Developing photo-activable ruthenium (II) complexes for PDT: Synthesis, characterization, photophysical and biological studies

The easy tunable photophysical properties of Ru(II) polypyridyl complexes, together with their water solubility, photochemical stability and high biocompatibility make them suitable as agents for photodynamic therapy (PDT). The development of complexes containing new ligands is a step forward in the improvement and application of these compounds as photosensitizer and photocytotoxic agents. We report the synthesis of a set of Ru(II)-polypyridyl complexes with different electronic properties and delocalized pi systems: one homoleptic complex [RuII(dpbpy)3](PF6)2 (1), and three heteroleptic complexes [RuII(dpbpy)2(phen)](PF6)2 (2), [RuII(dpbpy)(phen)2](PF6)2 (3) and [RuII(dpbpy)2(CN-Me)](PF6)2 (4). All of them contain 4,4 '-diphenyl-2,2 '- bipyridine (dpbpy) and 1,10-phenantroline (phen) or N-methyl-N '-2-pyridilimidazolium (CN-Me) ligands. The complexes have been characterized by spectroscopic, structural and electrochemical methods. UV-vis absorption in solution show the red shift for the metal to ligand charge transfer (MLCT) transitions after changing phen by dpbpy and carbene ligands. The photoluminescence emission spectra of 1-4 supported by theoretical calculations using time-dependent density-functional theory (TDDFT) suggest that the lowest energy excited state is mainly 3MLCT. Complex 2 exhibits the highest phosphorescence emission with a quantum yield (phi P) in CH2Cl2 of 44.1 %, followed by complex 1 (phi P = 40.0 %), whereas complex 4 shows the lowest quantum efficiency (phi P = 16.0 %), what suggest that the introduction of the CN-Me carbene ligand produces a significant quenching of the phosphorescence. Phosphorescence triplet state lifetimes between 0.96 and 1.74 mu s were shown for 1-4 in degassed CH2Cl2. All complexes are proven to be efficient singlet oxygen photosensitizers. The trend in the redox potentials becomes more positive by increasing the number of phen ligands in the complexes, in full agreement with the HOMO's energy level and the blue shift of the MLCT transitions in the absorption spectra. Complexes internalization was analysed in tumorigenic mammary epithelial SKBR-3 cells, being complexes 1 and 2 the most well internalized. The effect of the photodynamic treatment using light-activated complexes 1 and 2 for 10 min demonstrated to increase cell death, being the homoleptic complex 1 an outstanding candidate as potential theranostic agent for bioimaging and PDT.