Aug 31, 2016

Cubic three-dimensional hybrid silica solids for nuclear hyperpolarization

Baudouin, D., et al., Cubic three-dimensional hybrid silica solids for nuclear hyperpolarization. Chemical Science, 2016.

Hyperpolarization of metabolites by dissolution dynamic nuclear polarization (D-DNP) for MRI applications often requires fast and efficient removal of the radicals (polarizing agents). Ordered mesoporous SBA-15 silica materials containing homogeneously dispersed radicals, referred to as HYperPolarizing SOlids (HYPSOs), enable high polarization - P(1H) = 50% at 1.2 K - and straightforward separation of the polarizing HYPSO material from the hyperpolarized solution by filtration. However, the one-dimensional tubular pores of SBA-15 type materials are not ideal for nuclear spin diffusion, which may limit efficient polarization. Here, we develop a generation of hyperpolarizing solids based on a SBA-16 structure with a network of pores interconnected in three dimensions, which allows a significant increase of polarization, i.e. P(1H) = 63% at 1.2 K. This result illustrates how one can improve materials by combining a control of the incorporation of radicals with a better design of the porous network structures.

Aug 29, 2016

Structural biology applications of solid state MAS DNP NMR #DNPNMR

Akbey, U. and H. Oschkinat, Structural biology applications of solid state MAS DNP NMR. J Magn Reson, 2016. 269: p. 213-24.

Dynamic Nuclear Polarization (DNP) has long been an aim for increasing sensitivity of nuclear magnetic resonance (NMR) spectroscopy, delivering spectra in shorter experiment times or of smaller sample amounts. In recent years, it has been applied in magic angle spinning (MAS) solid-state NMR to a large range of samples, including biological macromolecules and functional materials. New research directions in structural biology can be envisaged by DNP, facilitating investigations on very large complexes or very heterogeneous samples. Here we present a summary of state of the art DNP MAS NMR spectroscopy and its applications to structural biology, discussing the technical challenges and factors affecting DNP performance.

Aug 26, 2016

On The Potential of Dynamic Nuclear Polarization Enhanced Diamonds in Solid-State and Dissolution 13 C NMR Spectroscopy #DNPNMR

Bretschneider, C.O., et al., On The Potential of Dynamic Nuclear Polarization Enhanced Diamonds in Solid-State and Dissolution 13 C NMR Spectroscopy. ChemPhysChem, 2016: p. n/a-n/a.

Dynamic nuclear polarization (DNP) is a versatile option to improve the sensitivity of NMR and MRI. This versatility has elicited interest for overcoming potential limitations of these techniques, including the achievement of solid-state polarization enhancement at ambient conditions, and the maximization of 13 C signal lifetimes for performing in vivo MRI scans. This study explores whether diamond's 13 C behavior in nano- and micro-particles could be used to achieve these ends. The characteristics of diamond's DNP enhancement were analyzed for different magnetic fields, grain sizes, and sample environments ranging from cryogenic to ambient temperatures, in both solution and solid-state experiments. It was found that 13 C NMR signals could be boosted by orders of magnitude in either low- or room-temperature solid-state DNP experiments by utilizing naturally occurring paramagnetic P1 substitutional nitrogen defects. We attribute this behavior to the unusually long electronic/nuclear spin-lattice relaxation times characteristic of diamond, coupled with a time-independent cross-effect-like polarization transfer mechanism facilitated by a matching of the nitrogen-related hyperfine coupling and the 13 C Zeeman splitting. The efficiency of this solid-state polarization process, however, is harder to exploit in dissolution DNP-enhanced MRI contexts. The prospects for utilizing polarized diamond approaching nanoscale dimensions for both solid and solution applications are briefly discussed.

Aug 24, 2016

Dynamics of 4-oxo-TEMPO-d16-(15)N nitroxide-propylene glycol system studied by ESR and ESE in liquid and glassy state in temperature range 10-295K

Goslar, J., S.K. Hoffmann, and S. Lijewski, Dynamics of 4-oxo-TEMPO-d16-(15)N nitroxide-propylene glycol system studied by ESR and ESE in liquid and glassy state in temperature range 10-295K. J Magn Reson, 2016. 269: p. 162-75.

ESR spectra and electron spin relaxation of nitroxide radical in 4-oxo-TEMPO-d16-(15)N in propylene glycol were studied at X-band in the temperature range 10-295K. The spin-lattice relaxation in the liquid viscous state determined from the resonance line shape is governed by three mechanisms occurring during isotropic molecular reorientations. In the glassy state below 200K the spin-lattice relaxation, phase relaxation and electron spin echo envelope modulations (ESEEM) were studied by pulse spin echo technique using 2-pulse and 3-pulse induced signals. Electron spin-lattice relaxation is governed by a single non-phonon relaxation process produced by localized oscillators of energy 76cm(-1). Electron spin dephasing is dominated by a molecular motion producing a resonance-type peak in the temperature dependence of the dephasing rate around 120K. The origin of the peak is discussed and a simple method for the peak shape analysis is proposed, which gives the activation energy of a thermally activated motion Ea=7.8kJ/mol and correlation time tau0=10(-8)s. The spin echo amplitude is strongly modulated and FT spectrum contains a doublet of lines centered around the (2)D nuclei Zeeman frequency. The splitting into the doublet is discussed as due to a weak hyperfine coupling of nitroxide unpaired electron with deuterium of reorienting CD3 groups.

Aug 22, 2016

Dynamic nuclear polarization at 40 kHz magic angle spinning #DNPNMR

Chaudhari, S.R., et al., Dynamic nuclear polarization at 40 kHz magic angle spinning. Phys Chem Chem Phys, 2016. 18(15): p. 10616-22.

DNP-enhanced solid-state NMR spectroscopy under magic angle spinning (MAS) is rapidly developing into a powerful analytical tool to investigate the structure of a wide range of solid materials, because it provides unsurpassed sensitivity gains. Most developments and applications of DNP MAS NMR were so far reported at moderate spinning frequencies (up to 14 kHz using 3.2 mm rotors). Here, using a 1.3 mm MAS DNP probe operating at 18.8 T and approximately 100 K, we show that signal amplification factors can be increased by up to a factor two when using smaller volume rotors as compared to 3.2 mm rotors, and report enhancements of around 60 over a range of sample spinning rates from 10 to 40 kHz. Spinning at 40 kHz is also shown to increase (29)Si coherence lifetimes by a factor three as compared to 10 kHz, substantially increasing sensitivity in CPMG type experiments. The contribution of quenching effects to the overall sensitivity gain at very fast MAS is evaluated, and applications are reported on a functionalised mesostructured organic-inorganic material.

Aug 19, 2016

Solvent responsive catalyst improves NMR sensitivity via efficient magnetisation transfer #DNPNMR

Ruddlesden, A.J. and S.B. Duckett, Solvent responsive catalyst improves NMR sensitivity via efficient magnetisation transfer. Chem Commun (Camb), 2016. 52(54): p. 8467-70.

A bidentate iridium carbene complex, Ir(kappaC,O-L1)(COD), has been synthesised which contains a strongly electron donating carbene ligand that is functionalised by a cis-spanning phenolate group. This complex acts as a precursor to effective magnetisation transfer catalysts which form after reaction with H2 and a suitable two electron donor. In solvents such as benzene, containing pyridine, they are exemplified by neutral, chiral Ir(H)2(kappaC,O-L1)(py)2 with inequivalent hydride ligands and Ir-O bond retention, whilst in methanol, Ir-O bond cleavage leads to zwitterionic [Ir(H)2(kappaC,O(-)-L1)(py)3](+), with chemically equivalent hydride ligands. The active catalyst's form is therefore solvent dependent. Both these complexes break the magnetic symmetry of the hydride ligands and are active in the catalytic transfer of polarisation from parahydrogen to a loosely bound ligand. Test results on pyridine, nicotinaldehyde and nicotine reveal up to approximately 1.2% single spin proton polarisation levels in their (1)H NMR signals which compare to the normal 0.003% level at 9.4 Tesla. These results exemplify how rational catalyst design yields a solvent dependent catalyst with good SABRE activity.

Aug 17, 2016

Silica materials with wall-embedded nitroxides provide efficient polarization matrices for dynamic nuclear polarization NMR #DNPNMR

Besson, E., et al., Silica materials with wall-embedded nitroxides provide efficient polarization matrices for dynamic nuclear polarization NMR. Chem Commun (Camb), 2016. 52(32): p. 5531-3.

Hybrid mesoporous silica materials with wall-embedded nitroxides are shown to efficiently polarize impregnated substrates in high-field dynamic nuclear polarization magic-angle spinning solid-state NMR experiments.

Aug 15, 2016

Single spin magnetic resonance

Wrachtrup, J. and A. Finkler, Single spin magnetic resonance. J Magn Reson, 2016. 269: p. 225-36.

Different approaches have improved the sensitivity of either electron or nuclear magnetic resonance to the single spin level. For optical detection it has essentially become routine to observe a single electron spin or nuclear spin. Typically, the systems in use are carefully designed to allow for single spin detection and manipulation, and of those systems, diamond spin defects rank very high, being so robust that they can be addressed, read out and coherently controlled even under ambient conditions and in a versatile set of nanostructures. This renders them as a new type of sensor, which has been shown to detect single electron and nuclear spins among other quantities like force, pressure and temperature. Adapting pulse sequences from classic NMR and EPR, and combined with high resolution optical microscopy, proximity to the target sample and nanoscale size, the diamond sensors have the potential to constitute a new class of magnetic resonance detectors with single spin sensitivity. As diamond sensors can be operated under ambient conditions, they offer potential application across a multitude of disciplines. Here we review the different existing techniques for magnetic resonance, with a focus on diamond defect spin sensors, showing their potential as versatile sensors for ultra-sensitive magnetic resonance with nanoscale spatial resolution.

Aug 12, 2016

Low-field thermal mixing in [1-(13)C] pyruvic acid for brute-force hyperpolarization

Peat, D.T., et al., Low-field thermal mixing in [1-(13)C] pyruvic acid for brute-force hyperpolarization. Phys Chem Chem Phys, 2016. 18(28): p. 19173-82.

We detail the process of low-field thermal mixing (LFTM) between (1)H and (13)C nuclei in neat [1-(13)C] pyruvic acid at cryogenic temperatures (4-15 K). Using fast-field-cycling NMR, (1)H nuclei in the molecule were polarized at modest high field (2 T) and then equilibrated with (13)C nuclei by fast cycling ( approximately 300-400 ms) to a low field (0-300 G) that activates thermal mixing. The (13)C NMR spectrum was recorded after fast cycling back to 2 T. The (13)C signal derives from (1)H polarization via LFTM, in which the polarized ('cold') proton bath contacts the unpolarised ('hot') (13)C bath at a field so low that Zeeman and dipolar interactions are similar-sized and fluctuations in the latter drive (1)H-(13)C equilibration. By varying mixing time (tmix) and field (Bmix), we determined field-dependent rates of polarization transfer (1/tau) and decay (1/T1m) during mixing. This defines conditions for effective mixing, as utilized in 'brute-force' hyperpolarization of low-gamma nuclei like (13)C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for tmix approximately 100-300 ms and Bmix approximately 30-60 G. Three forms of frozen neat pyruvic acid were tested: two glassy samples, (one well-deoxygenated, the other O2-exposed) and one sample pre-treated by annealing (also well-deoxygenated). Both annealing and the presence of O2 are known to dramatically alter high-field longitudinal relaxation (T1) of (1)H and (13)C (up to 10(2)-10(3)-fold effects). Here, we found smaller, but still critical factors of approximately (2-5)x on both tau and T1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., tau approximately 30-70 ms and T1m approximately 1-20 s, each growing vs. Bmix. Mixing 'turns off' for Bmix > approximately 100 G. That T1m>>tau is consistent with earlier success with polarization transfer from (1)H to (13)C by LFTM.

Aug 10, 2016

A triarylmethyl spin label for long-range distance measurement at physiological temperatures using T1 relaxation enhancement #DNPNMR

Yang, Z., et al., A triarylmethyl spin label for long-range distance measurement at physiological temperatures using T1 relaxation enhancement. J. Magn. Reson., 2016. 269: p. 50-54.

Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy has become an important tool for measuring distances in proteins on the order of a few nm. For this purpose pairs of spin labels, most commonly nitroxides, are site-selectively introduced into the protein. Recent efforts to develop new spin labels are focused on tailoring the intrinsic properties of the label to either extend the upper limit of measurable distances at physiological temperature, or to provide a unique spectral lineshape so that selective pairwise distances can be measured in a protein or complex containing multiple spin label species. Triarylmethyl (TAM) radicals are the foundation for a new class of spin labels that promise to provide both capabilities. Here we report a new methanethiosulfonate derivative of a TAM radical that reacts rapidly and selectively with an engineered cysteine residue to generate a TAM containing side chain (TAM1) in high yield. With a TAM1 residue and Cu2+ bound to an engineered Cu2+ binding site, enhanced T1 relaxation of TAM should enable measurement of interspin distances up to 50 Å at physiological temperature. To achieve favorable TAM1-labeled protein concentrations without aggregation, proteins are tethered to a solid support either site-selectively using an unnatural amino acid or via native lysine residues. The methodology is general and readily extendable to complex systems, including membrane proteins.

Aug 8, 2016

Orphan Spin Polarization: A Catalyst for High-Throughput Solid-State NMR Spectroscopy of Proteins

Not an article that directly relates to DNP-NMR spectroscopy, but another interesting technique to enhance sensitivity that can be combined with DNP.

Gopinath, T. and G. Veglia, Orphan Spin Polarization: A Catalyst for High-Throughput Solid-State NMR Spectroscopy of Proteins, in Annual Reports on NMR Spectroscopy, Academic Press.

Magic-angle spinning solid-state NMR (MAS ssNMR) spectroscopy is a powerful method for structure determination of biomacromolecules that are recalcitrant to crystallization (membrane proteins and fibrils). Relatively low sensitivity and poor resolution of protein samples require long acquisition times for multidimensional ssNMR experiments. Conventional multidimensional ssNMR pulse sequences acquire one experiment at a time, which is time consuming and often discards orphan (unused) spin operators. Here, we describe our recent progress in the development of multiple acquisition ssNMR methods for protein structure determination. A family of experiments called polarization optimized experiments (POE) was designed, in which we utilized the orphan spin operators that are discarded in classical NMR experiments to recover them and acquire simultaneously multiple 2D and 3D experiments using conventional probes and spectrometers with one receiver. Three strategies namely, DUMAS, MEIOSIS, and MAeSTOSO were used for the concatenation of various 2D and 3D pulse sequences. These methods open up new avenues for reducing the acquisition time of multidimensional experiments for biomolecular ssNMR spectroscopy.

Aug 3, 2016

Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI

Félix-González, N., et al., Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI. Concepts in Magnetic Resonance Part A, 2015. 44A(5): p. 279-286.

In magnetic resonance imaging (MRI), the use of magnetic nanoparticles (MNPs) as contrast agent (CA) greatly enhances the possibility to identify several diseases hardly diagnosed by other means. The efficacy of a new CA is described by the longitudinal and transverse relaxivity. Nuclear Magnetic Relaxation Dispersion (NMRD) profiles represent the evolution of relaxivities with magnetic field. Many efforts have been taken to develop theoretical models to depict water proton relaxation in presence of magnetic compounds. The use of theoretical models in junction with NMRD profiles has become a powerful tool to characterize MNPs as CA. In this work, a heuristical theoretical model was implemented, verified and assessed with different magnetic materials. It has been demonstrated that the model works well when using iron cores but fails with other magnetic compounds. A weighting factor associated with Langevin function was introduced to the model. This extra calibration enables the model to be used with other magnetic compounds to characterize new CAs in MRI.

Aug 1, 2016

Nuclear magnetic resonance studies of DNP-ready trehalose obtained by solid state mechanochemical amorphization #DNPNMR

Filibian, M., et al., Nuclear magnetic resonance studies of DNP-ready trehalose obtained by solid state mechanochemical amorphization. Phys Chem Chem Phys, 2016. 18(25): p. 16912-20.

(1)H nuclear spin-lattice relaxation and Dynamic Nuclear Polarization (DNP) have been studied in amorphous samples of trehalose sugar doped with TEMPO radicals by means of mechanical milling, in the 1.6-4.2 K temperature range. The radical concentration was varied between 0.34 and 0.81%. The highest polarization of 15% at 1.6 K, observed in the sample with concentration 0.50%, is of the same order of magnitude of that reported in standard frozen solutions with TEMPO. The temperature and concentration dependence of the spin-lattice relaxation rate 1/T1, dominated by the coupling with the electron spins, were found to follow power laws with an exponent close to 3 in all samples. The observed proportionality between 1/T1 and the polarization rate 1/Tpol, with a coefficient related to the electron polarization, is consistent with the presence of Thermal Mixing (TM) and a good contact between the nuclear and the electron spins. At high electron concentration additional relaxation channels causing a decrease in the nuclear polarization must be considered. These results provide further support for a more extensive use of amorphous DNP-ready samples, obtained by means of comilling, in dissolution DNP experiments and possibly for in vivo metabolic imaging.