Strategy to Optimize the Biological Activity of Arene Ruthenium Metalla-Assemblies

Three
new dinuclear arene ruthenium metalla-clips of the general
formula [(p-cymene)2­Ru2Cl2­(μ-L)] have been prepared from [(p-cymene)2­Ru2Cl2­(μ-Cl)2] and H2L organic linkers (H2La = diethyl-1,2-diazenedicarboxylate, H2Lb = N,N′-bis­(2-hydroxy­ethyl)­oxamide,
H2Lc = N,N′-bis­{2-(2-hydroxy­ethoxy)­ethyl}­ethanediamide). The
bis-chelating bridging-linkers possess two functional groups that
can be synthetically modified for physico-chemical optimizations.
Reaction of these three dinuclear metalla-clips with 4,4′-bipyridine,
1,2-bis­(4-pyridyl)­ethylene, and 4,4′-azopyridine affords,
in the presence of AgCF3SO3, nine tetracationic
tetranuclear metalla-rectangles. Similarly, the tridentate ligands
2,4,6-tris­(4-pyridyl)-1,3,5-triazine and 1,3,5-tris­{2-(4-pyridyl)­vinyl}­benzene
were used to generate six hexacationic hexanuclear metalla-prisms.
All metalla-assemblies and the dinuclear complexes were evaluated
as anticancer agents against cancerous (A2780) and noncancerous (HEK293)
cell lines, showing an excellent selectivity for cancer cells. The
IC50 values of the cationic metalla-assemblies were typically
<1 μM, whereas, for the neutral dinuclear metalla-clips,
the IC50 values were >100 μM.