Reversible Covalent Approach

The preorganisation approach (b) involves formation of strong reversible covalent arrangements (boronate esters, imines, ketals) of the monomers... 

Two different techniques have been developed for MIP production, namely the covalent and the non-covalent approaches. The covalent way is based on the chemical derivatization of the template with molecules containing polymerizable groups using reversible covalent bonds. Different chemical reactions can be ap-... 

Along these lines and as a proof of principle, reversible imine formation was implemented in 1997 for the generation of enzyme (carbonic anhydrase) inhibitors from a dynamic covalent library [43] and reversible covalent selection approaches to catalytic systems were presented [44]. 

Non-biomimetic interfaces which are constructed as they are from supramolecular associations or reversible covalent linkages. An approach to such an interface can be envisaged through the application of supramolecular chemistry and dynamic constitutional chemistry which are both conducive to adaptive structures. 

AI-Acetyl- DL-homocy steine Isocitrate dehydrogenase in general, useful for reversible covalent immobilization approach... 

Another approach is to introduce a suitable chemical function in between the two hydrogen bonding groups of the monomer. For example, this can be an organometallic complex cleaved by addition of a suitable ligand [ 134,135] or a reversible covalent bond [136] or an ionic interaction controlled by the presence ofC02 [137-139] or pH [140]. 

The fundamental difference between the non-covalent and the covalent approach is that the latter involves template molecules which are covalently bound to monomer units prior to their addition to the reaction mixture. Subsequent co-polymerisation in the presence of a cross-linking reagent results in the incorporation of the template molecule within a polymer matrix. An important requirement is that the bond between the template and polymer is readily reversed as, to remove the template molecules, the covalent bonds between template and polymer must be cleaved. This cleavage step is very important and must be performed under conditions that will not profoundly alter the functionality or spatial arrangement at the imprinted site. The polymer is finally washed to leave the vacant imprinted sites. 

DCL) of equilibrating compounds.In this approach, building blocks that form reversible covalent bonds are used to build a DCL (Figure 21). Stabilization of a library member upon addition of a template results in a new equilibrium. The end result in accord with Le Chatelier s principle, is amplification of stabilized products in the mixture. 

Two main approaches are used to produce MIPs the noncovalent [48] and the covalent [49] approach. In the covalent approach (Figure 5.12a), the functional monomer is covalently bonded to the template molecule before polymerization. When polymerization is complete, the covalent bonds between the template molecule and the polymer are cleaved and the template molecule is extracted. The resulting imprint is then able to recognize and rebind the imprinted analyte via reversible covalent bonds. However, this technique suffers from lack of generality owing to the difficulties of finding suitable monomers. 

The covalent approach or the pre-organized approach implies the formation of a template-functional monomer complex through reversible covalent bonds prior to polymerization. After synthesis and removal of the template, in the subsequent rebinding step, the initial covalent linkage is reconstituted between the polymer and template. Therefore, only a low number of non-selective binding sites are expected to be formed because of the well-defined stoichiometry taking place between the functional monomer and template. Unfortunately, this approach is only applicable to a limited number of template molecules. 

The semi-covalent approach combines the advantages of the previous two methods, employing reversible covalent bonds in the imprinting step and noncovalent interactions in the recognition process, after the cleavage of the template from the polymer. 

The covalent approach does not suffer from any of the problems caused by using an excess of functional monomer, since the template is covalently bound to an appropriate stoichiometric amount of functional monomer in the polymerization mixture. The result is that all functional groups in the resultant imprinted polymer are present only in the imprint sites and in the precise spatial arrangement for rebinding. This would appear to represent an ideal situation for the creation of an imprint, however, the range of template functionality for which efficient reversible complex formation is... 

In the covalent approach (Figure 2), a polymerizable derivative of the template is obtained by linking the template with a vinyl functional monomer via a strong reversible covalent bond (e.g., boronate esters, Schiff bases, or ketal). The derivatized print molecule is then radical copolymerized with an excess amount of a cross-linking agent, using either thermal or photochemical radical initiation. Reaction conditions are... 

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