Comment on "Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion" and "Molecular Diffusivity of Click Reaction Components: The Diffusion Enhancement Question".

We provide arguments why we consider as inaccurate two recent Articles which disagree with our laboratory's report of boosted diffusion during the copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. In the first paper (DOI: 10.1021/jacs.1c09455), Fillbrook et al. claim that their diffusion NMR experiments offer no evidence for boosted diffusion, but we argue that their use of Gd-chelates to speed up NMR relaxations times is flawed conceptually, the authors interpreting Gd-chelates as inert. Actually, the same features that make gadolinium ions useful as contrast agents in magnetic resonance imaging render them unsuitable for diffusion NMR. Nonetheless, by correctly adjusting technical aspects of the measurements, we confirm boosted diffusion even in the presence of this MRI contrast agent. The second paper of which we are skeptical, by Rezaei-Ghaleh et al. (DOI: 10.1021/jacs.1c11754), makes comparisons to a reference state that is not physically meaningful.