Monday, February 27, 2017

Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water


Kurzbach, D., et al., Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water. Angew. Chem. Int. Ed., 2017. 56(1): p. 389-392.


Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent-exposed residues and therefore selectively enhances signals in 1H-15N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.

Friday, February 24, 2017

Large dose hyperpolarized water with dissolution-DNP at high magnetic field


Lipsø, K.W., et al., Large dose hyperpolarized water with dissolution-DNP at high magnetic field. J. Magn. Reson., 2017. 274: p. 65-72.


We demonstrate a method for the preparation of hyperpolarized water by dissolution Dynamic Nuclear Polarization at high magnetic field. Protons were polarized at 6.7 T and 1.1 K to >70% with frequency modulated microwave irradiation at 188G Hz. 97.2 ± 0.7% of the radical was extracted from the sample in the dissolution in a two-phase system. 16 ± 1 mL of 5.0 M 1H in D2O with a polarization of 13.0 ± 0.9% in the liquid state was obtained, corresponding to an enhancement factor of 4000 ± 300 compared to the thermal equilibrium at 9.4 T and 293 K. A longitudinal relaxation time constant of 16 ± 1 s was measured. The sample was polarized and dissolved in a fluid path compatible with clinical polarizers. The volume of hyperpolarized water produced by this method enables angiography and perfusion measurements in large animals, as well as NMR experiments for studies of e.g. proton exchange and polarization transfer to other nuclei.

Wednesday, February 22, 2017

Theoretical treatment of pulsed Overhauser dynamic nuclear polarization: Consideration of a general periodic pulse sequence #DNPNMR


Nasibulov, E.A., et al., Theoretical treatment of pulsed Overhauser dynamic nuclear polarization: Consideration of a general periodic pulse sequence. JETP Letters, 2016. 103(9): p. 582-587.


A general theoretical approach to pulsed Overhauser-type dynamic nuclear polarization (DNP) is presented. Dynamic nuclear polarization is a powerful method to create non-thermal polarization of nuclear spins, thereby enhancing their nuclear magnetic resonance signals. The theory presented can treat pulsed microwave irradiation of electron paramagnetic resonance transitions for periodic pulse sequences of general composition. Dynamic nuclear polarization enhancement is analyzed in detail as a function of the microwave pulse length for rectangular pulses and pulses with finite rise time. Characteristic oscillations of the DNP enhancement are found when the pulse-length is stepwise increased, originating from coherent motion of the electron spins driven by the pulses. Experimental low-field DNP data are in very good agreement with this theoretical approach.

Monday, February 20, 2017

A combined EPR and MD simulation study of a nitroxyl spin label with restricted internal mobility sensitive to protein dynamics


Oganesyan, V.S., et al., A combined EPR and MD simulation study of a nitroxyl spin label with restricted internal mobility sensitive to protein dynamics. J. Magn. Reson., 2017. 274: p. 24-35.


EPR studies combined with fully atomistic Molecular Dynamics (MD) simulations and an MD-EPR simulation method provide evidence for intrinsic low rotameric mobility of a nitroxyl spin label, Rn, compared to the more widely employed label MTSL (R1). Both experimental and modelling results using two structurally different sites of attachment to Myoglobin show that the EPR spectra of Rn are more sensitive to the local protein environment than that of MTSL. This study reveals the potential of using the Rn spin label as a reporter of protein motions.

Friday, February 17, 2017

Using signal amplification by reversible exchange (SABRE) to hyperpolarise 119Sn and 29Si NMR nuclei


Olaru, A.M., et al., Using signal amplification by reversible exchange (SABRE) to hyperpolarise 119Sn and 29Si NMR nuclei. Chem Commun (Camb), 2016. 52(100): p. 14482-14485.


The hyperpolarisation of the 119Sn and 29Si nuclei in 5-(tributylstannyl)pyrimidine (ASn) and 5-(trimethylsilyl)pyrimidine (BSi) is achieved through their reaction with [IrCl(COD)(IMes)] (1a) or [IrCl(COD)(SIMes)] (1b) and parahydrogen via the SABRE process. 1a exhibits superior activity in both cases. The two inequivalent pyrimidine proton environments of ASn readily yielded signal enhancements totalling approximately 2300-fold in its 1H NMR spectrum at a field strength of 9.4 T, with the corresponding 119Sn signal being 700 times stronger than normal. In contrast, BSi produced analogous 1H signal gains of approximately 2400-fold and a 29Si signal that could be detected with a signal to noise ratio of 200 in a single scan. These sensitivity improvements allow NMR detection within seconds using micromole amounts of substrate and illustrate the analytical potential of this approach for high-sensitivity screening. Furthermore, after extended reaction times, a series of novel iridium trimers of general form [Ir(H)2Cl(NHC)(mu-pyrimidine-kappaN:kappaN')]3 precipitate from these solutions whose identity was confirmed crystallographically for BSi.

Wednesday, February 15, 2017

Hyperpolarized Nanodiamond Surfaces #DNPNMR


Rej, E., et al., Hyperpolarized Nanodiamond Surfaces. J Am Chem Soc, 2017. 139(1): p. 193-199.


The widespread use of nanodiamond as a biomedical platform for drug-delivery, imaging, and subcellular tracking applications stems from its nontoxicity and unique quantum mechanical properties. Here, we extend this functionality to the domain of magnetic resonance, by demonstrating that the intrinsic electron spins on the nanodiamond surface can be used to hyperpolarize adsorbed liquid compounds at low fields and room temperature. By combining relaxation measurements with hyperpolarization, spins on the surface of the nanodiamond can be distinguished from those in the bulk liquid. These results are likely of use in signaling the controlled release of pharmaceutical payloads.

Tuesday, February 14, 2017

[NMR] Multiple postdoc positions in Hyperpolarized 13C MR

From the Ampere Magnetic Resonance List


Multiple Postdoctoral Research Fellowship Positions in Hyperpolarized 13C Metabolic Imaging

The University of Maryland School of Medicine has expanded its molecular imaging and interventional research capabilities by establishing the Center for Metabolic Imaging and Therapeutics. The center houses a GE SpinLabTM dynamic nuclear polarizer suitable for preclinical and clinical applications, a GE 3T 750w MR scanner, and an MR Solutions MRS 3017 Preclinical Benchtop MR scanner. The GE MR scanner is also integrated with two Insightec 1024-element high-intensity focused ultrasound (HIFU) systems for image-guided interventions. Our goal is to facilitate both basic science and clinical research by exploring novel molecular imaging agent-based technologies for screening, early disease detection and treatment response, and real-time image-guided interventions.

Multiple postdoctoral research fellowship positions are available in the metabolic imaging group led by Dr. Dirk Mayer. Specific areas of research include optimized acquisition and reconstruction techniques, kinetic modeling for quantitative analysis, and new probe development. These methods will be applied to animal models (e.g., traumatic brain injury, cancer, liver disease) with translation to patients scheduled for summer 2017. This is an exciting opportunity to work at one of the first sites that will do translational/clinical hyperpolarized 13C MRI/MRS.

The candidate should have a Ph.D. (or equivalent degree) in engineering, physics, physical chemistry, or similar fields. The ideal candidate has a strong background in NMR physics with particular emphasis on in vivo imaging and/or spectroscopy, data acquisition and signal/image processing/analysis. Experience in pulse sequence programming (ideally on GE and/or MR Solutions scanners), knowledge of computer languages, such as C++, Matlab and IDL, and experience in performing small animal imaging is also desirable. Qualified applicants should also have a track record of peer-reviewed publications.

Interested individuals should send a letter detailing their research interests, an updated CV and contact information for at least two references to Dirk Mayer, Ph.D. (dmayer@som.umaryland.edu).

--
Dirk Mayer, Dr. rer. nat.
Associate Professor
Diagnostic Radiology & Nuclear Medicine
University of Maryland School of Medicine

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[NMR] Training School on Principles and Applications of Dissolution DNP, Nov 13-17, 2017, Copenhagen

From the Ampere Magnetic Resonance List


Dear all

We would like to announce the training school, Principles and Applications of Dissolution DNP. The training school takes place at the Center for Hyperpolarization in Magnetic Resonance, at the Technical University of Denmark, Kgs Lyngby, Denmark from Nov 13-17, 2017.

We have three fantastic external lecturers signed up for the teaching, Tom Wenckebach, Matthew Merritt and Arnaud Comment, together with the faculty of the group. The school covers DNP theory, relaxation, kinetic modelling, sample preparation, polarizer instrumentation and operation, acquisition strategies as well as in vitro and in vivo applications. There will be plenty of hands-on exercises and in-depth discussion in small groups.

Registration opens May 1. More details of the workshop will appear on our website: http://www.hypermag.dtu.dk/Research/Dissolution-DNP-Course.

Please forward this email on to anyone who may be interested.

Thanks, and best regards, Jan
Jan Henrik Ardenkjaer-Larsen
Professor, Center Leader
Center for Magnetic Resonance
Technical University of Denmark
Department of Electrical Engineering
Ørsted Plads, bldg. 349, room 126
DK-2800 Kgs Lyngby

Phone +45 45253918

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Monday, February 13, 2017

Dynamic Nuclear Polarization and Relaxation of H and D Atoms in Solid Mixtures of Hydrogen Isotopes #DNPNMR


Sheludiakov, S., et al., Dynamic Nuclear Polarization and Relaxation of H and D Atoms in Solid Mixtures of Hydrogen Isotopes. Journal of Low Temperature Physics, 2016: p. 1-11.


We report on a study of dynamic nuclear polarization and electron and nuclear spin relaxation of atomic hydrogen and deuterium in solid molecular matrices of H2, D2, and HD mixtures. The electron and nuclear spin relaxation times (T1e and T1N ) were measured within the temperature range 0.15–2.5 K in a magnetic field of 4.6 T, conditions which ensure a high polarization of electron spins. We found that T1e is nearly temperature independent in this temperature range, while T1N decreased by two orders of magnitude upon raising temperature. Such strong temperature dependence is typical for the nuclear Orbach mechanism of relaxation via the electron spins. We found that the nuclear spins of H atoms in solid D2 and D2:HD can be efficiently polarized by the Overhauser effect. Pumping the forbidden transitions of H atoms also leads to DNP, with the efficiency strongly dependent on the concentration of D atoms. This behavior indicates the cross effect mechanism of the DNP and nuclear relaxation, which turns out to be well resolved in the conditions of our experiments. Efficient DNP of H atoms was also observed when pumping the middle D line located in the center of the ESR spectrum. This phenomenon can be explained in terms of clusters or pairs of H atoms with a strong exchange interaction. These clusters have partially allowed transitions in the center of the ESR spectrum, and DNP may be created via the resolved cross effect.

Sunday, February 12, 2017

[NMR] Postdoc position University of Florida / National High Magnetic Field Laboratory

From the Ampere Magnetic Resonance List



Dear Colleagues,

I have a Postdoctoral Associate position available immediately to study functional amyloid formation by Streptococcus mutans, particularly as it relates to biofilm development. The focus of this project is to characterize the ultrastructure and amyloid properties of the adhesion P1 and other amyloidogenic surface proteins utilizing solution NMR, DNP-enhanced solid state NMR, cryoelectron microscopy, and diffraction techniques to study their structure in fibrillar and nonfibrillar forms. This project is in collaboration with Dr. Jeannine Brady, an expert in bacterial adhesion and biofilm formation.

NMR facilities include several solid state and solution spectrometers located at UF and the National High Magnetic Field Laboratory ranging from 500-900 MHz, including a 600 MHz ssNMR instrument with DNP capabilities. Extensive facilities for protein production and purification, cryoelectron microscopy, x-ray crystallography, and high performance computing are in close proximity to the Long and Brady labs as part of the UF centers for structural biology and high performance computing.

Minimum Requirements:
A Ph.D. and English language proficiency are required. Applicants should have a strong background in biomolecular NMR spectroscopy (either solution or solid state), molecular microbiology, and biochemistry with an emphasis on protein structure/dynamics/function. Experience with standard cloning and recombinant DNA methodologies, protein chemistry, chromatography, and heterologous protein expression and purification is necessary.

Preferred Qualifications:
Familiarity with techniques to evaluate protein-protein interactions, protein crystallization and X-ray diffraction methodologies, mass spectrometry, and electron microscopy will be given preference. Also desirable would be familiarity with assays to assess amyloid fibrillization including use of fluorescent dyes and spectral shift assays, Congo-red induced birefringence, confocal microscopy and immunogold electron microscopy.

This is a grant-funded position and is annually renewable based on the availability of research funds. Salary commensurate with NIH postdoctoral stipend guidelines.

For information on applying and any specific question related to the position, please contact me at jrlong@ufl.edu.


Joanna R. Long, PhD
Associate Professor of Biochemistry & Molecular Biology
Director, Advanced Magnetic Resonance Imaging & Spectroscopy Facility
Assoc. Director, National High Magnetic Field Laboratory
McKnight Brain Institute, LG-187
Box 100245
University of Florida
Gainesville, FL 32605
(352)294-8399 ***NOTE: phone number changed 8/22/2016***

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Friday, February 10, 2017

Hyperpolarized [1,4-(13)C]-diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging


Billingsley, K.L., et al., Hyperpolarized [1,4-(13)C]-diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging. NMR Biomed, 2014. 27(3): p. 356-62.


The tricarboxylic acid (TCA) cycle performs an essential role in the regulation of energy and metabolism, and deficiencies in this pathway are commonly correlated with various diseases. However, the development of non-invasive techniques for the assessment of the cycle in vivo has remained challenging. In this work, the applicability of a novel imaging agent, [1,4-(13)C]-diethylsuccinate, for hyperpolarized (13)C metabolic imaging of the TCA cycle was explored. In vivo spectroscopic studies were conducted in conjunction with in vitro analyses to determine the metabolic fate of the imaging agent. Contrary to previous reports (Zacharias NM et al. J. Am. Chem. Soc. 2012; 134: 934-943), [(13)C]-labeled diethylsuccinate was primarily metabolized to succinate-derived products not originating from TCA cycle metabolism. These results illustrate potential issues of utilizing dialkyl ester analogs of TCA cycle intermediates as molecular probes for hyperpolarized (13)C metabolic imaging.

Wednesday, February 8, 2017

[NMR] PhD & Postdoc positions on dissolution-DNP / Sami Jannin's group / Lyon

From the Ampere Magnetic Resonance List



PhD and Postdoctoral positions
Remote Dissolution Dynamic Nuclear Polarization


PhD and Postdoctoral positions are available working in the group of Sami Jannin at the Analytical Sciences Institute in the city of Lyon, France (http://isa-lyon.fr).

We will develop a series of new concepts to extend the lifetime of hyperpolarized MRI tracers to days (see proof-of-concept experiment doi:10.1038/ncomms13975) through a combination of innovative methods, instrumentation, and chemistry (see doi:10.1073/pnas.1407730111). Applications in the fields of metabolic MRI, drug discovery and metabolomics will be pursued.

We are looking for highly motivated candidates with strong scientific background, independence, and who enjoy teamwork. For postdoctoral positions, you must hold a PhD in Physics, chemistry or related disciplines. Skills in one of the following fields of expertise will be appreciated:

• Experimental nuclear magnetic resonance / electron spin resonance,
• Hardware development for dynamic nuclear polarization,
• Theory / simulation of nuclear spin relaxation / diffusion,
• Chemistry / Synthesis of mesoporous silica material / porous polymers.

The Center for Very High Field NMR is one of the world’s leading magnetic resonance laboratories, and is part of the Analytical Sciences Institute, located in the great city of Lyon, which is affiliated to the Lyon-1 University, the CNRS (French National Center for Scientific Research) and the Ecole Normale Supérieure de Lyon. The center is equipped with state of the art NMR spectrometers (500 - 700 - 800 MHz, and the world's first 1 GHz spectrometer) and soon will be equipped with a state of the art dissolution-DNP machine. It hosts research groups of worldwide-recognized excellence.

Motivated candidates can get directly in touch with Sami Jannin (+33 6 67 90 77 52) for further details on the positions or directly send their CV to sami.jannin@univ-lyon1.fr


Prof. Sami Jannin
UCBL1 / ENS-Lyon / CNRS
Institut des Sciences Analytiques - UMR 5280
5 rue de la Doua - 69100 Villeurbanne - France
mobile: +33 6 67 90 77 52
bureau: +33 4 26 23 38 57

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Producing Radical-Free Hyperpolarized Perfusion Agents for In Vivo Magnetic Resonance Using Spin-Labeled Thermoresponsive Hydrogel

Cheng, T., et al., Producing Radical-Free Hyperpolarized Perfusion Agents for In Vivo Magnetic Resonance Using Spin-Labeled Thermoresponsive Hydrogel. Macromol Rapid Commun, 2016. 37(13): p. 1074-8.


Dissolution dynamic nuclear polarization (DNP) provides a way to tremendously improve the sensitivity of nuclear magnetic resonance experiments. Once the spins are hyperpolarized by dissolution DNP, the radicals used as polarizing agents become undesirable since their presence is an additional source of nuclear spin relaxation and their toxicity might be an issue. This study demonstrates the feasibility of preparing a hyperpolarized [1-(13) C]2-methylpropan-2-ol (tert-butanol) solution free of persistent radicals by using spin-labeled thermoresponsive hydrophilic polymer networks as polarizing agents. The hyperpolarized (13) C signal can be detected for up to 5 min before the spins fully relax to their thermal equilibrium. This approach extends the applicability of spin-labeled thermoresponsive hydrogel to the dissolution DNP field and highlights its potential as polarizing agent for preparing neat slowly relaxing contrast agents. The hydrogels are especially suited to hyperpolarize deuterated alcohols which can be used for in vivo perfusion imaging.

Monday, February 6, 2017

Chemisorption of Water on the Surface of Silicon Microparticles Measured by DNP-Enhanced NMR #DNPNMR


Guy, M.L., et al., Chemisorption of Water on the Surface of Silicon Microparticles Measured by DNP-Enhanced NMR. The Journal of Physical Chemistry C, 2017.


We use dynamic nuclear polarization (DNP) enhanced nuclear magnetic resonance (NMR) at liquid helium temperatures to directly detect hydrogen attached to the surface of silicon microparticles. The proton NMR spectrum from a dry sample of polycrystalline silicon powder (1-5 μm) shows a distinctively narrow Lorentzian-shaped resonance with a width of 6.2 kHz, indicative of a very sparse distribution of protons attached to the silicon surface. These protons are within a few atomic monolayers of the silicon surface. The high sensitivity NMR detection of surface protons from low surface area (0.26-1.3 m2/g) particles is enabled by an overall signal enhancement of 4150 over the room temperature NMR signal at the same field. When the particles were suspended in a solvent with 80% H2O and 20% D2O, the narrow peak was observed to grow in intensity over time, indicating growth of the sparse surface proton layer. However, when the particles were suspended in a solvent with 20% H2O and 80% D2O, the narrow bound-proton peak was observed to shrink due to exchange between the surface protons and the deuterium in solution. This decrease was accompanied by a concomitant growth in the intensity of the frozen solvent peak, as the relative proton concentration of the solvent increased. When the particles were suspended in the organic solvent hexane, the proton NMR spectra remained unchanged over time. These results are consistent with the known chemisorption of water on the silicon surface resulting in the formation of hydride and hydroxyl species. Low-temperature DNP NMR can thus be used as a non-destructive probe of surface corrosion for silicon in aqueous environments. This is important in the context of using silicon MEMS and bioMEMS devices in such environments, for silicon micro- and nano-particle MRI imaging agents, and the use of nanosilicon for splitting water in fuel cells.

Friday, February 3, 2017

Producing Radical-Free Hyperpolarized Perfusion Agents for In Vivo Magnetic Resonance Using Spin-Labeled Thermoresponsive Hydrogel


Cheng, T., et al., Producing Radical-Free Hyperpolarized Perfusion Agents for In Vivo Magnetic Resonance Using Spin-Labeled Thermoresponsive Hydrogel. Macromol Rapid Commun, 2016. 37(13): p. 1074-8.


Dissolution dynamic nuclear polarization (DNP) provides a way to tremendously improve the sensitivity of nuclear magnetic resonance experiments. Once the spins are hyperpolarized by dissolution DNP, the radicals used as polarizing agents become undesirable since their presence is an additional source of nuclear spin relaxation and their toxicity might be an issue. This study demonstrates the feasibility of preparing a hyperpolarized [1-(13) C]2-methylpropan-2-ol (tert-butanol) solution free of persistent radicals by using spin-labeled thermoresponsive hydrophilic polymer networks as polarizing agents. The hyperpolarized (13) C signal can be detected for up to 5 min before the spins fully relax to their thermal equilibrium. This approach extends the applicability of spin-labeled thermoresponsive hydrogel to the dissolution DNP field and highlights its potential as polarizing agent for preparing neat slowly relaxing contrast agents. The hydrogels are especially suited to hyperpolarize deuterated alcohols which can be used for in vivo perfusion imaging.

Wednesday, February 1, 2017

Dynamic nuclear polarisation via the integrated solid effect II: experiments on naphthalene-h8doped with pentacene-d14 #DNPNMR


Eichhorn, T.R., et al., Dynamic nuclear polarisation via the integrated solid effect II: experiments on naphthalene-h8doped with pentacene-d14. Mol. Phys., 2013. 112(13): p. 1773-1782.


In dynamic nuclear polarisation (DNP), also called hyperpolarisation, a small amount of unpaired electron spins is added to the sample containing the nuclear spins, and the polarisation of these unpaired electron spins is transferred to the nuclear spins by means of a microwave field. Traditional DNP polarises the electron spin of stable paramagnetic centres by cooling down to low temperature and applying a strong magnetic field. Then weak continuous wave microwave fields are used to induce the polarisation transfer. Complicated cryogenic equipment and strong magnets can be avoided using short-lived photo-excited triplet states that are strongly aligned in the optical excitation process. However, a much faster transfer of the electron spin polarisation is needed and pulsed DNP methods like nuclear orientation via electron spin locking (NOVEL) and the integrated solid effect (ISE) are used. To describe the polarisation transfer with the strong microwave fields in NOVEL and ISE, the usual perturbation methods cannot be used anymore. In the previous paper, we presented a theoretical approach to calculate the polarisation transfer in ISE. In the present paper, the theory is applied to the system naphthalene-h8 doped with pentacene-d14 yielding the photo-excited triplet states and compared with experimental results.

[NMR] EPR position in TU Dortmund (PhD)

From the Ampere Magnetic Resonance List



Our group aims to understand the structure and function of proteins, protein complexes and other biomolecules at the atomic level via electron paramagnetic resonance (EPR) spectroscopy. We invite applications for a PhD position to participate in one of the projects listed below:


- Studying the role of tyrosyl radicals in catalysis of essential enzymes
- Testing the hypothesis that enzyme adaptation is driven by protein dynamics
- Understanding the role of π-stacked tyrosine dyad in proton-coupled electron transfer reactions

The candidate should have a strong background in biochemistry and/or chemistry and hold a Master’s degree (or equivalent) in any of these fields and willing to learn advanced EPR spectroscopic techniques. Experience with protein expression and purification techniques is preferred. We are looking for a highly motivated, collaborative and interactive candidate. Our group is located in Max-Planck-Institute for Biophysical Chemistry (Göttingen) at the moment but we will move to Technical University of Dortmund within 2017.

Please send your application including cover letter (explaining background and motivation) and CV via e-mail as single PDF file to:


JProf. Dr. Müge Kasanmascheff
Research Group of EPR Spectroscopy on Biological and Chemical Systems
Technical University of Dortmund
Faculty of Chemistry and Chemical Biology
Otto-Hahn-Str. 6, 44227 Dortmund

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