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

被引：22
作者：
Blazevic, Amir [1 ]
Hummer, Alfred A. [1 ]
Heffeter, Petra [2 ]
Berger, Walter [2 ]
Filipits, Martin [2 ]
Cibin, Giannantonio [3 ]
Keppler, Bernhard K. [4 ]
Rompel, Annette [1 ]
机构：
[1] Univ Vienna, Fak Chem, Inst Biophys Chem, Althanstr 14, A-1010 Vienna, Austria
[2] Med Univ Wien, Comprehens Canc Ctr & Forschungsplattform Transla, Inst Krebsforsch, Borschkegasse 8a, A-1010 Vienna, Austria
[3] Diamond Light Source, Didcot OX11 0DE, Oxon, England
[4] Univ Vienna, Fak Chem, Inst Anorgan Chem & Forschungsplattform Translat, Wahringer Str 42, A-1010 Vienna, Austria
来源：
SCIENTIFIC REPORTS | 2017年 / 7卷
基金：
奥地利科学基金会;
关键词：
X-RAY-ABSORPTION; CHLORINE K-EDGE; IN-VIVO; RUTHENIUM COMPLEXES; ANTICANCER AGENT; METAL-COMPLEXES; SERUM-ALBUMIN; NAMI-A; SPECTROSCOPY; KP1019;
D O I：
10.1038/srep40966
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 (RuN2Cl4)-N-III to (RuClx)-Cl-III(N/O)(6-x) (X = 1 or 2).
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页数：8
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