Highly charged ruthenium(II) polypyridyl complexes as effective photosensitizer in photodynamic therapy

: A comparative study between two novel, highly water soluble, ruthenium(II) polypyridyl complexes, [Ru(phen)2 L'] and [Ru(phen)2 Cu(II)L'] (L and L-CuII ), containing the polyaazamacrocyclic unit 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L'), is herein reported. L and L-CuII interact with calf-thymus DNA and efficiently cleave DNA plasmid when light-activated. They also possess great penetration abilities and photo-induced biological activities, evaluated on an A375 human melanoma cell line, with L-CuII being the most effective. Our study highlights the key role of the Fenton active CuII center within the macrocycle framework, that would play a synergistic role with light activation in the formation of cytotoxic ROS species. Based on these results, an optimal design of RuII polypyridyl systems featuring specific CuII -chelating polyamine units could represent a suitable strategy for the development of novel and effective photosensitizers in photodynamic therapy.