ABSTRACT
The incidence of fungal coinfections, such as Aspergillus spp., in patients with COVID-19 has been widely reported. Voriconazole is the first-line treatment for aspergillosis. A challenging sample preparation process is required to perform therapeutic drug monitoring of voriconazole. Recently, Molecularly Imprinted Polymers (MIP) have been shown to improve the separation selectivity for biological samples. Monomer selection in MIP is often performed by trial and error, without a design strategy. Therefore, this study aimed to construct a high-affinity MIP for voriconazole based on its interaction with functional monomers. All structures were optimized with B3LYP/6-311G++(d,p) and DFT-D3 dispersion correction method. Calculations of vacuum and solvated frequencies were carried out using a structure with maximum binding energy from molecular docking. The results showed that complex five was the most stable, exothermic, spontaneous, and enthalpy-driven among the complexes. In addition, there are nine intermolecular interactions and one moderate hydrogen bond in the QTAIM and NBO analysis, whereas hydrogen bonds, van der Waals interactions, and hydrophobic interactions were observed in the NCI-RDG analysis. The findings of this preliminary investigation showed that voriconazole possesses high stability when combined with functional monomers. It also provides information and assistance for further laboratory MIP synthesis.