Ruthenium(II) polypyridyl complexes as versatile tools in the design of photoresponsive compounds for biological applications

Photodynamic therapy (PDT) is attracting a growing interest in the study of new anticancer as well as antibacterial agents, thanks to the possibility to overcome some of the most crucial drawbacks related to the use of commonly employed drugs. The possibility to achieve a temporal and spatial control over the drug-activation allows a better discrimination between malignant and surrounding healthy tissues, permitting to considerably limit the common side effects incurring with standard antibacterial and anticancer drugs. In this context, ruthenium(II) polypyridyl compounds represent some very challenging tools. Indeed, they possess a rich chemical-physical repertoire, that includes the capacity to efficiently sensitize ROS (reactive oxygen species) upon exposure to visible light, and the possibility to easily modulate their absorption profiles by tuning the nature of ancillary ligands. In this work, we present a series of Ru(II)-polypyridyl complexes, containing peculiar polyamino-macrocycles. These frameworks conferred to the resulting complexes a series of advantages, namely improved hydrophilicity and capacity to interact with important biological targets (such as DNA or proteins), without affecting the good ROS sensitization properties of Ru(II) cores. The biological behavior of these systems was then evaluated in various types of cancer cells, including human melanoma and ovarian carcinoma cells, and non-cancerous cell lines. In addition, hindered ancillary ligands were inserted into metal complexes to introduce a “distortion feature” in their octahedral geometries. This permits light irradiation to promote the loss of bioactive ligands resulting in the generation of active Ru(II)-based photoproducts, thus providing alternative modes of action that do not rely on molecular oxygen. The aim of this work is to demonstrate that the versatility of this class of compounds makes these systems promising candidates as light-activated drugs for a variety of biological applications.