Computational and Experimental Comparison of Molecularly Imprinted Polymers Prepared by Different Functional Monomers—Quantitative Parameters Defined Based on Molecular Dynamics Simulation

Background: In recent years, the advancement of computational chemistry has offered new insights into the rational design of molecularly imprinted polymers (MIPs). From this aspect, our study tried to give quantitative parameters for evaluating imprinting efficiency and exploring the formation mechanism of MIPs by combining simulation and experiments. Methods: The pre-polymerization system of sulfadimethoxine (SDM) was investigated using a combination of quantum chemical (QC) calculations and molecular dynamics (MD) simulations. MIPs were prepared on the surface of silica gel by a surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP). Results: The results of the QC calculations showed that carboxylic monomers exhibited higher bonding energies with template molecules than carboxylic ester monomers. MD simulations confirmed the hydrogen bonding sites predicted by QC calculations. Furthermore, it was observed that only two molecules of monomers could bind up to one molecule of SDM, even when the functional monomer ratio was up to 10. Two quantitative parameters, namely, the effective binding number (EBN) and the maximum hydrogen bond number (HBNMax), were defined. Higher values of EBN and HBNMax indicated a higher effective binding efficiency. Hydrogen bond occupancies and RDF analysis were performed to analyze the hydrogen bond formation between the template and the monomer from different perspectives. Furthermore, under the influence of the EBN and collision probability of the template and the monomers, the experimental results show that the optimal molar ratio of template to monomer is 1:3. Conclusions: The method of monomer screening presented in this study can be extended to future investigations of pre-polymerization systems involving different templates and monomers.