Seeking Citius: Photochemical Access of Reactive Intermediates for Faster Bioorthogonal Reactions

Abstract Fast bioorthogonal reactions are sought after because of their superior performance in labeling low‐abundance biomolecules in native cellular environments. An attractive strategy to increase reaction kinetics is to access the reactive intermediates through photochemical activation. To this end, significant progress was made in the last few years in harnessing two highly reactive intermediates—nitrile imine and tetrazine—generated through photoinduced ring rupture and catalytic photooxidation, respectively. The efficient capture of these reactive intermediates by their cognate reaction partners has enabled bioorthogonal fluorescent labeling of biomolecules in live cells.