Metal Complexes with Glycoconjugated Ligands: From Synthesis to Cellular Localization

具有糖共轭配体的金属配合物：从合成到细胞定位

• 批准号: RGPIN-2022-02996
• 负责人: Jalilehvand, Farideh
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747924
• 关键词: Metal; Complexes; Glycoconjugated; Ligands; Synthesis

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.

金属离子以不同的方式影响着我们的日常生活：有些是必需的，如血红蛋白中的铁，有些是有毒的，如汞，有些是医学上的应用，如钆基MRI造影剂，有些在工业上作为催化剂加速反应，否则需要高能量（温度/压力）才能发生。金属配合物的水溶性是影响其生物医学应用的重要因素。对于工业用途，当反应发生在均相催化剂的存在下时，使用水作为低成本、不易燃、无毒的溶剂将是一种环境友好和“绿色”的选择。我们将制备一系列由贵金属（Re, Rh, Ru）和糖基分子（糖缀合配体）组成的水溶性配合物，这些配合物可以由我们体内自然存在的“绿色”底物氨基葡萄糖制成。这些手性配体的主要优点是其水溶性和生物相容性。它们的金属配合物将在未来作为催化剂有潜在的应用，例如用于CO2还原的Re(CO)3+配合物，用于水还原和制氢的dirhodium（II）羧酸盐，以及用于碳氢活化的Ru(arene)2+配合物。这些金属配合物，以及它们的镧系对应物，也将有潜在的治疗应用。我们将确定这些金属配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）来表征它们的结构，其中我们使用同步加速器设施（如加拿大光源）提供的强x射线。我们还将利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的分布（如Ca2+离子）。我们还将研究它们的光物理性质，例如它们产生高活性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具有工业和生物医学用途潜在应用的新型“绿色”金属配合物，使其能够与其他研究小组合作进一步探索其催化和生物活性。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训练，提高他们的批判性思维和沟通能力。他们将获得利用先进的光谱技术如XAS和XFM合成和表征金属配合物的能力。这些高素质的人才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。