To illustrate the practical value, we explored the potential to screen reactive molecules with the AIMNet2 RSE workflow. Our first investigation focused on the 1,3-dipolar cycloaddition of cyclooctynes with azides, a key reaction in "copper-free click chemistry" widely applied in drug design . The release of RSE in cyclooctynes serves as a driving force in this reaction, making the effective computation of RSE valuable for predicting cyclooctyne reactivity and guiding rational molecule design. We selected cyclooctyne derivatives to validate the correlation between RSE and reactivity. The reactivity of cyclooctyne derivatives was characterized by experimental second-order rate constants, sourced from several experimental reports . The list of cyclooctyne derivatives is available in the Figure .