Copper(II) complexes based on thiosemicarbazone ligand: Preparation, crystal structure, Hirshfeld surface, energy framework, antiMycobacterium activity, in silico and molecular docking studies

Considering the promising previous results on the remarkable activity exhibited by cobalt(III) and manganese(II) thiosemicarbazone compounds as antibacterial agents, the present study aimed to prepare and then evaluate the antibacterial activity of two different types of Cu(II) complexes based on a 2-acetylpyridine-N(4)-methyl-thiosemicarbazone ligand (Hatc-Me), a monomer complex [CuCl(atc-Me)] and a novel dinuclear complex [{Cu(μ-atc-Me)}2μ-SO4]. The compounds were characterized by infrared spectra, ultraviolet visible and CHN elemental analysis. In addition, the crystalline structures of the complexes were determined by single-crystal X-ray diffraction. In both cases, the Schiff base ligand coordinated in a tridentate mode via the pyridine nitrogen, imine nitrogen and sulfur atoms. The two Cu(II) atoms in the dimer are five coordinate, consisting of three NNS-donor atoms from the thiosemicarbazone ligand connected by a sulfate bridge. The Hirshfeld surface and energy framework of the complexes were additionally analyzed to verify the intermolecular interactions. The biological activity of the Cu(II) salts, the free ligand and its Cu(II) complexes was evaluated against six strains of mycobacteria including Mycobacterium tuberculosis. The complexes showed promising results as antibacterial agents for M. avium and M. tuberculosis, which ranged from 6.12 to 12.73 μM. Furthermore, molecular docking analysis was performed and the binding energy of the docked compound [{Cu(μ-atc-Me)}2μ-SO4] with M. tuberculosis and M. avium strains were extremely favorable (−11.11 and − 14.03 kcal/mol, respectively). The in silico results show that the complexes are potential candidates for the development of new antimycobacterial drugs. [Display omitted] •A monomer and a binuclear Cu(II) complex were studied by X-ray crystallography.•The binuclear Cu(II) complex presented a distorted square pyramidal geometry.•Antibacterial activity was performed against M. tuberculosis, M. avium and M. kansassi.•The docking studies showed better results for the binuclear complex.•The in silico results of the monomer complex showed a promising pharmacokinetic profile.