Electronic State of Sodium trans-[Tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) in Tumor, Liver and Kidney Tissue of a SW480-bearing Mouse

Author(s)
Amir Blazevic, Alfred A. Hummer, Petra Heffeter, Walter Berger, Martin Filipits, Giannantonio Cibin, Bernhard K. Keppler, Annette Rompel
Abstract

Ruthenium complexes are promising candidates for anticancer agents, especially NKP-1339 (sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]), which is on the edge to clinical applications. The anticancer mechanism seems to be tightly linked to the redox chemistry but despite progress in human clinical trials the in vivo Ru oxidation state and the coordination of Ru remains unclear. The Ru-based anticancer drug NKP-1339 was studied applying XANES (Cl K-and Ru L

2,3-edges) in tumor, kidney and liver tissue of a SW480 bearing mouse. Based on coordination charge and 3D XANES plots containing a series of model compounds as well as pre-edge analysis of the ligand Cl K-edge it is suggested that NKP-1339 remains in its +III oxidation state after 24 hours and at least one of the four chlorido ligands remain covalently bound to the Ru ion showing a biotransformation from Ru

III N

2 Cl

4 to Ru

III Cl

x (N/O)

6-x (X = 1 or 2).

Organisation(s)
Department of Biophysical Chemistry, Department of Inorganic Chemistry
External organisation(s)
Medizinische Universität Wien, Diamond Light Source Ltd
Journal
Scientific Reports
Volume
7
No. of pages
8
ISSN
2045-2322
DOI
https://doi.org/10.1038/srep40966
Publication date
01-2017
Peer reviewed
Yes
Austrian Fields of Science 2012
106006 Biophysics, 106002 Biochemistry
Keywords
Portal url
https://ucrisportal.univie.ac.at/en/publications/945bf1a5-805e-4740-b93b-9286d64f74e4