Highly Charged Ruthenium(II) Polypyridyl Complexes as Effective Photosensitizer in Photodynamic Therapy

Abstract: A comparative study between two novel, highly water soluble, ruthenium(II) polypyridyl complexes, [Ru(-phen)2L’]and [Ru(phen)2Cu(II)L’](L and L-Cu(II)), containing the polyaazamacrocyclic unit 4,4’-(2,5,8,11,14-pentaaza[15])-2,2’-bipyridilophane (L’), is herein reported. L and L-Cu(II) interact with calf-thymus DNA and efficiently cleave DNA plasmid when light-activated. They also possess great penetration abilities and photoinduced biological activities, evaluated on an A375 human melanoma cell line, with L-Cu(II) being the most effective. Our study highlights the key role of the Fenton active Cu(II) 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 Ru(II) polypyridyl systems featuring specific Cu(II)-chelating polyamine units could represent asuitable strategy for the development of novel and effective photosensitizers in photodynamic therapy.