Abstract

Bioorthogonal chemistries have enabled the interrogation of biomolecules under physiological conditions with minimal perturbances to the native environment. These powerful tools have allowed us to image and retrieve specific targets, but existing reactions remain limited in scope. The current toolbox of bioorthogonal transformations is weighted toward cycloadditions, and many cannot be employed in tandem due to cross-reactivity. This restriction presents a significant challenge when simultaneous probing of multiple entities is desired. To address this limitation, I leveraged the unique chemistry between bioorthogonal cyclopropenones (CpOs) and phosphines. When a CpO and phosphine react, a ketene-ylide intermediate is formed. This reactive electrophile can then be leveraged to label off dynamic biomolecules with spatiotemporal control.