Abstract:
The use of light to activate the action of a drug has become important as mode of cancer therapy, in some cases superior to traditional treatments, because it significantly less invasive and poses low levels of systemic toxicity to the patient. Photoinduced ligand exchange, which can be used to release caged drugs or to induce covalent DNA binding with spatiotemporal control, together with the sensitization of 1O2, represent important reactions initiated by light with potential applications in photochemotherapy (PCT). These photoinduced reactions of Ru(II) and Rh2(II,II) complexes will be presented, along with their activity towards biological targets and cancer cells. Importantly, Ru(II) complexes were recently discovered to undergo multiple photochemical pathways following activation with light, and this property was used to design new dual-action compounds. These new complexes are able to both release a medically relevant compound and to produce 1O2 and were shown to exhibit significant enhancement of activity stemming from their ability to induce cell death via two different, independent pathways. A schematic representation of these processes with pyridine as a model compound representing a caged drug is shown in the figure below, along with observed excited state dynamics and distortions around the Ru(II) center that lead to efficient photodissociation of pyridine. New strategies developed for the photoinduced exchange of pyridine-containing drugs and their attachment to tumor-targeting antibodies will also be presented. These new complexes provide a new platform for drug delivery and enhanced therapeutic activity upon excitation with low energy light.
