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.