Utility of MIPs

A recent review by Pichon and Haupt169 summarizes the progress in the area of utilization of MIPs for sample preparation purposes and cites several examples of solid phase extraction (MISPE) from biological matrices. The requirements and applications of MIPs are reviewed in a recent book170 and other literature.171-176... 

The advantages of using MIPs instead of antibodies in binding assays are the same attractive features that drive the utilization of MIPs as affinity chromatographic media ease of preparation, lower cost, tolerance to extreme chemical and thermal conditions, long shelf life, and no need for animal immunization. For example, MIA protocols employ organic solvents, offering an attractive alternative to conventional immunoassays. Additionally, MIPs have been found to provide affinity/avidity, and cross reactivity comparable to antibodies. 

Utilization in Aqueous Environment of MIPs Synthesized in Organic Solvents... 

MIP beads or microspheres are also widely used for sensing purposes [166]. They are prepared by precipitation polymerization and then they are embedded in a dedicated matrix, which is immobilized on the transducer surface. Moreover, the MIP beads are used to serve as stationary phases in HPLC [167] and for catalytic purposes. Other systems, such as self-assembled monolayers, SAMs [168], sol-gel matrices [169] and preformed polymers [170] have also been utilized for fabrication of MIP constructs. 

Molecularly imprinted polymers with a variety of shapes have also been prepared by polymerizing monoliths in molds. This in situ preparation of MIPs was utilized for filling of capillaries [20], columns [21], and membranes [22, 23]. Each specific particle geometry however needs optimization of the respective polymerization conditions while maintaining the correct conditions for successful imprinting. It would be advantageous to separate these two processes, e.g., to prepare a molecularly imprinted material in one step, which then can be processed in a mold process in a separate step to result the desired shape. 

As the imprinting field moves toward commercial applications, the need to conveniently and efficiently produce the polymers in different formats is becoming increasingly important. In this section, the primary methods utilized for the preparation of MIPs and their relative merits for various applications will be presented. 

The reports of MIP-design protocols utilizing quantum chemical methods, i.e., semi-empirical, ah initio and DFT are becoming increasingly common in the design and evaluation of MIPs, in particular for studies of the MIP prepolymerization stage [Nicholls et al., 2009]. 

So far, the use of MIPs in catalysis has been limited to transformations involving specifically imprinted compounds. From a practical standpoint, it is unrealistic to envision the current technology utilized in natural product syntheses or method development procedures. Useful catalysts are reactive and selective towards entire families of substrates, and imprinting technology is not currently suited for this. 

Matsui and coworkers reported the use of cobalt ion MIPs for chromatography based recognition studies on imprinted compounds. The authors chose to utilize an imprinting system described previously for the catalysis of aldol condensations (vide supra). This system was shown to be amenable to the study of MIP-metal ion mediated recognition. Preliminary studies were conducted to provide evidence for the complex formation between cobalt, polymerizable ligands, and dibenzoyl-methane, 28. Compleximetric titration of 28 in a model prepolymerization reaction mixture containing cobalt (II) acetate and pyridine in chloroform/methanol (5 1) showed formation of a complex with 1 1 stoichiometry between 28 and Co(II) (Fig. 19). 

The construction of catalysts for bimolecular reactions represents a special challenge. Due to entropic reasons, the product- catalyst complex is likely to be more stable than the ternary substrate-catalyst-complex. Consequently, turnover is often low or not even observed. For Diels-Alder reactions, the difficulty to obtain turnover is further increased by the fact that the transition-state and the final product are similar in shape. Nevertheless, a catalytic MIP for a Diels-Alder reaction has successfully been prepared [17]. The trick employed to overcome the problem of similarity between TSA and product is the utilization of a reaction in which the product spontaneously decomposes (Fig. 9). The same reaction had been previously studied with catalytic antibodies. For the catalytic MIP, significant rate enhancements and Michaelis-Menten kinetics were observed. Addition of the template reduces the rate of the reaction to 41% of the original value whereas the control... 

An attractive alternative to improve the general activity of catalytic MIPs is the utilization of transition metal catalysts. In this case, polymeric catalyst with turnover frequencies of >100 h and turnover numbers of >100 can be prepared. For this type of MIP catalysts, the imprinting procedure should be regarded as a method to... 

The scintillation proximity MIA developed by Ye and Mosbach [39] was the first MIA to obviate the need for a separation step. They utilized microsphere MIPs imprinted with -propranolol and containing the scintillation monomer 4-hydro-xymethyl-2,5-diphenyloxazole acrylate. Binding of the probe H-5 -propranolol to the microspheres enabled excitation of the scintillant and photoemission could be detected, which was suppressed when analyte was present and displaced the probe. The initial MIA was performed in toluene/AcOH (99.5 0.5) and appeared to be of... 

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