Coordination Behavior of Acylthiourea Ligands in Their Ru(II)–Benzene Complexes─Structures and Anticancer Activity

Acylthiourea ligands have applications in both synthetic and applied chemistry. The skeleton of the ligand contains several heteroatoms which offer variable coordination modes in their complexes. Herein, we report one such erratic behavior of these types of complexes upon crystallization. Six Ru(II)–benzene complexes (B1–B6) containing the acylthiourea ligand were synthesized and adequately characterized using analytical and spectroscopic techniques. In contrast to the spectroscopic data confirming the monodentate coordination of the ligands to the Ru(II) ion, the bidentate version in the crystal structure of their Ru(II)–benzene complexes was observed. To the best of our knowledge, this is the only report as of now on N,S-coordinated acylthiourea ligands forming a four-membered ring in Ru(II)–benzene complexes, while the same ligands in the Ru(II)–p-cymene system showed a monodentate coordination. The complexes (B1–B6) exhibited good anticancer potential in A549, overcame cisplatin resistance in cisRA549, but unfortunately exhibited toxicity toward normal human umbilical vein endothelial cell lines. An increase in chain length at the C-terminal and the conjugation at the N-terminal of the acylthiourea ligands seemed to improve the cytotoxic profile of the complexes. 5-Ethynyl-2′-deoxyuridine staining helped to visualize the interruption of DNA synthesis by the active complexes B4 and B5, which was further authenticated using flow cytometry, wherein the complexes arrested the cell cycle in the S phase. The latter also proved the apoptosis mode of cell death induced by the active complexes, and the morphological changes due to apoptosis were visualized using acridine orange/ethidium bromide staining.