Binuclear 3,3?,5,5?-tetramethyl-1H,H-4,4?-bipyrazole Ruthenium(II) complexes: Synthesis, characterization and biological studies

Organometallic Ru(II) arene complexes have emerged as potential alternative to platinum anti-tumor drugs due to their stability in solution and in the solid state, significant biological activity and reduced toxicity and hydrophobicity of their ancillary arene groups. We report here a series of Ru(II)-arene dinuclear complexes prepared from 3,3?,5,5?-tetramethyl-1H,H-4,4?-bipyrazole and [(?-arene)RuCl] dimers. The new compounds were spectroscopically (FT-IR, H, C, ESI-MS) and structurally characterized. These complexes were found to adopt the piano stool coordination geometry around the Ru(II) ions, with the bipyrazole ligand bridging two metal centers through its pyridinic nitrogen. Their in vitro cytotoxicity was paralleled in human epithelial normal, cancerous and cisplatin-resistant cancerous cells. Ultimately, two possible mechanisms of drug biochemical action underlying the observed effects (DNA targeting and proteasome inhibitory abilities) were explored.