Synthesis, structural characterization, density functional theory, anticancer, and antimicrobic studies of Ni²⁺ and Cu²⁺ complexes encompassing tridentate ONS‐donor azo‐thiosemicarbazone

This study focuses on the synthesis of azo‐thiosemicarbazone ligand, which is designed by reacting 2‐hydroxy‐5‐(phenyldiazenyl)benzaldehyde with hydrazine carbothioamide. Hence, this ligand was exploited for chelation with nickel and cupric salts in (1 M:1 L) molar ratio. These synthetics were structurally investigated using a variety of physical, analytical, and spectroscopic (1D/2D‐NMR, UV–Vis, FT‐IR, and E‐mass) tools as well as theoretically. The finding demonstrated that the resulting azo‐thiosemicarbazone (H 4 Azo‐TSC) bonded with the nickel and cupric ions as mono/di‐basic tridentate chelators, binding them via deprotonated phenolic oxygen, imino nitrogen, and thionic/thiol sulfur atoms adopting square planar geometry. The theoretical investigation was examined by DFT/B3LYP/LanL2dZ, including energetic parameters, HOMO‐LUMO energy gap, dipole moment, and geometrical optimization, which were applied to support the complexes' geometrical structure. The in vitro microbicidal activities of the azo‐thiosemicarbazone, compared with its Ni 2+ and Cu 2+ complexes, display superior activity over the metal complexes against different bacterial and fungal species. The anticancer efficacy of the synthetics was tested against human lung fibroblast (WI38) and mammary gland breast cancer (MCF‐7) compared with Doxorubicin as a standard drug. The cytotoxic efficiency of metallic complexes exceeded that of un‐chelated azo‐thiosemicarbazone. The most effective complex is Ni 2+ complex with IC 50 equal to 11.75 and 14.05 μg/ml, respectively. It has been demonstrated that Ni 2+ and Cu 2+ complexes are more biocompatible than free azo‐thiosemicarbazone; this finding may be related to the chelation process.