Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal-organic photodynamic therapy.

A new family of ten dinuclear Ru(ii) complexes based on the bis[pyrrolyl Ru(ii)] triad scaffold, where two Ru(bpy) centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(ii)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients () ≥ 10 at 600-620 nm and longer. Phosphorescence quantum yields ( ) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ( ) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC values in the range of 10-100 μM and phototherapeutic indices (PIs) as large as 5400 and 260 with broadband visible (28 J cm, 7.8 mW cm) and 625 nm red (100 J cm, 42 mW cm) light, respectively. The bis[pyrrolyl Ru(ii)] triad with a pyrenyl linker () was especially potent, with an EC value of 1 nM and PI > 27 000 with visible light and subnanomolar activity with 625 nm light (100 J cm, 28 mW cm). The lead compound was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxicity in this more resistant model (EC = 60 nM and PI > 1200 with 625 nm light) despite a lower dark cytotoxicity. The PDT effects of extended to bacteria, where submicromolar EC values and PIs >300 against and were obtained with visible light. This activity was attenuated with 625 nm red light, but PIs were still near 50. The ligand-localized ππ* state contributed by the pyrenyl linker of likely plays a key role in its phototoxic effects toward cancer cells and bacteria.