JBIC Journal of Biological Inorganic Chemistry

, Volume 15, Issue 3, pp 429–440

Rhodium(III) and iridium(III) complexes with 1,2-naphthoquinone-1-oximate as a bidentate ligand: synthesis, structure, and biological activity

  • Stefan Wirth
  • Christoph J. Rohbogner
  • Marcin Cieslak
  • Julia Kazmierczak-Baranska
  • Stefan Donevski
  • Barbara Nawrot
  • Ingo-Peter Lorenz
Original Paper

DOI: 10.1007/s00775-009-0615-4

Cite this article as:
Wirth, S., Rohbogner, C.J., Cieslak, M. et al. J Biol Inorg Chem (2010) 15: 429. doi:10.1007/s00775-009-0615-4

Abstract

The synthesis and characterization of three novel iridium(III) complexes and one rhodium(III) complex with 1-nitroso-2-naphthol (3) chelating as a 1,2-naphthoquinone-1-oximato ligand are described. The reaction of μ2-halogenido-bridged dimers [(η5-C5Me5)IrX2]2 [X is Cl (1a), Br (1b), I (1c)] and [(η5-C5Me5)RhCl2]2 (2a) with 3 in CH2Cl2 yields the mononuclear complexes (η5-C5Me5)IrX(η2-C10H6N2O) (4a, 4b, 4c) and (η5-C5Me5)RhCl(η2-C10H6N2O) (5a). All compounds were characterized by their 1H and 13C NMR, IR, and mass spectra, UV/vis spectra were recorded for 4a and 5a. The X-ray structure analyses revealed a pseudo-octahedral “piano-stool” configuration for the metals with bidentate coordination through oximato-N and naphthoquinone-O, forming a nearly planar five-membered metallacycle. The metal complexes 4a and 5a were evaluated in respect to their cytotoxicity and binding affinity toward double-stranded DNA. As determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, both exerted a much stronger cytotoxic effect toward HeLa and HL60 cancer cell lines than did cisplatin. The remarkable cytotoxicity of the compounds tested may be attributed to necrosis, rather than to apoptosis, as it is evidenced by the caspase-3/7 activation assay. No clear evidence was found for interaction with double-stranded DNA. The melting experiments showed no significant differences between thermodynamic parameters of intact DNA and DNA incubated with 3, 4a, or 5a, although these derivatives altered DNA recognition by the BamHI restriction enzyme. Therefore, the screened iridium and rhodium complexes 4a and 5a may still be interesting as potential anticancer drugs owing to their high cytotoxicity toward cancer cell lines, whereas they do not modify DNA in a way similar to that of cisplatin.

Keywords

RhodiumIridiumN,O chelateCytotoxicityDNA binding

Supplementary material

775_2009_615_MOESM1_ESM.pdf (988 kb)
Supplementary material (PDF 989 kb)

Copyright information

© SBIC 2009

Authors and Affiliations

  • Stefan Wirth
    • 1
  • Christoph J. Rohbogner
    • 1
  • Marcin Cieslak
    • 2
  • Julia Kazmierczak-Baranska
    • 2
  • Stefan Donevski
    • 2
  • Barbara Nawrot
    • 2
  • Ingo-Peter Lorenz
    • 1
  1. 1.Department of Chemistry and BiochemistryLudwig-Maximilian University MunichMunichGermany
  2. 2.Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular StudiesPolish Academy of SciencesLodzPoland