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

Brian Herry, Lucinda K. Batchelor, Basile Roufosse, Dario Romano, Judith Baumgartner, Marina Borzova, Tim Reifenstahl, Thomas Collins, Amal Benamrane, Jordana Weggelaar, Marie C. Correia, Paul J. Dyson, Burgert Blom*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Two heterobimetallic μ-dppm bridged Fe,Ru complexes, [(η6-Arene)RuCl2(μ-dppm)Fe(CO)I(η5-C5H5)] (Ar = C6H6 (1) and p-cymene (2), dppm = 1,1-bis(diphenylphosphino)methane) were obtained in a facile reaction between [Fe(η5-C5H5)I(CO)(κ1-dppm)] (5) and the corresponding [(η6-Arene)RuCl2]2 complexes by dimer cleavage, mediated by the pendant -PPh2 in 5. The homodinuclear Ru,Ru complex, [(η6-C6H6)RuCl2(μ-dppm)RuCl2(η6-C6H6)] (3), was also isolated in a straightforward fashion upon reaction of [(η6-C6H6)RuCl2(κ1-dppm)] (4) with [(η6-C6H6)RuCl2]2. All complexes were fully characterized by multinuclear (1H, 13C{1H}, 31P{1H}) 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.
Original languageEnglish
Article number120934
Number of pages9
JournalJournal of Organometallic Chemistry
Volume901
DOIs
Publication statusPublished - 15 Nov 2019

Keywords

  • Bioorganometallic chemistry
  • Heterobimetallic complexes
  • Homobimetallic complexes
  • Metal-based drugs
  • Cytotoxicity studies
  • CONTAINING HETEROMETALLIC COMPLEXES
  • TRANSITION-METAL-COMPLEXES
  • CANCER STEM-CELLS
  • RUTHENIUM COMPLEXES
  • NAMI-A
  • RUTHENIUM(II)-ARENE COMPOUND
  • CYCLOPENTADIENYL COMPLEXES
  • PHOSPHORUS LIGANDS
  • PLATINUM COMPOUNDS
  • CRYSTAL-STRUCTURE

Cite this

Herry, B., Batchelor, L. K., Roufosse, B., Romano, D., Baumgartner, J., Borzova, M., Reifenstahl, T., Collins, T., Benamrane, A., Weggelaar, J., Correia, M. C., Dyson, P. J., & Blom, B. (2019). Heterobimetallic Ru(μ-dppm)Fe and homobimetallic Ru(μ-dppm)Ru complexes as potential anti-cancer agents. Journal of Organometallic Chemistry, 901, [120934]. https://doi.org/10.1016/j.jorganchem.2019.120934