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 (H(2)L) 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⋯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 P1̄ 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⋯Ni distances. The non-bonded Ni-Ni distance (Ni⋯Ni separation) seems to be 3.356 à and 3.214 à 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 à ) but longer than the sum of their covalent radii (2.50 à ), indicating that there is a Ni⋯Ni interaction but not a Ni-Ni bond. The discrete molecules are π-stacked and connected via weak intermolecular interactions (C-H⋯O and C-H⋯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.