  Micrometer-sized objects are widely known to exhibit chemically-driven
motility in systems away from equilibrium. Experimental observation of
reaction-induced motility or enhancement in diffusivity at the much shorter
length scale of small molecules is however still a matter of debate. Here, we
investigate the molecular diffusivity of reactants, catalyst and product of a
model reaction, the copper-catalyzed azide-alkyne cycloaddition click reaction,
and develop new NMR diffusion approaches that allow the probing of
reaction-induced diffusion enhancement in nano-sized molecular systems with
higher precision than the state of the art. Following two different approaches
that enable the accounting of time-dependent concentration changes during NMR
experiments, we closely monitored the diffusion coefficient of reaction
components during the reaction. The reaction components showed distinct changes
in the diffusivity: while the two reactants underwent a time-dependent decrease
in their diffusivity, the diffusion coefficient of the product gradually
increased and the catalyst showed only slight diffusion enhancement within the
range expected for reaction-induced sample heating. The decrease in diffusion
coefficient of the alkyne, one of the two reactants of click reaction, was not
reproduced during its copper coordination when the second reactant, azide, was
absent. Our results do not support the catalysis-induced diffusion enhancement
of the components of click reaction and, instead, point to the role of a
relatively large intermediate species within the reaction cycle with
diffusivity lower than both the reactants and product molecule.
