Friday, March 30, 2012

Dynamic nuclear polarization in the solid state: a transition between the cross effect and the solid effect

Shimon, D., et al., Dynamic nuclear polarization in the solid state: a transition between the cross effect and the solid effect. Phys. Chem. Chem. Phys., 2012. 14(16): p. 5729-5743.

Proton Dynamic Nuclear Polarization (DNP) experiments were conducted on a 3.4 T homebuilt hybrid pulsed-EPR-NMR spectrometer, on static samples containing 10 mM or 40 mM TEMPOL in frozen glassy solutions of DMSO/water. During DNP experiments proton-NMR signals are enhanced with the help of microwave (MW) irradiation on or close to the Electron Paramagnetic Resonance (EPR) spectrum of the free radicals in the sample, transferring polarization from the free electrons to the nuclei. In the solid state a distinction is made between three DNP enhancement mechanisms: the Solid Effect (SE), the Cross Effect (CE) and Thermal Mixing (TM). In an effort to determine the dominant DNP mechanisms responsible for the enhancement of the nuclear signals, electron and nuclear spin-lattice relaxation rates, enhancement buildup times and microwave (MW) swept DNP spectra were measured as a function of temperature and MW irradiation strength. We observed lineshape variations of the DNP spectra that indicated changes in the relative contributions of SE-DNP and CE-DNP with temperature and MW power. Using a theoretical model describing the SE-DNP and CE-DNP the DNP spectra could be analyzed without involving the TM-DNP mechanism and the relative SE-DNP and CE-DNP contributions to the nuclear enhancement could be determined. From this analysis it follows that lowering the temperature beyond 20 K increases the SE-DNP and decreases the CE-DNP contributions. Possible explanations for this behavior are suggested.

Monday, March 26, 2012

Postdoctoral position in hyperpolarized singlet NMR

A postdoctoral position is available in the lab of Malcolm Levitt in Southampton, UK. The project is funded by the European Research Council and is for developing and applying hyperpolarized singlet NMR and MRI. The long lifetime of nuclear singlet states create obvious opportunities in combination with nuclear hyperpolarization. The lab is already well-equipped with NMR spectrometers: we are also acquiring a new solution NMR instrument, a DNP polarizer and microimaging hardware, under this project. We are particularly interested in working with a postdoc who is excited about the new experimental possibilities of this frontier technology and who has practical experience of one or more of the following topics: DNP, EPR/ESR, microwave technology, cryogenics, and MRI. The position may involve helping with the design and construction of novel hardware, so some experience of this is essential. 

The position is available for an initial period of 2 years. 

The position is open for applications at<> under the code 107812EB, see 107812EB Postdoctoral Research Fellow in Nuclear Magnetic Resonance - Recruitment at the University of Southampton<

The application deadline is 30 April 2012.

Sunday, March 25, 2012

Solution-State Dynamic Nuclear Polarization (Chapter 3)

Lingwood, M.D. and S. Han, Chapter 3 - Solution-State Dynamic Nuclear Polarization, in Annual Reports on NMR Spectroscopy, A.W. Graham, Editor. 2011, Academic Press. p. 83-126.

Abstract Solution-state dynamic nuclear polarization (DNP) is an increasingly popular method of enhancing nuclear spin polarization that has many applications in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). The theory, methods and applications of DNP in the solution state using the Overhauser effect are distinctly different from those of solid-state DNP or what is known as dissolution DNP. This review discusses the theory and recent experimental advances of Overhauser DNP techniques in the solution state at various field strengths ranging from the earth's magnetic field to 9.2&#xa0;T, covering the literature from 1986 to late 2010. Most of the focus in this review is on spectroscopy applications of DNP, although proton–electron double resonance imaging (PEDRI) and remotely enhanced liquids for imaging contrast (RELIC) applications are briefly covered.

Friday, March 23, 2012

Dynamic Nuclear Polarization with a Water-Soluble Rigid Biradical

Kiesewetter, M.K., et al., Dynamic Nuclear Polarization with a Water-Soluble Rigid Biradical. J. Am. Chem. Soc., 2012. 134(10): p. 4537-4540.

A new biradical polarizing agent, bTbtk-py, for dynamic nuclear polarization (DNP) experiments in aqueous media is reported. The synthesis is discussed in light of the requirements of the optimum, theoretical, biradical system. To date, the DNP NMR signal enhancement resulting from bTbtk-py is the largest of any biradical in the ideal glycerol/water solvent matrix, ε = 230. EPR and X-ray crystallography are used to characterize the molecule and suggest approaches for further optimizing the biradical distance and relative orientation.

Wednesday, March 21, 2012

Effect of freezing conditions on distances and their distributions derived from Double Electron Electron Resonance (DEER): A study of doubly-spin-labeled T4 lysozyme

Another article that does not directly cover DNP spectroscopy. However, sample preparation, especially the right choice of a solvent that makes a good glass at cryogenic temperatures is critical for optimum performance in DNP experiments.

Georgieva, E.R., et al., Effect of freezing conditions on distances and their distributions derived from Double Electron Electron Resonance (DEER): A study of doubly-spin-labeled T4 lysozyme. J. Magn. Reson., 2012. 216(0): p. 69-77.

Pulsed dipolar ESR spectroscopy, DEER and DQC, require frozen samples. An important issue in the biological application of this technique is how the freezing rate and concentration of cryoprotectant could possibly affect the conformation of biomacromolecule and/or spin-label. We studied in detail the effect of these experimental variables on the distance distributions obtained by DEER from a series of doubly spin-labeled T4 lysozyme mutants. We found that the rate of sample freezing affects mainly the ensemble of spin-label rotamers, but the distance maxima remain essentially unchanged. This suggests that proteins frozen in a regular manner in liquid nitrogen faithfully maintain the distance-dependent structural properties in solution. We compared the results from rapidly freeze-quenched (⩽100μs) samples to those from commonly shock-frozen (slow freeze, 1s or longer) samples. For all the mutants studied we obtained inter-spin distance distributions, which were broader for rapidly frozen samples than for slowly frozen ones. We infer that rapid freezing trapped a larger ensemble of spin label rotamers; whereas, on the time-scale of slower freezing the protein and spin-label achieve a population showing fewer low-energy conformers. We used glycerol as a cryoprotectant in concentrations of 10% and 30% by weight. With 10% glycerol and slow freezing, we observed an increased slope of background signals, which in DEER is related to increased local spin concentration, in this case due to insufficient solvent vitrification, and therefore protein aggregation. This effect was considerably suppressed in slowly frozen samples containing 30% glycerol and rapidly frozen samples containing 10% glycerol. The assignment of bimodal distributions to tether rotamers as opposed to protein conformations is aided by comparing results using MTSL and 4-Bromo MTSL spin-labels. The latter usually produce narrower distance distributions.

Tuesday, March 20, 2012

5 Grants available for Chianti/INSTRUCT Workshop on Bio-NMR


APPLY NOW! (deadline for submitting your CV is March 23rd) 

Registration deadline is March 31st, hurry up! 

12th Chianti/INSTRUCT Workshop on Bio-NMR – Electron and Nuclear Relaxation for Structural Biology 

Montecatini Terme (Pistoia), Italy, June 17-22, 2012 

The 12th Chianti/INSTRUCT Workshop on Bio-NMR – Electron and Nuclear Relaxation for Structural Biology will be held in Montecatini Terme, the ‘spa capital’ of Tuscany, from June 17th to 22nd 2012. In the tradition of the Chianti Workshops, electron and nuclear relaxation will be the central theme of the scientific program. A blend of novelty will come from an increased focus on biological systems, that fits in the frame of INSTRUCT. The Organizers trust that this will be a major event within the scientific community of magnetic resonance. The conference program will include invited talks and poster presentations and – as always at the Chianti Workshops – ample time will be allocated for interactions among the participants. 

Registration is open! Please visit the 'Registration' page on the website: 

Monday, March 19, 2012

Overhauser dynamic nuclear polarization amplification of NMR flow imaging

Lingwood, M.D., et al., Overhauser dynamic nuclear polarization amplification of NMR flow imaging. J. Magn. Reson., 2012. 216(0): p. 94-100.

We describe the first study comparing the ability of phase shift velocity imaging and Overhauser dynamic nuclear polarization (DNP)-enhanced imaging to generate contrast for visualizing the flow of water. Prepolarization of water by the Overhauser DNP mechanism is performed in the 0.35 T fringe field of an unshielded 2.0 T non-clinical MRI magnet, followed by the rapid transfer of polarization-enhanced water to the 2.0 T imaging location. This technique, previously named remotely enhanced liquids for image contrast (RELIC), produces a continuous flow of hyperpolarized water and gives up to an −8.2-fold enhanced signal within the image with respect to thermally polarized signal at 2.0 T. Using flow through a cylindrical expansion phantom as a model system, spin-echo intensity images with DNP are compared to 3D phase shift velocity images to illustrate the complementary information available from the two techniques. The spin-echo intensity images enhanced with DNP show that the levels of enhancement provide an estimate of the transient propagation of flow, while the phase shift velocity images quantitatively measure the velocity of each imaging voxel. Phase shift velocity images acquired with and without DNP show that DNP weights velocity values towards those of the inflowing (DNP-enhanced) water, while velocity images without DNP more accurately reflect the average steady-state velocity of each voxel. We conclude that imaging with DNP prepolarized water better captures the transient path of water shortly after injection, while phase shift velocity imaging is best for quantifying the steady-state flow of water throughout the entire phantom.

Saturday, March 17, 2012

Ultra-high resolution in MAS solid-state NMR of perdeuterated proteins: Implications for structure and dynamics

This article is not directly related to DNP-enhanced NMR spectroscopy. However, since deuteration of the sample material plays an important role in DNP spectroscopy, this article could be of great interest to researchers in the field.

Bernd, R., Ultra-high resolution in MAS solid-state NMR of perdeuterated proteins: Implications for structure and dynamics. J. Magn. Reson., 2012. 216(0): p. 1-12.

High resolution proton spectra are obtained in MAS solid-state NMR in case samples are prepared using perdeuterated protein and D2O in the recrystallization buffer. Deuteration reduces drastically 1H, 1H dipolar interactions and allows to obtain amide proton line widths on the order of 20 Hz. Similarly, high-resolution proton spectra of aliphatic groups can be obtained if specifically labeled precursors for biosynthesis of methyl containing side chains are used, or if limited amounts of H2O in the bacterial growth medium is employed. This review summarizes recent spectroscopic developments to access structure and dynamics of biomacromolecules in the solid-state, and shows a number of applications to amyloid fibrils and membrane proteins.

Thursday, March 15, 2012

The effect of biradical concentration on the performance of DNP-MAS-NMR

Lange, S., et al., The effect of biradical concentration on the performance of DNP-MAS-NMR. J. Magn. Reson., 2012. 216(0): p. 209-212.

With the technique of dynamic nuclear polarization (DNP) signal intensity in solid-state MAS-NMR experiments can be enhanced by 2–3 orders of magnitude. DNP relies on the transfer of electron spin polarization from unpaired electrons to nuclear spins. For this reason, stable organic biradicals such as TOTAPOL are commonly added to samples used in DNP experiments. We investigated the effects of biradical concentration on the relaxation, enhancement, and intensity of NMR signals, employing a series of samples with various TOTAPOL concentrations and uniformly 13C, 15N labeled proline. A considerable decrease of the NMR relaxation times (T1, T2∗, and T1rho) is observed with increasing amounts of biradical due to paramagnetic relaxation enhancement (PRE). For nuclei in close proximity to the radical, decreasing T1rho reduces cross-polarization efficiency and decreases in T2∗ broaden the signal. Additionally, paramagnetic shifts of 1H signals can cause further line broadening by impairing decoupling. On average, the combination of these paramagnetic effects (PE; relaxation enhancement, paramagnetic shifts) quenches NMR-signals from nuclei closer than 10Å to the biradical centers. On the other hand, shorter T1 times allow the repetition rate of the experiment to be increased, which can partially compensate for intensity loss. Therefore, it is desirable to optimize the radical concentration to prevent additional line broadening and to maximize the signal-to-noise observed per unit time for the signals of interest.

Wednesday, March 14, 2012

COST Action EuroHyperpol annual meeting Dublin 29th June -1st July

The COST Action TD1103 EuroHyperPol (European Network for Hyperpolarisation Physics and Methodology in NMR and MRI) has its first open annual meeting scheduled as a satellite meeting to the EUROMAR 2012 conference in Dublin. 
The satellite meeting will start on Friday 29th June and finish on Sunday 1st July at noon. The meeting will offer a broad overview of research activities related to spin hyperpolarisation physics and methodology and will provide plenty of opportunities for information exchange and discussions. 

Please visit 

for the preliminary list of speakers and the provisional program. 

Sunday, March 11, 2012

PASADENA Hyperpolarized 13C Phospholactate

Shchepin, R.V., et al., PASADENA Hyperpolarized 13C Phospholactate. J. Am. Chem. Soc., 2012. 134(9): p. 3957-3960.

We demonstrate that potassium 1-13C-phosphoenolpyruvate becomes hyperpolarized potassium 1-13C-phospholactate with 13C T1 = 36 s after molecular hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment). This proof-of-principle study was conducted with a fully protonated molecular precursor. 13C was polarized to a level of 1%, corresponding to nearly 4000-fold sensitivity enhancement at 3 T. The relevant homo- and heteronuclear spin?spin couplings are reported.

Friday, March 9, 2012

Zero-Field NMR Enhanced by Parahydrogen in Reversible Exchange

Theis, T., et al., Zero-Field NMR Enhanced by Parahydrogen in Reversible Exchange. J. Am. Chem. Soc., 2012. 134(9): p. 3987-3990.

We have recently demonstrated that sensitive and chemically specific NMR spectra can be recorded in the absence of a magnetic field using hydrogenative parahydrogen induced polarization (PHIP)(1-3) and detection with an optical atomic magnetometer. Here, we show that non-hydrogenative parahydrogen-induced polarization(4-6) (NH-PHIP) can also dramatically enhance the sensitivity of zero-field NMR. We demonstrate the detection of pyridine, at concentrations as low as 6 mM in a sample volume of 250 ?L, with sufficient sensitivity to resolve all identifying spectral features, as supported by numerical simulations. Because the NH-PHIP mechanism is nonreactive, operates in situ, and eliminates the need for a prepolarizing magnet, its combination with optical atomic magnetometry will greatly broaden the analytical capabilities of zero-field and low-field NMR.

Wednesday, March 7, 2012

Review Article in 2011 about DNP-NMR Spectroscopy

2011 was a good year for DNP-NMR review article. Here is a list of five review articles that give a broad overview of the research field for experts in the field and newcomers.

Sze, K., et al., Dynamic Nuclear Polarization: New Methodology and Applications. 2011: p. 1-28.

Prisner, T. and M.J. Prandolini, Dynamic Nuclear Polarization (DNP) at High Magnetic Fields, in Multifrequency Electron Paramagnetic Resonance. 2011, Wiley-VCH Verlag GmbH & Co. KGaA. p. 921-946.

Mieville, P., et al., NMR of Insensitive Nuclei Enhanced by Dynamic Nuclear Polarization. Chimia, 2011. 65(4): p. 260-263.

Günther, U., Dynamic Nuclear Hyperpolarization in Liquids. 2011: p. 1-47.

Atsarkin, V.A., Dynamic nuclear polarization: Yesterday, today, and tomorrow. Journal of Physics: Conference Series, 2011. 324(1): p. 012003.

Monday, March 5, 2012

Dynamic Nuclear Polarization (DNP) at High Magnetic Fields

Prisner, T. and M.J. Prandolini, Dynamic Nuclear Polarization (DNP) at High Magnetic Fields, in Multifrequency Electron Paramagnetic Resonance. 2011, Wiley-VCH Verlag GmbH & Co. KGaA. p. 921-946.

This chapter contains sections titled: * Introduction * Historical Aspects (Metals, Solids and Liquids) at Lower Magnetic Fields * Theory * Hardware (High-Frequency Microwave Equipment, SS-MAS DNP, HF-Liquid DNP, Dissolution DNP, Shuttle-DNP) * First Applications and Outlook * Acknowledgments * Pertinent Literature * References

Friday, March 2, 2012

NMR of Insensitive Nuclei Enhanced by Dynamic Nuclear Polarization

Mieville, P., et al., NMR of Insensitive Nuclei Enhanced by Dynamic Nuclear Polarization. Chimia, 2011. 65(4): p. 260-263.

Despite the powerful spectroscopic information it provides, Nuclear Magnetic Resonance (NMR) spectroscopy suffers from a lack of sensitivity, especially when dealing with nuclei other than protons. Even though NMR can be applied in a straightforward manner when dealing with abundant protons of organic molecules, it is very challenging to address biomolecules in low concentration and/or many other nuclei of the periodic table that do not provide as intense signals as protons. Dynamic Nuclear Polarization (DNP) is an important technique that provides a way to dramatically increase signal intensities in NMR. It consists in transferring the very high electron spin polarization of paramagnetic centers (usually at low temperature) to the surrounding nuclear spins with appropriate microwave irradiation. DNP can lead to an enhancement of the nuclear spin polarization by up to four orders of magnitude. We present in this article some basic concepts of DNP, describe the DNP apparatus at EPFL, and illustrate the interest of the technique for chemical applications by reporting recent measurements of the kinetics of complexation of 89Y by the DOTAM ligand.

Thursday, March 1, 2012

Inhomogeneous dynamic nuclear polarization of protons in a lamella-forming diblock copolymer investigated by a small-angle neutron scattering method

Noda, Y., et al., Inhomogeneous dynamic nuclear polarization of protons in a lamella-forming diblock copolymer investigated by a small-angle neutron scattering method. Journal of Applied Crystallography, 2011. 44(3): p. 503-513.

By combining two methods of selective doping of paramagnetic species into a microdomain and small-angle neutron scattering (SANS), the spatially inhomogeneous proton polarization created by dynamic nuclear polarization (DNP) has been precisely evaluated. A lamella-forming diblock copolymer composed of polystyrene (PS) and polyisoprene (PI) block chains (PS-b-PI) was employed, the SANS profile of which clearly shows scattering peaks up to the third order due to interlamellar interference. As a source of electron spin for DNP, 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) was doped into one or other of the microdomains; samples with PS or PI microdomains selectively doped with TEMPO are designated PS.-b-PI and PS-b-PI., respectively.