Oxadiazole-2-thione based Co(II) complexes as antiproliferative agents: Synthesis and structural characterization

Abstract

The study of mixed-ligand complexes of transition metal ions has attracted significant interest due to their diverse applications and unique bonding properties. In this work, we report the synthesis of two potassium salts, [5-(4-pyridyl)-1,3,4]-oxadiazole-2-thione (Kpot) and 5-phenyl-1,3,4-oxadiazole-2-thione (Kphot), and their corresponding Co(II) complexes, [Co(pot)<inf>2</inf>(en)<inf>2</inf>] (1) and [Co(phot)<inf>2</inf>(en)<inf>2</inf>] (2). These ligands and complexes were characterized through spectroscopic techniques. In addition, complexes 1 and 2 were characterized by single-crystal X-ray diffraction (XRD) data. Both complexes crystallize in the monoclinic system with the space group P2<inf>1</inf>/n. The ligands act as uninegative monodentate donors, coordinating with Co(II) ions along with two ethylenediamine (en) molecules as co-ligands. Emission spectra revealed that the complexes exhibit higher fluorescence intensity than the free ligands. Intermolecular interactions in complexes 1 and 2 were further analyzed using Hirshfeld surface analysis. The anticancer potential of the ligands and their Co(II) complexes was evaluated using the MTT assay, where both complexes exhibited significant suppression of tumor cell viability. Notably, complex 2 demonstrated superior activity compared to both the ligands and complex 1. Additionally, the anticancer effects were confirmed using DAPI and AO/EB staining techniques under confocal microscopy, as well as Annexin V/PI staining analyzed via flow cytometry. DAPI and AO/EB staining revealed compromised plasma membranes and chromatin condensation, indicative of apoptosis. Flow cytometry analysis further demonstrated that treatment with complex 2 induced both apoptosis and necrosis in tumor cells. © 2025 Elsevier B.V.