Transition metal mediated bioorthogonal release

Abstract

Bioorthogonal chemistry offers powerful tools to study and manipulate biological systems without interfering with the biological processes. Of paramount interest is the possibility to exploit bioorthogonal tools to deliver novel therapeutic applications. Bioorthogonal prodrug activation is one of the most exciting areas of research and is currently progressing toward phase I clinical trials. Despite their limitations in biological media, transition-metal catalysts have been engineered to enact abiotic cofactors and trigger bond-breaking reactions widely employed for the release of small molecules from masking groups. Here, we highlight the challenges and opportunities of metal-mediated bioorthogonal cleavage reactions for the release of cargo molecules and other emerging applications such as protein activation and RNA degradation.