Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

Wen-Ying Zhang, Hannah E Bridgewater, Samya Banerjee, Joan J Soldevila-Barreda, Guy J Clarkson, Huayun Shi, Cinzia Imberti, Peter J Sadler

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28 Citations (Scopus)
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Abstract

We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp XRh(C ^N)Z] 0/+, in which Cp X = Cp*, Cp ph, or Cp biph, C ^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X-ray crystal structures showing the expected “piano-stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl complex [Cp biphRh(benzo-[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD + and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [Cp biphRh(benzo[h]quinoline)py] + (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5-fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand-controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.

Original languageEnglish
Pages (from-to)1052-1060
Number of pages9
JournalEuropean Journal of Inorganic Chemistry
Volume2020
Issue number11-12
Early online date20 Oct 2019
DOIs
Publication statusPublished - 27 Mar 2020
Externally publishedYes

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Funder

Funding Information:
This research was supported by the EPSRC (grant no. EP/P030572/1), Chancellor's International PhD Scholarships from the University of Warwick (for W.‐Y. Z. and H. S.), an EPSRC and Mike Enfys Bagguley PhD studentship for H. E. B, a Royal Society‐SERB Newton International Fellowship (NF151429 for S. B.), and the Wellcome Trust (209173/Z/17/Z for C. I.).

Funding Information:
This research was supported by the EPSRC (grant no. EP/P030572/1), Chancellor's International PhD Scholarships from the University of Warwick (for W.-Y. Z. and H. S.), an EPSRC and Mike Enfys Bagguley PhD studentship for H. E. B, a Royal Society-SERB Newton International Fellowship (NF151429 for S. B.), and the Wellcome Trust (209173/Z/17/Z for C. I.).

Keywords

  • Antitumor agents
  • Cyclopentadienyl ligands
  • Cytotoxicity
  • Reactive oxygen species
  • Rhodium

ASJC Scopus subject areas

  • Inorganic Chemistry

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