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

Two nickel(ii) coordination complexes [Ni(L)](2)(1) and [Ni(L)](n)(2) of a tetradentate Schiff base ligand (H2L) derived from 2-hydroxy-1-naphthaldehyde with ethylenediamine were synthesized, designed, and characterized via spectroscopic and single crystal XRD analyses. Both nickel(ii) complexes exhibited unusual Ni center dot center dot center dot Ni interactions and were fully characterized via single-crystal X-ray crystallography. Nickel(ii) complexes [Ni(L)](2)(1) and [Ni(L)](n)(2) crystallize in monoclinic and triclinic crystal systems with P2(1)/c and P (1) over bar space groups, respectively, and revealed square planar geometry around each Ni(ii) ion. The structure of both the complexes have established the existence of a new kind of metal system containing nickel(ii)-nickel(ii) interactions with a square planar-like geometry about the nickel(ii) atoms. Both square planar Ni(ii) complexes were often stacked with relatively short Ni center dot center dot center dot Ni distances. The non-bonded Ni-Ni distance (Ni center dot center dot center dot Ni separation) seems to be 3.356 angstrom and 3.214 angstrom from the nickel atoms of [Ni(L)](2)(1) and [Ni(L)](n)(2), respectively. These distances are shorter than the sum of their van der Waals radii (4.80 angstrom) but longer than the sum of their covalent radii (2.50 angstrom), indicating that there is a Ni center dot center dot center dot Ni interaction but not a Ni-Ni bond. The discrete molecules are pi-stacked and connected via weak intermolecular interactions (C-H center dot center dot center dot O and C-H center dot center dot center dot N). Cyclic voltammetry measurements were obtained for both the complexes, and their pharmacokinetic and chemoinformatics properties were also explored. Detailed structural analysis and non-covalent supramolecular interactions were investigated using single-crystal structure analysis and computational approaches. Both the unique structures show good inhibition performance for the Omicron spike proteins of the SARS CoV-2 virus. To gain insights into potential SARS-CoV-2 Omicron drugs and find inhibitors against the Omicron variants of SARS-CoV-2, we examined the molecular docking of the nickel(ii) complexes [Ni(L)](2)(1) and [Ni(L)](n)(2) with the SARS-CoV-2 Omicron spike protein (PDB ID: 7WK2 and 7WVO). A strong binding was predicted between Ni(ii) coordination complexes [Ni(L)](2)(1) and [Ni(L)](n)(2) with the SARS-CoV-2 Omicron variant receptor protein through the negative value of binding affinity. Molecular docking of Nil(ii) complexes [Ni(L)](2)(1) and [Ni(L)](n)(2) with a DNA duplex (PDB ID: 7D3T) and RNA (PDB ID: 7TDC) binding protein was also studied. Overall, this study suggests that Ni(ii) complexes can be considered as drug candidates against the Omicron variants of SARS-CoV-2.