Investigation of Metal-Organic Hybrids as Photosensitizers for Bioinorganic Applications

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I maintain a successful multidisciplinary NSERC DG program aimed at making new fundamental discoveries in the photosciences that will facilitate the design of better photosensitizers for bioinorganic applications (and other light-based technologies). My last NSERC DG period explored coordination complexes as DNA photocleaving agents, compounds that have utility as photosensitizers for photodynamic therapy (PDT). This strategy for treating cancer, whereby light activation of a photosensitizer produces cytotoxic singlet oxygen, is compromised by its reliance on oxygen, which is often limited in the most aggressive tumours.  My group used its multidisciplinary expertise to exploit novel photophysical principles in coordination chemistry to elicit oxygen-independent DNA photodamage by certain photosensitizer constructs. We were the first to show that highly reactive triplet intraligand (3IL) excited states damage DNA and kill cancer cells regardless of oxygen tension, and with wavelengths of light that penetrate tissue best (red and near-infrared). This fundamental insight spawned considerable interest from the academic community as well as industry.***This proposal will explore the influence of 3IL configurations on the excited state dynamics in a variety of metal complex classes: coordination, organometallic, and photoejecting systems. Through a detailed investigation of the photophysics and photochemistry of these classes, my group will outline the scope and limitations of these photosensitizers for photobiological applications such as PDT. The methodologies that we will employ include synthesis/characterization of coordination complexes, photophysical/photochemical studies in cell-free environments in the presence and absence of biological macromolecules (e.g., DNA), and photobiological studies using cells. Trainees will work at the interface of chemistry, photophysics, and biology, mastering the diverse experimental techniques and instrumentation necessary for multidisciplinary science. The fundamental insight gained through this program will lead to better photosensitizers for bioinorganic applications, but will also benefit researchers in other fields that seek thermally stable metal complexes with highly photosensitizing excited states: luminescent oxygen-sensing, photocatalysis, and solar energy conversion as examples. ***Successful outcomes from my current NSERC DG leveraged additional funding, and attracted an industry partner that is commercializing a family of my compounds for bladder cancer PDT. This partnership demonstrates the anticipated outcome of the requested NSERC DG funding, which will lead to new fundamental insights in the photosciences with far-reaching impact. Improvements in technology related to PDT and dye-sensitized solar cells have the potential to benefit all Canadians through advances in health and energy. **