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Uncovering the key role of distortion in tetrazine ligations guides the design of bioorthogonal tools that defy the reactivity/stability tradeoff
The tetrazine/trans-cyclooctene ligation stands out from the bioorthogonal toolbox due to its exceptional reaction kinetics, enabling multiple molecular technologies in vitro and in living systems. Highly reactive 2-pyridyl-substituted tetrazines have become state-of-the-art for time-critical processes and selective reactions at very low concentration. It is widely accepted that the enhanced reactivity of these chemical tools is attributed to the electron-withdrawing effect of the heteroaryldoi:10.33774/chemrxiv-2021-vnwzk-v2 fatcat:k2tmohvrorhfxiizqoz2n5lyia