Synthetic Mechanism of Molecular Imprinting at the Solid Phase

The standard mechanism of molecular imprinting centers on the formation of a monomer–template complex in the prepolymerization mixture which remains trapped in the polymeric network following polymerization in the presence of a cross-linker. The release of the template leaves behind a binding site with functional groups “frozen” in a conformation complementary to the structure of the template and its analogues. Herein, we discuss the limitations of this model and present an alternative, in which imprinting is a result of dynamic interactions among the template, monomers, oligomers, and growing polymers in a solution. As a model, we have chosen the solid-phase synthesis of molecularly imprinted polymer (MIP) nanoparticles. Evidence is provided from the surface plasmon resonance-based binding analysis of MIP and “protoparticles”, literature sources, and theoretical considerations. We conclude that the alternative mechanism may explain some behavioral inconsistency of the conventional model, including the impact of temperature, cross-linking, and computational molecular models, and describe some possibilities for improvement in MIP affinity and selectivity.