De Novo Labile C–N Bonds Enable Dynamic Covalent Chemistry and Reversible Bioimaging

Dynamic covalent bonds (DCBs) enable reversible bond formation/cleavage, offering exciting possibilities for smart and adaptive materials, yet challenges such as slow kinetics and stringent conditions required for the reverse reaction currently hinder their broader use. We present a novel C-N σ-bond with exceptional reversibility and ultrafast kinetics (<i>t</i>_1/2 = 200 ms) across diverse primary aliphatic amine substrates, occurring spontaneously under ambient conditions without catalysts or external energy input, which is enabled by remarkably low activation barriers and near-equilibrium energetics. We showcase this transformative DCB's versatility in reversible gas-fixation, programmable transamination, and construct the first reversible chemical probes for real-time quantitative tracking of spatiotemporal histamine dynamics in live cells and in vivo within the brain under inflammatory pathology. This work redefines C-N σ-bonds as dynamic linkages, opening avenues for innovation in organic chemistry, adaptive materials, and dynamic biosystems.