Friday, March 29, 2013

PhD Position in DNP

A three-year PhD studentship is available at Aix-Marseille Université. The PhD is fully funded with a maintenance allowance of 20,300 € per year (gross income). The studentship is open to students who have a degree in chemistry or physics. The studentship starts on September 2013, while the closing date for application is 13 May 2013. 

Project: 
The goal of this project is to investigate molecular crystals that cannot be studied with conventional analytical methods. For that purpose, this project will take advantage of the recent developments of solid-state Nuclear Magnetic Resonance (SSNMR) [1-2] and will involve further methodology developments for the detection of long-range structural information in strongly coupled spin-networks. Moreover, it should be possible to detect these long-range structural information using Dynamic Nuclear Polarization (DNP), which can enhance SSNMR signals by up to 2 orders of magnitude [3]. 

Contact: 

The student will be jointly supervised by Stéphane Viel and Pierre Thureau. For further information, do not hesitate to contact us at: 


References 

1) Thureau, P.; Sauerwein, A. C.; Concistrè, M.; Levitt, M. H. Phys. Chem. Chem. Phys. 2011, 13, 93. 
2) Mollica, G.; Madhu, P. K.; Ziarelli, F.; Thévand, A.; Thureau, P.; Viel, S. Phys. Chem. Chem. Phys. 2012, 14, 4359. 
3) Ouari, O.; Phan, T.; Ziarelli, F.; Aussenac, F.; Casano, G.; Thureau, P.; Gigmes, D.; Tordo, P.; Viel, S. 2013, Submitted 

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Analysis of sensitivity enhancement by dynamic nuclear polarization in solid-state NMR: a case study of functionalized mesoporous materials

Kobayashi, T., et al., Analysis of sensitivity enhancement by dynamic nuclear polarization in solid-state NMR: a case study of functionalized mesoporous materials. Phys Chem Chem Phys, 2013. 15(15): p. 5553-62.


We systematically studied the enhancement factor (per scan) and the sensitivity enhancement (per unit time) in (13)C and (29)Si cross-polarization magic angle spinning (CP-MAS) NMR boosted by dynamic nuclear polarization (DNP) of functionalized mesoporous silica nanoparticles (MSNs). Specifically, we separated contributions due to: (i) microwave irradiation, (ii) quenching by paramagnetic effects, (iii) the presence of frozen solvent, (iv) the temperature, as well as changes in (v) relaxation and (vi) cross-polarization behaviour. No line-broadening effects were observed for MSNs when lowering the temperature from 300 to 100 K. Notwithstanding a significant signal reduction due to quenching by TOTAPOL radicals, DNP-CP-MAS at 100 K provided global sensitivity enhancements of 23 and 45 for (13)C and (29)Si, respectively, relative to standard CP-MAS measurements at room temperature. The effects of DNP were also ascertained by comparing with state-of-the-art two-dimensional heteronuclear (1)H{(13)C} and (29)Si{(1)H} correlation spectra, using, respectively, indirect detection or Carr-Purcell-Meiboom-Gill (CPMG) refocusing to boost signal acquisition. This study highlights opportunities for further improvements through the development of high-field DNP, better polarizing agents, and improved capabilities for low-temperature MAS.

Wednesday, March 27, 2013

Dynamic Nuclear Polarization Study of Inhibitor Binding to the M218-60 Proton Transporter from Influenza A

Andreas, L.B., et al., Dynamic Nuclear Polarization Study of Inhibitor Binding to the M218-60 Proton Transporter from Influenza A. Biochemistry, 2013.


We demonstrate the use of dynamic nuclear polarization (DNP) to elucidate ligand binding to a membrane protein using dipolar recoupling magic angle spinning (MAS) NMR. In particular, we detect drug binding in the proton transporter M218-60 from influenza A using recoupling experiments at room temperature and with cryogenic DNP. The results indicate that the pore binding site of rimantadine is correlated with previously reported widespread chemical shift changes, suggesting functional binding in the pore. Furthermore, the 15N labeled ammonium of rimantadine was observed near A30 13Cbeta and G34 13Calpha suggesting a possible hydrogen bond to A30 Carbonyl. Cryogenic DNP was required to observe the weaker external binding site(s) in a ZF-TEDOR spectrum. This approach is generally applicable, particularly for weakly bound ligands, in which case the application of MAS NMR dipolar recoupling requires the low temperatures to quench dynamic exchange processes. For the fully protonated samples investigated, we observed DNP signal enhancements of ~10 at 400 MHz using only 4-6 mM of the polarizing agent TOTAPOL. At 600 MHz/395 GHz and with DNP, we measured a distance between the drug and the protein to a precision of 0.2 A.



Friday, March 22, 2013

High power THz technologies using high frequency gyrotrons

Idehara, T., et al. High power THz technologies using high frequency gyrotrons. in Infrared, Millimeter, and Terahertz Waves (IRMMW-THz), 2012 37th International Conference on. 2012.


Gyrotrons are extremely high power radiation sources even in THz frequency region comparing conventional radiation sources. We have developed gyrotron FU CW series for application to many high power THz technologies. Up to the present, nine CW gyrotrons were developed. Each gyrotron has its own objective and was optimized for respective application subject. Now, the applications are extended to wide fields including DNP-NMR measurement, ESR echo experiment, direct and precise measurement on hyperfine structure of positronium, experiment on effective operation of Bloch oscillator using semiconductor super lattice, etc. In this paper, we will introduce such high power THz technologies opened by high power THz radiation sources. Gyrotrons.

Wednesday, March 20, 2013

Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate

Barb, A.W., et al., Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate. J. Magn. Reson., 2013. 228(0): p. 59-65.


Hyperpolarized metabolites offer a tremendous sensitivity advantage (>104 fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, 13C-enriched analog of pyruvic acid, 13C3D3-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct 13C observation and indirect observation through methyl protons introduced by ALT-catalyzed H–D exchange. Exchange on injecting hyperpolarized 13C3D3-pyruvate into ALT dissolved in buffered 1H2O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5 s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized 13C3-pyruvate and products in imaging applications are discussed.



COST Action TD1103 EuroHyperPol satellite meeting 28&29 June on Crete

The COST Action TD1103 EuroHyperPol (European Network for Hyperpolarisation Physics and Methodology in NMR and MRI) has its second open annual meeting scheduled as a satellite meeting to the EUROMAR 2013 conference in Hernessios, Crete. 

The satellite meeting will start on Friday 28th June and finish on Saturday 29th June with the closed management committee meeting on the morning of Sunday 30th June. 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  http://www.euromar2013.org/cost.html for the preliminary list of speakers and the provisional program. 

The satellite meeting is limited to 175 participants. The registration fee is 85 ? and includes all plenary, poster and workgroup sessions, coffee breaks and the lunch and social evening on Saturday. 

Registration and booking of accommodation can be performed through the EUROMAR website. Please be aware that accommodation bookings can only be guaranteed if received by 1st April 2013. After this date all types of accommodation from the EUROMAR hotel-list will be on request and subject to availability only. 

There will be an opportunity to discuss the activities of this network in smaller working groups during the satellite meeting. You can find more details about the working groups on the network webpage: 


**************************************************** 
Prof. Dr. Joerg Matysik 
skype: joerg.matysik 
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Institut fuer Analytische Chemie 
Universitaet Leipzig 
Linnéstr.3 (visit) 
Johannisallee 29 (mail) 
D-04103 Leipzig 
Tel: +49-341-9736112 (direct) 
Tel: +49-341-9736100 (Secr.) 
Fax: +49-341-9736115 

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Leiden Institute of Chemistry, University of Leiden 
PO Box 9502, 2300 RA Leiden (mail) 
Einsteinweg 55, 2333 AC Leiden (visit/courier) 
The Netherlands 
Tel: +31-71-5274198 
Fax: +31-71-5274603 
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Monday, March 18, 2013

Solvent-Free Dynamic Nuclear Polarization of Amorphous and Crystalline ortho-Terphenyl

Ong, T.-C., et al., Solvent-Free Dynamic Nuclear Polarization of Amorphous and Crystalline ortho-Terphenyl. The Journal of Physical Chemistry B, 2013. 117(10): p. 3040-3046.


Dynamic nuclear polarization (DNP) of amorphous and crystalline ortho-terphenyl (OTP) in the absence of glass forming agents is presented in order to gauge the feasibility of applying DNP to pharmaceutical solid-state nuclear magnetic resonance experiments and to study the effect of intermolecular structure, or lack thereof, on the DNP enhancement. By way of 1H?13C cross-polarization, we obtained a DNP enhancement (ε) of 58 for 95% deuterated OTP in the amorphous state using the biradical bis-TEMPO terephthalate (bTtereph) and ε of 36 in the crystalline state. Measurements of the 1H T1 and electron paramagnetic resonance experiments showed the crystallization process led to phase separation of the polarization agent, creating an inhomogeneous distribution of radicals within the sample. Consequently, the effective radical concentration was decreased in the bulk OTP phase, and long-range 1H?1H spin diffusion was the main polarization propagation mechanism. Preliminary DNP experiments with the glass-forming anti-inflammation drug, indomethacin, showed promising results, and further studies are underway to prepare DNP samples using pharmaceutical techniques.



Monday, March 11, 2013

Phase cycling with a 240 GHz, free electron laser-powered electron paramagnetic resonance spectrometer

This is not an article directly related to DNP spectroscopy. However, it shows the tremendous progress made in the development of high-frequency, high-power sources that can be utilized for high-field EPR and eventually DNP experiments.


Edwards, D.T., et al., Phase cycling with a 240 GHz, free electron laser-powered electron paramagnetic resonance spectrometer. Phys. Chem. Chem. Phys., 2013.


Electron paramagnetic resonance (EPR) powered by a free electron laser (FEL) has been shown to dramatically expand the capabilities of EPR at frequencies above [similar]100 GHz, where other high-power sources are unavailable. High-power pulses are necessary to achieve fast (<10 ns) spin rotations in order to alleviate the limited excitation bandwidth and time resolution that typically hamper pulsed EPR at these high frequencies. While at these frequencies, an FEL is the only source that provides [similar]1 kW of power and can be tuned continuously up to frequencies above 1 THz, it has only recently been implemented for one- and two-pulse EPR, and the capabilities of the FEL as an EPR source are still being expanded. This manuscript presents phase cycling of two pulses in an FEL-EPR spectrometer operating at 240 GHz. Given that the FEL, unlike amplifiers, cannot be easily phase-locked to a reference source, we instead apply retrospective data processing to measure the relative phase of each FEL pulse in order to correct the signal phase accordingly. This allows the measured signal to be averaged coherently, and the randomly changing phase of the FEL pulse results in a stochastic phase cycle, which, in the limit of many pulses, efficiently cancels artifacts and improves sensitivity. Further, the relative phase between the first and second pulse, which originates from the difference in path length traversed by each pulse, can be experimentally measured without phase-sensitive detection. We show that the relative phase of the two pulses can be precisely tuned, as well as distinctly switched by a fixed amount, with the insertion of a dielectric material into the quasi-optical path of one of the pulses. Taken together, these techniques offer many of the advantages of arbitrary phase control, and allow application of phase cycling to dramatically enhance signal quality in pulsed EPR experiments utilizing high-power sources that cannot be phase-locked.





Friday, March 8, 2013

High Resolution Para-Hydrogen Induced Polarization in Inhomogeneous Magnetic Fields

Buljubasich, L., et al., High Resolution Para-Hydrogen Induced Polarization in Inhomogeneous Magnetic Fields. J. Magn. Reson., 2013(0).


The application of parahydrogen for the generation of hyperpolarization has increased continuously during the last years. When the chemical reaction is carried out at the same field as the NMR experiment (PASADENA protocol) an antiphase signal is obtained, with a separation of the resonance lines of a few Hz. This imposes a stringent limit to the homogeneity of the magnetic field in order to avoid signal cancellation. In this work we detect the signal arising from hyperpolarized Hexene by means of a CPMG pulse train. After Fourier transformation the obtained J-Spectra not only presents an enhanced spectral resolution but also avoids partial peak cancellation.

Wednesday, March 6, 2013

Effect of glassy modes on electron spin–lattice relaxation in solid ethanol

Merunka, D., et al., Effect of glassy modes on electron spin–lattice relaxation in solid ethanol. J. Magn. Reson., 2013. 228(0): p. 50-58.


Electron spin-lattice relaxation (SLR) of TEMPO radical was measured in the crystalline and glassy states of deuterated ethanol in the temperature range 5-80K using X-band electron paramagnetic resonance (EPR). The measured SLR rates are higher in the glassy than in crystalline state and the excess SLR rate in glassy state is much lower than in ethanol. This result suggests that extra modes in glassy state, i.e. glassy modes, produce the excess SLR rate via the electron-nuclear dipolar (END) interaction between the electron spin of radical and the matrix protons or deuterons. Using the soft-potential model and assuming the END interaction between the electron spin and the matrix protons, the contributions to SLR rate of various mechanisms of glassy modes were theoretically analyzed. The evaluations of SLR rates in glassy ethanol indicate two main mechanisms of glassy modes: thermally activated relaxation of double-well systems and phonon-induced relaxation of quasi-harmonic local modes. The SLR rates induced by these mechanisms correlate well with the experimental data.



Monday, March 4, 2013

Dynamic Nuclear Polarization Enhanced Natural Abundance 17O Spectroscopy

Blanc, F., et al., Dynamic Nuclear Polarization Enhanced Natural Abundance 17O Spectroscopy. J. Am. Chem. Soc., 2013. 135(8): p. 2975-2978.


We show that natural abundance oxygen-17 NMR of solids could be obtained in minutes at a moderate magnetic field strength by using dynamic nuclear polarization (DNP). Electron spin polarization could be transferred either directly to 17O spins or indirectly via 1H spins in inorganic oxides and hydroxides using an oxygen-free solution containing a biradical polarization agent (bTbK). The results open up a powerful method for rapidly acquiring high signal-to-noise ratio solid-state NMR spectra of 17O nuclear spins and to probe sites on or near the surface, without the need for isotope labeling.



Friday, March 1, 2013

NMR of hyperpolarised probes

Witte, C. and L. Schroder, NMR of hyperpolarised probes. NMR Biomed, 2012: p. n/a-n/a.


Increasing the sensitivity of NMR experiments is an ongoing field of research to help realise the exquisite molecular specificity of this technique. Hyperpolarisation of various nuclei is a powerful approach that enables the use of NMR for molecular and cellular imaging. Substantial progress has been achieved over recent years in terms of both tracer preparation and detection schemes. This review summarises recent developments in probe design and optimised signal encoding, and promising results in sensitive disease detection and efficient therapeutic monitoring. The different methods have great potential to provide molecular specificity not available by other diagnostic modalities. Copyright (c) 2012 John Wiley & Sons, Ltd.