Investigation of Metal-Organic Hybrids as Photosensitizers for Bioinorganic Applications

我维持着一个成功的多学科NSERC DG项目，旨在光科学领域取得新的基础性发现，促进为生物无机应用(和其他基于光的技术)设计更好的光敏剂。我的上一期NSERC DG探索了作为DNA光裂解剂的配位化合物，这些化合物作为光动力疗法(PDT)的光敏剂具有实用价值。这种治疗癌症的策略，即光敏剂的光激活产生细胞毒性单线态氧，受到其对氧的依赖的影响，而氧通常仅限于最具侵袭性的肿瘤。我的团队利用其多学科的专业知识，利用配位化学中的新的光物理原理，通过某些光敏剂结构诱导不依赖氧的DNA光损伤。我们是第一个证明高活性三重态排列(3IL)激发态损伤DNA并杀死癌细胞的，而不考虑氧气的压力，以及最能穿透组织的光的波长(红色和近红外)。这一基本观点引起了学术界和工业界的极大兴趣。*这项提议将探索3IL组态对各种金属络合物类激发态动力学的影响：配位系统、有机金属系统和光喷射系统。通过对这些课程的光物理和光化学的详细研究，我的团队将概述这些光敏剂在光生物应用(如PDT)中的范围和局限性。我们将采用的方法包括配位络合物的合成/表征，在生物大分子(如DNA)存在和不存在的情况下在无细胞环境中的光物理/光化学研究，以及利用细胞进行光生物学研究。学员将在化学、光物理和生物学的界面上工作，掌握多学科科学所需的各种实验技术和仪器。通过该计划获得的基本见解将导致更好的光敏剂用于生物无机应用，但也将有助于其他领域的研究人员寻找具有高度光敏激发态的热稳定金属络合物：发光氧敏、光催化和太阳能转换等。*我目前的NSERC DG的成功成果利用了额外的资金，并吸引了一个行业合作伙伴，该合作伙伴正在将我的一系列用于膀胱癌PDT的化合物商业化。这一伙伴关系证明了所请求的NSERC DG资金的预期结果，这将导致对光科学具有深远影响的新的基本见解。PDT和染料敏化太阳能电池相关技术的改进有可能通过健康和能源方面的进步惠及所有加拿大人。**

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. **