Dynamic nuclear polarization at 40 kHz magic angle spinning

Chaudhari, Sachin Rama; Berruyer, Pierrick; Gajan, David; Reiter, Christian; Engelke, Frank; Silverio, Daniel L.; Copéret, Christophe; Lelli, Moreno; Lesage, Anne; Emsley, Lyndon

doi:10.1039/c6cp00839a

Cited by 79 publications

(82 citation statements)

References 81 publications

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“…However, our data clearly indicate that increasing the MAS rate does not lead to more pronounced depolarization effects over a frequency range of 5-40 kHz, in contrast to what has been observed with AMUPol. 24 At 9.4 T, a contribution factor of about 50 % is observed for HyTEK2, which additionally shows a small decrease with the MAS rate ( Figure S47). At 9.4 T, the intermolecular nitroxide-nitroxide CE contributes to the overall enhancement, as can be seen from the field profiles ( Figure 1).…”

Section: Acs Paragon Plus Environmentmentioning

confidence: 95%

“…26 Second, the overall sensitivity gain provided by dinitroxides decreases significantly with increasing spinning frequencies. [21][22][23][24][25][26][27] As detailed by Thurber and Tycko and by Mentink-Vigier et al, the MAS-induced modulation of the two electron frequencies leads to a sizeable probability of non-adiabatic electron-electron crossings, which attenuate the spin polarization differences among electrons, subsequently reducing the nuclear spin polarization via CE mechanisms. In the absence of microwaves (µw), this can lead to a depolarization of the nuclei.…”

Section: Introductionmentioning

confidence: 99%

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BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T

et al. 2018

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Dynamic Nuclear Polarization (DNP) solid-state NMR has developed into an invaluable tool for the investigation of a wide range of materials. However, the sensitivity gain achieved with many polarizing agents suffers from an unfavorable field and Magic Angle Spinning (MAS) frequency dependence. We present a series of new hybrid biradicals, soluble in organic solvents, that consist of an isotropic narrow EPR line radical, BDPA, tethered to a broad line nitroxide. By tuning the distance between the two electrons and the substituents at the nitroxide moiety, correlations between the electron-electron interactions and the electronic spin relaxation times on one hand, and the DNP enhancement factors on the other hand are established. The best radical in this series has a short methylene linker and bears bulky phenyl spirocyclohexyl ligands. In a 1.3 mm prototype DNP probe, it yields enhancements of up to 185 at 18.8 T (800 MHz 1H resonance frequency) and 40 kHz MAS. We show that this radical gives enhancement factors of over 60 in 3.2 mm sapphire rotors at both 18.8 and 21.1 T (900 MHz 1H resonance frequency), the highest magnetic field available today for DNP. The effect of the rotor size and of the microwave irradiation inside the MAS rotor is discussed. Finally, we demonstrate the potential of this new series of polarizing agents by recording high field 27Al and 29Si DNP Surface Enhanced NMR spectra (DNP SENS) of amorphous aluminosilicates and 17O NMR on silica nanoparticles.

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Section: Acs Paragon Plus Environmentmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T

et al. 2018

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“…DNP polarizing agents, AMUPol 63 and TOTAPOL (1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol) 64 , were kindly provided by Bruker Biospin. DMPC (1,2-dimyristoyl- sn -glycero-3-phosphocholine) was purchased from Avanti Polar Lipids, Inc. (Alabaster, AL).…”

Section: Methodsmentioning

confidence: 99%

Transmembrane Interactions of Full-length Mammalian Bitopic Cytochrome-P450-Cytochrome-b5 Complex in Lipid Bilayers Revealed by Sensitivity-Enhanced Dynamic Nuclear Polarization Solid-state NMR Spectroscopy

Yamamoto

Caporini

et al. 2017

Sci Rep

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The dynamic protein-protein and protein-ligand interactions of integral bitopic membrane proteins with a single membrane-spanning helix play a plethora of vital roles in the cellular processes associated with human health and diseases, including signaling and enzymatic catalysis. While an increasing number of high-resolution structural studies of membrane proteins have successfully manifested an in-depth understanding of their biological functions, intact membrane-bound bitopic protein-protein complexes pose tremendous challenges for structural studies by crystallography or solution NMR spectroscopy. Therefore, there is a growing interest in developing approaches to investigate the functional interactions of bitopic membrane proteins embedded in lipid bilayers at atomic-level. Here we demonstrate the feasibility of dynamic nuclear polarization (DNP) magic-angle-spinning NMR techniques, along with a judiciously designed stable isotope labeling scheme, to measure atomistic-resolution transmembrane-transmembrane interactions of full-length mammalian ~72-kDa cytochrome P450-cytochrome b5 complex in lipid bilayers. Additionally, the DNP sensitivity-enhanced two-dimensional 13C/13C chemical shift correlations via proton driven spin diffusion provided distance constraints to characterize protein-lipid interactions and revealed the transmembrane topology of cytochrome b5. The results reported in this study would pave ways for high-resolution structural and topological investigations of membrane-bound full-length bitopic protein complexes under physiological conditions.

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“…The development of PA designed for OE DNP or biradical PA containing radicals with an isotropic EPR spectrum has allowed DNP enhancements greater than 50 to be obtained at magnetic fields above 16.4 T . Probes capable of MAS at frequencies above 40 kHz have also been demonstrated . Notably, fast MAS has allowed OE DNP enhancements of over 100 to be obtained at a high magnetic field of 18.8 T .…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

DNP‐enhanced solid‐state NMR spectroscopy of active pharmaceutical ingredients

Zhao

Pinon

Emsley

et al. 2018

Magnetic Reson in Chemistry

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Solid-state NMR spectroscopy has become a valuable tool for the characterization of both pure and formulated active pharmaceutical ingredients (APIs). However, NMR generally suffers from poor sensitivity that often restricts NMR experiments to nuclei with favorable properties, concentrated samples, and acquisition of one-dimensional (1D) NMR spectra. Here, we review how dynamic nuclear polarization (DNP) can be applied to routinely enhance the sensitivity of solid-state NMR experiments by one to two orders of magnitude for both pure and formulated APIs. Sample preparation protocols for relayed DNP experiments and experiments on directly doped APIs are detailed. Numerical spin diffusion models illustrate the dependence of relayed DNP enhancements on the relaxation properties and particle size of the solids and can be used for particle size determination when the other factors are known. We then describe the advanced solid-state NMR experiments that have been enabled by DNP and how they provide unique insight into the molecular and macroscopic structure of APIs. For example, with large sensitivity gains provided by DNP, natural isotopic abundance, C- C double-quantum single-quantum homonuclear correlation NMR spectra of pure APIs can be routinely acquired. DNP also enables solid-state NMR experiments with unreceptive quadrupolar nuclei such as H, N, and Cl that are commonly found in APIs. Applications of DNP-enhanced solid-state NMR spectroscopy for the molecular level characterization of low API load formulations such as commercial tablets and amorphous solid dispersions are described. Future perspectives for DNP-enhanced solid-state NMR experiments on APIs are briefly discussed.

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Dynamic nuclear polarization at 40 kHz magic angle spinning

Abstract: DNP-enhanced solid-state NMR spectroscopy is shown to maintain performance over a wide range of sample spinning rates up to 40 kHz.

Cited by 79 publications

References 81 publications

BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T

BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T

Transmembrane Interactions of Full-length Mammalian Bitopic Cytochrome-P450-Cytochrome-b5 Complex in Lipid Bilayers Revealed by Sensitivity-Enhanced Dynamic Nuclear Polarization Solid-state NMR Spectroscopy

DNP‐enhanced solid‐state NMR spectroscopy of active pharmaceutical ingredients

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