Ruthenium polypyridyl complexes show great promise as new photodynamic therapy (PDT) agents. However, a lack of detailed understanding of their mode of action in cells poses a challenge to their development. We have designed a new Ru(II) PDT candidate that efficiently enters cells by incorporation of the lipophilic aromatic pdppz ([2,3-h]dipyrido[3,2-a:2',3'-c]phenazine) ligand and exhibits photoactivity through incorporation of 1,4,5,8-tetraazaphenanthrene ancillary ligands. Its photoreactivity toward biomolecules was studied in vitro, where light activation caused DNA cleavage. Cellular internalization occurred via an energy dependent mechanism. Confocal and transmission electron microscopy revealed that the complex localizes in various organelles, including the mitochondria. The complex is nontoxic in the dark, with cellular clearance within 96 h; however, upon visible light activation it induces caspase-dependent and reactive-oxygen-species-dependent apoptosis, with low micromolar IC50 values. This investigation greatly increases our understanding of such systems in cellulo, aiding development and realization of their application in cancer therapy.

The synthesis and photophysical properties of 1 and 2, two Ru(II)-polypyridyl based-1,8-naphthalimide Tro¨ger's bases, are described; these were found to stabilize double stranded DNA, undergo rapid cellular uptake, displaying good luminescence without affecting cell viability even after 24 hours of incubation.Tro¨ger's base was first discovered in 1887, formed upon reaction of para-toluidine with formaldehyde under acidic conditions.

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Publication date 2011 Publication informationChemical communications (Cambridge, England), 47 (2)

Quaternarized pdppz: Synthesis, DNA-Binding and Biological Studies of a Novel dppz Derivative (I) that Causes Cellular Death upon Light Irradiation. -(ELMES, R. B. P.; ERBY, M.; CLOONAN, S. M.; QUINN, S. J.; WILLIAMS, D. C.; GUNNLAUGSSON*, T.; Chem. Commun. (Cambridge) 47 (2011) 2, 686-688, http://dx.doi.org/10.1039/c0cc04303f ; Sch. Chem., Trinity Coll., Dublin, Ire.; Eng.) -R. Staver 16-171