Photodynamic Therapy (PDT) is a photochemistry-based modality useful in the treatment of localized disease and tumors. Successful PDT agents are nontoxic in the dark, but become highly cytotoxic upon photoactivation . Within the current armamentarium of approved PDT agents, toxicity is achieved through a variety of photosensitization pathways. These include the production of reactive oxygen species (ROS), direct binding to biological molecules and induction of redox damage within cells. Although PDT agents often exhibit one dominate photochemical pathway, a new approach to PDT for the treatment of cancers is a multifaceted ROS assault. Using multiple reactive species has been indicated to yield a greater toxicity and acts to decrease acquired resistance. Recently, we have developed a photoactivated analog to the drug cisplatin. In addition to photosubstitution reactions, these polypyridal complexes of ruthenium (II) have shown to act as photosensitizers. Moreover, the absorbance for photoactivation has been shown to be tunable by substitution of the phenanthorline ligand with a quinolate derivative (5-R-8-hydroxyquinoline) ligands. Here, we report the spectroscopy, photochemistry and biological activity of a series of these ruthenium (II) quinolate complexes. The motif [Ru(phen)2(5-R-quo)]+ (where R = –H, –NO2, –Cl, –SO3) results in a red shift in the MLCT absorbance (λmax = 520 nm). In addition, a increasing oxidation potential observed for increasing electron-withdrawing nature of the substituted ligand. TD-DFT calculations show that this correlates with decreased metal character in the HOMO. Lastly, we have identified multiple ROS species produced by these complexes. dsDNA mobility gels have confirmed the photoreactivity and toxicity. A mechanistic study has revealed the generation of multiple reactive partners and offers a “combination approach” to cellular damage in these photoactivated species.

Synthesis, characterization and photosensitization in a series of Ru(phen)2(quo)]+ complexes

253rd National Meeting (2017)

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