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JBIC Journal of Biological Inorganic Chemistry

, Volume 23, Issue 7, pp 1159–1164 | Cite as

Understanding the interactions of diruthenium anticancer agents with amino acids

  • Alexey A. NazarovEmail author
  • Maria-Grazia Mendoza-Ferri
  • Muhammad Hanif
  • Bernhard K. Keppler
  • Paul J. Dyson
  • Christian G. HartingerEmail author
Original Paper
Part of the following topical collections:
  1. Alison Butler: Papers in Celebration of Her 2018 ACS Alfred Bader Award in Bioorganic or Bioinorganic Chemistry

Abstract

The dinuclear anticancer agents 1,n-bis{chlorido[3-(oxo-κO)-2-methyl-4-(1H)-pyridinonato-κO4](η6-p-cymene)-ruthenium(II)}alkane (PyRu 2 n ) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein revealed uncommon protein–DNA and DNA–DNA crosslinking ability. We report here studies on the reactions of the diruthenium organometallics PyRu 2 6 and PyRu 2 8 in comparison with a mononuclear analogue PyRu3 with amino acids using mass spectrometry and NMR spectroscopy. The compounds behave very similarly, independent of the spacer length between the metal center and of the nuclearity of the complexes. Incubation with l-cysteine (Cys) results in fast release of the pyridone ligand, with the Ru complexes able to form Cys adducts. In contrast, l-methionine forms, initially, adducts with the metal centers, but over time, the adducts decompose. Similar behavior was observed for the reaction with l-histidine with [Ru(η6-p-cymene)(l-histidine)] species detected.

Graphical abstract

Keywords

Amino acid interaction Bioorganometallics Dinuclear compounds Mass spectrometry NMR spectroscopy Ruthenium(arene) complexes 

Notes

Acknowledgements

We thank the organizations and foundations that have supported our research efforts in this area, especially the Universities of Auckland and Vienna, EPFL, and A.A.N. is grateful to the RFBR (16-03-00743).

Supplementary material

775_2018_1597_MOESM1_ESM.pdf (252 kb)
Supplementary material 1 (PDF 252 kb)

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Copyright information

© SBIC 2018

Authors and Affiliations

  1. 1.M. V. Lomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute of Inorganic ChemistryUniversity of ViennaViennaAustria
  3. 3.School of Chemical SciencesUniversity of AucklandAucklandNew Zealand
  4. 4.Institute of Chemical Sciences and EngineeringSwiss Federal Institute of Technology (EPFL)LausanneSwitzerland

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