The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds

• New family of [Ru(η5-C5H5)(bipyridine)(L)][PF6] complexes
• Structure–activity correlations drawn by spectroscopic, electrochemical and DFT data
• ‘L’ has a crucial role in the fine-tuning of the electronic density at Ru center.
• Best cytotoxic effect in human cancer cells found for the best electronic activation of bipyridine

A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA = human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(η5-C5H5)(bipy)(PPh3)][PF6] (7; bipy = bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(η5-C5H5)(bipy)(PPh3)]+ cation complex in the racemic crystal packing.

New family of [Ru(η5-C5H5)(bipyridine)(L)][PF6] complexes shows that ‘L’ plays an important role in electronic activation of the bipyridine. The best cytotoxic effect was observed for the best electronic activation of this ligand.Figure optionsDownload as PowerPoint slide