title: X-ray absorption near edge structure spectroscopy to resolve the in vivo chemistry of the redox-active indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019).
abstract: Indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (1, KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (2, KP1339) are promising redox-active anticancer drug candidates that were investigated with X-ray absorption near edge structure spectroscopy. The analysis was based on the concept of the coordination charge and ruthenium model compounds representing possible coordinations and oxidation states in vivo. 1 was investigated in citrate saline buffer (pH 3.5) and in carbonate buffer (pH 7.4) at 37 °C for different time intervals. Interaction studies on 1 with glutathione in saline buffer and apo-transferrin in carbonate buffer were undertaken, and the coordination of 1 and 2 in tumor tissues was studied too. The most likely coordinations and oxidation states of the compound under the above mentioned conditions were assigned. Microprobe X-ray fluorescence of tumor thin sections showed the strong penetration of ruthenium into the tumor tissue, with the highest concentrations near blood vessels and in the edge regions of the tissue samples.
authors.affiliation: Institut für Biophysikalische Chemie, Universität Wien, Althanstrasse 14, 1090 Wien, Austria.
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Hummer
authors.forename: Petra
authors.initials: P
authors.lastname: Heffeter
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.forename: David
authors.initials: D
authors.lastname: Batchelor
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Büchel
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Annette
authors.initials: A
authors.lastname: Rompel
mesh_terms: D007191:Indazoles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D025341:Principal Component Analysis; D017975:Ruthenium Compounds; D056928:X-Ray Absorption Spectroscopy / Q000379:methods*
chemical_list: D007191:Indazoles; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))