Template-monomer interaction

There are two general classes of imprinted polymers covalent and noncovalent MlPs. These two categories refer to the types of interactions between the functional monomer and the template in the prepolymerization complex. There are also hybrid MlPs that utilize a combination of covalent and noncovalent interactions in the preparation and rebinding events (Klein et al. 1999). Covalent MlPs utilize reversible covalent interactions to bind the template to the functional monomers. In contrast, noncovalent MlPs rely on weaker noncovalent functional monomer-template interactions. Each type has specific advantages and disadvantages with respect to sensing applications that will be addressed in subsequent sections. 

Also of considerable importance is the mechanism of site formation. At what stage in the polymerisation are the high energy sites formed and stabilised Does the solution structure of the monomer-template assemblies reflect the disposition of functional groups at the binding sites [24] (See Chapter 5 for a further discussion.) Attempts to correlate the association constants determined for the monomer-template interactions in homogeneous solution with the rebinding association... 

The quantity and quality of MIP recognition sites that arise out of binding event is a direct function of the nature and extent of the monomer-template interactions present... 

The solvent should be capable of fully solubilizing the monomers and template in one pot. For monomer-template interactions stabilized by polar forces, non-protic solvents of low polarity should be chosen, since they are less likely to compete with the monomers for the template. The functional monomer-template complexes are often based on hydrogen bond interactions. If the solvent is a good hydrogen bond donor or acceptor, it will compete with the monomers and destabilize the complexes. For monomer-template systems stabilized by solvatophoic forces, more polar solvents and higher temperatures may be favorable. 

Covalent bonds involving Schiff bases [75], esters [76], amides [77], and ketals [57,78] have also been used. However, their much slower monomer-template interaction kinetics have excluded them from several types of application. 

A primary indication on how well the monomers have been chosen is to simply see whether they are capable of assisting solubilization of the template in the prepolymerization mixture. A small-scale solubility test may thus be a good way to initially screen the monomers for strong monomer-template interactions. Weak interactions may be revealed by complexation induced spectral changes (in NMR,UVor fluorescence spectra). The complexation induced shifts of the characteristic H-NMR signals of the template upon increasing monomer concentrations are often used to estimate the monomer-template association constants. Prior to this, however, knowledge about the stoichiometry of the monomer-template complexation and the tendency of the monomer and template to self-associate are required.The former can be obtained by means of a so-called Job s plot whereas the latter by a dilution experiment. 

A similar approach has been adopted by Whitcombe et al. [15], where NMR chemical shift studies allowed the calculation of dissociation constants and a potential means for predicting the binding capacities of MIPs. The NMR characterization of functional monomer-template interactions has also been applied to the study of the interaction of 2,6-bis(acrylamido) pyridine and barbiturates [16], and of 2-aminopyridine and methacrylic acid [17]. Recent NMR work in our laboratory [18] has involved the determination of template-monomer interactions for a nicotine-methacrylic acid system. Significantly, it was shown in this study that template self-association complexes are present in the prepolymerization mixture and that the extent template self-association is dependent both upon solvent and the presence of monomer. 

In this and following examples, the workstation used to simulate monomers-template interactions was a Silicon Graphics Octane running the IRIX 6.6 operating system. The workstation was configured with two 195 MHz reduced instruction set processors, 712 MB memory and a 12 GB fixed drive. The system that was used to execute the software packages was SYBYL 6.7 Tripos Inc. (St. Louis, MI, USA). 

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