Author: Johannes Leisen

A nice person left this NMR tree in the lab. Thank you!

The South Eastern Magnetic Resonance Conference took place from 10/23 – 10/26 2024.

It was organized by a team of researchers from Georgia Tech (Anant Paravastu, Andrew McShan, Hongwei Wu and Hanno Leisen) and Emroy (David Reiter and Kurt Warncke). Over 3 days we had a great exchange discussing new research in the field of NMR, MRI and EPR.

People liked our conference poster, which was designed by Andrew McShan with some help from AI.

Over 100 people participated in the conference. The picture shows the most enthusiastic group who stayed until the end of the conference, which was on a Saturday afternoon.

We awarded prizes to trainees for the best posters and talk.

Here is the list of winners:

Prizes for the Best Talks:

Lauren Daley, Emory and Georgia Institute of Technology: Towards multimodal imaging in awake, behaving mice

and

Carl Fleischer, Florida State University and National High Magnetic Field Laboratory: New Applications of Quadrupolar NMR Crystallography Guided Crystal Structure Prediction

Prizes for the best posters in the categories solution and solid-state NMR:

Combining Solid-State NMR and Cryo-EM to Probe Structure of Designer α-Helical Filament. D. Dinakarapandian, A. Das, A. Robang, V.P. Conticello, A.K. Paravastu, Georgia Institute of Technology

Experimental and computational advances in solid-state NMR spectroscopy of the platinum group elements. S. Holmes, Y. Xu, S. Termos, A. Philips, A. Fernández Alarcón, J.J. Kimball, A. Altenhof, J. Autschbach, R.W. Schurko, Florida State University & National High Magnetic Field Laboratory

Quantification of NMR Relaxometry Data with Machine Learning. S. Li, D. Vasiliu, T.K. Meldrum, The College of William & Mary

19F NMR study of binding between functionalized polystyrene nanoparticles and perfluorooctanoic acid (PFOA). S.O. Dauda, R. Rai, E. Cushman, L. Casabianca, Clemson University

Prizes for the best posters in the category EPR:

Observing multi-photon charge carrier spin transitions between Floquet states in organic light-emitting diodes. S. Atwood, V.V. Mkhitaryan, S. Hosseinzadeh, C. Nuibe, S. Dhileepkumar, T.H. Tennahewa, W. Jiang, T.A. Darwish, P. Burn, H. Malissa, J. Lupton, C. Boehme, National High Magnetic Field Laboratory & University of Utah

Exploring the effect of Mn2+ on cyclic GMP-AMP synthase activity. E. Dey, E. Flood, M. Gaddy, L. Jolley, J. lobb, E. Parks, K. Williamson, M.M. Lockart, Samford University

Prizes for the best posters in the category MRI:

Quantitative blood oxygen level dependent (qBOLD) MRI of the pancreas during glucose stimulation in type 2 diabetes: Initial comparisons with beta cell function. E. Ray, S. Edwards, O. Oladejo, P. Vellanki, D. Reiter, Emory University & Georgia Institute of Technology

Development and characterization of hProCA32.Collagen1: A novel protein-based MRI contrast agent for enhanced liver disease diagnosis. F. Dorabadizare, F.S. Akinlotan, O.S. Bamishaye, Z. Gui, J. Yang, Georgia State University

Sekinah Dauda is the proud winner of a prize for one of the best posters.

Thank you also one more time to our sponsors:

• The National High Magnetic Filed Laboratory
• The Schools of Chemistry and Biochemistry as well as the School of Chemical and Biomolecular Engineering

as well as the following companies:

• Bruker
• Mediso
• Alegre Science
• Tecmag
• Doty Scientific
• Phoenix NMR
• Cambridge Isotope Laoratories, Inc.
• New Era

Until 2022 it used to be the “workshop: Magnetic Resonance at Georgia Tech”

In 2023 it was organized by Prof Jenny Yang at Georgia State and it became the “Atlanta Magnetic Resonance Symposium”.

This year it will be organized by Prof. David Reiter at at Emory and it will the the “Georgia Magnetic Resonance Symposium” .

Pls mark your calendar – and register. It is worth attending this symposium.

Coming in 2025: “World Magnetic Resonance Symposium organized by Georgia Tech!

This year’s Nobel Price in Chemistry was awarded to David Baker, Demis Hassabis and John Jumper. We can be proud that our own Prof. Andrew McShan and team are co-authors in a publication with David Baker.

Pls congratulate Hongwei Wu, Miriam Simma, Claire Tharp and Andrew McShan for their publication in  Nature Biotechnology:

https://www.nature.com/articles/s41587-024-02395-w

Our trusted instruments Luke and Rey can also be proud to have served in this important work.

What to do if your sample does not dissolve? Can you still record a 1H or 13C spectrum with a high resolution?

Here are your options:

(i)

Have you checked all solvents? Sometimes it pays to try solvents beyond CDCl3, DMSO-d6 and D2O. For instance polypropylene will dissolve at high temperatures in o-dichlorobenzene.

(ii)

You can do solid-state NMR of your dry sample. This is certainly an option, however you should keep in mind that the property of a molecule in a solid is often inherently more complicated than that of a molecule in solution. Effects such as the crystallinity of the sample will have an influence on the NMR spectrum. For instance: the 13C solid-state MAS NMR spectrum of Polyethylene (CH2-CH2)n shows two peaks: one corresponding the amorphous and one for the crystalline components. Furthermore, the quantum-chemical interactions between nuclei are more complicated in the solid than they are in the solution where many of the orientational dependent interactions are described by average values. Spinning the sample at the magic angle of 54.74 degree with respect to the magnetic field will remove many of the angular dependences leading to high resolution-type spectra in the so call MAS technique. This works well for 13C NMR spectra, high resolution 1H spectra of solids can often only be measured with an extreme experimental effort (ultra-high magnetic fields and MAS spinning frequencies in combination with special pulse sequences).

(iii)

Cases, of semi-solid samples are quite common. This would be for instance samples, which can be swelled but not dissolved. Other examples include intact biological tissue. For these samples it is possible to measure high resolution 1H spectra under conditions of slow-medium Magic Angle Spinning. This is done in a special High Resolution MAS probe, which has the option of a lock and a gradient. This probe allows the convenience of automatic gradient shimming (Bruker calls it topshim). Most experiments, which are possible for solutions can be conducted with semi-solid samples in a HR MAS probe. I see great promise of this technique for NMR metabolomics studies of tissue samples from biopsies.

HR-MAS experiments require the addition of some deuterated solvent and a special sample cell, which is inserted into a regular MAS rotor.

Thanks to Dr. Paravastu the GT NMR center operates a HR-MAS probe on our 500 MHz AV3-HD instrument (yoda).

It might be time to reiterate our policy for the backup and storage of data.

Generally: every user is responsible for their data. So after every session you should spend a minute or so ensuring that your data are well organized and stored at a safe location. You cannot expect us to search for your data several years after you measured them. This has happened more than once!

Connecting a flash-drive or external hard drive to the NMR computer is not a good option. The NMR computes run under Linux and we have seen cases where external storage devices and/or the NMR operating system were corrupted due to the use of flash-drives.

A favorite option is sending NMR data to your OneDrive account. Instructions can be found on this very website. Advantage is that your data are now 100% under your control. However you should work with your lab and PI to ensure that your NMR data are well documented and saved such that they are accessible and usable even after you might leave Georgia Tech. I have tested both OneDrive and Dropbox and found that OneDrive provides the easier, faster and more reliable options for our specific systems. This might have changed as both cloud-storage systems are continuously evolving.

We also support the option of backing up data to labarchives. This is an electronic web-based laboratory notebook. The backup provides you the option of storing your data together with your research findings. For instance you can post your (zipped) data together with a screenshot displaying your spectrum and a text, where you not your observations and findings. Instructions for labarchives are also on our Website.

We also do bi-weekly backups of each of our NMR systems, where data will be stored on an external server. Those backups however are mostly done in order to secure our systems from hard- and software failures. The retrieval of measured data is possible but extremely tedious such that we would do this only in exceptional cases.

NMRium is an entirely Web-based processing software for 1D and 2D data. It is very suitable for the quick viewing of NMR data. Just open the NMR link https://www.nmrium.org/nmrium from your webbrowser and drag the folder, containing your Bruker-NMR data into the window. You are able to zoom into your spectra to see details, and you can do simple processing steps such as integration, phase correction or baseline-corrections.

More advanced but important steps for the data processing such as apodization functions (line-broadening) can also be performed but the only means to perform a simple exponential line-broadening was to delete the sub-folder “pdata” from the original folder containing Bruker data and then reloading the data with another drag and drop. In this case NMRium will display you the FID and the menu-icons on the left will allow you to interactively set the apodization function, which must be followed by clicking the icon for the Fourier-Transformation.

Many if not most Solid-State NMR experiments require that the sample is rotated with high frequencies at an angle of 54.74 degree relative to the magnetic field. This is the so-called Magic Angle Spinning.

This requires special sample containers, the so called rotors. Most first time users, who see such a rotor, think that such a little container could not cost much more than a few dollars. Live in solid-state NMR would be so much easier if this would be the case. For the most part we use 4mm MAS rotors, which currently list on Bruker’s website for $927.39 (including caps). Smaller rotor sizes are even significantly more expensive.

So what makes the rotor so expensive: it is a ZrO2 high-precision ceramic. Alternative materials include Sapphire and Diamond. These ceramics need to be machined!

An essential part of the rotor is its cap, which is used to seal the rotor; on its outside it has turbine shovels. In most instances the cap is made out of different kind of plastics. Pls check the information from the manufacturer since the cap-material can lead to a background in the detected NMR signal.

4mm MAS rotor

Due to its high cost, the NMR center has a small supply of MAS rotors. We lend those to our users such that nobody has to bear the initial cost of purchasing one or several rotors.

Our friends at Georgia State will organize the “Atlanta Magnetic Resonance Symposium”, which will take place in the Petit Science Center on the GSU campus.

This symposium is dear to us since it is the follow-up of the “workshop: Magnetic Resonance at Georgia Tech”, which took place many times and always featured great talks from students and post-docs along with fun and a year-end celebration of our accomplishments.

Idea of this Symposium is to present a great variety of applications to a broad audience so that the symposium is interesting for experts but also provides an entry into NMR and MRI for novices.

This year’s symposium will also have a poster session and I encourage everyone to register for the attendance and a poster at the link shown below.

Our laboratory has instruments from two Manufacturers: Varian and Bruker.

Our Varian instruments are both a early-mid  1990 vintage. Our Bruker spectrometers are of the AV3 and AV3-HD generation, which were produced from the ~2010 until ~2016. The company Varian was one of the pioneers in commercial NMR spectrometers. Unfortunately it sold off its NMR division to Agilent in 2010, which then decided to exit the NMR business in 2014.  Regrettably this ended a healthy competition with Bruker, a competition, which lead to important innovations in the field of NMR. However, in my opinion my opinion depsite the loss of a real competitor Bruker has continued the development of NMR technology. 

So what is the advantage of a modern Bruker 400 MHz NMR spectrometer over a Varian spectrometer, which is older than almost all of our graduate students? 

• The probe and electronics is more sensitive.  This will become relevant for nuclei other than ¹H.   However, the difference is really not that relevant when it comes to the “quick 1H spectrum”. 16 or 32 scans measures a decent 1H spectrum on both platforms provided that the sample is well prepared.

• The modern instrument comes with a great variety of experiments. Bruker instruments come with an extensive library of pulse sequences and associated parameter sets.  Out of those not all will run on a basic 400 MHz instrument.  But there is a whole set of 2D experiments, which run well on the Bruker experiment; for the Varian instrument it is not even worth trying to get these experiments to run.

•  The Bruker instrument (at least in our  AV3 version) can run nuclei other than 1H and 13C. In fact, we routinely run 19F and 31P experiments on our Bruker spectrometer. We have conducted NMR experiments of many other nuclei (29Si, 27Al, 11B, 109Ag to name just a few).

•  The Bruker instrument has a gradient probe. In addition to sending and receiving radio-frequency pulses the probe has also the option of sending pulsed magnetic field gradients. I.e. the usually very homogeneous magnetic field can be made inhomogeneous in a controlled manner. This opens the door for many new experiments such as the DOSY experiment, which correlates the diffusion coefficient for Brownian motion with the chemical shift of molecules. Gradients also help to eliminate the need for complex phase cycles, i.e. they remove unwanted magnetization components which are generated during 2D experiments, therefore leading to cleaner spectra, which can be recorded in a shorter acquisition time.

• The operation of the Bruker instrument is more automated. The command “atma” automatically tunes the probe, i.e. stepper motors automatically adjust the resonating circuit in the probe to be on-resonance with the desired measuring frequency. Then the command “topshim” starts an automated sequence leading to an automatic adjustment of the shim coils to achieve a homogenous magnetic field.  The automation of adjustments procedures facilitates the operation of the instrument; more important it makes the recording of spectra more reproducible and independent of the operator. The Varian Mercury spectrometer has a pre-tuned probe, where tuning of routine samples is not required. Shimming must be done manually, by adjusting shim currents and watching the intensity of the 2H signal (lock) on a clock-like display.

Does the Varian instrument have one advantage over the Bruker instrument?  Yes it does. A skilled operator can easily achieve a good shim in a shorter amount of time than Bruker’s Topshim software. So the simple 1H spectrum can be recorded quicker on the good old Varian instrument than on a modern Bruker instrument. And sometimes it is just cool to go vintage!