Molecular Diffusivity of Click Reaction Components: The Diffusion Enhancement Question

TL;DR

This study investigates molecular diffusivity changes during the copper-catalyzed azide-alkyne cycloaddition click reaction using advanced NMR techniques, finding no evidence of reaction-induced diffusion enhancement but highlighting the role of large intermediate species.

Contribution

Developed new NMR diffusion methods to accurately monitor reaction component diffusivity, revealing the absence of diffusion enhancement during click reactions.

Findings

Diffusivity of reactants decreases over time during the reaction.

Diffusivity of the product increases gradually.

Large intermediate species exhibit lower diffusivity than reactants and products.

Abstract

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.