Category Archives: high-field DNP

Dynamic Nuclear Polarization of 13C Nuclei in the Liquid State over a 10 Tesla Field Range #DNPNMR

Orlando, Tomas, Rıza Dervişoğlu, Marcel Levien, Igor Tkach, Thomas F. Prisner, Loren B. Andreas, Vasyl P. Denysenkov, and Marina Bennati. “Dynamic Nuclear Polarization of 13C Nuclei in the Liquid State over a 10 Tesla Field Range.” Angewandte Chemie International Edition 58, no. 5 (January 28, 2019): 1402–6.

https://doi.org/10.1002/anie.201811892.

Nuclear magnetic resonance (NMR) techniques play an essential role in natural science and medicine. In spite of the tremendous utility associated with the small energies detected, the most severe limitation is the low signal-to-noise ratio. Dynamic nuclear polarization (DNP), a technique based on transfer of polarization from electron to nuclear spins, has emerged as a tool to enhance sensitivity of NMR. However, the approach in liquids is still facing several challenges. Here we report the observation of room temperature, liquid DNP 13C signal enhancements in organic small molecules as high as 600 at 9.4 Tesla and 800 at 1.2 Tesla. A mechanistic investigation of the 13CDNP field dependence shines light on parameters governing the underlying scalar DNP, indicating that DNP efficiency is raised by proper choice of the polarizing agent (paramagnetic center) and by halogen atoms as mediators of scalar hyperfine interaction. Observation of sizable DNP of 13CH2 and 13CH3 groups in organic molecules at 9.4 T opens perspective for a broader application of this method.

Large volume liquid state scalar Overhauser dynamic nuclear polarization at high magnetic field #DNPNMR

Dubroca, Thierry, Sungsool Wi, Johan van Tol, Lucio Frydman, and Stephen Hill. “Large Volume Liquid State Scalar Overhauser Dynamic Nuclear Polarization at High Magnetic Field.” Physical Chemistry Chemical Physics 21, no. 38 (2019): 21200–204.

https://doi.org/10.1039/C9CP02997D

Dynamic Nuclear Polarization (DNP) can increase the sensitivity of Nuclear Magnetic Resonance (NMR), but it is challenging in the liquid state at high magnetic fields. In this study we demonstrate significant enhancements of NMR signals (up to 70 on 13C) in the liquid state by scalar Overhauser DNP at 14.1 T, with high resolution (∼0.1 ppm) and relatively large sample volume (∼100 μL).

Overhauser DNP in Liquids on 13C Nuclei #DNPNMR

Bennati, Marina, and Tomas Orlando. “Overhauser DNP in Liquids on 13C Nuclei” 8 (2019): 8.

https://doi.org/10.1002/9780470034590.emrstm1581

Dynamic nuclear polarization (DNP) in solution is known since the early days of magnetic resonance to deliver information about molecular motion and electron–nuclear spin relaxation. The method has emerged as a potentially powerful tool to increase sensitivity of high-field solution NMR. In this article, we summarize our recent insights into the mechanism of Overhauser DNP for 13C nuclei, which led to the observation of NMR signal enhancements in liquids up to three orders of magnitude and at magnetic fields of 3.4 T. In contrast to the well-studied case of Overhauser DNP with 1H nuclei, the 13C DNP mechanism can lead to signal enhancements increasing toward high magnetic fields. A key feature of these large high-field enhancements is the underlying scalar relaxation mechanism, which is responsive to correlation times on the subpicosecond time scale. Experiments using microwave (mw) cavities with exquisite control of mw irradiation fields have allowed for disentangling the counteracting effect of dipolar and scalar mechanisms as well as the impact of the 13C chemical environment. These mechanistic insights open up new perspectives for Overhauser liquid DNP as a general tool to increase sensitivity in high-field liquid NMR.

High-Field Liquid-State Dynamic Nuclear Polarization in Microliter Samples #DNPNMR

Yoon, Dongyoung, Alexandros I. Dimitriadis, Murari Soundararajan, Christian Caspers, Jeremy Genoud, Stefano Alberti, Emile de Rijk, and Jean-Philippe Ansermet. “High-Field Liquid-State Dynamic Nuclear Polarization in Microliter Samples.” Analytical Chemistry 90, no. 9 (May 2018): 5620–26.

https://doi.org/10.1021/acs.analchem.7b04700

Nuclear hyperpolarization in liquid state by dynamic nuclear polarization (DNP) has been of great interest because of its potential use in NMR spectroscopy of small samples of biological and chemical compounds in aqueous media. Liquid state DNP generally requires microwave resonators in order to generate an alternating magnetic field strong enough to saturate electron spins in the solution. As a consequence, the sample size is limited to dimensions of the order of the wavelength, and this restricts the sample volume to less than 100 nL for DNP at 9 T (~ 260 GHz). We show here a new approach that overcomes this sample size limitation. Large saturation of electron spins was obtained with a high-power (~ 150 W) gyrotron without microwave resonators. Since high power microwaves can cause serious dielectric heating in polar solutions, we designed a planar probe which effectively alleviates dielectric heating. A thin liquid sample of 100 μm of thickness is placed on a block of high thermal conductivity aluminum nitride with a gold coating, that serves both as a ground plane and as a heat sink. A meander or a coil were used for NMR. We performed 1H DNP at 9.2 T (~ 260 GHz) and at room temperature with 10 μL of water, a volume that is more than 100 times larger than reported so far. The 1H NMR signal is enhanced by a factor of about -10 with 70 W of microwave power. We also demonstrated liquid state 31P DNP in fluorobenzene containing triphenylphosphine, and obtained an enhancement of ~200.

High frequency dynamic nuclear polarization: New directions for the 21st century #DNPNMR

Griffin, Robert G., Timothy M. Swager, and Richard J. Temkin. “High Frequency Dynamic Nuclear Polarization: New Directions for the 21st Century.” Journal of Magnetic Resonance 306 (September 2019): 128–33.

https://doi.org/10.1016/j.jmr.2019.07.019

Dynamic nuclear polarization (DNP) is a technique that permits the sensitivity of nuclear magnetic resonance (NMR) experiments to be enhanced by a factor of (γe/γn) where the γ’s are the gyromagnetic ratios of the electron and a nuclear spin, respectively. When the nuclear spin is 1H, then optimally (γe/γH) ∼ 660. At present, ε ∼ 100 is readily achieved but even this “modest” enhancement means that the experimental acquisition time is reduced by a factor of 104. Thus, an experiment can be done in a single day that would otherwise require ∼ 30 years of signal averaging. Accordingly, the incorporation of DNP into MAS and solution experimental protocols has enabled many experiments that are otherwise simply not possible. Furthermore, DNP experiments are in principle quite straightforward to perform and involve introducing a paramagnetic polarizing agent such as a bisnitroxide biradical into a glassy matrix containing the solute molecule of interest. Subsequently, the sample is irradiated with high frequency microwaves that excite electron-nuclear spin transitions, and, via a number of mechanisms discussed below, the large polarization in the electron spin reservoir is transferred to the nuclei.

Diastereoisomers of L-proline-linked trityl-nitroxide biradicals: synthesis and effect of chiral configurations on exchange interactions #DNPNMR

Zhai, Weixiang, Yalan Feng, Huiqiang Liu, Antal Rockenbauer, Deni Mance, Shaoyong Li, Yuguang Song, Marc Baldus, and Yangping Liu. “Diastereoisomers of L-Proline-Linked Trityl-Nitroxide Biradicals: Synthesis and Effect of Chiral Configurations on Exchange Interactions.” Chemical Science 9, no. 19 (May 16, 2018): 4381–91.

https://doi.org/10.1039/C8SC00969D

The exchange (J) interaction of organic biradicals is a crucial factor controlling their physiochemical properties and potential applications and can be modulated by changing the nature of the linker. In the present work, we for the first time demonstrate the effect of chiral configurations of radical parts on the J values of trityl-nitroxide (TN) biradicals. Four diastereoisomers (TNT1, TNT2, TNL1 and TNL2) of TN biradicals were synthesized and purified by the conjugation of a racemic (R/S) nitroxide with the racemic (M/P) trityl radical viaL-proline. The absolute configurations of these diastereoisomers were assigned by comparing experimental and calculated electronic circular dichroism (ECD) spectra as (M, S, S) for TNT1, (P, S, S) for TNT2, (M, S, R) for TNL1 and (P, S, R) for TNL2. Electron paramagnetic resonance (EPR) results showed that the configuration of the nitroxide part instead of the trityl part is dominant in controlling the exchange interactions and the order of the J values at room temperature is TNT1 (252 G) > TNT2 (127 G) ≫ TNL2 (33 G) > TNL1 (14 G). Moreover, the J values of TNL1/TNL2 with the S configuration in the nitroxide part vary with temperature and the polarity of solvents due to their flexible linker, whereas the J values of TNT1/TNT2 are almost insensitive to these two factors due to the rigidity of their linkers. The distinct exchange interactions between TNT1,2 and TNL1,2 in the frozen state led to strongly different high-field dynamic nuclear polarization (DNP) enhancements with ε = 7 for TNT1,2 and 40 for TNL1,2 under 800 MHz DNP conditions.

Unprecedented Carbon Signal Enhancement in Liquid-State NMR Spectroscopy #DNPNMR

Pinter, G. and H. Schwalbe, Unprecedented Carbon Signal Enhancement in Liquid-State NMR Spectroscopy. Angew Chem Int Ed Engl, 2017. 56(29): p. 8332-8334.

https://www.ncbi.nlm.nih.gov/pubmed/28544115

We shall overcome: As a result of efforts to overcome the sensitivity challenge of liquid-state NMR spectroscopy, a thousand-fold signal enhancement was achieved by dynamic nuclear polarization (DNP) for 13 C signals at high magnetic field (3.4 T) and room temperature, thereby exceeding the predicted limitations of high-field liquid-state in situ DNP.

A tailored multi-frequency EPR approach to accurately determine the magnetic resonance parameters of dynamic nuclear polarization agents: application to AMUPol #DNPNMR

This is a very nice article illustrating the importance of understanding the EPR parameters of a polarizing agent used in DNP-NMR spectroscopy. Here the 9, 95 and 275 GHz EPR spectroscopy is used to characterize AMUPol and predict its performance in high-field DNP.

Gast, P., et al., A tailored multi-frequency EPR approach to accurately determine the magnetic resonance parameters of dynamic nuclear polarization agents: application to AMUPol. Phys. Chem. Chem. Phys., 2017. 19(5): p. 3777-3781.

https://www.ncbi.nlm.nih.gov/pubmed/28098267

To understand the dynamic nuclear polarization (DNP) enhancements of biradical polarizing agents, the magnetic resonance parameters need to be known. We describe a tailored EPR approach to accurately determine electron spin-spin coupling parameters using a combination of standard (9 GHz), high (95 GHz) and ultra-high (275 GHz) frequency EPR. Comparing liquid- and frozen-solution continuous-wave EPR spectra provides accurate anisotropic dipolar interaction D and isotropic exchange interaction J parameters of the DNP biradical AMUPol. We found that D was larger by as much as 30% compared to earlier estimates, and that J is 43 MHz, whereas before it was considered to be negligible. With the refined data, quantum mechanical calculations confirm that an increase in dipolar electron-electron couplings leads to higher cross-effect DNP efficiencies. Moreover, the DNP calculations qualitatively reproduce the difference of TOTAPOL and AMUPol DNP efficiencies found experimentally and suggest that AMUPol is particularly effective in improving the DNP efficiency at magnetic fields higher than 500 MHz. The multi-frequency EPR approach will aid in predicting the optimal structures for future DNP agents.

Efficient Dynamic Nuclear Polarization at 800 MHz/527 GHz with Trityl-Nitroxide Biradicals

Mathies, G., et al., Efficient Dynamic Nuclear Polarization at 800 MHz/527 GHz with Trityl-Nitroxide Biradicals. Angew Chem Int Ed Engl, 2015: p. n/a-n/a.

http://www.ncbi.nlm.nih.gov/pubmed/26268156

Cross-effect (CE) dynamic nuclear polarization (DNP) is a rapidly developing technique that enhances the signal intensities in magic-angle spinning (MAS) NMR spectra. We report CE DNP experiments at 211, 600, and 800 MHz using a new series of biradical polarizing agents referred to as TEMTriPols, in which a nitroxide (TEMPO) and a trityl radical are chemically tethered. The TEMTriPol molecule with the optimal performance yields a record 1 H NMR signal enhancement of 65 at 800 MHz at a concentration of 10 mM in a glycerol/water solvent matrix. The CE DNP enhancement for the TEMTriPol biradicals does not decrease as the magnetic field is increased in the manner usually observed for bis-nitroxides. Instead, the relatively strong exchange interaction between the trityl and nitroxide moieties determines the magnetic field at which the optimum enhancement is observed.

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