Synthesis, characterization and cytotoxicity of arene-ruthenium(ii) complexes with acylpyrazolones functionalized with aromatic groups in the acyl moiety.

A series of neutral ruthenium(ii)-arene complexes, [(arene)Ru(Q)Cl] (arene = p-cymene or hexamethylbenzene), containing 4-acyl-5-pyrazolonate (Q) ligands with aromatic substituents in the acyl moiety (a phenyl in Q and a 1-naphthyl in Q) and related ionic complexes [(arene)Ru(Q)(PTA)][PF] (PTA = 1,3,5-triaza-7-phosphaadamantane) have been synthesized and characterized by IR, H, C and P NMR spectroscopy, elemental analysis and ESI mass spectrometry. The structures of five of these compounds were also determined by X-ray crystallography. DFT studies have been performed on all complexes and, in the case of two cationic [(arene)Ru(Q)(PTA)][PF], the existence of two conformers with a different relative orientation of the naphthyl group in the Q ligand has been assessed, showing that they possess similar energies, in agreement with the experimentally observed NMR spectra in solution. The cytotoxicity of the 4-acyl-5-pyrazolonate proligands (HQ) and complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR) and non-tumorous human embryonic kidney (HEK293) cells. In general, each complex is about equally cytotoxic to all three cell lines and the PTA derivatives with the naphthyl-modified Q ligands are the most active of the series.