Preparation of new half sandwich ruthenium arene complexes with aminophosphines as potential chemotherapeutics

Abstract Aminophosphines 2-(diphenylphosphino)-1-methylimidazole (dpim) and diphenyl-2-pyridylphosphine (PPh 2 py) have been used to prepare two series of Ru(II) arene complexes of formulae [(η 6 - p -cymene)Ru(κ 2 - O,O′ -X)(κ 1 - P -dpim)]Y (series a: 1a·Y – 3a·Y ) and [(η 6 - p -cymene)Ru(κ 2 - O,O′ -X)(κ 1 - P -PPh 2 py)]Y (series b: 1b·Y – 3b·Y ) (where X = acac, acetylacetonate; bzac, benzoyl acetonate; dbzm, dibenzoyl methanoate; Y = BF 4 , BPh 4 ). The structures of 1a·BF 4 , 1a·BPh 4 , 3a·BF 4 , 1b·BPh 4 and 3b·BPh 4 were determined by X-ray diffraction. The tetrafluoroborate derivatives are more soluble in organic solvents than their tetraphenylborate counterparts. Five BF 4 − derivatives (all except the unstable 1b·BF 4 ) were selected to evaluate the cytotoxic behavior in vitro against the human cancer cell lines MCF-7 (breast cancer) and CAPAN-1 (pancreatic cancer). 2b·BF 4 and 3b·BF 4 exhibited IC 50 values similar to those of cisplatin. Electrophoresis and AFM studies showed good correspondence between the biological activity levels of 2b·BF 4 and 3b·BF 4 and their ability to modify the DNA structure. Hydrolytic studies indicate that aquation could be involved in the activation mechanism of these complexes and confirm that the hydrolysis rate of 3b·BF 4 is higher than that of 3a·BF 4 . Thus, the cytotoxic activity trends are explained in terms of the higher reactivity of derivatives from series b, which in turn is rationalized as being the result of the electronic features of dpim and PPh 2 py established by cyclic voltammetry measurements.