Metal Complexes with Glycoconjugated Ligands: From Synthesis to Cellular Localization

金属离子以不同的方式影响我们的日常生活：有些是必需的，如血红蛋白中的铁，有些是有毒的，如汞，有些具有医疗应用，如基于钆的MRI造影剂，有些在工业中作为催化剂，以加速反应，否则需要高能量（温度/压力）发生。 金属配合物的水溶性是其生物医学应用的重要因素。对于工业目的，当反应在均相催化剂存在下进行时，使用水作为低成本、不易燃、无毒的溶剂将是环境友好和“绿色”的选择。 我们将用贵金属（Re，Rh，Ru）和糖基分子（糖基配体）制备一系列水溶性配合物，这些配合物可以由我们体内天然存在的“绿色”底物葡萄糖胺制成。这些手性配体的主要优点是它们的水溶性和生物相容性。它们的金属配合物具有潜在的应用前景，如用于CO2还原的Re（CO）3+配合物、用于水还原和制氢的羧酸二铑（II）配合物以及用于C-H活化的Ru（芳烃）2+配合物。这些金属配合物以及它们的镧系对应物也将具有潜在的治疗应用。 我们将确定这些金属络合物在溶液中的化学形态，并通过采用先进的光谱技术，包括X射线吸收光谱（XAS），在那里我们使用强烈的X射线同步加速器设施，如加拿大光源表征其结构。我们还将使用基于同步加速器的X射线荧光显微镜（XFM）探测它们的生物相容性，亲脂性和进入细胞的能力，以获得元素分布图，揭示它们在哪些细胞器中积累，以及它们的细胞摄取是否会影响细胞中必需元素（如Ca 2+离子）的分布。我们还将研究它们的生物物理特性，例如它们产生高活性1 O2（细胞中氧化应激的来源）的能力，并测试它们的催化潜力。我的研究计划将导致一系列新的“绿色”金属配合物在工业和生物医学目的的潜在应用，使其催化和生物活性的进一步探索与其他研究小组的合作。一些研究生和本科生将在这样一个跨学科的研究环境中接受培训，提高他们的批判性思维和沟通能力。他们将获得使用先进光谱技术（如XAS和XFM）合成和表征金属络合物的能力。这些高素质的人员将能够领导加拿大机构/行业的创新跨学科研究，并成为加拿大光源，我们的国家同步加速器设施的未来用户。

Metal ions impact our daily lives in different ways: some are essential like iron in hemoglobin, some are toxic like mercury, some have medical applications like gadolinium-based MRI contrast agents, and some act as catalysts in industry to accelerate reactions that otherwise require high energy (temperature/pressure) to occur. Water solubility of metal complexes is an important factor for their biomedical applications. For industrial purposes, when reactions take place in the presence of homogeneous catalysts, the use of water as a low cost, non-flammable, non-toxic solvent would be an environmentally friendly and "green" choice. We will prepare a series of water-soluble complexes with noble metals (Re, Rh, Ru) and sugar-based molecules (glycoconjugated ligands), which can be made from the "green" substrate glucosamine that naturally occurs in our body. The main advantages of these chiral ligands are their water solubility and biocompatibility. Their metal complexes will have potential future applications as catalysts, e.g. Re(CO)3+ complexes for CO2 reduction, dirhodium(II) carboxylates for water reduction and hydrogen production, and Ru(arene)2+ complexes for C-H activation. These metal complexes, as well as their lanthanide counterparts, will also have potential therapeutic applications. We will determine the chemical speciation of these metal complexes in solution, and characterize their structures by employing advanced spectroscopic techniques, including X-ray absorption spectroscopy (XAS), where we use intense X-rays available at synchrotron facilities such as the Canadian Light Source. We will also probe their biocompatibility, lipophilicity and ability to enter cells using synchrotron-based X-ray fluorescence microscopy (XFM) to obtain elemental distribution maps that reveal in which cellular organelles they accumulate, and whether their cellular uptake e.g. could affect the distribution of essential elements in the cell (such as Ca2+ ions). We will also examine their photophysical properties, such as their ability to generate highly reactive 1O2, a source of oxidative stress in cells, and test their catalytic potential. My research program will lead to a series of novel "green" metal complexes with potential applications in industry and for biomedical purposes, enabling further exploration of their catalytic and biological activities in collaboration with other research groups. Several graduate and undergraduate students will receive training in such a transdisciplinary research environment enhancing their critical thinking and communication skills. They will gain competence in synthesis and characterization of metal complexes using advanced spectroscopic techniques such as XAS and XFM. Such highly qualified personnel will be able to lead innovative transdisciplinary research in Canadian institutions/ industry and be future users of the Canadian Light Source, our national synchrotron facility.