Engineering ruthenium-based organometallic complexes for biological applications

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Because of the wide range of coordination numbers and geometries, accessible redox states, and the thermodynamic/kinetic properties and nature of the coordinating ligands, metal-based complexes are a special class of compounds which display reactivities with biomolecules that are very different than simple organic molecules. In the past years, our research group has aimed at getting a better understanding of the fate of metal-based complexes in biological settings, and the factors that influence their interactions with biomolecules. We have been particularly interested in the study of ruthenium-based organometallic complexes due to their excellent biological and catalytical activities, but also due to the fact that they can easily be fine-tuned, allowing the introduction of different targeting/cell-penetrating agents within their structure, generating molecules with enhanced biological activities and selectivity towards different biological targets for various applications. Based on our recent findings, the general objectives of the proposed research program for the next 5 years (which will train 3 PhD, 4 MSc and 5 UG students) are divided into two themes. Theme A. We recently discovered that some borates counterions that are commonly found as an integrative part of the structure of ruthenium-based organometallic complexes do play an important role in their biological activity (and hence might play a role in their ability to enter human cells). One of our main objectives will be to elucidate the fundamental role of these borate counterions on the biological/catalytical activities of Ru-based organometallic complexes. Theme B. We have also recently been highly interested in getting a deeper fundamental understanding of the behaviour of thermoresponsive linkages such as furan-maleimide Diels-Alder cycloadditions in biological settings (and have made great advances), to use them as a tool to deliver ruthenium-based organometallic complexes within human/bacterial cells, and enhance their intracellular biological/catalytic activities. Our second main objective will then be to evaluate the potential of such linkages for this purpose. Exporting the potential of complexes based on an exogenous metal such as ruthenium to the biological arena and study the factors that have an impact on their internalization/cellular delivery might open unforeseen opportunities for metabolic interventions, and unveil new tools in diagnosis, imaging, catalysis or therapy. This research program will positively impact various industrial sectors by offering novel tools at the interface of chemistry and biology. Undertaken at INRS-AFSB, located in Laval's "Biotech City", this project will undoubtedly lead to numerous collaborations with the industry, which will help the discoveries we make in our research laboratories find their way to commercial applications that will certainly positively impact the lives of countless Canadians and people worldwide.