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

Three new dinuclear arene ruthenium metalla-clips of the general formula [(p-cymene)(2)Ru2Cl2(mu-L)] have been prepared from {(p-cymene)(2)Ru2Cl2(p-Cl)(2)] and H2L organic linkers (H2La = diethyl-1,2-diazeneclicarboxylate, 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 100 mu M.