Synthesis, characterization, and reaction pathways for the formation of a GMP adduct of a cytotoxic thiocyanato ruthenium arene complex
详细信息 查看全文
- 作者：Fuyi Wang ; Abraha Habtemariam ; Erwin P. L. van der Geer ; Robert J. Deeth ; Robert Gould ; Simon Parsons and Peter J. Sadler
- 关键词：Organometallic ruthenium ; Thiocyanate ligand ; Anticancer agents ; GMP
- 刊名：Journal of Biological Inorganic Chemistry
- 出版年：2009
- 出版时间：September, 2009
- 年：2009
- 卷：14
- 期：7
- 页码：1065-1076
- 全文大小：824.0 KB
文摘
The organoruthenium complex [(η6-hmb)Ru(en)(Cl)][PF6] (hmb is hexamethylbenzene, en is ethylenediamine) undergoes facile aquation and then reacts with KSCN in unbuffered solution to give the S-coordinated thiocyanato product [(η6-hmb)Ru(en)(S-SCN)]+ which slowly converts to the thermodynamically favored N-bound complex [(η6-hmb)Ru(en)(N-NCS)]+ (1 +). Complex 1 was synthesized and characterized by X-ray crystallography and mass spectrometry. Despite its lack of hydrolysis over 24 h, complex 1 exhibits moderate cytotoxicity (IC50 24 μM) towards the human ovarian cancer cell line A2780, comparable with that of the chlorido analogue which is thought to be activated (towards potential target DNA) via a rapid aquation (Wang et. al. in Proc Natl Acad Sci USA 102:18269–18274, 2005). Detailed kinetic studies suggest that complex 1 binds to guanosine 5′-monophosphate (GMP) through direct N7 substitution of the N-bound SCN ligand. In the presence of a high concentration of chloride (104 mM), however, complex 1 may bind partly to GMP via Cl substitution.