Response to Comment on “Following molecular mobility during chemical reactions: no evidence for active propulsion” and “Molecular diffusivity of click reaction components: the diffusion enhancement question”

In their Comment (Huang, T.; Granick, S. ChemRxiv 2022) on two related publications (J. Am. Chem. Soc. 2021, 143, 20884-20890; J. Am. Chem. Soc. 2022, 144, 1380-1388), Huang et al. comment on the diffusion NMR measurements of molecules during a copper-catalyzed azide-alkyne cycloaddition (CuAAC) “click” reaction. Here we respond to these comments and maintain that no measurable diffusion enhancement was observed during the reaction. We expand on the physical arguments presented in our earlier JACS paper regarding the appropriate reference state for the diffusion coefficient and present new data showing that the use of other reference states as suggested by Huang et al. will still support our conclusion that the two reactants and one product of click reaction do not exhibit boosted mobility during the reaction.