Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis(diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions.

Matylda Odachowski, Robin Neven, Giuditta Perversi, Dario Romano, Cathryn A Slabber, Mouna Hadiji, Maarten Honing, Yuandi Zhao, Orde Q Munro, Burgert Blom

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe2+, Ru2+] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η5–C5H5)Fe(CO)2(κ1–PPh2(CH2)nPPh2)]{PF6} (n = 1–5), compounds 1–5, and heterodinuclear [Fe2+, Ru2+] complexes, [(η5–C5H5)Fe(CO)2(μ–PPh2(CH2)nPPh2))(η6–p–cymene)RuCl2]{PF6} (n = 2–5) (compounds 7–10), were synthesized and characterised. The mononuclear complexes were moderately cytotoxic against two ovarian cancer cell lines (A2780 and cisplatin resistant A2780cis) with IC50 values ranging from 2.3 ± 0.5 μM to 9.0 ± 1.4 μM. For 7–10, the cytotoxicity increased with increasing Fe⋅⋅⋅Ru distance, consistent with their DNA affinity. UV–visible spectroscopy suggested the chloride ligands in heterodinuclear 8–10 undergo stepwise substitution by water on the timescale of the DNA interaction experiments, probably affording the species [RuCl(OH2)(η6-p-cymene)(PRPh2)]2+ and [Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (where PRPh2 has R = [−(CH2)5PPh2–Fe(C5H5)(CO)2]+). One interpretation of the combined DNA-interaction and kinetic data is that the mono(aqua) complex may interact with dsDNA through nucleobase coordination. Heterodinuclear 10 reacts with glutathione (GSH) to form stable mono- and bis(thiolate) adducts, 10-SG and 10-SG2, with no evidence of metal ion reduction (k1 = 1.07 ± 0.17 × 10−1 min−1 and k2 = 6.04 ± 0.59 × 10−3 min−1 at 37 °C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes.
Original languageEnglish (US)
Pages (from-to)112156
JournalJournal of Inorganic Biochemistry
StatePublished - Feb 15 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-03-01
Acknowledgements: We are grateful to Prof. Paul J. Dyson for constructive comments in the preparation of this manuscript and for cytotoxicity testing. BB Thanks Maastricht University, the Faculty of Science and Engineering, and the Maastricht Science Programme for funding and support of this work and the Universiteitsfonds Linburg: SWOL for support. OQM and CAS thank the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation (NRF) of South Africa (SARChI grant number 64799) and the University of the Witwatersrand for generous financial support. OQM thanks the Centre for High Performance Computing (CHPC, Cape Town, RSA; programme CHEM1065) for computational resources.

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry


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