Monday, December 30, 2013

Solid-Phase Polarization Matrixes for Dynamic Nuclear Polarization from Homogeneously Distributed Radicals in Mesostructured Hybrid Silica Materials


Gajan, D., et al., Solid-Phase Polarization Matrixes for Dynamic Nuclear Polarization from Homogeneously Distributed Radicals in Mesostructured Hybrid Silica Materials. J. Am. Chem. Soc., 2013. 135(41): p. 15459-15466.


Mesoporous hybrid silica?organic materials containing homogeneously distributed stable mono- or dinitroxide radicals covalently bound to the silica surface were developed as polarization matrixes for solid-state dynamic nuclear polarization (DNP) NMR experiments. For TEMPO-containing materials impregnated with water or 1,1,2,2-tetrachloroethane, enhancement factors of up to 36 were obtained at ?100 K and 9.4 T without the need for a glass-forming additive. We show that the homogeneous radical distribution and the subtle balance between the concentration of radical in the material and the fraction of radicals at a sufficient inter-radical distance to promote the cross-effect are the main determinants for the DNP enhancements we obtain. The material, as well as an analogue containing the poorly soluble biradical bTUrea, is used as a polarizing matrix for DNP NMR experiments of solutions containing alanine and pyruvic acid. The analyte is separated from the polarization matrix by simple filtration.

Friday, December 27, 2013

Magic-Angle Spinning NMR of Cold Samples

Solid-state DNP experiments are often performed at cryogenic temperatures and this article is an excellent review about the current technologies to spin samples at (very) low temperatures.

ConcistrÈ, M., et al., Magic-Angle Spinning NMR of Cold Samples. Acc. Chem. Res., 2013.


Magic-angle-spinning solid-state NMR provides site-resolved structural and chemical information about molecules that complements many other physical techniques. Recent technical advances have made it possible to perform magic-angle-spinning NMR experiments at low temperatures, allowing researchers to trap reaction intermediates and to perform site-resolved studies of low-temperature physical phenomena such as quantum rotations, quantum tunneling, ortho-para conversion between spin isomers, and superconductivity. In examining biological molecules, the improved sensitivity provided by cryogenic NMR facilitates the study of protein assembly or membrane proteins. The combination of low-temperatures with dynamic nuclear polarization has the potential to boost sensitivity even further. Many research groups, including ours, have addressed the technical challenges and developed hardware for magic-angle-spinning of samples cooled down to a few tens of degrees Kelvin. In this Account, we briefly describe these hardware developments and review several recent activities of our group which involve low-temperature magic-angle-spinning NMR. Low-temperature operation allows us to trap intermediates that cannot be studied under ambient conditions by NMR because of their short lifetime. We have used low-temperature NMR to study the electronic structure of bathorhodopsin, the primary photoproduct of the light-sensitive membrane protein, rhodopsin. This project used a custom-built NMR probe that allows low-temperature NMR in the presence of illumination (the image shows the illuminated spinner module). We have also used this technique to study the behavior of molecules within a restricted environment. Small-molecule endofullerenes are interesting molecular systems in which molecular rotors are confined to a well-insulated, well-defined, and highly symmetric environment. We discuss how cryogenic solid state NMR can give information on the dynamics of ortho-water confined in a fullerene cage. Molecular motions are often connected with fundamental chemical properties; therefore, an understanding of molecular dynamics can be important in fields ranging from material science to biochemistry. We present the case of ibuprofen sodium salt which exhibits different degrees of conformational freedom in different parts of the same molecule, leading to a range of line broadening and line narrowing phenomena as a function of temperature.

Monday, December 23, 2013

SedNMR: On the Edge between Solution and Solid-State NMR


Sedimented samples (states) can be described as a "microcrystaline glass", which provide a new approach for the preparation of DNP samples. This was described in a post this year you can find here (http://blog.bridge12.com/2013/02/dynamic-nuclear-polarization-of.html).

The following article gives more details about the approach.



Bertini, I., et al., SedNMR: on the edge between solution and solid-state NMR. Acc Chem Res, 2013. 46(9): p. 2059-69.


Solid-state NMR (SS-NMR) of proteins requires that those molecules be immobilized, usually by crystallization, freezing, or lyophilization. However, self-crowding can also slow molecular rotation sufficiently to prevent the nuclear interactions from averaging. To achieve self-crowding, researchers can use a centrifugal field to create a concentration gradient or use regular ultracentrifugation to produce highly concentrated, gel-like solutions. Thus sedimented solute NMR (SedNMR) provides a simple method to prepare biological samples for SS-NMR experiments with minimal perturbation. This method may also give researchers a way to investigate species that are not otherwise accessible by NMR. We induce the sedimentation in one of two ways: (1) by the extreme centrifugal force exerted during magic angle spinning (MAS-induced sedimentation or in situ) or (2) by an ultracentrifuge (UC-induced sedimentation or ex situ). Sedimentation is particularly useful in situations where it is difficult to obtain protein crystals. Furthermore, because the proteins remain in a largely hydrated state, the sedimented samples may provide SS-NMR spectra that have better resolution than the spectra from frozen solutions or lyophilized powders. If sedimentation is induced in situ, the same protein sample can be used for both solution and SS-NMR studies. Finally, we show that in situ SedNMR can be used to detect the NMR signals of large molecular adducts that have binding constants that are too weak to allow for the selective isolation and crystallization of the complexed species. We can selectively induce sedimentation for the heaviest molecular species. Because the complexed molecules are subtracted from the bulk solution, the reaction proceeds further toward the formation of complexes.

Friday, December 20, 2013

Dynamic nuclear polarization of (17)o: direct polarization


Michaelis, V.K., et al., Dynamic nuclear polarization of (17)o: direct polarization. J Phys Chem B, 2013. 117(48): p. 14894-906.


Dynamic nuclear polarization of (17)O was studied using four different polarizing agents: the biradical TOTAPOL and the monoradicals trityl and SA-BDPA, as well as a mixture of the latter two. Field profiles, DNP mechanisms, and enhancements were measured to better understand and optimize directly polarizing this low-gamma quadrupolar nucleus using both mono- and biradical polarizing agents. Enhancements were recorded at <88 K and were >100 using the trityl (OX063) radical and <10 with the other polarizing agents. The >10 000-fold savings in acquisition time enabled a series of biologically relevant small molecules to be studied with small sample sizes and the measurement of various quadrupolar parameters. The results are discussed with comparison to room temperature studies and GIPAW quantum chemical calculations. These experimental results illustrate the strength of high field DNP and the importance of radical selection for studying low-gamma nuclei.

Postdoc @ INAC (CEA / Grenoble university)

From the Ampere list:



Position: Researcher/Engineer at CEA INAC (Institute for Nanoscience and
Cryogenics)
Location: Grenoble/France
Field of research: Ultra Low Temperature Magic Angle Spinning Dynamic Nuclear
Polarization
Duration: 12 months, with possible extension upon results and funding.

We have an opening for a research/engineer position in ultra-low temperature MAS-DNP NMR at the Institute for Nanosciences and Cryogenics (CEA - Commissariat à l'Energie Atomique et aux Energies Alternatives / University of Grenoble). 

Starting date: Beginning of 2014

The lab is equipped with a state of the art Bruker MAS-DNP system (400 MHz / 263 GHz) and is currently running a program to access MAS temperatures below 100 K using Helium spinning. Researchers/Engineers with a strong background or interest in Dynamic Nuclear Polarization / NMR methodology are welcomed to apply. PhD in solid-state NMR/ EPR or MRI is required. Experience with magnetic resonance hardware is heavily desired. A large part of the work will be conducted in close collaboration with Bruker Biospin.

Recent DNP papers from the group :
H. Takahashi et al., Angew. Chem. Intl. Ed. 51 (2012) 11766-11769. 
D. Lee et al., J. Am. Chem. Soc. 134 (2012) 18491-18494.
H. Takahashi et al., J. Am. Chem. Soc. 135 (2013) 5105-5110. 
H. Takahashi et al., Angew. Chem. Intl. Ed. 52 (2013) 6979-6982.

This fellowship is funded by the French National Research Agency. The initial
contract is for 12 months with the possibility of extension.

For further information regarding details of the work and of the appointment,
interested candidates should contact me directly at gael.depaepe@cea.fr.

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Wednesday, December 18, 2013

Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid


Zeng, H., et al., Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid. J Magn Reson, 2013. 237(0): p. 73-8.


Hyperpolarization produces nuclear spin polarization that is several orders of magnitude larger than that achieved at thermal equilibrium thus providing extraordinary contrast and sensitivity. As a parahydrogen induced polarization (PHIP) technique that does not require chemical modification of the substrate to polarize, Signal Amplification by Reversible Exchange (SABRE) has attracted a lot of attention. Using a prototype parahydrogen polarizer, we polarize two drugs used in the treatment of tuberculosis, namely pyrazinamide and isoniazid. We examine this approach in four solvents, methanol-d4, methanol, ethanol and DMSO and optimize the polarization transfer magnetic field strength, the temperature as well as intensity and duration of hydrogen bubbling to achieve the best overall signal enhancement and hence hyperpolarization level.

Monday, December 16, 2013

2nd TeraHertz: New opportunities for industry





2nd TeraHertz: New opportunities for industry – Formation courte

How the TeraHertz revolution impacts your business

12 – 14 February 2014


Target audience

R&D managers, engineers and scientists seeking a comprehensive update on TeraHertz technologies and applications, a disruptively evolving field.
A general background in science & technology is sufficient.

Overview

TeraHertz (THz), the frequencies between electronics and optics, was until recently the last unexploited part of the electromagnetic spectrum. The harnessing of THz-based technologies has the potential of impacting globally a vast number of industries, like both electronics in the 70’s and optics in the 80’s did.
THz applications span over a wide array of fields, including:
  • Quality Control and Non-destructive testing
  • Surface analysis
  • Security
  • Chemical and Bio-Medical analysis
  • Telecommunications

Filling the Terahertz “gap” has led to unprecedented creativity in the development and commercialization of TeraHertz sources, transmission components and detectors.
This course is a unique opportunity to network with specialists, converge know-how, and scout for innovative applications.

Objectives

  • Learn about the latest TeraHertz technologies and their market potential
  • Discover examples of TeraHertz applications and the corresponding industrial opportunities
  • Network with specialists in this emerging field

Topics and Hands-on

  • THz test & measurements instrumentations: Network Analyzers
  • THz solid state sources
  • THz on-chip measurements
  • High speed Electronics
  • THz analysis of volatile mixtures

Certification

A certificate of participation will be delivered at the end of the course.

Organization

  • Nanostructured Materials Physics Laboratory (LPMN)
  • Institute of Condensed Matter Physics (ICMP)
  • School of Basic Sciences (FSB)
  • Ecole Polytechnique Fédérale de Lausanne (EPFL)

In collaboration with

  • SWISSto12 SA, a company issued from the EPFL Science Park

Steering committee

  • Prof. Jean-Philippe Ansermet, School of Basic Sciences, ICMP, EPFL
  • Dr. Alessandro MacorSWISSto12 SA
  • Emile de Rijk, SWISSto12 SA

Confirmed Speakers from

  • Agilent
  • BrightSpec
  • Becker-Photonik
  • Cascade Microtech
  • Nuvotronics
  • Radiometer Physics
  • Teledyne Scientific
  • Virginia Diodes

Training

  • Keynote speakers from industry will give an overview of applications and challenges.
  • Hands-on experience with demonstrators

Dates and schedule

  • Wednesday, 12 February 2014, 1.30 pm to 6 pm
  • Thursday, 13 February 2014, 9 am to 6 pm
  • Friday, 14 February 2014, 9 am to 1 pm

Course venue

EPFL Innovation Park, Lausanne, Switzerland

Registration

Course fee : Early registration (before 29th November 2013)
600.- Swiss Francs (includes course material and refreshments)
Late registration
800.- Swiss Francs
Limited places available.
Registration deadline: 13th December 2013
- See more at: http://www.formation-continue-unil-epfl.ch/thz#sthash.tzgRxl5O.dpuf

Shortening spin–lattice relaxation using a copper-chelated lipid at low-temperatures – A magic angle spinning solid-state NMR study on a membrane-bound protein


Yamamoto, K., et al., Shortening spin–lattice relaxation using a copper-chelated lipid at low-temperatures – A magic angle spinning solid-state NMR study on a membrane-bound protein. J. Magn. Reson., 2013. 237(0): p. 175-181.


Inherent low sensitivity of NMR spectroscopy has been a major disadvantage, especially to study biomolecules like membrane proteins. Recent studies have successfully demonstrated the advantages of performing solid-state NMR experiments at very low and ultralow temperatures to enhance the sensitivity. However, the long spin-lattice relaxation time, T1, at very low temperatures is a major limitation. To overcome this difficulty, we demonstrate the use of a copper-chelated lipid for magic angle spinning solid-state NMR measurements on cytochrome-b5 reconstituted in multilamellar vesicles. Our results on multilamellar vesicles containing as small as 0.5mol% of a copper-chelated lipid can significantly shorten T1 of protons, which can be used to considerably reduce the data collection time or to enhance the signal-to-noise ratio. We also monitored the effect of slow cooling on the resolution and sensitivity of (13)C and (15)N signals from the protein and (13)C signals from lipids.

Friday, December 13, 2013

Cryogenics free production of hyperpolarized (129)Xe and (83)Kr for biomedical MRI applications


Hughes-Riley, T., et al., Cryogenics free production of hyperpolarized (129)Xe and (83)Kr for biomedical MRI applications. J Magn Reson, 2013. 237(0): p. 23-33.


As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures were extracted directly from the spin exchange optical pumping (SEOP) process through expansion followed by compression to ambient pressure for biomedical MRI applications. The omission of cryogenic gas separation generally requires the usage of high xenon or krypton concentrations at low SEOP gas pressures to generate hp (129)Xe or hp (83)Kr with sufficient MR signal intensity for imaging applications. Two different extraction schemes for the hp gasses were explored with focus on the preservation of the nuclear spin polarization. It was found that an extraction scheme based on an inflatable, pressure controlled balloon is sufficient for hp (129)Xe handling, while (83)Kr can efficiently be extracted through a single cycle piston pump. The extraction methods were tested for ex vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with oxygen, which may be of interest for potential in vivo applications, was accomplished during the extraction process using a piston pump. The (83)Kr bulk gas phase T1 relaxation in the mixtures containing more than approximately 1% O2 was found to be slower than that of (129)Xe in corresponding mixtures. The experimental setup also facilitated (129)Xe T1 relaxation measurements as a function of O2 concentration within excised lungs.

Wednesday, December 11, 2013

Dynamic Nuclear Polarization NMR Spectroscopy Allows High-Throughput Characterization of Microporous Organic Polymers


Blanc, F., et al., Dynamic nuclear polarization NMR spectroscopy allows high-throughput characterization of microporous organic polymers. J Am Chem Soc, 2013. 135(41): p. 15290-3.


Dynamic nuclear polarization (DNP) solid-state NMR was used to obtain natural abundance (13)C and (15)N CP MAS NMR spectra of microporous organic polymers with excellent signal-to-noise ratio, allowing for unprecedented details in the molecular structure to be determined for these complex polymer networks. Sensitivity enhancements larger than 10 were obtained with bis-nitroxide radical at 14.1 T and low temperature ( approximately 105 K). This DNP MAS NMR approach allows efficient, high-throughput characterization of libraries of porous polymers prepared by combinatorial chemistry methods.

Monday, December 9, 2013

[NMR] Postdoctoral position at BMRZ / Goethe University Frankfurt

From the Ampere Magnetic Resonance List

Dear colleagues,


Applications are invited for a postdoctoral research position in Solid-state DNP Spectroscopy in the Emmy Noether research group led by Dr. Björn Corzilius at the Goethe University Frankfurt/Main, Germany (E13 TV-G-U, 100 %). The postdoctoral researcher will be placed at the seam between the BMRZ and the Institute of Physical and Theoretical Chemistry. The research group focuses on method development and basic research of DNP towards biomolecular applications.

To qualify, the applicant must hold a doctoral degree in chemistry, physics, biochemistry, or biophysics. The applicant must be ambitious and demonstrate a strong motivation and an appropriate background to help develop the proposed research area. Several years of research experience in magnetic resonance methods, especially in DNP, NMR, or EPR are required and should be supported by publications in high-ranking scientific journals and conference contributions. Good language skills in English are a crucial requirement.

The applicant will lead small research groups and work in a cutting-edge field situated at the seam between EPR and NMR and will therefore be able to build or extend an integral knowledge and expertise in the field of magnetic resonance. Experiments will be performed using state-of-the-art instrumentation at the BMRZ or external collaboration sites.

The successful candidate must have very good collaborative skills, have integrity and be flexible and capable of working in a structured and efficient way. The successful candidates should also be able to contribute to the innovative climate within the group.

Please send your relevant and comprehensive application material to Dr. Björn Corzilius: corzilius@em.uni-frankfurt.de.

The contract is fixed term, based on the regulations of the "Wissenschaftszeitvertragsgesetz" and the "Hessische Hochschulgesetz". Initial appointment is for 1 year, with possible extension upon mutual agreement. The University is an equal opportunity employer and strongly encourages women to apply. In case of equal qualification, preference will be given to applicants with disabilities.

-- 

Dr. Björn Corzilius
Emmy Noether Research Group Leader

Institute for Physical and Theoretical Chemistry,
Institute for Biophysical Chemistry
and Center for Biomolecular Magnetic Resonance (BMRZ)

Goethe University Frankfurt
Campus Riedberg
Building N140, Room 1

Max-von-Laue-Str. 7
60438 Frankfurt am Main

phone: +49-(0)69-798-29467
fax: +49-(0)69-798-29404

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Probing the mobility of ibuprofen confined in MCM-41 materials using MAS-PFG NMR and hyperpolarised-(129)Xe NMR spectroscopy


Guenneau, F., et al., Probing the mobility of ibuprofen confined in MCM-41 materials using MAS-PFG NMR and hyperpolarised-(129)Xe NMR spectroscopy. Phys Chem Chem Phys, 2013. 15(43): p. 18805-8.


The continuous-flow hyperpolarised (HP)-(129)Xe NMR and magic angle spinning-pulsed field gradient (MAS-PFG) NMR techniques have been used for the first time to study the distribution and the dynamics of ibuprofen encapsulated in MCM-41 with two different pore diameters.

Friday, December 6, 2013

Dynamic nuclear polarization of spherical nanoparticles


Akbey, U., et al., Dynamic nuclear polarization of spherical nanoparticles. Phys Chem Chem Phys, 2013. 15(47): p. 20706-16.


Spherical silica nanoparticles of various particle sizes ( approximately 10 to 100 nm), produced by a modified Stoeber method employing amino acids as catalysts, are investigated using Dynamic Nuclear Polarization (DNP) enhanced Nuclear Magnetic Resonance (NMR) spectroscopy. This study includes ultra-sensitive detection of surface-bound amino acids and their supramolecular organization in trace amounts, exploiting the increase in NMR sensitivity of up to three orders of magnitude via DNP. Moreover, the nature of the silicon nuclei on the surface and the bulk silicon nuclei in the core (sub-surface) is characterized at atomic resolution. Thereby, we obtain unique insights into the surface chemistry of these nanoparticles, which might result in improving their rational design as required for promising applications, e.g. as catalysts or imaging contrast agents. The non-covalent binding of amino acids to surfaces was determined which shows that the amino acids not just function as catalysts but become incorporated into the nanoparticles during the formation process. As a result only three distinct Q-types of silica signals were observed from surface and core regions. We observed dramatic changes of DNP enhancements as a function of particle size, and very small particles (which suit in vivo applications better) were hyperpolarized with the best efficiency. Nearly one order of magnitude larger DNP enhancement was observed for nanoparticles with 13 nm size compared to particles with 100 nm size. We determined an approximate DNP penetration-depth ( approximately 4.2 or approximately 5.7 nm) for the polarization transfer from electrons to the nuclei of the spherical nanoparticles. Faster DNP polarization buildup was observed for larger nanoparticles. Efficient hyperpolarization of such nanoparticles, as achieved in this work, can be utilized in applications such as magnetic resonance imaging (MRI).

Wednesday, December 4, 2013

THz Gyrotron and BWO Designed for Operation in DNP-NMR Spectrometer Magnet


Bratman, V.L., et al., THz Gyrotron and BWO Designed for Operation in DNP-NMR Spectrometer Magnet. J Infrared Milli Terahz Waves, 2013. 34(12): p. 837-846.


Dynamic nuclear polarization (DNP) in high-field nuclearmagnetic resonance (NMR) spectroscopy requires medium-power terahertz radiation, which nowadays can be provided basically by gyrotrons with superconducting magnets. As the electron cyclotron frequency is very close to the frequency of electron paramagnetic resonance for the samemagnetic field, under certain conditions the gyrotron can be installed inside the same solenoid used for NMR spectrometer. This eliminates the need for an additional superconducting magnet, results in a shorter terahertz transmission line, and can make DNP systems practical. In addition to an extremely low-voltage gyrotron (“gyrotrino”), we analyze also advantages of strong magnetic field for a slow-wave electron device as an alternative terahertz source.

Monday, December 2, 2013

Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization


Bowen, S. and J.H. Ardenkjaer-Larsen, Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization. J Magn Reson, 2013. 236(0): p. 26-30.


Hyperpolarization by the dissolution dynamic nuclear polarization (DNP) technique permits the generation of high spin polarization of solution state. However, sample formulation for dissolution-DNP is often difficult, as concentration and viscosity must be optimized to yield a dissolved sample with sufficient concentration, while maintaining polarization during the dissolution process. The unique chemical properties of choline permit the generation of highly soluble salts as well as deep eutectic mixtures with carboxylic acids and urea. We describe the formulation of these samples and compare their performance to more traditional sample formulations. Choline yields stable samples with exceptional polarization performance while simultaneously offering the capability to easily remove the choline after dissolution, perform experiments with the hyperpolarized choline, or anything in between.

Friday, November 29, 2013

Over 35% liquid-state (13)C polarization obtained via dissolution dynamic nuclear polarization at 7 T and 1 K using ubiquitous nitroxyl radicals


Cheng, T., et al., Over 35% liquid-state (13)C polarization obtained via dissolution dynamic nuclear polarization at 7 T and 1 K using ubiquitous nitroxyl radicals. Phys Chem Chem Phys, 2013. 15(48): p. 20819-22.


The most versatile method to increase liquid-state (13)C NMR sensitivity is dissolution dynamic nuclear polarization. The use of trityl radicals is usually required to obtain very large (13)C polarization via this technique. We herein demonstrate that up to 35% liquid-state (13)C polarization can be obtained in about 1.5 h using ubiquitous nitroxyl radicals in (13)C-labeled sodium salts by partially deuterating the solvents and using a polarizer operating at 1 K and 7 T.

Wednesday, November 27, 2013

A comparative study of (1)H and (19)F Overhauser DNP in fluorinated benzenes


Neudert, O., et al., A comparative study of (1)H and (19)F Overhauser DNP in fluorinated benzenes. Phys Chem Chem Phys, 2013. 15(47): p. 20717-26.


Hyperpolarization techniques, such as Overhauser dynamic nuclear polarization (DNP), can provide a dramatic increase in the signal obtained from nuclear magnetic resonance experiments and may therefore enable new applications where sensitivity is a limiting factor. In this contribution, studies of the (1)H and (19)F Overhauser dynamic nuclear polarization enhancements at 345 mT are presented for three different aromatic solvents with the TEMPO radical for a range of radical concentrations. Furthermore, nuclear magnetic relaxation dispersion measurements of the same solutions are analyzed, showing contributions from dipolar and scalar coupling modulated by translational diffusion and different coupling efficiency for different solvents and nuclei. Measurements of the electron paramagnetic resonance linewidth are included to support the analysis of the DNP saturation factor for varying radical concentration. The results of our study give an insight into the characteristics of nitroxide radicals as polarizing agents for (19)F Overhauser DNP of aromatic fluorinated solvents. Furthermore, we compare our results with the findings of the extensive research on Overhauser DNP that was conducted in the past for a large variety of other radicals.

Monday, November 25, 2013

Sensitivity-enhanced solid-state NMR detection of expansin's target in plant cell walls


Wang, T., et al., Sensitivity-enhanced solid-state NMR detection of expansin's target in plant cell walls. Proc Natl Acad Sci U S A, 2013. 110(41): p. 16444-9.


Structure determination of protein binding to noncrystalline macromolecular assemblies such as plant cell walls (CWs) poses a significant structural biology challenge. CWs are loosened during growth by expansin proteins, which weaken the noncovalent network formed by cellulose, hemicellulose, and pectins, but the CW target of expansins has remained elusive because of the minute amount of the protein required for activity and the complex nature of the CW. Using solid-state NMR spectroscopy, combined with sensitivity-enhancing dynamic nuclear polarization (DNP) and differential isotopic labeling of expansin and polysaccharides, we have now determined the functional binding target of expansin in the Arabidopsis thaliana CW. By transferring the electron polarization of a biradical dopant to the nuclei, DNP allowed selective detection of (13)C spin diffusion from trace concentrations of (13)C, (15)N-labeled expansin in the CW to nearby polysaccharides. From the spin diffusion data of wild-type and mutant expansins, we conclude that to loosen the CW, expansin binds highly specific cellulose domains enriched in xyloglucan, whereas more abundant binding to pectins is unrelated to activity. Molecular dynamics simulations indicate short (13)C-(13)C distances of 4-6 A between a hydrophobic surface of the cellulose microfibril and an aromatic motif on the expansin surface, consistent with the observed NMR signals. DNP-enhanced 2D (13)C correlation spectra further reveal that the expansin-bound cellulose has altered conformation and is enriched in xyloglucan, thus providing unique insight into the mechanism of CW loosening. DNP-enhanced NMR provides a powerful, generalizable approach for investigating protein binding to complex macromolecular targets.

Sunday, November 24, 2013

[NMR] NMR Post-doc position at CEA Saclay, France

From the Ampere Magnetic Resonance List



Post-doc in hyperpolarized 129Xe MRI

A project untitled: « Polarized Xenon-MRI for diagnosis and follow up of Chest Tumors » is granted by the French programme « Projets de recherche dans le domaine de la physique, des mathématiques ou des sciences de l'ingénieur appliqués au cancer ». We are looking for a post-doctoral fellow for one year starting January 2014. The place is CEA-Saclay (25 km in the S-W of Paris).

Abstract
Diagnosis and treatment of early stages of non-small-cell lung cancer (NSCLC) could drastically modify the outcome in terms of disease-free and overall survival.
MRI offers several advantages owing to its low invasiveness, its harmlessness and its spatial in-depth resolution but suffers from poor sensitivity. Very few MRI methods are able to detect events at the air-liquid interface (i.e. lung epithelium), due to the low number of detectable atoms present and the strong local magnetic field inhomogeneity. Different strategies can be used to improve MRI detection threshold in lungs including the use of hyperpolarized gases such as 3He and 129Xe. These species can be detected at very low concentration thanks to the gain by several orders of magnitude in nuclear polarization. Hyperpolarized xenon presents interesting properties for medical applications:

  • it is a non-toxic, freely diffusive tracer that crosses the cell membrane in some tens of milliseconds without polarization loss,
  • its spectral signature is strongly dependent on its environment,
  • it can be encapsulated in host molecules functionalized to target specific receptors (hereafter denoted biosensors).

In the project with Institut Gustave Roussy (IGR) and CEA/DSV, we propose a new approach based on 129Xe MRI biosensors for the early diagnosis of NSCLC and follow up of treatment efficacy.
The candidate will belong to the team having in charge the NMR/MRI part. He/she must have a strong background in MRI, an experience of in vivo experiments, and some notions of spin hyperpolarization. The laboratory owns several high-field spectrometers and two home-built setups for optical pumping of noble gases, and has access to the high-field small animal MR imagers at NeuroSpin (40 meters apart).
Interested candidate must send a detailed curriculum vitae and a letter of motivation to : 
Patrick Berthault 
CEA Saclay
IRAMIS/SIS2M/UMR3299
PC #9
91191 Gif sur Yvette, France
 Tel: (+33) 169 08 42 45


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[NMR] Postdoctoral position in NMR Hyperpolarisation

From the Ampere Magnetic Resonance List



The Korvink group at the Department of Microsystems Engineering, University of Freiburg, is inviting applications for a postdoctoral position in NMR hyperpolarisation. The research work is funded by an ERC project that targets novel NMR detector concepts in the broad area of miniaturised NMR. The successful candidate brings along research experience in para Hydrogen induced polarisation (PHiP). Any additional experience from the broad areas of NMR or MEMS will be of benefit.

The ideal candidate will be a recent PhD graduate with practical experience in PHiP. This may include as examples: catalyst design, substrate design, and/or pulse sequence development for efficient polarization transfer.  Responsibilities will include supervision of graduate students and leading PHiP activities within the context of the broader goals of the NMCEL project. As a highly interdisciplinary project, strong team and communication skills are imperative. 

The environment at IMTEK offers an outstanding scientific setting, including state-of-the-art microsystem fabrication facilities, an RF lab, and a dedicated 500 MHz wide-bore Bruker NMR spectrometer. The NMCEL team will be composed of 1-2 postdocs, 3-4 PhD students, and 3-4 masters students. The University of Freiburg offers several facilities suitable for supporting this project and is within one hour from Bruker headquarters in Karlsruhe for potential collaborative efforts.

The position is immediately available, at the E13 level for one year, and is extendable to a total duration of 2 years. Applications for the position should contain a motivational cover letter, a curriculum vitae, a publications list, and a copy of the applicant's most significant journal publication, preferably submitted via email as a single PDF file, to korvink@imtek.uni-freiburg.de. Applicants should be willing to travel to Freiburg for an interview. The university is currently seeking to increase the amount of female employees and is thus especially pleased to receive applications from qualified female candidates.

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Friday, November 22, 2013

Highly Efficient, Water-Soluble Polarizing Agents for Dynamic Nuclear Polarization at High Frequency


Sauvee, C., et al., Highly Efficient, Water-Soluble Polarizing Agents for Dynamic Nuclear Polarization at High Frequency. Angew Chem Int Ed Engl, 2013. 52(41): p. 10858-10861.

Well polarized: Two new polarizing agents PyPol and AMUPol soluble in glycerol/water mixtures are used for dynamic nuclear polarization (DNP) NMR spectroscopy. The enhancement factors (epsilon) are about 3.5 to 4 times larger than for the established agent TOTAPOL at 263 and 395 GHz. For AMUPol, the temperature dependence of epsilon allows DNP experiments to be performed at temperatures significantly higher than for typical high-field DNP NMR experiments.

Wednesday, November 20, 2013

Quantitative cw Overhauser effect dynamic nuclear polarization for the analysis of local water dynamics


Franck, J.M., et al., Quantitative cw Overhauser effect dynamic nuclear polarization for the analysis of local water dynamics. Prog Nucl Magn Reson Spectrosc, 2013. 74(0): p. 33-56.

Liquid state Overhauser effect Dynamic Nuclear Polarization (ODNP) has experienced a recent resurgence of interest. The ODNP technique described here relies on the double resonance of electron spin resonance (ESR) at the most common, i.e. X-band ( approximately 10GHz), frequency and (1)H nuclear magnetic resonance (NMR) at approximately 15MHz. It requires only a standard continuous wave (cw) ESR spectrometer with an NMR probe inserted or built into an X-band cavity. We focus on reviewing a new and powerful manifestation of ODNP as a high frequency NMR relaxometry tool that probes dipolar cross relaxation between the electron spins and the (1)H nuclear spins at X-band frequencies. This technique selectively measures the translational mobility of water within a volume extending 0.5-1.5nm outward from a nitroxide radical spin probe that is attached to a targeted site of a macromolecule. It allows one to study the dynamics of water that hydrates or permeates the surface or interior of proteins, polymers, and lipid membrane vesicles. We begin by reviewing the recent advances that have helped develop ODNP into a tool for mapping the dynamic landscape of hydration water with sub-nanometer locality. In order to bind this work coherently together and to place it in the context of the extensive body of research in the field of NMR relaxometry, we then rephrase the analytical model and extend the description of the ODNP-derived NMR signal enhancements. This extended model highlights several aspects of ODNP data analysis, including the importance of considering all possible effects of microwave sample heating, the need to consider the error associated with various relaxation rates, and the unique ability of ODNP to probe the electron-(1)H cross-relaxation process, which is uniquely sensitive to fast (tens of ps) dynamical processes. By implementing the relevant corrections in a stepwise fashion, this paper draws a consensus result from previous ODNP procedures and then shows how such data can be further corrected to yield clear and reproducible saturation of the NMR hyperpolarization process. Finally, drawing on these results, we broadly survey the previous ODNP dynamics literature. We find that the vast number of published, empirical hydration dynamics data can be reproducibly classified into regimes of surface, interfacial, vs. buried water dynamics.

Monday, November 18, 2013

Cross Polarization for Dissolution Dynamic Nuclear Polarization Experiments at Readily Accessible Temperatures 1.2 < T < 4.2 K


Bornet, A., et al., Cross Polarization for Dissolution Dynamic Nuclear Polarization Experiments at Readily Accessible Temperatures 1.2 < T < 4.2 K. Appl. Magn. Reson., 2012. 43(1-2): p. 107-117.


Cross polarization can provide significant enhancements with respect to direct polarization of low-γ nuclei such as 13 C. Substantial gains in sample throughput (shorter polarization times) can be achieved by exploiting shorter build-up times τ DNP ( 1 H) < τ DNP ( 13 C). To polarize protons rather than low-γ nuclei, nitroxide radicals with broad ESR resonances such as TEMPO are more appropriate than Trityl and similar carbon-based radicals that have narrow lines. With TEMPO as polarizing agent, the main Dynamic Nuclear Polarization (DNP) mechanism is thermal mixing (TM). Cross polarization makes it possible to attain higher polarization levels at 2.2 K than one can obtain with direct DNP of low-γ nuclei with TEMPO at 1.2 K, thus avoiding complex cryogenic technology.

Friday, November 15, 2013

Diradicals


For solid-state DNP-NMR spectroscopy very large enhancement factors can be achieved when employing the cross-effect, which is especially sufficient when using bi-radicals (e.g. TOTAPOL,bTbk ...). Bi-radicals (or Di-radicals) were not invented for DNP-NMR spectroscopy and a huge amount of EPR literature is available describing their magnetic resonance related properties.
The article cited below gives a comprehensive overview and can a source of new inspiration in the hunt for more efficient polarizing agents for DNP-NMR spectroscopy.

Abe, M., Diradicals. Chem. Rev., 2013. 113(9): p. 7011-7088.

Unfortunately no abstract available.


Wednesday, November 13, 2013

Level anti-crossings in ParaHydrogen Induced Polarization experiments with Cs-symmetric molecules


Buljubasich, L., et al., Level anti-crossings in ParaHydrogen Induced Polarization experiments with Cs-symmetric molecules. J Magn Reson, 2012. 219(0): p. 33-40.


Hyperpolarization by means of ParaHydrogen Induced Polarization (PHIP) has found increasing applications since its discovery. However, in the last decade only a few experiments have been reported describing the hydrogenation of symmetric molecules. A general AA'BB' system is studied here. Calculations of the spin dynamics with the density matrix formalism support the experimental findings, providing profound understanding of the experiments in Cs-symmetric molecules. Level anti-crossings between states related to the triplet and the singlet state of one pair of the protons are identified as being responsible for hyperpolarization transfer in a PHIP experiment, when the former p-H(2) protons occupy the sites AA'. The hydrogenation of acetylene dicarboxylic acid dimethylester with parahydrogen is used to illustrate the case. The theoretical treatment applied to this particular reaction explains the signal enhancements in both groups of protons in the spectrum when the sample is placed in the proper magnetic field strength, including the phase inversion of the signal of the methyl group. The treatment described here can be extended to every molecule which can be approximated as an AA'BB' system.

Friday, November 8, 2013

Factors Affecting DNP NMR in Polycrystalline Diamond Samples


Casabianca, L.B., et al., Factors Affecting DNP NMR in Polycrystalline Diamond Samples. The Journal of Physical Chemistry C, 2011. 115(39): p. 19041-19048.


This work examines several polycrystalline diamond samples for their potential as polarizing agents for dynamic nuclear polarization (DNP) in NMR. Diamond samples of various origin and particle sizes ranging from a few nanometers to micrometers were examined by EPR, solid-state NMR and DNP techniques. A correlation was found between the size of the diamond particles and the electron spin–lattice relaxation time, the 13C nuclear spin–lattice relaxation times in room temperature magic-angle-spinning experiments, and the ability of the diamond carbons to be hyperpolarized by irradiating unpaired electrons of inherent defects by microwaves at cryogenic temperatures. As the size of the diamond particles approaches that of bulk diamond, both electron and nuclear relaxation times become longer. NMR signal enhancement through DNP was found to be very efficient only for these larger size diamond samples. The reasons and implications of these results are briefly discussed, in the light of these EPR, DNP, and NMR observations.

Wednesday, November 6, 2013

Transmit-Only/Receive-Only Radiofrequency System for Hyperpolarized 13C MRS Cardiac Metabolism Studies in Pigs


Giovannetti, G., et al., Transmit-Only/Receive-Only Radiofrequency System for Hyperpolarized 13C MRS Cardiac Metabolism Studies in Pigs. Appl. Magn. Reson., 2013. 44(10): p. 1125-1138.


Hyperpolarized 13C magnetic resonance spectroscopy in pig models enables metabolic activity mapping, providing a powerful tool for the study of the heart physiology, but requires the development of dedicated radiofrequency coils, capable of providing large field of view with high signal-to-noise ratio (SNR) data. This work describes the simulations and the tests of a transmit-only (TX) volume coil/receive-only (RX) surface coil both designed for hyperpolarized studies of pig heart with a clinical 3T scanner. The coil characterization is performed by developing an SNR model for coil performance in terms of coil resistance, sample induced resistance and magnetic field pattern. In particular, coil resistances were calculated from Ohm’s law, while magnetic field patterns and sample-induced resistances were calculated using a numerical finite-difference time-domain algorithm. Experimental phantom chemical shift image, showed good agreement with the theoretical SNR-vs-depth profiles and highlighted the advantage of the novel configuration over the single transmit–receive coils throughout the volume of interest for cardiac imaging in pig. Finally, the TX-birdcage/RX-circular configuration was tested by acquiring metabolic maps with hyperpolarized [1-13C] pyruvate injected i.v. in a pig. The results of the phantom and pig experiments show the ability of the coil configuration to image well the metabolites distribution.

Monday, November 4, 2013

Theoretical Aspects of Dynamic Nuclear Polarization in the Solid State: The Influence of High Radical Concentrations on the Solid Effect and Cross Effect Mechanisms


Hovav, Y., et al., Theoretical Aspects of Dynamic Nuclear Polarization in the Solid State: The Influence of High Radical Concentrations on the Solid Effect and Cross Effect Mechanisms. Appl. Magn. Reson., 2012. 43(1-2): p. 21-41.


Dynamic nuclear polarization (DNP) is used to enhance signals in NMR and MRI experiments. During these experiments microwave (MW) irradiation mediates transfer of spin polarization from unpaired electrons to their neighboring nuclei. Solid state DNP is typically applied to samples containing high concentrations (i.e. 10–40 mM) of stable radicals that are dissolved in glass forming solvents together with molecules of interest. Three DNP mechanisms can be responsible for enhancing the NMR signals: the solid effect (SE), the cross effect (CE), and thermal mixing (TM). Recently, numerical simulations were performed to describe the SE and CE mechanisms in model systems composed of several nuclei and one or two electrons. It was shown that the presence of core nuclei, close to DNP active electrons, can result in a decrease of the nuclear polarization, due to broadening of the double quantum (DQ) and zero quantum (ZQ) spectra. In this publication we consider samples with high radical concentrations, exhibiting broad inhomogeneous EPR line-shapes and slow electron cross-relaxation rates, where the TM mechanism is not the main source for the signal enhancements. In this case most of the electrons in the sample are not affected by the MW field applied at a discrete frequency. Numerical simulations are performed on spin systems composed of several electrons and nuclei in an effort to examine the role of the DNP inactive electrons. Here we show that these electrons also broaden the DQ and ZQ spectra, but that they hardly cause any loss to the DNP enhanced nuclear polarization due to their spin-lattice relaxation mechanism. Their presence can also prevent some of the polarization losses due to the core nuclei.

Friday, November 1, 2013

DAC-board based X-band EPR spectrometer with arbitrary waveform control

Some instrumentation that is very interesting.



Kaufmann, T., et al., DAC-board based X-band EPR spectrometer with arbitrary waveform control. J Magn Reson, 2013. 235(0): p. 95-108.


We present arbitrary control over a homogenous spin system, demonstrated on a simple, home-built, electron paramagnetic resonance (EPR) spectrometer operating at 8-10 GHz (X-band) and controlled by a 1 GHz arbitrary waveform generator (AWG) with 42 dB (i.e. 14-bit) of dynamic range. Such a spectrometer can be relatively easily built from a single DAC (digital to analog converter) board with a modest number of stock components and offers powerful capabilities for automated digital calibration and correction routines that allow it to generate shaped X-band pulses with precise amplitude and phase control. It can precisely tailor the excitation profiles "seen" by the spins in the microwave resonator, based on feedback calibration with experimental input. We demonstrate the capability to generate a variety of pulse shapes, including rectangular, triangular, Gaussian, sinc, and adiabatic rapid passage waveforms. We then show how one can precisely compensate for the distortion and broadening caused by transmission into the microwave cavity in order to optimize corrected waveforms that are distinctly different from the initial, uncorrected waveforms. Specifically, we exploit a narrow EPR signal whose width is finer than the features of any distortions in order to map out the response to a short pulse, which, in turn, yields the precise transfer function of the spectrometer system. This transfer function is found to be consistent for all pulse shapes in the linear response regime. In addition to allowing precise waveform shaping capabilities, the spectrometer presented here offers complete digital control and calibration of the spectrometer that allows one to phase cycle the pulse phase with 0.007 degrees resolution and to specify the inter-pulse delays and pulse durations to </= 250 ps resolution. The implications and potential applications of these capabilities will be discussed.

Wednesday, October 30, 2013

Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research


Kurhanewicz, J., et al., Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia, 2011. 13(2): p. 81-97.


A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as (13)C or (15)N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism-poor sensitivity-while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care.

Tuesday, October 29, 2013

Postdoc position (in vivo hyperpolarized 13C MR)



The University of Maryland School of Medicine is expanding its molecular imaging and interventional research capabilities with the addition of a Dynamic Nuclear Polarizer and High-Intensity Focused Ultrasound as part of the recently established Center for Integration of Metabolic Imaging and Therapeutics (CIMIT). This expansion is aimed to facilitate both basic science and clinical research by exploring novel molecular imaging agent based technologies for screening, early detection, and real-time image-guided interventions.

In this process a postdoctoral research fellowship position is available in the metabolic imaging group led by Dr. Dirk Mayer within the Magnetic Resonance Research Center (MRRC). The primary focus of the position will be on the development and evaluation of new in vivo acquisition methods for hyperpolarized 13C spectroscopic imaging in both animal models and humans. 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 background in NMR physics with particular emphasis on in vivo spectroscopy, data acquisition and processing. Experience in pulse sequence programming (ideally on a GE clinical scanner) is preferred. Knowledge of other computer languages, including C++, Matlab and IDL, and experience in performing small animal imaging experience is also desirable. Qualified applicants should also have a track record of first-author research papers published in peer-reviewed journals.

Interested individuals should send a letter detailing their research interests, an updated CV and contact information for at least two references to Dr. Dirk Mayer at dirk@umaryland.edu.

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Monday, October 28, 2013

Dynamic nuclear polarization-enhanced 1H–13C double resonance NMR in static samples below 20 K

I think I missed this one from 2012


Potapov, A., et al., Dynamic nuclear polarization-enhanced 1H–13C double resonance NMR in static samples below 20 K. J. Magn. Reson., 2012. 221(0): p. 32-40.


We demonstrate the feasibility of one-dimensional and two-dimensional 1H–13C double resonance NMR experiments with dynamic nuclear polarization (DNP) at 9.4 T and temperatures below 20 K, including both 1H–13C cross-polarization and 1H decoupling, and discuss the effects of polarizing agent type, polarizing agent concentration, temperature, and solvent deuteration. We describe a two-channel low-temperature DNP/NMR probe, capable of carrying the radio-frequency power load required for 1H–13C cross-polarization and high-power proton decoupling. Experiments at 8 K and 16 K reveal a significant T2 relaxation of 13C, induced by electron spin flips. Carr–Purcell experiments and numerical simulations of Carr–Purcell dephasing curves allow us to determine the effective correlation time of electron flips under our experimental conditions. The dependence of the DNP signal enhancement on electron spin concentration shows a maximum near 80&#xa0;mM. Although no significant difference in the absolute DNP enhancements for triradical (DOTOPA-TEMPO) and biradical (TOTAPOL) dopants was found, the triradical produced greater DNP build-up rates, which are advantageous for DNP experiments. Additionally the feasibility of structural measurements on 13C-labeled biomolecules was demonstrated with a two-dimensional 13C–13C exchange spectrum of selectively 13C-labeled β-amyloid fibrils.

Friday, October 25, 2013

Proton polarization in photo-excited aromatic molecule at room temperature enhanced by intense optical source and temperature control


Sakaguchi, S., et al., Proton polarization in photo-excited aromatic molecule at room temperature enhanced by intense optical source and temperature control. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2013(0).


Proton polarization at room temperature, produced in a p-terphenyl crystal by using electron population difference in a photo-excited triplet state of pentacene, was enhanced by utilizing an intense laser with an average power of 1.5 W. It was shown that keeping the sample temperature below 300 K is critically important to prevent the rise of the spin–lattice relaxation rate caused by the laser heating. It is also reported that the magnitude of proton polarization strongly depends on the time structure of the laser pulse such as its width and the time interval between them.

Thursday, October 24, 2013

REMINDER: Course on "Dissolution Dynamic Nuclear Polarization" November 13-15, 2013 at EPFL, Switzerland

This is from the Ampere Magnetic Resonance List:


We would like to announce a three-day course for PhD students and Post-Docs on

"Dissolution Dynamic Nuclear Polarization"

The course will start at 1pm on Wednesday November the 13th and will end at 5pm on Friday 15th, and will be held at the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, at the Laboratory of Biomolecular Magnetic Resonance (LRMB).

* Registration
please register at the following adress:
subscription fees: 100 CHF

* Information
geoffrey.bodenhausen (at) epfl.ch
sami.jannin (at) epfl.ch

* Objectives
Dissolution Dynamic Nuclear Polarization (D-DNP) provides a way to enhance NMR signals in liquids by more than 4 orders of magnitude. We present the current state-of-the-art and most recent advances of this technique, and we propose experimental demonstrations with hands-on participation. 

* Content
Lectures and seminars: 11 Hours
Hands-on: 7 Hours
Day 1: Lectures, 1 pm - 5 pm: Theoretical aspects of DNP

- Introduction to DNP-enhanced NMR
- Principles of Dissolution-DNP
- Low temperature DNP mechanisms
- Cross Polarization techniques
- Applications to imaging and chemistry

Day 2: Lectures, 9 am - 12 am: Experimental aspects of DNP

- Hardware for DNP
- Hardware for Cross Polarization 
- Hardware for Dissolution

Experiments, 1 pm - 5 pm

- Sample Preparation
- Preparation of a dissolution DNP experiment

Day 3: Experiments, 9 am - 12 am: Practical DNP at the Laboratory of Biomolecular Magnetic Resonance (LRMB)

- Low temperature DNP
- Cross Polarization with DNP 
- Dissolution DNP

Seminars, 1 pm - 5 pm

- All participants are invited to give a short presentation, possibly on DNP and/or related to their own research subjects.

*Required prior knowledge

Basic understanding of NMR

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Wednesday, October 23, 2013

Overhauser dynamic nuclear polarization-enhanced NMR relaxometry


Franck, J.M., R. Kausik, and S. Han, Overhauser Dynamic Nuclear Polarization-Enhanced NMR Relaxometry. Microporous Mesoporous Mater, 2013. 178(0): p. 113-118.


We present a new methodological basis for selectively illuminating a dilute population of fluid within a porous medium. Specifically, transport in porous materials can be analyzed by now-standard nuclear magnetic resonance (NMR) relaxometry and NMR pulsed field gradient (PFG) diffusometry methods in combination with with the prominent NMR signal amplification tool, dynamic nuclear polarization (DNP). The key components of the approach introduced here are (1) to selectively place intrinsic or extrinsic paramagnetic probes at the site or local volume of interest within the sample, (2) to amplify the signal from the local solvent around the paramagnetic probes with Overhauser DNP, which is performed in situ and under ambient conditions, and (3) to observe the ODNP-enhanced solvent signal with 1D or 2D NMR relaxometry methods, thus selectively amplifying only the relaxation dynamics of the fluid that resides in or percolates through the local porous volume that contains the paramagnetic probe. Here, we demonstrate the proof of principle of this approach by selectively amplifying the NMR signal of only one solvent population, which is in contact with a paramagnetic probe and occluded from a second solvent population. An apparent one-component T 2 relaxation decay is shown to actually contain two distinct solvent populations. The approach outlined here should be universally applicable to a wide range of other 1D and 2D relaxometry and PFG diffusometry measurements, including T 1-T 2 or T 1-D correlation maps, where the occluded population containing the paramagnetic probes can be selectively amplified for its enhanced characterization.

Friday, October 18, 2013

Evidence for Coherent Transfer of para-Hydrogen-Induced Polarization at Low Magnetic Fields


Kiryutin, A.S., et al., Evidence for Coherent Transfer of para-Hydrogen-Induced Polarization at Low Magnetic Fields. The Journal of Physical Chemistry Letters, 2013. 4(15): p. 2514-2519.


We have investigated the mechanism of para-hydrogen-induced polarization (PHIP) transfer from the original strongly aligned protons to other nuclei at low external magnetic fields. Although it is known that PHIP is efficiently transferred at low fields, the nature of the transfer mechanism, that is, coherent spin mixing or cross-relaxation, is not well established. Polarization transfer kinetics for individual protons of styrene was, for the first time, measured and modeled theoretically. Pronounced oscillations were observed indicating a coherent transfer mechanism. Spin coherences were excited by passing through an avoided level crossing of the nuclear spin energy levels. Transfer at avoided level crossings is selective with respect to spin order. Our work provides evidence that the coherent PHIP transfer mechanism is dominant at low magnetic fields.

Wednesday, October 16, 2013

Asymmetric Collapse in Biomimetic Complex Coacervates Revealed by Local Polymer and Water Dynamics


Ortony, J.H., et al., Asymmetric Collapse in Biomimetic Complex Coacervates Revealed by Local Polymer and Water Dynamics. Biomacromolecules, 2013. 14(5): p. 1395-1402.


Complex coacervation is a phenomenon characterized by the association of oppositely charged polyelectrolytes into micrometer-scale liquid condensates. This process is the purported first step in the formation of underwater adhesives by sessile marine organisms, as well as the process harnessed for the formation of new synthetic and protein-based contemporary materials. Efforts to understand the physical nature of complex coacervates are important for developing robust adhesives, injectable materials, or novel drug delivery vehicles for biomedical applications; however, their internal fluidity necessitates the use of in situ characterization strategies of their local dynamic properties, capabilities not offered by conventional techniques such as X-ray scattering, microscopy, or bulk rheological measurements. Herein, we employ the novel magnetic resonance technique Overhauser dynamic nuclear polarization enhanced nuclear magnetic resonance (DNP), together with electron paramagnetic resonance (EPR) line shape analysis, to concurrently quantify local molecular and hydration dynamics, with species- and site-specificity. We observe striking differences in the structure and dynamics of the protein-based biomimetic complex coacervates from their synthetic analogues, which is an asymmetric collapse of the polyelectrolyte constituents. From this study we suggest charge heterogeneity within a given polyelectrolyte chain to be an important parameter by which the internal structure of complex coacervates may be tuned. Acquiring molecular-level insight to the internal structure and dynamics of dynamic polymer complexes in water through the in situ characterization of site- and species-specific local polymer and hydration dynamics should be a promising general approach that has not been widely employed for materials characterization.

Monday, October 14, 2013

Computation of DNP coupling factors of a nitroxide radical in toluene: seamless combination of MD simulations and analytical calculations


Sezer, D., Computation of DNP coupling factors of a nitroxide radical in toluene: seamless combination of MD simulations and analytical calculations. Phys. Chem. Chem. Phys., 2013. 15(2): p. 526-540.


Dynamic nuclear polarization (DNP) employs paramagnetic species to increase the NMR signal of nuclear spins. In liquids, the efficiency of the effect depends on the strength of the interaction between the electron and nuclear spins and the time scales on which this interaction is modulated by the physical motion of the spin-bearing molecules. An approach to quantitatively predict the contribution of molecular motions to the DNP enhancement using molecular dynamics (MD) simulations is developed and illustrated for the nitroxide radical TEMPOL in liquid toluene. A multi-resolution strategy that combines explicit treatment of the solvent at short distances from the free radical with implicit description at large intermolecular distances is adopted. Novel analytical expressions are obtained to correct for the finite spatial extent of the MD simulations. The atomistic and analytical descriptions are sewn seamlessly together by ensuring that for molecular trajectories that start in the near (explicit) region and end in the distant (implicit) region the analytical dipolar spectral densities reproduce the MD estimates. The spectral densities obtained from the developed approach are used to calculate DNP coupling factors separately for the ring and methyl protons of toluene. The agreement with previously reported experimental DNP data at a magnetic field of 3.4 T is noteworthy and encouraging. Maximum obtainable DNP enhancements at other magnetic fields are predicted.

Friday, October 11, 2013

Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates


Xing, Y., et al., Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates. J. Magn. Reson., 2013. 234(0): p. 75-81.


In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral-spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-(13)C]lactate generated from [1-(13)C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.

Wednesday, October 9, 2013

Nanoemulsion Contrast Agents with Sub-picomolar Sensitivity for Xenon NMR


Stevens, T.K., R.M. Ramirez, and A. Pines, Nanoemulsion Contrast Agents with Sub-picomolar Sensitivity for Xenon NMR. J. Am. Chem. Soc., 2013. 135(26): p. 9576-9579.


A new type of contrast agent for Xe NMR based on surfactant-stabilized perfluorocarbon-in-water nanoemulsions has been produced. The contrast agent uses dissolved hyperpolarized xenon gas as a nonperturbing reporting medium, as xenon freely exchanges between aqueous solution and the perfluorocarbon interior of the droplets, which are spectroscopically distinguishable and allow for chemical exchange saturation transfer (CEST) detection of the agent. Nanoemulsions with droplet diameters between 160 and 310 nm were produced and characterized using hyperpolarized 129Xe combined with CEST detection. Saturation parameters were varied and data were modeled numerically to determine the xenon exchange dynamics of the system. Nanoemulsion droplets were detected at concentrations as low as 100 fM, corresponding to <1 ?L of perfluorocarbon per liter of solution. The straightforward, inexpensive production of these agents will facilitate future development toward molecular imaging and chemical sensing applications.

Monday, October 7, 2013

Dynamic nuclear polarization of water by a nitroxide radical: rigorous treatment of the electron spin saturation and comparison with experiments at 9.2 Tesla

And another great article from 2009 that I missed.



Sezer, D., et al., Dynamic nuclear polarization of water by a nitroxide radical: rigorous treatment of the electron spin saturation and comparison with experiments at 9.2 Tesla. Phys. Chem. Chem. Phys., 2009. 11(31): p. 6638-6653.


The interaction between nuclear and electronic spins is of interest for structural characterization of biomolecules and biomedical imaging based on nuclear magnetic resonance. The polarization of the nuclear spins can be increased significantly if the electron spin polarization is kept out of equilibrium. We employ semiclassical relaxation theory to analyze the electronic polarization of the two-spin system characteristic of nitroxide radicals. Atomistic molecular dynamics simulations of the nitroxide TEMPOL in water are performed to account for the effects of tumbling and spin-rotation coupling on the spin-spin and spin-lattice relaxation times. Concentration effects on the electron saturation are introduced by allowing for Heisenberg spin exchange between two nitroxides. Polarization enhancement profiles, calculated from the computed saturation, are directly compared with liquid-state dynamic nuclear polarization experiments conducted at 260 GHz/400 MHz. The contribution of the separate hyperfine lines to the saturation can be easily disentangled using the developed formalism.

Friday, October 4, 2013

Site-specific dynamic nuclear polarization of hydration water as a generally applicable approach to monitor protein aggregation

This article was already published in 2009 but unfortunately I missed it.


Pavlova, A., et al., Site-specific dynamic nuclear polarization of hydration water as a generally applicable approach to monitor protein aggregation. Phys. Chem. Chem. Phys., 2009. 11(31): p. 6833-6839.


We present a generally applicable approach for monitoring protein aggregation by detecting changes in surface hydration water dynamics and the changes in solvent accessibility of specific protein sites, as protein aggregation proceeds in solution state. This is made possible through the Overhauser dynamic nuclear polarization (DNP) of water interacting with stable nitroxide spin labels tethered to specific proteins sites. This effect is highly localized due to the magnetic dipolar nature of the electron-proton spin interaction, with >80% of their interaction occurring within 5 A between the unpaired electron of the spin label and the proton of water. We showcase our tool on the aggregation of tau proteins, whose fibrillization is linked to neurodegenerative disease pathologies known as taupathies. We demonstrate that the DNP approach to monitor local changes in hydration dynamics with residue specificity and local contrast can distinguish specific and neat protein-protein packing leading to fibers from non-specific protein agglomeration or precipitation. The ability to monitor tau assembly with local, residue-specific, resolution, under ambient conditions and in solution state will help unravel the mechanism and structural characteristics of the gradual process of tau aggregation into amyloid fibers, which remains unclear to this day.

Wednesday, October 2, 2013

Matrix-free dynamic nuclear polarization enables solid-state NMR (13)C-(13)C correlation spectroscopy of proteins at natural isotopic abundance


Takahashi, H., S. Hediger, and G. De Paepe, Matrix-free dynamic nuclear polarization enables solid-state NMR (13)C-(13)C correlation spectroscopy of proteins at natural isotopic abundance. Chem Commun (Camb), 2013. 49(82): p. 9479-81.


We introduce a general approach for dynamic nuclear polarization (DNP) enhanced solid-state NMR that overcomes the current problems in DNP experiments caused by the use of frozen solutions. Notably, we report for the first time a 2D (13)C-(13)C correlation spectrum of a protein without the use of isotopic labeling.

Monday, September 30, 2013

Open position at Bridge12: Engineer (entry-level)

Bridge12 has currently an opening for an engineer (entry level). We are looking for a junior engineer to support our team at our facilities in Framingham (MA, USA).
Your tasks will include:
  • ·       Mechanical design using state-of-the-art 3D CAD software
  • ·       Preparation of engineering drawings
  • ·       Work on the product assembly and testing
  • ·       Documentation of design process
  • ·       Requesting quotes for manufacturing and negotiate pricing with suppliers
  • ·       Preparing manufacturing cost estimates for parts and subassemblies


This is an entry-level position and applications of recent college graduates are encouraged. For more information visit: http://www.bridge12.com/content/open-position-engineer-entry-level