Using NMR to Test Molecular Mobility during a Chemical Reaction

Abstract

We evaluate critically the use of pulsed gradient spin–echo nuclear magnetic resonance to measure molecular mobility during chemical reactions. With raw NMR spectra available in a public depository, we confirm the boosted mobility during the click chemical reaction (Science2020369537541) regardless of the order of magnetic field gradient (linearly increasing, linearly decreasing, random sequence). We also confirm boosted mobility for the Diels–Alder chemical reaction. The conceptual advantage of the former chemical system is that a constant reaction rate implies a constant catalyst concentration, whereas that of the latter is the absence of a paramagnetic catalyst, precluding paramagnetism as an objection to the measurements. The data and discussion in this paper show the reliability of experiments when one avoids convection, allows decay of nuclear spin magnetization between successive pulses and recovery of its intensity between gradients, and satisfies quasi-steady state during the time window to acquire each datum. Especially important is to make comparisons on the time scale of the actual chemical reaction kinetics. We discuss possible sources of mistaken conclusions that are desirable to avoid.

Viewpoint: Reply to Comment on 'Using NMR to Test Molecular Mobility During a Chemical Reaction'

“…1B shows the "Australia" dataset does not depend on magnetic field sequence (random, increasing or decreasing). This is consistent with data from this laboratory 2 . But inconsistent with the authors' claims 13 .…”

“…It is an interesting question whether the overall spin-lattice relaxation time T1 of water increases, during the click reaction, beyond the 2-4 s that one finds in the literature 17 , and we plan to investigate this in the future. We varied delay times in our earlier paper 1 , 3 to 10 s, and obtained consistent findings 2 . One should notice that T1 is also related to the molecular tumbling rate such that T1 increases when molecular motion slows 18 .…”

“…Our Reply to the authors' first Comment 14 was followed by our longer paper amplifying it 2 . In this, their second Comment, the authors now raise objections to our long paper.…”

“…To some researchers, reports in the literature about boosted mobility during certain chemical and enzymatic reactions [1][2][3][4][5][6][7][8][9] are so counter-intuitive that they feel their colleagues must have measured artifact. This is the context of the present Viewpoint 10 expressing concerns about technicalities of how to analyze data we deposited online [11][12] regarding the click reaction [1][2] .…”

“…These data for two independent chemical systems agree qualitatively in the sense that they begin at one number, rise during the chemical reaction, and finally return to their original value (the experimental design to make this plain involves using mismatched reactant stoichiometry 16 ). To generate these data points from the raw NMR spectra we used automated methods of NMR peak integration, described elsewhere 16 to improve on the manual integration we had used in the original publications [1][2] . These data illustrate why we insist on the conclusion of boosted diffusion.…”