[Urbanium]

Hello,

I have one reaction that seemed not to work in bulk (common lab microscale in solution) so I run the kinetic profiling with 10x smaller quantities on NMR.

It was easy to follow the onset of the reaction and the peaks correspond to "disappearance" of reagents and formation of the expected product, however one thing was very different, and instead of getting two expected singlets for two methyl groups (shifts should be different), I got one huge broad singlet with integral 6 that only afterwards changes into two distinct signals with two sharp minor peaks on their inner sides (pic attached). I'm pretty sure these sharp peaks have nothing to do with bad shimming or instrument itself.

I asked one physical chemist for the opinion, and he told me I should run T1 and T2 relaxation measurements. I've heard about these terms and googled a bit, but could anyone explain to me why should I measure these and what can these tell me about the nature of the reaction (in general)? Or they are useful just for kinetics?

[Yggdrasil]

It seems to me like you might be having chemical exchange occuring during your NMR measurements.  In essence, the two methyl groups are able to switch between two chemical environments with different chemical shifts (e.g. , so instead of two sharp peaks, you get a one very broad peak (see for example http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/Lecture_ExchangeDynamics_2012.pdf).  It's hard to say if this is likely without knowing more details about the particular reaction you're monitoring, but one way to address the problem might be to try measuring at a different temperature to try and shift the timescale of your dynamics to a regime where the dynamics either result in one sharp peak (where the dynamics occur on a faster timescale than the NMR measurements) or two sharp peaks (where the dynamics occur on a slower timescale than the NMR measurements).

[Urbanium]

Thanks for the suggestion. I considered that some kind of Exchange is happening, and I'll probably do the measurements at lower temperature, it might be interesting. I was still puzzled by this, since I have no idea how could the "mixed" state look like.

But still, can somebody explain why are T1 and T2 relaxation measuremens interesting (and advisable in this case) and what kind of thing(s) can we in general observe and conclude from them?

[Babcock_Hall]

Very short answer: molecular motions.

[Urbanium]

Any more insightful reply?

[Babcock_Hall]

There is a great deal implied in what I wrote (which counts as insight as far as I am concerned); what it is lacking is detail.  Scroll down to the section on fast timescale dynamics in this link on protein NMR, which is near the bottom.  There is a great deal of literature using T1, T2, and NOE together to look at rapid motions in proteins using something called the order parameter S²:  http://dasher.wustl.edu/bio5357/lectures/lecture-15.pdf

This link also has some good introductory material:  http://casegroup.rutgers.edu/lnotes/NMR_lecture_dynamics.pdf

Some of what is discussed at these two links is equally applicable to small molecules.

[Ingeniosuccinimide]

You should also check the textbook by Friebolin or Levitt.

[Irlanur]

it would also be helpful if you tell us the reaction and the conditions of the NMR measurements.