Heterobimetallic Ru(mu-dppm)Fe and homobimetallic Ru(mu-dppm)Ru complexes as potential anti-cancer agents

Two heterobimetallic mu-dppm bridged Fe,Ru complexes, [(eta(6)-Arene)RuCl2(mu-dppm)Fe(CO)I(eta(5)-C5H5)] (Ar - C6H6 (1) and p-cymene (2), dppm-1,1-bis(diphenylphosphino)methane) were obtained in a facile reaction between [Fe(eta(5)-C5H5)I(CO)(kappa(1)-dppm)] (5) and the corresponding (eta(6)-Arene)RuCl2 complexes by dimer cleavage, mediated by the pendant-PPh2 in 5. The homodinuclear Ru,Ru complex, [(eta(6)-C6H6) RuCl2(mu-dppm)RuCl2(eta(6)-C6H6)] (3), was also isolated in a straightforward fashion upon reaction of [(eta(6)-C6H6)RuCl2(kappa(1)-dppm)] (4) with (eta(6)-(CH6)-H-6)RuCl2. All complexes were fully characterized by multinuclear (H-1, C-13{H-1}, P-31{H-1}) NMR, UV-Vis, IR spectroscopy and HRMS (ESI), and additionally complex 3 was characterized by single crystal X-ray diffraction. Density functional theory (DFT) calculations (Level of theory B3LYP, basis set for H, C, P, O, N and Cl is 6-31 + G(d,p) and for Ru,Fe DGDZVP) of 1, 2 and 3 are also reported. Complexes 1 and 2 feature HOMOs and LUMOs delocalized over the iron-centered terminus of the bimetallic complexes. The cytotoxicity of 1-5 were evaluated on A2780 and A2780cisR (Human ovarian carcinoma) cell lines and the HEK293 (Human embryonic kidney) cell line. The complexes containing iron are more cytotoxic than cisplatin in the A2780 cells and significantly more active in the A2780cisR cell line and exhibit some selectivity towards the cancer cells. The dinuclear Ru,Ru complex 3 and the mononuclear complex 4 exhibit moderate activity on A2780 and A2780cisR cells also with some cancer cell selectivity. This study hence reveals the potential of Fe,Ru complexes as potent cytotoxic agents. (C) 2019 Elsevier B.V. All rights reserved.