Molecular designing, crystal structure determination and in silico screening of copper(II) complexes bearing 8-hydroxyquinoline derivatives as anti-COVID-19

Abstract

The pandemic by COVID-19 is hampering everything on the earth including physical and mental health, daily life and global economy. At the moment, there are no defined drugs, while few vaccines are available in the market to combat SARS-CoV-2. Several organic molecules were designed and tested against the virus but they did not show promising activity. In this work we designed two copper complexes from the ligands analogues with chloroquine and hydroxychloroquine. Both the ligands and complexes were well characterized by using various spectroscopic, thermal and X-ray diffraction techniques. Both the complexes as well as ligands were screened through in silico method with the chloroquine and hydroxychloroquine which essentially proved pivotal for successful understanding towards the target protein and their mechanism of action. The results indicated that the balanced hydrophobic and polar groups in the complexes favor their binding in the active site of the viral ADP-ribose-1 monophosphatase enzyme over the parent organic molecules.

Keywords: ADP-ribose-1 monophosphatase enzyme; COVID-19; Chloroquine; Copper complex; Hydroxychloroquine.

Graphical abstract

Fig. 1

Designing of ligands L1 and L2 by mimicking chloroquine and hydroxychloroquine.

Fig. 2

Asymmetric unit of ligands (a) L1 and (b) L2.

Fig. 3

A view of (a) crystal packing structure of ligand L1 which showing arabesque like pattern and (b) formation of supramolecular structure via hydrogen bonding and other weak interactions along with crystallographic b-axis.

Fig. 4

A view of (a) crystal packing showing herringbone pattern and (b) supramolecular network formation via H-bonding and other weak interactions along with c-axis in ligand L2.

Fig. 5

(a) Synthesis of complex 1 and 2, ortep representation of asymmetric unit of (b) complex 1 and (c) complex 2.

Fig. 6

Docking poses of (a) complex 1 and (b) complex 2 in the active site of the ADP-ribose-1 monophosphatase of COVID-19.