Molecular imprinting limitations

Possible applications of MIP membranes are in the field of sensor systems and separation technology. With respect to MIP membrane-based sensors, selective ligand binding to the membrane or selective permeation through the membrane can be used for the generation of a specific signal. Practical chiral separation by MIP membranes still faces reproducibility problems in the preparation methods, as well as mass transfer limitations inside the membrane. To overcome mass transfer limitations, MIP nanoparticles embedded in liquid membranes could be an alternative approach to develop chiral membrane separation by molecular imprinting [44]. 

In spite of the fact that molecular imprinting allows materials to be prepared with high affinity and selectivity for a given target molecule, a number of limitations of the materials prevent their use in real applications. The main limitations are ... 

Molecular imprinting is not limited to organic polymer matrices, but can also be applied to silica-based materials and even proteins. Proteins freeze-dried in the presence of a transition state analogue as template have been used successfully as catalysts, e.g., for the dehydrofluorination of a fluorobutanone. For instance, lyophilized 3-lactoglobulin imprinted in this manner with N-isopropyl-N-ni-trobenzyl-amine could accelerate the dehydrofluorination by a factor of 3.27 compared to the non-imprinted protein see Table 5 [62]. In a similar procedure, BSA was imprinted with N-methyl-N-(4-nitrobenzyl)-S-aminovaleric acid and showed an enhancement of the catalytic effect by a factor of 3.3 compared to the control protein for the same reaction see Table 5 [113]. 

Some limitations of this molecular imprinting technique are obvious the template must be available in preparative amounts, it must be soluble in the monomer mixture and it must be stable and unreactive under the conditions of the polymerization. The solvent must be chosen considering the stability of the monomer-template assemblies and it should result in the porous structure necessary for rapid kinetics of the template interaction with the binding sites. If these criteria are satisfied, a robust material capable of selectively rebinding the template can be easily prepared and evaluated in a short period of time. 

Concerning the use of ATRP with MIPs, the major limitation for this technique in the context of MIP synthesis is the small choice of monomers with suitable functional groups. Typical monomers used for molecular imprinting such as methacrylic acid (MAA) are incompatible, as they inhibit the metal-ligand complex involved in ATRP. With other monomers like methacrylamide [59] and vinylpyridine [60] it is difficult to achieve high monomer conversion. Template molecules also often carry functional groups that may inhibit the catalyst. All this seems to make ATRP not the best choice for molecular imprinting. Nevertheless,... 

As it was shown in the previous sections, there is at present a wide variety of available methods for the preparation of molecularly imprinted micro-and nanoparticles. Little has been done however to compare directly two or more of these various synthetic strategies in order to better ascertain their advantages and limitations, and in particular their capability to yield efficient MIPs. 

Abstract Most analytical applications of molecularly imprinted polymers are based on their selective adsorption properties towards the template or its analogs. In chromatography, solid phase extraction and electrochromatography this adsorption is a dynamic process. The dynamic process combined with the nonlinear adsorption isotherm of the polymers and other factors results in complications which have limited the success of imprinted polymers. This chapter explains these problems and shows many examples of successful applications overcoming or avoiding the problems. 

Mosbach and co-workers developed a method to prepare molecularly imprinted polymers by precipitation polymerization [24]. They started from a dilute, homogenous solution of the monomer methacrylic acid (MAA) and the crosslinker trimethylolpropane trimethacrylate (TRIM) or ethylene glycol dimethacrylate (EGDMA). The polymer formed in the presence of the template molecule 17/1-estradiol, theophylline, or caffeine contained a high proportion of discrete spheres of diameter less than a micron. Because the effect of coalescence becomes predominant with higher solid content of the reaction mixture, this approach is limited to solid contents of typically <2 wt%. 

Although molecular imprinting is a fascinating tool for tailoring the enantioselectivity of a CSP, from a practical standpoint MlP-type CSPs are problematic for analytical applications. This is mainly due to (i) their poor efficiency, in particular for the high-affinity enantiomer and print molecule, and (ii) the limited range of applicability, i.e. only for the racemate of the print molecule and structurally closely related SAs for which cross-selectivity exists. These major limitations are the main reasons why there are no MlP-type CSPs currently available on the market. 

To overcome the problem of their limited range of applicability and to extend the spectrum of application other than to the imprint molecule, molecularly imprinted polymer combinatorial libraries for multiple simultaneous chiral separations have been prepared [ 191 ], demonstrating that the ligand cross-reactivities of molecularly imprinted polymers can be beneficially employed for the simultaneous separation of different stereoisomeric structures. 

---