In Silico Design of Molecularly Imprinted Poly(o-aminophenol) for Melamine and Cyanuric Acid Detection and Extraction

Melamine (MEL) is a heterocyclic aromatic compound that is carcinogenic to humans and causes damage to organs through prolonged or repeated exposure. It is typically used in the resin-coating industry as a cross-linker to produce durable plastic packaging. Molecularly imprinted polymer (MIP)-based structures seem very promising for the detection/extraction of some organic compounds. Therefore, in this study, density functional theory (DFT-D4) is used to guide the in silico design of an MIP suitable for the detection/extraction of melamine and cyanuric acid. The MIP preparation steps, including analysis of candidate monomers, analysis of the oligomer's oxidation state and flexibility, optimization of prepolymer complex composition, formation of binding sites, and studies of the analytes' rebinding, are evaluated. Three monomers (aniline (ANI), o-phenylenediamine (oPD), and o-aminophenol (oAP)) and their corresponding oligomers are evaluated to select the optimal receptor for the target analytes based on their binding energies, hydrogen bonding, electrochemical properties, and electrostatic potential maps. The obtained values indicate a higher electron affinity for poly-(o-aminophenol) (PoAP). The analysis of conformations also reveals greater flexibility in PoAP, which allows for more efficient formation of imprinted cavities. Moreover, the effect of the solvent on the hydrogen bonding and binding energies is screened. Dimethyl sulfoxide (DMSO) is the best solvent, showing minimal interference. The modeled MIP's binding sites demonstrate the role of homogeneous cavity formation in achieving improved selectivity, characterized by the higher specific noncovalent interactions attained by imprinted PoAP. A nonimprinted polymer (NIP) is modeled as a reference to evaluate imprinting efficiency. Accordingly, approximate imprinting factors (IF) of 2.71 for melamine and 1.91 for cyanuric acid are obtained.