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”

Abstract

In their Comment (DOI: 10.1021/jacs.2c02965) on two related publications by our group (J. Am. Chem. Soc.2022, 144, 1380–1388; DOI: 10.1021/jacs.1c11754) and another (J. Am. Chem. Soc.2021, 143, 20884–20890; DOI: 10.1021/jacs.1c09455), Huang and Granick refer to the diffusion NMR measurements of molecules during a copper-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reaction. Here we respond to their comments and maintain that no measurable diffusion enhancement was observed during the reaction. We expand on the physical arguments presented in our original JACS Article 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 and Granick, will still support our conclusion that the two reactants and one product of the CuAAC reaction do not exhibit boosted mobility during the reaction.