Chromene-based Ni(II), Cu(II) and Zn(II) Schiff base complexes: Synthesis, X-ray diffraction, spectroscopic analyses and evaluation of SARS-CoV-2 entry inhibition by molecular docking

Three salen-type chromene Schiff base ligands were synthesized by condensation of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde with ethylenediamine, 2,2-dimethylpropanediamine, and 4,5-dimethyl-1,2-phenylenediamine, and their corresponding mononuclear Cu(II) complexes were prepared. Mononuclear Ni(II) and dinuclear Zn(II) complexes were also prepared for the ligand derived from dimethylphenylenediamine. The ligands and metal complexes were characterized by mass spectrometry and UV–Vis, IR and/or NMR spectroscopy. Further characterization of the metal complexes by single-crystal X-ray diffraction analysis revealed that the rigidity of the diamine linker influenced the coordination geometry of the ligands to the metal ion center. The Cu(II) and Ni(II) complexes adopted a four-coordinate, slightly distorted square planar geometry, while the Zn(II) complex adopted a five-coordinate, slightly distorted square pyramidal geometry. Molecular docking analysis of the ligands and metal complexes with the SARS-CoV-2 spike protein in complex with the ACE2 enzyme (PDB ID: 6M0J ) was used to determine the potential of the compounds to function as SARS-CoV-2 viral entry inhibitors. The compounds displayed strong docking affinity (−8.1 to −10.4 kcal/mol) for the spike RBD-ACE2 complex, which was better than that observed for Remdesivir (−7.7 kcal/mol), and showed interaction with key residues involved in stabilizing the complex. These findings indicate that these salen-type chromene Schiff bases and metal complexes may potentially act as SARS-CoV-2 viral entry inhibitors. • Synthesis of salen-type chromene Schiff base ligands. • Preparation of Schiff base Ni(II), Cu(II) and Zn(II) complexes. • Interaction of synthesized compounds with the SARS CoV-2 spike RBD-ACE2 complex.