The homodesmotic equation for characterizing the strain release is defined as shown in We computed the RSE for 21 cyclooctyne derivatives, of which the experimental secondorder reaction constant rates were summarized by Bertozzi et al . for ring strain release and rate constants are recorded in Table . Overall, this demonstrates that the AIMNet2 RSE workflow can effectively compute ring strain release, and we can use ring strain release as a selective criterion for reactive cyclooctyne derivatives.