Cyclopropanol can function as a caged dual-functional warhead for selective electrochemical bioconjugation.

Bioorthogonal reactions enable the study and modulation of biological systems, but achieving precise control over when and where the reactions occur remains challenging. Here we show that cyclopropanol (CPol) can serve as a compact, energy-loaded chemical handle that is stable under physiological conditions, yet can be selectively activated using mild electrochemical stimuli. This strategy generates reactive β-haloketone moieties in situ, enabling efficient protein labelling for cellular imaging and proteomic analysis. Unexpectedly, CPol preferentially modifies acidic amino acids, such as glutamate and aspartate, within hydrophobic regions of proteins, rather than more commonly targeted residues. The electrochemical reaction is compatible with living cells, allowing real-time visualization using fluorogenic probes. We further demonstrate its utility by developing a choline-derived CPol probe that integrates into membrane lipid metabolism to label membrane-associated and cytoplasmic proteins. By combining bioorthogonality with electrochemical control, this approach offers a general and controllable platform for protein conjugation, with broader applications in chemical biology and live-cell studies.