Synthesis, characterization, and reaction pathways for the formation of a GMP adduct of a cytotoxic thiocyanato ruthenium arene complex

Abstract

The organoruthenium complex [(eta(6)-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 [(eta(6)-hmb)Ru(en)(S-SCN)]+ which slowly converts to the thermodynamically favored N-bound complex [(eta(6)-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 (IC(50) 24 microM) 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.

Ruthenium–Arene Complexes of Curcumin: X-Ray and Density Functional Theory Structure, Synthesis, and Spectroscopic Characterization, in Vitro Antitumor Activity, and DNA Docking Studies of (p-Cymene)Ru(curcuminato)chloro

“…Figure shows these results for the most sensitive three lines while the dose-dependent behavior is shown in Supporting Information Figure S8, specific IC 50 values are presented in Table . The activity of the title compound on the ovarian tumor cell line A2780 yields an IC 50 value similar to that reported for the cationic complex [(hexamethylbenzene)Ru(ethylendiamine)(NCS)] + (23.38 ± 3.334 μM vs 24 μM, respectively) . A more specific comparison with related β-diketonato Ru complexes, that contain the same p -cymene arene, shows an IC 50 of 19 μM for [( p -cymene)Ru(R1C(O)CHC(O)R2)Cl] (R1 = CH 3 , R2 = H), 14 μM (R1 = t -Bu 3 , R2 = H), 11 μM (R1 = Ph, R2 = H), 24 μM (R1 = CH 3 , R2 = Cl) .…”

Photoinduced and Thermal Linkage Isomerizations of an Organometallic Ionic Liquid Containing a Half-Sandwich Ruthenium Thiocyanate Complex

“…Linkage isomerization is a typical reaction of metal complexes with ambidentate ligands − Noteworthy examples include vapor-induced solid-state isomerization, which enables colorimetric vapor detection, , and photoisomerization associated with a spin transition . Although such studies focus mainly on simple polypyridyl complexes, some half-sandwich thiocyanate compounds also exhibit linkage isomerization. − We hypothesized that the isomerization mechanism may be useful for developing novel stimuli-responsive organometallic ionic liquids.…”