Following molecular mobility during chemical reactions: no evidence for active propulsion

2021

Article

pf

The reported changes in self-diffusion of small molecules during reactions have been attributed to “boosted mobility”. We demonstrate the critical role of changing concentrations of paramagnetic ions on nuclear magnetic resonance (NMR) signal intensities, which lead to erroneous measurements of diffusion coefficients. We present simple methods to over-come this problem. The use of shuffled gradient amplitudes allows accurate diffusion NMR measurements, even with time-dependent relaxation rates caused by changing concentrations of paramagnetic ions. The addition of a paramagnetic relaxation agent allows accurate determination of both diffusion coefficients and reaction kinetics during a single experi-ment. We analyze a copper-catalyzed azide-alkyne cycloaddition ‘click’ reaction, for which boosted mobility has been claimed. With our methods, we accurately measure the diffusive behavior of the solvent, starting materials and product, and find no global increase in diffusion coefficients during the reaction. We overcome NMR signal overlap using an alter-native reducing agent to improve the accuracy of the diffusion measurements. The alkyne reactant diffuses slower as the reaction proceeds, due to binding to the copper catalyst during the catalytic cycle. The formation of this intermediate was confirmed by complementary NMR techniques and density functional theory calculations. Our work calls into question recent claims that molecules actively propel or swim during reactions, and establishes that time-resolved diffusion NMR measurements can provide valuable insight into reaction mechanisms.

@article{2021JPG3,
  title = {Following molecular mobility during chemical reactions: no evidence for active propulsion},
  author = {Fillbrook, Lucy L. and G{\"u}nther, Jan-Philipp and Majer, G{\"u}nter and O'Leary, Daniel J.and Price, William S. and Van Ryswyk, Hal and Fischer, Peer and Beves, Jonathan, E.},
  journal = {Journal of the American Chemical Society},
  volume = {143},
  number = {49},
  pages = {20884--20890},
  month = dec,
  year = {2021},
  doi = {10.1021/jacs.1c09455},
  url = {https://pubs.acs.org/doi/10.1021/jacs.1c09455},
  month_numeric = {12}
}