Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties.

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5- f ][1,10]phenanthroline (IP- n T) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb) 2 (IP- n T)] 2+ scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy) 3 ] 2+ . Ru-1T - Ru-4T have additional oxidations due to the n T group and additional reductions due to the 4,4'-btfmb ligands. Ru-2T - Ru-4T also exhibit n T-based reductions. Ru-4T exhibits two oxidations and eight reductions within the potential window of -3 to +1.5 V. The lowest-lying triplets (T 1 ) for Ru-0T - 2T are metal-to-ligand charge-transfer ( 3 MLCT) excited states with lifetimes around 1 μs, whereas T 1 for Ru-3T - 4T is longer-lived (∼20-24 μs) and of significant intraligand charge-transfer ( 3 ILCT) character. Phototoxicity toward melanoma cells (SK-MEL-28) increases with n , with Ru-4T having a visible EC 50 value as low as 9 nM and PI as large as 12,000. Ru-3T and Ru-4T retain some of this activity in hypoxia, where Ru-4T has a visible EC 50 as low as 35 nM and PI as high as 2900. Activity over six biological replicates is consistent and within an order of magnitude. These results demonstrate the importance of lowest-lying 3 ILCT states for phototoxicity and maintaining activity in hypoxia.