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

Abstract

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.