor capable of selective detection of specific nerve agents is imperative in today’s atmosphere of terrorism. The sensor needs to be inexpensive, portable, reliable, absent of false positives and available to all military and first responders. By utilizing the techniques of molecular imprinting, combinatorial chemistry, silica sol-gel synthesis and lanthanide luminescence, a sensor for the detection of the hydrolysis product of the nerve agent soman is being developed. There are many parameters that require investigation in order for the sensor to become a reality. These parameters include 1) the selection of a chelate that can bind to the lanthanide and anchor the nerve agent simulant during the formation of the molecularly imprinted polymer, 2) the determination of the environment best suited for this complex formation, 3) the formation, as well as modification of the silica sol-gel for molecular imprinting to take place, and 4) the proper quantity and ratios of monomers used to create the three dimensional imprint. Key to the success of optimizing these parameters is the development of a combinatorial assay that allows for the synthesis and testing of tens of thousands of combinations of parameters. Work on the development of the combinatorial assay has lead to a method of preparing thin film polymers capable of analyzing the presence of nerve agent simulants. Current work is underway to validate the combinatorial assay and to synthesize and evaluate a library of sensor materials selective for nerve agents.

The goal of this research is to develop molecular imprinted polymers (MIP) for biomimetic recognition of viruses. Our experimental results indicate that hydrogels can be produced, which can specifically and selectively bind recombinant baculoviruses. Although it is expected that imprinted cavities will be distorted due to the swelling of the hydrogel in water, our experiments show that even the swollen gels exhibit remarkable affinity toward recombinant baculovirus. The proposed methodologies for the synthesis and characterization of MIPs thus offer exciting avenues for the development of virus recognition techniques. The virus MIPs must function in aqueous environments. Our approach employs a more flexible non-covalent imprinting method, starting from a readily available polyamine polymer, and both MIP synthesis and testing are performed in aqueous solutions. The development of a virus imprinted MIP, which would apply to the identification, classification, and removal of viruses. This is currently a very difficult task, but the need is widespread in diverse sectors, including national security, human and animal health, crop protection, and biologics production. The development of general methods using MIPs capable of specific recognition of biological analytes would have an enormous value in medicine and bioanalytics.

A resin, imprinted with 3-hydroxybenzoic acid (3HBA), was synthesized from acrylamide (AA, the functional monomer) and ethylene glycol dimethacrylate (EGDMA, the crosslinking agent). Batch analyses showed that the imprinted polymer has a special affinity for the meta-substituted 3HBA, but not for its para-substituted isomer (4HBA) nor for benzoic acid (BA). These results are consistent with the principle that an imprinted resin's ability to recognize is dependent on the target's size, shape, and functionality. Another resin, prepared from AA and EGDMA but in the absence of a template, had similar affinities for 3HBA, 4HBA, and BA; and thus it could not differentiate among the three. The results can be interpreted with a simple two-binding-site model with one site special for 3HBA and the other being more general with similar affinities for 3HBA, 4HBA and BA. The binding of 3HBA to the imprinted resin is characterized by an association constant and the density of each kind of site using a two-site Scatchard equation. The binding sites common to both the imprinted resin and the non-imprinted reference resin were found to have greater affinity but are less numerous than the sites unique to the imprinted resin.

The goal of this research is to produce molecular imprinted polymers (MIPs), which selectively bind glucose over other sugars. MIP hydrogels against glucose exhibited binding capacities in excess of 0.6 grams of glucose per gram of dry gel in a 100 % DI H2O glucose solution, as well as in a 50–50 % glucose-fructose solution mixture. Equilibrium binding capacities of fructose were lower than those observed with respect to glucose, indicating an isomeric preference for the binding of glucose over fructose. Although it is expected that imprinted cavities will be distorted due to the swelling of the hydrogel in water, our experiments show that even the swollen gels exhibit remarkable glucose recognition. This synthetic and characterization methodology for MIPs might thus offer exciting avenues for novel biomimetic recognition and isomeric separation techniques.

A new mechanistic diagram describing the non-covalent molecular imprinting process is put forth in the text. A significant consequence of the new mechanistic picture is that the pre-polymer complex structure does not necessarily reflect the structure of the final binding sites in the polymer. Two independent studies are presented in combined form that support the suggested changes to the mechanistic diagram. In the first study, the maximum number of functional groups surrounding the template molecule in solution are shown to be less than the average number of functional groups in the binding sites of the polymers. In the second study, shape selectivity is shown to be an important contributor to molecular recognition by the imprinted polymers; which is significant because contributions of shape cannot be predicted by the solution phase pre-polymer complex.

Molecularly imprinted micro- and nano-particles can be conveniently prepared using precipitation polymerization method. By controlling the initial reaction composition, the resulting polymer particles may be obtained as uniform beads that display favourable binding characteristics. Incorporation of a novel reporter element resulted in an imprinted scintillation polymer that displayed an enhanced signalling efficiency.

Molecularly imprinted polymers (MIPs) are used as recognition elements in biochemical sensors. In a fluorescence-based MIP sensor system, it can be difficult to distinguish the analyte fluorescence from the fluorescence of the polymer itself. We studied steady-state fluorescence anisotropy of anthracene imprinted in a polymer (polyurethane) matrix. Vertically polarized excitation light was incident on MIP films coated on silicon wafers; vertically and horizontally polarized emission was measured. We compared the fluorescence anisotropy of MIPs with imprinted molecules, MIPs with the imprinted molecules extracted, MIPs with rebound molecules, and non-imprinted control polymers. It is shown that differences in fluorescence anisotropy between the polymers and imprinted fluorescent molecules may provide a means to discriminate the fluorescence of analyte from that of the background polymer.

A high throughput synthesis technique was developed for the combinatorial optimization of polymers imprinted with 17□-Estradiol. This incorporated a liquid handling robot for the rapid dispensing of monomers, templates, solvents and initiator into the reaction vessels of a 96-well plate. A library of 80 polymers, each ca 80mg, was prepared using functional monomers containing acid functionalities (methacrylic acid (MAA), trifluoromethylacrylic acid (TFMAA)), basic functionalities (2-vinylpyridine (2-Vpy), 4-vinylpyridine (4-Vpy), diethyl-2-aminoethylmethycrylate (DEAEMA)) or neutral functional groups (2-hydroxyethylmethacrylate (HEMA), methacrylamide (MAAM), N-vinylpyrrolidone (NVP), acetoxystyrene (AST)). Four replicas each of imprinted and nonimprinted polymers were made for each functional monomer using ethyleneglycoldimethacrylate (EDMA) as crosslinking monomer and acetonitrile as solvent. Polymer washing and exchange of incubation solutions could be effectively carried out after transfer of the polymers to solvent resistant filter plates. The binding properties of the polymers could then be rapidly assessed in the batch mode by quantifying non-bound fractions in parallel using a fluorescence monochromator plate reader. These data showed an acceptable agreement with the data from a corresponding HPLC evaluation of the rebinding solutions. In agreement with other reports, the acid functional monomers MAA and TFMAA, the basic DEAEMA and the neutral MAAM exhibited the highest imprinting factors.

The effect of chemical environment surrounding a synthetic heterogeneous catalyst active site is investigated using the hydrophilic imprinting of silica. Two model reaction systems have been used for this study: (i) Knoevenagel condensation of 3-nitrobenzaldehyde and malononitrile and (ii) Suzuki coupling of bromobenzene and phenylboronic acid. Using a catalyst in which isolated imprinted amines are surrounded by an acidic silanol-rich environment led to rate accelerations of over 120-fold relative to catalysts in which the amines are surrounded by a hydrophobic environment consisting of trimethylsilyl functional groups for system (i). This result parallels our previous study on the effect of the outer sphere composition on rate acceleration of Knoevenagel reactions using isophthalaldehyde as the aldehyde reactant. We also extended our method for the hydrophilic imprinting of bulk silica to organometallic systems, by successfully synthesizing a tethered palladium complex within the imprinted pocket. This material was used as an active catalyst for (ii). Our results show that a hydrophobic framework environment results in higher initial turnover frequencies than an acidic silanol-rich framework for the Suzuki coupling reaction of bromobenzene and phenylboronic acid, albeit with a lower overall effect than observed in the Knoevenagel system (i). Altogether, these results demonstrate the control of chemical reactivity via the rational design of the outer sphere using an imprinting approach.

Molecular imprinting is a useful technique for making a chemically selective binding site. [1] The method involves building a synthetic polymeric scaffold of molecular compliments containing the target molecule with subsequent removal of the target to leave a cavity with a structural “memory” of the target. Molecularly imprinted polymers can be employed as selective adsorbents of specific molecules or molecular functional groups. Sensors for specific molecules can be made using optical transduction through chromophores residing in the imprinted site. The use of metal ions as chromophores can improve selectivity due to directional bonding. The combination of molecular imprinting and spectroscopic selectivity can result in sensors that are highly sensitive and nearly immune to interferences. [2]

Proteins, enzymes, and antibodies have the ability to discern specific molecules out of a whole host of species and selectively bind them with remarkable affinity. A route that would enable the creation of synthetic polymers with this binding ability would be a great advance with subsequent applications in chemical sensors, single-molecule separations, and even artificial enzymes. In this work we study the molecular imprinting process whereby a controlled nanostructure consisting of distinct binding sites is created in a polymer network through a templating procedure. Simulations were done to better understand the underlying network structure that gives rise to the increased uptake. An all-atom molecular dynamics simulation was coupled with a kinetic gelation approach to study network formation in the presence of a template. The monomers used were first studied with density-functional theory in order to parameterize a force field for various methacrylates. Simulation results showed three key functional group interactions that lead to successful imprinting and subsequent rebinding.

Worldwide, there is great interest in new processes for production of nanoscale features in materials surfaces. Our recent work explores imprinting of nanosized objects into thin films. In this paper, we present results from surface imprinting of TiOx sol-gel films with anodized alumina. Scanning Probe Microscopy provides evidence for the quality of the imprinting process.

Polyacrylonitrile having methacrylic acid [P(AN-co-MAA)] and acrylic acid [P(AN-co-AA)] was used for phase inversion imprinting of uracil (URA). Resultant imprinted membranes had porous morphology and showed permselective binding of URA, when 32 μM URA aqueous solution was permeated under pressure gradient of 100 Pa across the membrane. Under the circumstance, the imprinted P(AN-co-MAA) membrane bound 7.9 μmol/g of URA with 8.4×10−6 m3/m2·s of volume flux. The imprinted P(AN-co-AA) membrane showed loose selectivity relative to the P(AN-co-MAA) membrane. Binding behavior of URA and dimethyluracil (DMURA) was also compared in both imprinted membranes. Evidence was presented that P(AN-co-MAA) with methacrylic segments was effective for URA imprinting and resulted in high URA selectivity in the permselective binding experiments.