Synthesis, Spectroscopic Characterization, and Cytotoxic Assessment of Novel Cu(II) Thiosemicarbazone Complexes with Varying Anions

Abstract

In this study, three novel copper(II) thiosemicarbazone complexes, Cu1, Cu2, and Cu3, were synthesized using 5-bromosalicylaldehyde-S-methyl isothiosemicarbazone as the ligand and different copper(II) salts containing nitrate, chloride, and sulfate anions, respectively. The complexes were comprehensively characterized by elemental analysis, FT-IR, UV-Vis, ESI-MS, EPR spectroscopy, and single-crystal X-ray diffraction. Structural analyses revealed that Cu1 forms a five-coordinated monomeric complex with a distorted square-pyramidal geometry, Cu2 adopts a dimeric structure with square-planar copper centers, and Cu3 crystallizes as a dimeric salt incorporating both square-pyramidal and square-planar geometries. In vitro cytotoxicity was evaluated using the MTT assay against A549 (lung cancer), MDA-MB-231 (breast cancer), and HUVEC (healthy endothelial) cell lines. The free ligand exhibited no cytotoxicity (IC50>50 mu M), while Cu1 showed selective activity against MDA-MB-231 cells (IC50 = 1.53 mu M). Cu2 displayed moderate activity across all cell lines (IC50 approximate to 6-8 mu M), and Cu3 emerged as the most cytotoxic complex (IC50 = 1.07 mu M in A549, 1.14 mu M in MDA-MB-231), surpassing cisplatin (IC50 = 11.2 and 7.67 mu M, respectively). These findings highlight that the coordination environment and anion identity significantly influence the geometries and cytotoxic responses of Cu(II) thiosemicarbazone complexes, providing valuable insights into the design of metal-based anticancer agents.