Synthesis of MIPs

Liquid fluorocarbon was used as continuous phase by Perez-Moral and Mayes [19] as well. They proposed a new method for rapid synthesis of MIP beads, in that they prepared 36 polymers imprinted for propranolol and morphine with different amounts of EDMA as a cross-linker and different functional monomers (MAA, acrylic acid, hydroxyethyl methacrylate, 4-vinylpyridine) directly in SPE cartridges. The properties of MIP microspheres prepared by this method were very similar in terms of size, morphology and extent of rebinding to microspheres prepared by conventional suspension polymerisation in perfluorocarbons as well as to bulk polymers prepared in the same solvent. The most notable advantages of this method are no waste production (no transfer of beads during washing steps) and possible direct use for a variety of screening, evaluation and optimisation experiments. 

A very important issue in the synthesis of MIPs is the study of the pre-organized complexes formed between the functional monomer(s) and the template. Preferably, this complex should be sufficiently stable to withstand polymerization conditions on the one hand and satisfactorily labile to allow both facile release of a template after polymerization and fully reversible rebinding of an analyte on the other. 

The most outstanding feature of this work is that it describes the synthesis of MIPs which possess not only the attributes of typical imprinted polymers (number and strength of binding sites, pore size distribution) but that they are also transparent It is rather surprising that this has not been further exploited. Such MIPs could conceivably be used for the determination of any analyte possessing a suitable chromophore. Alternatively, they could be used, in conjunction with a chromogenic reporter, in competitive assays. 

The synthesis of MIPs is performed by copolymerization of appropriate monomers in the presence of a template ligand. The monomers interact with the template by non-covalent interactions, reversible covalent interactions, or metal ion-mediated interactions. The types of interactions that are usually exploited in molecular imprinting are as follows ... 

Selection of monomers for synthesis of MIPs based on the interaction energies Study of correlation between molecular volumes and pKa of templates and the retention factors... 

Perez-Moral, N. Mayes, A. G., Direct rapid synthesis of mip beads in spe cartridges, Biosens. Bioelectron. 2006, 21, 1798-1803... 

Much of the selectivity of MIPs arises from the interactions between the templates and the functional monomers. The functional monomers are chosen so that their functionalities complement the functionalities of the template molecules. A wide variety of functional monomers, including acidic, basic, neutral and hydrophobic ones, have been tested in MIP synthesis (Table 2.1). Methacrylic acid is the most widely used monomer and has been applied in the synthesis of MIPs selective for a wide range of templates. 

In addition, the synthesis of MIPs requires large quantities of guest molecule (50 to 500 pmoles per gram of polymer). So, when pure template molecule is difficult or expensive to obtain, reaching quantitative template extraction yields can be primordial. Extraction conditions must then be optimised to obtain yields of over 99% [126,127]. 

Polymerization Methods for Synthesis of MIPS for Pharmaceutical Applications... 

The precipitation polymerization was invented by Goh and Stover, [2002) and this method was first introduced by Ye et al. [2001) in molecular imprinting, since then it is applied to a large variety of target molecules and successfully applied for the synthesis of MIPs for various pharmaceutical templates [Table 18.2). 

However, many of the strategies developed for the automated synthesis of MIPs require expensive, specialized equipment that may not be available in many laboratories. For a discussion on combinatorial or computational approaches the reader is referred to Chapters 8 and 14, respectively. 

I. WHY DO WE NEED TO ADOPT A COMBINATORIAL APPROACH TO THE SYNTHESIS OF MIPs ... 

Let us write down a checklist of the operations you need to take into account to plan an experiment of statistical design applied to the synthesis of MIPs. 

The repertoire of strategies (see Scheme 3) involves on the one hand the adaptation of the main conventional or alternative MIP preparations to thin-film formation (see below), and on the other hand, the adaptation of state-of-the-art thin-film preparation technologies to the synthesis of MIPs (see Section III.C). 

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