Stochastic lattice model Simulations of molecularly imprinted polymers

A stochastic computer model was developed that simulates the formation and binding properties of molecularly imprinted polymers (MIPs). This simulation allowed examination of possible mechanisms in the imprinting process. The simulation enabled the rapid study of each variable in the imprinting process, which is difficult to do experimentally because of the interdependence of the variables. In particular, the simulation allowed examination of influence of binding site heterogeneity on the imprinting effect and on the binding properties of MIPs. The simulation was based on a lattice model in which monomer, template, cross-linker, and solvent units occupy positions in a square grid. A stochastic algorithm was utilized to position the monomer and template units in the lattice matrix based on the monomer-template binding constant. The lattice model simulation provides a method to study the imprinting mechanism and also to rapidly optimize the imprinting process. The model was able to simulate the imprinting effect as evidenced by a higher population of high-affinity binding sites in polymers made with the presence of template units. The lattice model simulation was also able to accurately reproduce the structural and energetic binding site heterogeneity of MIPs. Next, the effects of changing the imprinting variables such as the monomer- template stoichiometry and association constant were examined. Again, the simulated MIPs displayed the same trends as experimental MIPs formed under similar imprinting conditions. Finally, the simulation was carried out with isomeric template units to examine the origins of selectivity in MIPs. A clear preference for the imprinted isomer was observed. The ability of this lattice model to accurately replicate the binding.properties of MIPs gives credence to the importance of binding site heterogeneity in determining the binding properties of MIPs. The simulation gives support for the hypothesis that the diverse mixture of monomer- tempi ate complexes in the prepolymerization mixture is a major source of binding site heterogeneity in MIPs. The simulation suggests new mechanisms and strategies for improving the imprinting effect such as the careful optimization of the statistical ratios of monomer and template or the introduction of blocking groups to reduce the number of low-affinity background binding sites.