Subtle structural variations in new mixed-ligand Cu(II) complexes with NN'O type unsymmetrical Schiff bases: Molecular docking against SARS-Cov-2 and its Omicron variant main proteases

[Display omitted] •Ten new mixed-ligand Cu(II) complexes with subtle variations on Schiff-base main ligands were synthesized.•Crystal structures of four complexes were obtained.•Molecular docking was performed against SARS-Cov-2 Mpro (PDB ID: 6LU7) and its Omicron Variant protease (PDB ID: 7TLL).•The effects of substituents on main ligand as well as different coligands on EFBE were investigated. A variety of new mixed-ligand Schiff-base complexes with general formula [Cu(SBn)(py)]ClO4 (n = 1–5) and [Cu(SBn)(BTZ)]ClO4 (n = 1a–5a) were synthesized and characterized. In these complexes, the NN'O-type unsymmetrical Schiff-base ligands (SBn) were formed from the equimolar condensation of 1,2-ethylenediamine with salicylaldehyde (1, 1a), 3-methoxysalicylaldehyde (2, 2a), 3,5-dibromosalicylaldehyde (3, 3a), 3-methoxy-5-bromosalicylaldehyde (4, 4a) and 6-methoxysalicylaldehyde (5, 5a). The complexes were characterized by FT-IR and UV–Vis spectroscopy and elemental analysis. The crystal structures of the complexes 3, 2a, 3a, 4a and 5a were also obtained by single-crystal X-ray diffraction (SCXRD). Molecular docking studies were done on SARS-Cov-2 Mpro (PDB ID: 6LU7) and SARS-CoV-2 Omicron Variant protease (PDB ID: 7TLL). Based on estimated free binding energy (EFBE), the complex (3a) showed the highest activity. The complexes (2 and 1) against 6LU7, and (1 and 4) against 7TLL showed the least EFBE. The EFBE results were better than the four studied standard drugs (Remdesivir, Hydroxychloroquine, Dexamethasone and Oxford-AstraZeneca Covid-19 vaccine). The molecular docking results are discussed based on the structural properties of the main ligands in the complexes.