Tetrazine-based bioorthogonal chemistry has become a cornerstone of chemical biology due to the exceptional reaction rate and selectivity of the inverse electron-demand Diels-Alder (IEDDA) reaction. These properties have enabled a wide range of applications, from live-cell labeling to in vivo imaging and chemical manipulation of biomolecules. However, accumulating evidence indicates that rapid reaction kinetics alone are insufficient to ensure reliable performance in complex biological environme