Ruthenium arene complexes with triphenylphosphane ligands: Cytotoxicity towards pancreatic cancer cells, interaction with model proteins, and effect of ethacrynic acid substitution

The ruthenium-arene complexes [(η6-p-cymene)RuCl2(κP-PPh2(4-C6H4CO2H))], 1, [(η6-p-cymene)RuCl(κ2P,O-PPh2(2-C6H4CO2))], 2, [(η6-p-cymene)RuCl2(κP-PPh2(2-C6H4OCO-EA))], 3, and [(η6-p-cymene)RuCl2(κP-PPh2(4-C6H4CO2CH2CH2OCO-EA))], 4 (EA-CO2H = ethacrynic acid), were synthesized in good to high yields and characterized by analytical techniques, IR, UV-Vis and multinuclear NMR spectroscopy, and single crystal X-ray diffraction in the cases of 1 and 2. The unstable compounds [(η6-arene)RuCl2(κP-PPh2(2-C6H4CO2CH2CH2OCO-EA))] (arene = p-cymene, 5a; arene = C6H6, 5b) were obtained and identified in solution by NMR. Electrochemical and spectro-electrochemical experiments were performed in order to assess the redox behaviour of 1-4 in CH2Cl2. The in vitro cytotoxicity of 1-4 was determined on the human pancreatic cancer cell line BxPC3 and the mouse embryo fibroblast Balb/3T3 Clone A31 cell line, the latter acting as a model for normal cells. Furthermore, the interaction of 1, 3 and 4 with two model proteins was investigated by high resolution ESI-MS.