Theoretical insight and molecular recognition of fluconazole molecularly imprinted polymers: a combined computational and experimental analysis

Abstract

Insufficient surveillance and diagnosis result in a minimum of 150 million cases of serious fungal infections reported annually. The WHO has compiled a list of priority pathogens to encourage research and investment in fungal infections and antifungal resistance in late 2022. Among these, Candida albicans is classified as a critical pathogen. Fluconazole is widely recognized as an effective medication for the treatment and prevention of both mucosal and invasive candidiasis. Molecularly imprinted polymer (MIP) could enhance separation selectivity in fluconazole bioanalysis. The objective of this research is to develop an MIP for fluconazole by analyzing interactions identified in prior research and incorporating established improvements for MIP synthesis that cannot be observed through laboratory experimentation. Based on binding affinity, intermolecular hydrogen bonds, complexation energy, and thermodynamic characteristics, 2-acrylamido-1-ethanesulfonic acid was chosen as the optimal monomer. The HOMO–LUMO investigation revealed the localization of the orbitals from the guest to the host. The FMO study indicated that chloroform was the most suitable solvent for complex formation. The QTAIM, NBO, and NCI-RDG analyses identified the hydrogen bond formed between the H51 atom of the monomer and the N33 atom of fluconazole, determined to be the most significant hydrogen bond in the host–guest interaction. The interaction energy from multi-monomer interaction showed that a 1 : 6 ratio is the best ratio in forming a pre-polymerization complex between the template and monomer. Based on the findings of this study, it is anticipated that the computational analysis may be utilized for rational design for the enhancement of prior studies and future laboratory investigations.