Synthesis and Characterization of Ru(II) Complexes with π-Expansive Imidazophen Ligands for the Photokilling of Human Melanoma Cells

Ru(II) complexes were synthesized with pi-expanding (phenyl, fluorenyl, phenanthrenyl, naphthalen-1-yl, naphthalene-2-yl, anthryl and pyrenyl groups) attached at a 1H-imidazo[4,5-f][1,10]phenanthroline ligand and 4,4 '-dimethyl-2,2 '-bipyridine (4,4 '-dmb) coligands. These Ru(II) complexes were characterized by 1D and 2D NMR, and mass spectroscopy, and studied for visible light and dark toxicity to human malignant melanoma SK-MEL-28 cells. In the SK-MEL-28 cells, the Ru(II) complexes are highly phototoxic (EC50 = 0.2-0.5 mu m) and have low dark toxicity (EC50 = 58-230 mu m). The highest phototherapeutic index (PI) of the series was found with the Ru(II) complex bearing the 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline ligand. This high PI is in part attributed to the pi-rich character added by the pyrenyl group, and a possible low-lying and longer-lived (IL)-I-3 state due to equilibration with the (MLCT)-M-3 state. While this pyrenyl Ru(II) complex possessed a relatively high quantum yield for singlet oxygen formation (phi (increment) = 0.84), contributions from type-I processes (oxygen radicals and radical ions) are competitive with the type-II (O-1(2)) process based on effects of added sodium azide and solvent deuteration.