Dietrich et al. describe a noble, but ultimately failed, attempt to determine the crystal structure constraints that lead to the existence of a strong QRIP/Haupt effect in gamma-picoline. As stated by the authors, this effect relies on a large tunneling splitting in the cryogenic solid state which corresponds to a substantial energy splitting between the methyl spin isomers. Cooling such samples leads to an overpopulation of one spin isomer which persists when the sample is raised to ambient temperature; the recovery to thermal equilibrium induces transient hyperpolarization effects, as elucidated by some of the cited papers. The authors try to pin down which structural motifs lead to the large tunneling splitting. They investigate a variety of compounds which exhibit a similar motif of interacting methyl groups in their crystal structure. However, they only found a few compounds that do exhibit a QRIP effect and even then the effect was much weaker than in gamma-picoline. 

Although the results are largely negative, I do think that this study deserves to be in the scientific literature, since it demonstrates that either gamma-picoline and the few other compounds that show a strong QRIP possess some very subtle structural feature that has escaped detection by the authors in their detailed study, or possibly that the crystal structure is not the determining factor after all. For example some subtlety of the phonon spectrum might be responsible, although I confess that I have not much of an idea where to look. Nevertheless, I do suggest that in their conclusions, the authors might at least speculate on the possibility that molecular and crystal structures are not the determining factor for this phenomenon after all. 

A few small things should be corrected. It is not quite true that “only the methyl groups of a few substances seem to allow for the effect”. Very weak QRIP effects have also been observed in 17O water-endofullerene (doi.org/10.1103/PhysRevLett.120.266001). The authors cite Ludwig et al. (PNAS, 2010) as having studied QRIP, but the attribution of the described effects to QRIP have been disputed (doi.org/10.1016/j.jmr.2017.12.009). I was surprised to see that the article cited as Roy 2013 has a completely incorrect list of authors. That error suggests that all references should be rechecked carefully. 

A compilation of the studied molecular systems in one place would be helpful. In some cases one has to trawl through the text to find what a certain number refers to. 

I do not feel that providing the X-ray structural data of some of the compounds is worthwhile in the main text (figures 7, 8). The MAS spectra of the MOFs also do not seem worthy of display in the main manuscript, especially since the QRIP results were negative. 

On the other hand, the authors cite neutron scattering data which shows a tunneling splitting, but never provide this data at all. Personally, I would be more interested in seeing that. 

In summary this is a worthwhile study, and should be published, even though the authors were not able to shed much light on why a few special compounds exhibit a large methyl tunneling splitting, leading to a significant QRIP effect upon dissolution. Maybe the crystal structure is not the place to look for an explanation. 

In their paper "The relation between crystal structure and the occurence of quantum-rotor induced polarization", the authors search for structural motifs that give rise to substantial quantum rotor induced polarization, in an attempt to broaden the applicability of the phenomenon. The authors have studied a significant range of compounds, and their search criteria, e.g., crystal structures in which two methyl groups face each other, are perfectly reasonable. 

That said, it appears that the authors have not been able to observe a QRIP phenomenon on any of the newly tested compounds with plausible structures. To the contrary, QRIP is observed in substances with a substantial tunneling splitting, even if these substances violate the plausible assumptions on low barriers. This observation shows that it is indeed difficult to "guess" the tunneling splitting based on structural motifs.

While this represents a negative finding, it is still a rather conclusive one, and suited for publication in Magnetic Resonance.

I have the following suggestions for the manuscript:

- In the abstract, the authors write that "a high tunnel frequency is favorable". This should in my view be rephrased to "is required". After all, if the tunnel frequency is small, there is no quantum rotation, and - consequentially - no QRIP will be observed.

- It may be confusing to readers who are not very familiar with the effect, that a free rotor shows a large tunneling splitting. Indeed, in the limit of free rotation, there should be no tunneling. It would therefore be valuable to point out that the tunneling splitting is defined as the difference between the first two rotational states, and it is the population differences across these states that give rise to QRIP.

- The authors find a small, but significant tunneling splitting in compounds 8 and 12, but do not explicilty report details on their attempt to observe QRIP in this compound. Was such an attempt made? What was the concentration after dissolution? Is 13C labelling possible? Perhaps it is worth pointing out, that larger molecules will also tend to "loose" quantum-rotor-induced polarization more quickly due to their longer correlation times.

- The authors report on MAS QRIP experiments. How have these actually been conducted? QRIP requires equilibration at 4 Kelvin even in the most favourable cases. Have the authors performed such a temperature jump experiment with MAS? If yes, it would be prudent to give the details of temperature vs. time. A key parameter would be, after all, the time required to ramp the temperature from 4 K to say 30 K. If no such experiment has been conducted, the MAS data will be completely inconclusive with respect to QRIP, and should not be shown in the manuscript.

Finally, the manuscript is very well written overall, but the jubilee's spelling in the special issue statement should be checked.

This manuscript describes a search for quantum-rotor induced polarization effects in methyl groups of compounds similar to gamma picoline. The similarity is defined by having similar methyl-methyl distances and bond angle configurations. A number of identified compounds have been studied and the QRIP effect is either nonexistent or weak in them. This leads the authors to the conclusion that the molecular similarity criteria used are not sufficient to ensure the presence of this effect, and/or that nuances of the crystal structure are important for it to occur. The work therefore represents a negative result with regard to the initial hypothesis, while it does not preclude other factors and molecules being identified as displaying the QRIP effect in the future. A minor comment would be that clarity could be improved with regard to how narrow the initial hypothesis is. For example, is the concerted methyl rotation really the best way to insure the lowest amount of friction? Perhpas the authors may also wish to state that their study would indicate that it is not the case?Furthermore, I wonder whether relaxation effects could be of relevance here (e.g. through latttice dynamics / vibrations).