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Computational design of synthetic receptors for drug detection: interaction between molecularly imprinted polymers and MDMA (3,4-methylenedioxymethamphetamine)


For many decades, synthetic receptors have been used as sensor elements and are a promising alternative to natural receptors, which, despite its great selectivity, are so complex and instable. The rational design of this kind of receptors is currently one of the most researched topics in molecular recognition. Molecular imprinted polymers (MIPs) have become a growing highlight in polymer chemistry, once they possess a wide range of applications and can be used in several environments, due to their high chemical and thermal stability. The aim of this study was to perform a rational design for the MIP preparation, for 3,4-methylenedioxymethamphetamine (MDMA) detection. The theoretical measurements were employed at several stages of the process, using DFT and B3LYP/6-31G(d,p) level of theory, by means of optimization and frequency calculations. Among the several functional monomers tested, the itaconic acid was the most appropriated for MIP preparation with MDMA template, and the proper molar ratio found theoretically was 3:1 (itaconic acid/MDMA). In the preparation of pre-polymerization complex, polar solvents were found to perform a better stabilization, mainly those which are not protic solvents. As cross-linking agents, the better results were obtained for trimethylolpropane trimethacrylate and ethylene glycol dimethacrylate molecules, respectively. Finally, selectivity tests showed a high affinity of the studied MIP for MDMA and chemically similar molecules. The proposal theoretical strategy yielded novel, experimentally testable hypotheses for the design of MIPs. Additionally, from the theoretical point of view, the set of computational analyses presented in this paper constitutes a very useful protocol to predict optimal experimental conditions, which can considerably reduce the time and cost on the MIPs preparation.

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This work was supported by the Brazilian financial agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo ao Ensino e Pesquisa de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Federal University of Lavras (UFLA) (physical infrastructure and working space). This work was also supported by Long-term development plan UHK.

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Sales, T.A., Ramalho, T.C. Computational design of synthetic receptors for drug detection: interaction between molecularly imprinted polymers and MDMA (3,4-methylenedioxymethamphetamine). Theor Chem Acc 139, 31 (2020). https://doi.org/10.1007/s00214-020-2543-x

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  • DFT
  • Theoretical calculations
  • Rational design
  • Artificial receptors