Grant: Discovery Grants Program - Individual

DNA photocleaving agents are molecules capable of inducing single- or double-strand breaks in the DNA backbone. Molecules that cleave DNA upon activation with light are of significant interest for use in photodynamic therapy (PDT), a strategy that has been applied to the successful treatment of certain cancers, intravascular disease, and age-related macular degeneration. Briefly, PDT employs an organic photosensitizer that generates toxic oxygen species upon irradition with visible light. Unfortunately, organic photosensitizers rely on the presence of oxygen to function and cannot be activated by wavelengths of light where tissue is most transparent. Therefore, PDT is not effective in treating deep or hypoxic tissue, which comprises some of the most malignant and drug-resistant tumours. This proposal outlines a research plan that is devoted to overcoming such limitations by introducing transition metal complexes as photosensitizers for inorganic PDT. This proposal will identify inorganic systems that damage DNA when activated by near-IR light and do not require oxygen to function. Since DNA is the blueprint for all cellular function, new photosensitizers that target the genetic machinery will elicit maximal damage in a pre-selected area. A related research stream involves an in-depth study of the photophysics and photochemistry associated with good DNA photocleavers. The photochemistry of multimetallic systems is not well-documented, and their reactivity toward nucleic acids in particular remains largely unexplored. Therefore, information regarding the excited states of these molecules will enhance our fundamental scientific knowledge, enabling researchers to design better molecules for photonic applications. In our laboratory, we will use such information to identify molecules with good nonlinear optical properties that can be activated with near-IR light.