Experimental and theoretical studies of new Co(III) complexes of hydrazide derivatives proposed as multi-target inhibitors of SARS-CoV-2.

Cobalt(III) complexes with Schiff base ligands derived from hydrazone, (HL 1  = (E)-N'-(3,5-dichloro-2-hydroxybenzylidene)-4-hydroxybenzohydrazide, HL 2  = (E)-N'-(3,5-dichloro-2-hydroxybenzylidene)-4-hydroxybenzohydrazide (3,5-dibromo-2-hydroxybenzylidene), and HL 3  = (E)-4-hydroxy-N'-(2-hydroxy-3-ethoxybenzylidene)benzohydrazide), were synthesized and characterized by elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, UV-Vis spectroscopy, and cyclic voltammetry. X-ray diffraction was used to determine the single crystal structure of the complex (1). Co(III) was formed in a distorted, very regular octahedral coordination in this complex; three pyridine moieties complete this geometry. Schiff base complexes' redox behaviors are represented by irreversible (1), quasi-reversible (2), and quasi-reversible (3) voltammograms. A density functional theory (DFT)/B3LYP method was used to optimize cobalt complexes with a base set of 6-311G. Furthermore, fragments occupying the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were investigated at the same theoretical level. Quantum theory of atoms in molecules (QTAIM) computations were also done to study the coordination bonds and non-covalent interactions in the investigated structures. Hirshfeld surface analysis was used to investigate the nature and types of intermolecular exchanges in the crystal structure of the complex (1). The capacity of cobalt complexes to bind to the major protease SARS-CoV-2 and the molecular targets of human angiotensin-converting enzyme-2 (ACE-2) was investigated using molecular docking. The molecular simulation methods used to assess the probable binding states of cobalt complexes revealed that all three complexes were stabilized in the active envelope of the enzyme by making distinct interactions with critical amino acid residues. Interestingly, compound (2) performed better with both molecular targets and the total energy of the system than the other complexes.