Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: Molecular docking and DFT calculations

Abstract

Structure-activity relationships for hydroxychloroquine compound and its derivatives resulted in a potent antiviral activity. Where hydroxychloroquine derivatives showed an apparent efficacy against coronavirus related pneumonia. For this reason, the current study is focused on the structural properties of hydroxychloroquine and hydroxychloroquine sulfate. Optimized structures of these molecules have been reported by using DFT method at B3LYP/6-31G* level of theory. The geometric were determined and compared with the experimental crystal structure. The intra and intermolecular interactions which exist within these compounds are analyzed by different methods namely the topological analysis AIM, ELF and the reduced gradient of the density. These approaches make it possible in particular to study the properties of hydrogen bonds. The highest occupied molecular orbital and the lowest unoccupied molecular orbital energy levels are constructed and the corresponding frontier energy gaps are determined to realize the charge transfer within the molecule. The densities of state diagrams were determined to calculate contributions to the molecular orbitals. The molecular electrostatic potential surfaces are determined to give a visual representation of charge distribution of these ligands and to provide information linked to electrophilic and nucleophilic sites localization. Finally, these derivatives were evaluated for the inhibition of COVID-19 activity by using the molecular docking method.