Redox behavior of tumor-inhibiting ruthenium(III) complexes and effects of physiological reductants on their binding to GMP

Author(s): Petra Schluga, Christian Hartinger, Alexander Egger, Erwin Reisner, Mathea Sophia Galanski, Michael Jakupec, Bernhard Keppler
Abstract: Biotransformation of ruthenium(III) anticancer complexes hypothesized in the activation-by-reduction theory is the central topic of the present paper: The redox behavior of tetrachlorobis(azole)ruthenate(III)-type complexes was studied by NMR spectroscopy and square wave voltammetry. The influence of reducing agents on the binding behavior toward the DNA-modeling nucleotide GMP was determined by capillary electrophoresis, accompanied by identification of arising peaks by online coupling to electrospray ionization mass spectrometry. The determination of redox potentials enlightened that the biologically relevant reductants ascorbic acid and glutathione are capable of reducing the studied Ru(III) complexes under physiological conditions. Characteristic differences in reduction kinetics dependent on the pH value can be explained by higher reduction strength of ascorbic acid and glutathione at higher pH compared to the pH-independent redox response of ruthenium(III) complexes. Binding behavior of (H2ind)[trans-RuCl4(Hind)2] (Hind = 1H-indazole) toward GMP was found to be increased upon addition of two equivalents of glutathione but not of ascorbic acid. In contrast, only a minor influence on the GMP-binding under reductive conditions was found for (H2im)[trans-RuCl4(Him)2] (KP418, Him = 1H-imidazole).
Organisation(s): Department of Inorganic Chemistry, Department of Physical Chemistry
Journal: Dalton Transactions
Volume: 14
Pages: 1796-1802
No. of pages: 7
ISSN: 1477-9226
DOI: https://doi.org/10.1039/B511792E
Publication date: 2006
Peer reviewed: Yes
Austrian Fields of Science 2012: 104003 Inorganic chemistry, 104002 Analytical chemistry
Portal url: https://ucrisportal.univie.ac.at/en/publications/37b2fdff-cc07-4e9c-840b-ae52a0ba2015