Category Archives: Methodology

Solvent suppression in solid-state DNP NMR using Electronic Mixing-Mediated Annihilation (EMMA) #DNPNMR

Ziarelli, Fabio, Pierre Thureau, Stéphane Viel, and Giulia Mollica. “Solvent Suppression in Solid-State DNP NMR Using Electronic Mixing-Mediated Annihilation (EMMA).” Magnetic Resonance in Chemistry, January 23, 2020.

https://doi.org/10.1002/mrc.5001.

We show here that the Electronic Mixing-Mediated Annihilation (EMMA) method, previously reported for the suppression of background signals in solid-state NMR spectra, can be successfully applied to remove the solvent signals observed in the case of NMR spectra obtained with dynamic nuclear polarization (DNP). The methodology presented here is applied to two standard sample-preparation methods for DNP, namely glass forming and incipient wetness impregnation. It is demonstrated that the EMMA method is complementary to the different methods for solvent suppression based on relaxation filters, and that it can be used to preserve the quantitative information that might be present in the pristine spectra.

Ultrafast Single‐Scan 2D NMR Spectroscopic Detection of a PHIP‐Hyperpolarized Protease Inhibitor

Kiryutin, Alexey S., Grit Sauer, Daniel Tietze, Martin Brodrecht, Stephan Knecht, Alexandra V. Yurkovskaya, Konstantin L. Ivanov, Olga Avrutina, Harald Kolmar, and Gerd Buntkowsky. “Ultrafast Single‐Scan 2D NMR Spectroscopic Detection of a PHIP‐Hyperpolarized Protease Inhibitor.” Chemistry – A European Journal 25, no. 16 (March 15, 2019): 4025–30.

https://doi.org/10.1002/chem.201900079

Two-dimensional (2D) NMR is one of the most important spectroscopic tools for the investigation of biological macromolecules. However, owing to the low sensitivity of NMR it takes usually from several minutes to many hours to record such a spectrum. Here we show that a bioactive derivative of the sunflower trypsin inhibitor-1 (SFTI-1), a tetradecapeptide, can be detected by the combination of parahydrogen-induced polarization (PHIP) and ultrafast 2D-NMR spectroscopy (in the following abbreviated as 2D-NMR). The PHIP activity of the inhibitor was achieved by labeling with O-propargyl-Ltyrosine. In 1D-PHIP experiments an enhancement of approximately 1200 compared to normal NMR was found. This enhancement permits measurement of 2D-NMR correlation spectra of low concentrated SFTI-1 in less than 10 seconds, employing ultrafast single-scan 2D-NMR detection. As experimental examples PHIP assisted ultrafast single-scan TOCSY spectra of SFTI-1 are shown.

[NMR] PhD and Postdoctoral positions available to join the Emsley group at EPFL #DNPNMR

PhD and Postdoctoral positions available to join the Emsley group at EPFL, Lausanne


We are looking for highly motivated candidates to take up PhD and Postdoctoral positions developing new methods in NMR spectroscopy to address challenging problems in chemistry and materials science. In particular we will be working on extending dynamic nuclear polarization enhanced NMR crystallography to complex non-crystalline materials. Examples of our recent work and the application areas that we work on can be found on our website: http://lrm.epfl.ch


We are looking for highly motivated candidates with strong scientific background, independence, and who enjoy teamwork. You should hold a relevant qualification in chemistry, physics or related disciplines. Skills in one of the following fields of expertise are a plus:


• Experimental multi-dimensional nuclear magnetic resonance,
• 
Simulation, Theory, or Modelling of nuclear spin dynamics, NMR properties or chemical structures.
 

Our laboratory at EPFL is part of one the world’s leading chemistry departments, and is located Lausanne on the north shore of Lake Geneva. The laboratory is equipped with unique state of the art NMR spectrometers (including gyrotron DNP accessories at 400 and 900 MHz, a dissolution-DNP machine, and 100 kHz magic angle spinning probes).

 
Motivated candidates should contact Lyndon Emsley by email to lyndon.emsley@epfl.ch


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Solvent signal suppression for high-resolution MAS-DNP #DNPNMR

Lee, D., S.R. Chaudhari, and G. De Paepe, Solvent signal suppression for high-resolution MAS-DNP. J Magn Reson, 2017. 278: p. 60-66.

https://www.ncbi.nlm.nih.gov/pubmed/28365491

Dynamic nuclear polarization (DNP) has become a powerful tool to substantially increase the sensitivity of high-field magic angle spinning (MAS) solid-state NMR experiments. The addition of dissolved hyperpolarizing agents usually results in the presence of solvent signals that can overlap and obscure those of interest from the analyte. Here, two methods are proposed to suppress DNP solvent signals: a Forced Echo Dephasing experiment (FEDex) and TRAnsfer of Populations in DOuble Resonance Echo Dephasing (TRAPDORED) NMR. These methods reintroduce a heteronuclear dipolar interaction that is specific to the solvent, thereby forcing a dephasing of recoupled solvent spins and leaving acquired NMR spectra free of associated resonance overlap with the analyte. The potency of these methods is demonstrated on sample types common to MAS-DNP experiments, namely a frozen solution (of l-proline) and a powdered solid (progesterone), both containing deuterated glycerol as a DNP solvent. The proposed methods are efficient, simple to implement, compatible with other NMR experiments, and extendable past spectral editing for just DNP solvents. The sensitivity gains from MAS-DNP in conjunction with FEDex or TRAPDORED then permits rapid and uninterrupted sample analysis.

Solvent suppression in DNP enhanced solid state NMR #DNPNMR

Yarava, J.R., et al., Solvent suppression in DNP enhanced solid state NMR. J Magn Reson, 2017. 277: p. 149-153.

https://www.ncbi.nlm.nih.gov/pubmed/28288417

We show how DNP enhanced solid-state NMR spectra can be dramatically simplified by suppression of solvent signals. This is achieved by (i) exploiting the paramagnetic relaxation enhancement of solvent signals relative to materials substrates, or (ii) by using short cross-polarization contact times to transfer hyperpolarization to only directly bonded carbon-13 nuclei in frozen solutions. The methods are evaluated for organic microcrystals, surfaces and frozen solutions. We show how this allows for the acquisition of high-resolution DNP enhanced proton-proton correlation experiments to measure inter-nuclear proximities in an organic solid.

Rapid-melt Dynamic Nuclear Polarization

Sharma, M., et al., Rapid-melt Dynamic Nuclear Polarization. J Magn Reson, 2015. 258: p. 40-8.

http://www.ncbi.nlm.nih.gov/pubmed/26225439

In recent years, Dynamic Nuclear Polarization (DNP) has re-emerged as a means to ameliorate the inherent problem of low sensitivity in nuclear magnetic resonance (NMR). Here, we present a novel approach to DNP enhanced liquid-state NMR based on rapid melting of a solid hyperpolarized sample followed by ‘in situ’ NMR detection. This method is applicable to small (10nl to 1mul) sized samples in a microfluidic setup. The method combines generic DNP enhancement in the solid state with the high sensitivity of stripline (1)H NMR detection in the liquid state. Fast cycling facilitates options for signal averaging or 2D structural analysis. Preliminary tests show solid-state (1)H enhancement factors of up to 500 for H2O/D2O/d6-glycerol samples doped with TEMPOL radicals. Fast paramagnetic relaxation with nitroxide radicals, In nonpolar solvents such as toluene, we find proton enhancement factors up to 400 with negligible relaxation losses in the liquid state, using commercially available BDPA radicals. A total recycling delay (including sample freezing, DNP polarization and melting) of about 5s can be used. The present setup allows for a fast determination of the hyper-polarization as function of the microwave frequency and power. Even at the relatively low field of 3.4T, the method of rapid melting DNP can facilitate the detection of small quantities of molecules in the picomole regime.

Dynamic nuclear polarization in the hyperfine-field-dominant region

Lee, S.-J., et al., Dynamic nuclear polarization in the hyperfine-field-dominant region. J. Magn. Reson., 2015. 255(0): p. 114-121.

http://www.sciencedirect.com/science/article/pii/S1090780715000889

Dynamic nuclear polarization (DNP) allows measuring enhanced nuclear magnetic resonance (NMR) signals. Though the efficiency of DNP has been known to increase at low fields, the usefulness of DNP has not been throughly investigated yet. Here, using a superconducting quantum interference device-based NMR system, we performed a series of DNP experiments with a nitroxide radical and measured DNP spectra at several magnetic fields down to sub-microtesla. In the DNP spectra, the large overlap of two peaks having opposite signs results in net enhancement factors, which are significantly lower than theoretical expectations [30] and nearly invariant with respect to magnetic fields below the Earth’s field. The numerical analysis based on the radical’s Hamiltonian provides qualitative explanations of such features. The net enhancement factor reached 325 at maximum experimentally, but our analysis reveals that the local enhancement factor at the center of the rf coil is 575, which is unaffected by detection schemes. We conclude that DNP in the hyperfine-field-dominant region yields sufficiently enhanced NMR signals at magnetic fields above 1 μ T.

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