Bioorthogonal Chemistry of Polyoxometalates – Challenges and Prospects

Bioorthogonal chemistry enabled scientists to carry out controlled chemical processes in high yields in vivo while minimizing hazardous effects. Its extension to the field of polyoxometalates (POMs) could open up new possibilities and new applications in molecular electronics, sensing and catalysis, including inside living cells. However, this comes with many challenges that need to be addressed to effectively implement and exploit bioorthogonal reactions in the chemistry of POMs. In particular, how to protect POMs from the biological environment but make their reactivity selective towards specific bioorthogonal tags (and thereby reduce their toxicity), as well as which bioorthogonal chemistry protocols are suitable for POMs and how reactions can be carried out are questions that we are exploring herein. This Perspective conceptualizes and discusses advances in the supramolecular chemistry of POMs, their click chemistry, and POM-based surface engineering to develop innovative bioorthogonal approaches tailored to POMs and improve POM biological tolerance.