Computational investigation of stoichiometric effects, binding site heterogeneities, and selectivities of molecularly imprinted polymers

Abstract

A series of quantum mechanical (QM) computational optimizations of molecularly imprinted polymer (MIP) systems were used to determine optimal monomer-to-target ratios. Imidazole- and xanthine-derived target molecules were studied. The investigation included both small-scale models (3-7 molecules) and larger-scale models (15-35 molecules). The optimal ratios differed between the small and larger scales. For the larger models containing multiple targets, binding-site surface area analysis was used to quantify the heterogeneity of these sites. The more fully surrounded sites had greater binding energies. No discretization of binding modes was seen, furthering arguments for continuous affinity distribution models. Molecular mechanical (MM) docking was then used to measure the selectivities of the QM-optimized binding sites. Selectivity was also shown to improve as binding sites become more fully encased by the monomers. For internal sites, docking consistently showed selectivity favoring the molecules that had been imprinted via QM geometry optimizations. The computationally imprinted sites were shown to exhibit size-, shape-, and polarity-based selectivity. Here we present a novel approach to investigate the selectivity and heterogeneity of imprinted polymer binding sites, by applying the rapid orientation screening of MM docking to the highly accurate QM-optimized geometries. Modeling schemes were designed such that no computing clusters or other specialized modeling equipment would be required. Improving the in silico analysis of MIP system properties will ultimately allow for the production of more sensitive and selective polymers.

Preparation of stoichiometric molecularly imprinted polymer coatings on magnetic particles for the selective extraction of auramine O from water

“…The interaction between template and functional monomer plays an important role in recognition performance of molecularly imprinted polymers . Molecular recognition is based on the strength of interactions between the template and the functional monomer, which depends on the shape of cavities in the MIPs .…”

“…The ratio of functional monomer and template often plays a vital role in synthesis of molecularly imprinted polymers [17,[27][28][29], because it can affect the uniform distribution and higher affinity of specific binding sites, as well as the stability and yield of polymers [17,20,28,30]. Herein, a stoichiometric ratio of template and functional monomer is introduced to synthesize MIPs, which further facilitates the advancement and application of imprinted polymer materials [31][32][33]. It not only overcomes the spatial and steric mismatches of template, but also benefits by forming a highly specific and selective binding site [34,35].…”

“…In this paper, we report a novel MMIPs based on stoichiometric molecular imprinting. The optimization of polymer composition was carried out based on our previous work and other research . The MMIPs were successfully synthesized using the optimum stoichiometric ratio between template, cross‐linker, and functional monomer.…”

In silico characterization of enantioselective molecularly imprinted binding sites

“…The selectivity factor, α, is defined as the ratio of binding constants between the target molecule and an analog, typically a molecule similar to the target in size and shape. In our previous work, we used quantum mechanical (QM) and molecular mechanical (MM) modeling techniques to evaluate the ability of simulated MIP binding sites to select between molecules of different sizes, shapes, and polarities . However, the differences in polarity, hydrophobicity, and ionization states between the targets and the analogs complicates the analysis of what exactly is causing the imprinted selectivity .…”

“…Docking is a force field–based, rapid orientation screening strategy for determining binding modes and affinities between receptors and ligands and is commonly used in modern rational drug screening . Molecular docking has recently gained attention in MIP research …”