Self-assembled metalla-rectangles bearing azodipyridyl ligands: synthesis, characterization and antitumor activity

Sixteen arene-Ru based molecular-rectangles were self-assembled in high yields by the equimolar mixing of arene-Ru acceptors (Aa-Ad) with various azopyridyl ligands (1,2-di(pyridyl-4yl)diazene (L1), 1,2-bis(pyridin-4-ylmethylene)hydrazine (L2), 1,2-bis(1-(pyridin-4-yl)ethylidene)hydrazine (L3), 1,2-bis(pyridin-4-ylmethylene)hydrazine (L4)) in nitromethane-methanol solutions. These new molecular-rectangles were fully characterized by a host of analytical techniques including elemental analysis, (1)H and (13)C NMR and HR-ESI-MS. The solid-state structures of two molecular-rectangles (1b and 4d) were determined by single crystal X-ray diffraction data. UV-visible and fluorescence studies were also carried out for the entire suite of rectangles. As with recent studies of similar arene-Ru complexes, the anti-proliferative activities of these complexes were evaluated against SK-hep-1 (liver cancer) and A-549 (lung cancer) human cancer lines. Additionally, the cellular pharmacology and intracellular localizations in AGS (gastric cancer) human cancer cells were determined for selected complexes (1c, 1d and 4c) by apoptosis and fluorescence microscopy studies. These studies confirm that arene-Ru molecular-rectangles inhibit cell cycle progression to the G0 phase, in contrast to that of cisplatin which arrests cell growth in the G2 phase.