Synthesis, Characterization, and Bioactivity of a Tridentate Nitrogen–Sulfur Schiff Base Derived from Carbothioamide and Its (Fe, Co, Cu, Cd) Metal Complexes: DFT, Molecular Docking, and Biomedical Applications

This investigation presents a detailed examination of transition metal complexes derived from a recently synthesized Carbothioamide Schiff Base Ligand, denoted as (Z)-2-((E)-1-(2-(4-chlorophenyl)hydrazineylidene)propan-2-ylidene)-N-phenylhydrazine-1-carbothioamide or (ZHC), known for its biological potency. The synthesis involved condensation of (E)-1-(2-(4-chlorophenyl)hydrazineylidene)propan-2-one with N-phenylhydrazinecarbothioamide to yield the Schiff base ligand (ZHC). The (ZHC) and its metal complexes have been thoroughly analyzed using several techniques, including Elemental analysis, UV-visible spectroscopy, FT-IR, Mass spectrometry, and conductometry measurements. Density functional theory (DFT) calculations estimated their electronic properties, such as energy gaps and dipole moments, suggesting a distorted octahedral geometry. Additionally, Molecular Electrostatic Potential (MEP) calculations at the DFT level were correlated with experimental data. The complexes showed promising antimicrobial activity against a range of bacterial and fungal strains. The Cd (II) complex exhibited the highest efficacy against all tested organisms. Furthermore, the antitumor potential of the complexes against MCF-7 (Breast carcinoma) cells was evaluated with the [Cd(ZHC)Cl2(H2O)]. H2O complex demonstrating superior activity (IC50 value of 10μg/ml) compared to cisplatin. Importantly, it exhibited reduced cytotoxicity towards normal cells (VERO cells) compared to cisplatin. Molecular docking, utilizing DFT-optimized configurations of the (ZHC) and its Cd (II) complex, provided insights into their interactions with specific protein structures (3QX3 and 6XBH) associated with specific cellular targets, namely MCF cells and the COVID-19 virus protein. The analysis of the docking study offers valuable structural insights for potential inhibition studies. This comprehensive study underscores the synthesized compounds' multifaceted applications and promising bioactive properties.