Structure and Dynamics of Monomer−Template Complexation: An Explanation for Molecularly Imprinted Polymer Recognition Site Heterogeneity

Abstract

We here present the first simulation of a complete molecularly imprinted polymer prepolymerization system. Molecular dynamics studies were performed for a system comprising a total of 1199 discrete molecules, replicating the components and concentrations employed in the corresponding polymer synthesis. The observed interactions correlate well with results obtained from (1)H NMR spectroscopic studies. Comparison with simulations performed in the absence of cross-linking agent (ethylene dimethacrylate) demonstrated its significance in the formation of ligand recognition sites. Moreover, the influence of events such as template-template (bupivacaine) and monomer-monomer (methacrylic acid) self-association, porogen-template interactions, and template conformational variability was revealed. The template recognition capacity of the modeled polymer system was verified by synthesis of imprinted and reference polymers and subsequent radioligand binding analysis. Collectively, through a series of statistical analyses of molecular trajectories in conjunction with spectroscopic data it was demonstrated that an ensemble of complex structures is present in the prepolymerization mixture and that this diversity is the basis for the binding site heterogeneity observed in molecularly imprinted polymers (MIPs) prepared using the noncovalent strategy.

Rational design of core–shell molecularly imprinted polymer based on computational simulation and Doehlert experimental optimization: application to the separation of tanshinone IIA from Salvia miltiorrhiza Bunge

“…Recently, Karlsson et al [39] have addressed the importance of various possible interactions within the prepolymerization mixture, such as monomer…monomer and template…template self-association. In our studied systems, only the monomers prefer to self-associate through intermolecular hydrogen bonding.…”

Theoretical and Computational Strategies for the Study of the Molecular Imprinting Process and Polymer Performance

“…One particular complication appears to be the problems that can arise from the lack of an explicit solvent [44,45]. For electronic structure methods, the inclusion of a reasonable number of solvent molecules makes the calculation rather time-consuming; as a result, solvent effects are often omitted completely.…”

“…By also including the initiator and multiple templates in correct stoichiometries to represent an actual pre-polymerization system, Karlsson et al [45] were able to present a comprehensive investigation of all non-covalent interactions taking place in a bupivacaine imprinting procedure. Interestingly, the authors reported both a correlation between results obtained from a series of NMR spectroscopic studies on monomer-template complex stability and simulated data, and also the origin of the recognition-site heterogeneity frequently demonstrated in MIPs (see Fig.…”

Protein-imprinted materials: rational design, application and challenges

“…[22], with permission from The Royal Society of Chemistry can conducted by experimental or computational methods [37][38][39][40]. For protein imprinting, the monomer should be soluble in a polar solvent, ideally in water, because most proteins do not dissolve in nonpolar or medium polarity solvents.…”