Imprinted cavity

ORMOSIL are chemical sponges they adsorb and concentrate reactants at their surface, thereby enhancing reaction rates and sensitivity (in sensing applications). ORMOSIL-imprinted materials with a suitable chiral template such as a surfactant or a protein selectively adsorb (and detect) external reactants. A remarkable example is provided by thin materials that are generally enantioselective, namely where the chirally imprinted cavities can discriminate between enantiomers of molecules not used in the imprinting process, and completely different from the imprinting ones. 

Figure 12. Generalized scheme for the formation of a polymeric network with imprinted cavities base d on the chemical and special characteristics of the template (T) the natural polymerlike antibody-type proteins recognize xenobiotics, a fully synthetic polymer may recognize the preentrapped and afterwards washed out template (T) molecule.

Fig. 2 Strategy for the generation of imprinted cavities inside nanocapsules employed by Ki and Chang. Reproduced with permission from [62]...

Preformed polymers can also be employed to prepare imprinted core-shell particles [143]. The group of Chang recently prepared a poly(amic acid) bearing oestrone as a template molecule covalently bound to the polymer through a urethane linker (see Fig. 2). A layer of this polymer was subsequently deposited on silica particles (10 pm diameter) prefunctionalised with amino groups at their surface. Thermal imidisation of the polymer yielded finally a polyimide shell (thickness about 100 nm) on the silica particles. Subsequent template removal yielded the imprinted cavities, which exhibited selective rebinding of oestrone in HPLC experiments. 

The transport properties across an MIP membrane are controlled by both a sieving effect due to the membrane pore structure and a selective absorption effect due to the imprinted cavities [199, 200]. Therefore, different selective transport mechanisms across MIP membranes could be distinguished according to the porous structure of the polymeric material. Meso- and microporous imprinted membranes facilitate template transport through the membrane, in that preferential absorption of the template promotes its diffusion, whereas macroporous membranes act rather as membrane absorbers, in which selective template binding causes a diffusion delay. As a consequence, the separation performance depends not only on the efficiency of molecular recognition but also on the membrane morphology, especially on the barrier pore size and the thickness of the membrane. 

Mosbach and collaborators, in 2001, described an innovative approach to drug discovery using polymers imprinted with a biologically active template [31]. The approach, called anti-idiotypic for the similarity with anti-idiotypic antibodies in the immune-response, can be used to create synthetic receptors able to generate inhibitors or receptor antagonists by exploiting the complementarity with the cavity. The imprinted cavity promotes preferentially the formation of compounds with high affinity, which can later be evaluated for the inhibitory activity and the more active selected for further analysis. 

A second, equally powerful means to prepare such materials relies on traditional inorganic polymerization tools, most notably sol-gel polymerization.24 25 A number of excellent reviews have appeared on this subject as well.5,12,17 In sol-gel processing, the functional monomer [i.e., an organoalkoxysilane such as 3-aminopropyltrimethox-ysilane (APTMS)] is combined with the cross-linking agent [i.e., a tetrafunctional alkoxysilane such as tetramethoxysilane (TMOS) or tetraethoxysilane (TEOS)], a catalyst (such as hydrochloric acid or ammonia), and the template molecule. The resultant sol can be left to gel to form a monolith, which can then be dried, sieved, and extensively washed to remove the template. Alternatively, the sol can be spin coated, dip coated, or electrodeposited on a surface to yield a thin film, which can be subsequently washed with a solvent to remove the template and yield the imprinted cavities. 

Figure 40 (b) Sketch of the morphology of an imprinted polymer matrix [444]. Parts (a) and (b) reproduced from [444] by permission of Springer-Verlag. (c) Illustrative drawing, showing how imprinted cavities can act as selective catalysts [445]. With permission of Wiley-VCH... 

The template la can be split off by water or methanol to an extent of up to 95% (see Scheme 4.II). The accuracy of the steric arrangement of the binding sites in the resulting imprinted cavity can be tested by the ability of the polymer to resolve the racemate of the template, namely phenyl-a-D,L-mannopyranoside. The polymer was equilibrated in a batch procedure with a solution of the racemate under conditions that allowed a thermodynamically controlled partition of the enantiomers between polymer and solution. The enrichment of the antipodes in the polymer and in solution was determined and the separation factor a, i.e. the ratio of the distribution coefficients of the d- and L-enantiomer between polymer and solution, was calculated. After extensive optimisation of the procedure, a values between 3.5 and 6.0 were obtained [4]. This is an extremely high selectivity for racemic resolution that cannot be reached by most other methods. 

In the very early years of imprinting, carboxylic acid ester moieties were used as binding groups. The aim was the preparation of microreactors for regio- and stereoselective reactions. For this, the cavity was first imprinted with a possible product of the reaction and a precursor was then embedded into the cavity. The idea was to favour the formation of the product used as template by running the reaction within the imprinted cavity. The first experiments were carried out by the research groups of Shea [90,91] and Neckers [92], who performed cycloadditions that led to cyclo-propanedicarboxylic and cyclobutanedicarboxylic acids, respectively. The latter... 

Finally, the last few years have seen the first examples of the use of molecular-imprinted, polymer-supported catalysts for achieving product selectivity. The imprinted cavities are tailored in such a way that the course of a chemical reaction is directed towards one of the possible products. In the previous section it has already been shown that molecularly imprinted polymers used as microreactors are able to impart to a given reaction a different regio- and stereo-selectivity with respect to the same reaction in solution. Attempts towards an imprinted enantio-selective catalyst were reported by Gamez and co-workers who employed as template monomer an optically active, polymerisable ruthenium complex bearing in its coordination sphere an enantiomerically pure alkoxide [121]. After polymerisation, the alkoxide was split off and the resulting polymer-supported catalyst was used for enantio-selective hydride transfer reductions. The obtained selectivity was higher than for a polymer prepared without the optically active alkoxide but lower than for the same ruthenium complex in solution. 

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