Arene-ruthenium(II) complexes with pyrazole-based ligands bearing a pyridine moiety: Synthesis, structure, DFT calculations, and cytotoxicity

Abstract

Two pyrazole-based ligands bearing a pyridine moiety, 3-methyl-1-(pyridin-2-yl)-5-pyrazolone (HLpy), and 3-methyl-1-(pyridin-2-yl)-4-trifluoroacetyl-5-pyrazolone (HQpy,CF3), were prepared and fully characterized in the solid-state and the tautomerism of both ligands in solution was also rationalized by using Density Functional Theory. Neutral ruthenium(II) arene complexes of composition [Ru(arene)(Lpy)Cl] and [Ru(arene)(Qpy,CF3)Cl] [arene = p-cymene (cym) or hexamethylbenzene (hmb)]) were synthesized and characterized by IR, 1H, 13C, 15N and 19F NMR spectroscopy, elemental analysis and ESI mass spectrometry. The structures of complexes [Ru(hmb)(Lpy)Cl] and [Ru(hmb)(Qpy,CF3)Cl] were determined by X-ray crystallography, showing κ2-N,N’-coordination not only for Lpy but also for Qpy,CF3 ligand. DFT studies confirm that κ2O,O’-coordination, generally observed in metal complexes with 4-acyl-5-pyrazolone ligands, is not favored in this case. The cytotoxicity of ligands and complexes was evaluated against human ovarian carcinoma cells (A2780 and A2780cisR, cisplatin sensitive and cisplatin-resistant, respectively), and non-tumorous human embryonic kidney SV40 transformed (HEK293T) cells to reveal essentially equivalent activity in the cisplatin sensitive and cisplatin-resistant ovarian carcinoma cells.