The goal of performing bio-independent syntheses in complex biological environments, so-called bioorthogonal chemistry, has inspired the search for novel biocompatible transformations for more than a decade and found a niche of application as labelling techniques to study biomolecules in their native state. The incorporation of transition metal catalysts to the bioorthogonal toolbox has opened the possibility of producing supra-stoichiometric amounts of xenobiotics in living systems in a non-enzymatic fashion, opening up new avenues in chemical biology and biomedicine. Based on the biocompatibility of some transition metal catalysts (e.g. Pd or Au) and their remarkable catalytic properties, our lab has pioneered the use of heterogeneous catalysis to enable the site-specific “manufacture” of chemotherapeutic agents in specific anatomical locations (e.g. inside tumours). As opposed to biolabile prodrugs, whose activation process relies on metabolic pathways, an efficient bioorthogonally-activated prodrug therapy would be entirely dependent on the distinct catalytic properties of the metal and, ideally, the prodrug should remain intact in the absence of the metal source. Palladium and gold are the transition metals used as catalysts in this unique strategy. In this talk I will present the discovery of N and O-depropargylation reactions that take place under biocompatible conditions and their application as masking methods to eliminate the fluorescence and bioactivity of dyes and clinically-used drugs, respectively, while enabling the bioorthogonal rescue of the compounds’ properties by Pd or Au-functionalized devices in cancer cell culture, living organisms and tumours.

Bioorthogonal catalysis: Overview, applications, and state-of-the-art

2019 Spring National Meeting

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