9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, kenpaullone, which displays similarities in the activity profile to flavopiridol, was modified by chemical transformations at the lactam unit to provide a peripheral binding site able to accommodate metal ions. The first metal-based paullone has been prepared and characterized by single-crystal X-ray diffraction methods, solid-state cross-polarization magic angle spinning 13C NMR spectroscopy, electrospray ionization mass spectra, and electronic spectra. The gallium complex [GaL2]Cl.2.5H2O, the metal-free ligand (HL), and the starting compound used for the preparation of HL were assessed in vitro for their cytotoxicity in a panel of human tumor cell lines. The gallium complex was found to be 1.5-18-fold more cytotoxic than HL, with an average IC50 value of 2.0 microM.

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.

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