Orthogonal Metal Catalysis in Biological Systems

Abstract

Over the past two decades, the development of bioorthogonal chemistry has revolutionized the chemical tools available for cell research. In this thesis, we have developed novel ruthenium complexes that enable ruthenium-catalyzed azide-thioalkyne cycloadditions to occur under highly efficient micromolar conditions, even in the presence of cells. Moreover, we have successfully translated rutheniumcatalyzed alkene-alkyne coupling into aqueous and bioorthogonal conditions, enabling the modification of peptides to occur efficiently under micromolar conditions. Furthermore, we have engineered a new ruthenium isomerization reaction that can take place inside living mammalian cells, which can be used to effectively deplete the natural cell levels of GSH. Finally, we have demonstrated that discrete organometallic catalysts can be used in combination with natural enzymes to create a primitive artificial metabolic network, even inside living cells.