Metal Complexes with Glycoconjugated Ligands: From Synthesis to Cellular Localization

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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.