The use of in silico models for the rationalization of molecularly imprinted polymer synthesis

Molecularly imprinted polymers (MIPs) represent an advance in sample preparation techniques due to their inherent functionalized cavities with great rebinding capacity, leading to significant selectivity improvement for the desired target. However, the pursue of optimized MIPs is a very time-consuming process, especially in relation to monomer selection, which demands a considerable amount of synthesis. One strategy to reduce time and consequently minimize the waste of chemicals is to use reliable computational tools capable of providing suitable indications about the most optimal synthesis conditions, including the most appropriate monomer and solvent. These computational tools should accurately describe all parameters involved in the real scenario, such as the number of molecules, solvents, etc. Molecular dynamics methodology was employed in this work to select the most suitable functional monomer for imprinting scopolamine, a known drug of abuse molecule used as the template. The evaluated monomers were acrylic acid (AAC), methacrylic acid (MAA), and acrylamide (ACR). The interactions between template and monomers were characterized in terms of spatial distribution, hydrogen bonds, interaction energy, and crosslinker influence. Additionally, their mechanism of interaction was also discussed. The theoretical results identified acrylamide as the most interactive ligand and the one that suffers less competitive influence from the crosslinker. Imprinted and non-imprinted polymers were synthesized by bulk polymerization. The polymers were characterized by FT-IR, MEV, and BET. The imprinting factors (IF) calculated for acrylic acid, methacrylic acid, and acrylamide ligands were 1.2, 1.1, and 3.2, respectively, confirming a higher interaction between template and acrylamide, as suggested by simulations. The selectivity of the MIP with acrylamide was tested against atropine and hyoscine. The calculated selectivity factors (β) were 3.40 and 5.25 for atropine and hyoscine, respectively. The theoretical and experimental approaches showed great correlation. In conclusion, this paper offers a comprehensive and integrated protocol for the rational design and synthesis of molecularly imprinted polymers.