Unusual Ni⋯Ni interaction in Ni(ii) complexes as potential inhibitors for the development of new anti-SARS-CoV-2 Omicron drugs

Abstract

In this study, two nickel(ii) coordination complexes [Ni(L)]2(1) and [Ni(L)]n(2) of a tetradentate-N2O2 donor Schiff base ligand (H2L) were synthesized, designed and characterized via spectroscopic and SC-XRD analysis, and molecular docking study.

Synthesis of Zn(ii) coordination complexes, their molecular design and docking with SARS-CoV-2 RBD protein and Omicron spike protein

“…Based on the observation from the time-dependent UV-Vis spectra, it could be concluded that the Zn( ii ) complexes [Zn(L)(en)]ClO 4 ( 1 ) and [Zn(L) 2 ] ( 2 ) were stable in the buffer solution (pH 7.4). 44…”

“…84–87 The values of the binding energy (Δ G ) and inhibition/dissociation constant value ( K i / K d ) were also comparable to the reported values for Schiff base metal( ii ) complexes obtained from molecular docking. 40–44,58 A structure–activity relationship (SAR) was established between the experimental geometries of the Zn( ii ) complexes [Zn(L)(en)]ClO 4 ( 1 ) and [Zn(L) 2 ] ( 2 ) determined by the single-crystal X-ray diffraction technique and the theoretical geometries observed with interactions against SARS-CoV-2 RBD protein (PDB ID: ) and Omicron S protein (PDB ID: ), as tabulated in Table S7 (ESI†). Table S8 (ESI†) shows a comparison of the docking energies (Δ G ) and inhibition/dissociation constant values ( K i / K d ) of some new metal complexes obtained from in silico docking studies.…”

“…90 The binding energies (Δ G ) and inhibition/dissociation constant values ( K i / K d ) of the docked Zn( ii ) complexes [Zn(L)(en)]ClO 4 ( 1 ) and [Zn(L) 2 ] ( 2 ) and the controls ivermectin (IVM) and levosalbutamol (LVM) were also comparable to the values reported for Schiff base metal( ii ) complexes. 41–44,58…”

“…DNA studies could be useful for understanding the binding propensity of the complexes and play an important role in structural molecular biology and drug discovery. 44 In order to obtain more information about the interaction mode of the complexes, theoretical investigations of their DNA/protein binding were performed using a molecular docking approach. Molecular docking calculations of the Zn( ii ) complexes [Zn(L)(en)]ClO 4 ( 1 ) and [Zn(L) 2 ] ( 2 ) with DNA binding protein (PDB ID: ) were thus performed and the most favourable docked poses were predicted for both the Zn( ii ) complexes.…”

“…39 Schiff bases have a specific role as chelating ligands and several coordination complexes of these ligands with transition metal ions are promising compounds and are expected to exhibit biological activity, including anti-SARS-CoV-2 effects. 40–44 To gain insights into potential SARS-CoV-2 Omicron drugs and find inhibitors against the Omicron variants of SARS-CoV-2, herein we describe developments in the synthesis and design of two Zn( ii ) coordination complexes, namely [Zn(L)(en)]ClO 4 ( 1 ) and [Zn(L) 2 ] ( 2 ) [where, L = ( Z )- N -phenyl- N ′-(( Z )-phenyl(pyridin-2-yl)methylene)carbamohydrazonic acid, and en = ethylenediamine] as self-assembled vaccine candidates against the SARS-CoV-2 receptor binding-domain (RBD) protein and Omicron spike protein. Both the Zn( ii ) complexes were characterized via spectroscopic and single-crystal X-ray crystallography techniques.…”