The purpose of the present study was to investigate the influence of pi-expansive cydometalating ligands on the photophysical and photobiological properties of organometallic Ru(II) compounds. Four compounds with increasing pi conjugation on the cyclometalating ligand were prepared, and their structures were confirmed by HPLC, ID and 2D H-1 NMR, and mass spectrometry. The properties of these compounds differed substantially from their Ru(II) polypyridyl counterparts. Namely, they were characterized by red-shifted absorption, very weak to no room temperature phosphorescence, extremely short phosphorescence state lifetimes (<10 ns), low singlet oxygen quantum yields (0.5-8%), and efficient ligand-centered fluorescence. Three of the metal complexes were very cytotoxic to cancer cells in the dark (EC50 values = 1-2 mu M), in agreement with what has traditionally been observed for Ru(II)) compounds derived from small CAN ligands. Surprisingly, the complex derived from the most re-expansive cydometalating ligand exhibited no cytotoxicity in the dark (EC50 > 300 mu M) but was phototoxic to cells in the nanomolar regime. Exceptionally large phototherapeutic margins, exceeding 3 orders of magnitude in some cases, were accompanied by bright ligand-centered intracellular fluorescence in cancer cells. Thus, Ru(II) organometallic systems derived from mu-expansive cydometalating ligands, such 4,9,16-triazadibenzo[a,c]napthacene (pbpn), represent the first class of potent light-responsive Ru(II) cydometalating agents with theranostic potential.