Friday, September 26, 2014

Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR


Buratto, R., et al., Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR. ChemMedChem, 2014: p. n/a-n/a.


Transverse and longitudinal relaxation times (T1rho and T1 ) have been widely exploited in NMR to probe the binding of ligands and putative drugs to target proteins. We have shown recently that long-lived states (LLS) can be more sensitive to ligand binding. LLS can be excited if the ligand comprises at least two coupled spins. Herein we broaden the scope of ligand screening by LLS to arbitrary ligands by covalent attachment of a functional group, which comprises a pair of coupled protons that are isolated from neighboring magnetic nuclei. The resulting functionalized ligands have longitudinal relaxation times T1 (1 H) that are sufficiently long to allow the powerful combination of LLS with dissolution dynamic nuclear polarization (D-DNP). Hyperpolarized weak "spy ligands" can be displaced by high-affinity competitors. Hyperpolarized LLS allow one to decrease both protein and ligand concentrations to micromolar levels and to significantly increase sample throughput.

Wednesday, September 24, 2014

Determination of sample temperature in unstable static fields by combining solid-state 79Br and 13C NMR

This is not an article about DNP-NMR spectroscopy, however, it deals with the measurements of temperatures in solid-state NMR experiments using KBR and referencing its chemical shift to 13C of adamantane in unstable magnetic fields.




Purusottam, R.N., G. Bodenhausen, and P. Tekely, Determination of sample temperature in unstable static fields by combining solid-state (79)Br and (13)C NMR. J Magn Reson, 2014. 246(0): p. 69-71.


Monitoring the isotropic chemical shifts to calibrate the sample temperature presupposes a perfect stability of the static magnetic field. It can be difficult to satisfy this requirement in solid-state NMR measurements. This paper describes a simple way to recover the accurate temperature dependence of the (79)Br resonance after subtracting changes of resonance frequency due to variations of the static field, monitored by the (13)C resonance.

Meet Bridge12 at the FGMR Meeting in Berlin

I will be at the Fachgruppe Magnetische Resonance (FGMR) Meeting in Berlin, September 29th - October 2nd, and at the one-day meeting 'Progress in DNP' September 29th.

If you would like to know about our products such as gyrotrons for DNP, frequency measurement systems, calorimetric power loads or corrugated transmission lines, or generally want to chat about DNP-NMR feel free to pull me aside or contact me at tmaly@bridge12.com.

For more information about the FGMR meeting visit the conference website.

Cheers,
Thorsten

Friday, September 19, 2014

PostDoc Position at Institut for Biomedical Engineering, ETH Zurich

From the Ampere Magnetic Resonance List


The Institute for Biomedical Engineering at the University and ETH Zurich in collaboration with the Laboratory of Physical Chemistry at ETH Zurich is offering following position:

Postdoctoral Fellow in Hyperpolarized Magnetic Resonance

Magnetic Resonance (MR) imaging is a prime diagnostic modality today. Despite its success, MR remains a relatively insensitive technique when probing nuclei other than protons. To this end, dissolution Dynamic Nuclear Polarization (DNP) methods have shown great promise to provide signal enhancements by orders of magnitude over short periods of time.

The position offered concerns further development and application of the dissolution DNP principle of various nuclei including carbon-13 and silicon-29. The project is embedded in a program aimed at developing novel methods to hyperpolarize and image the fate of metabolically active substrates and functionalized particles.

The University and ETH Zurich offer an international and stimulating research environment with first class infrastructure including the full range of clinical and experimental Magnetic Resonance systems as well as an excellent network of scientific and industrial partners.

Requirements
• PhD in physics, physical chemistry or biomedical engineering
• Fundamental knowledge of NMR, ESR, MRI, MRS
• Fluent in computer programming (Matlab, C)
• Interest in magnetic resonance hardware and experimentation
• Innovative spirit, team player

Contact:
Prof Dr Sebastian Kozerke
Institute for Biomedical Engineering 
University and ETH Zurich 
Gloriastrasse 35, 8092 Zurich
+41 44 632 3549 

- -- 

+----------------------------------------+-----------------------------------+
| Matthias Ernst | Phone: +41-44-632-4366 |
| ETH Zürich, HCI D 227 | Fax: +41-44-632-1621 |
| Laboratorium für Physikalische Chemie | |
| Wolfgang-Pauli-Strasse 10 | Email: maer@ethz.ch |
| CH-8093 Zürich, Switzerland | maer@gmx.ch |
+----------------------------------------+-----------------------------------+

Short-term postdoctoral position DNP MRI/SRM in Bordeaux

From the Ampere Magnetic Resonance List:


Postdoctoral position in DNP MR imaging and NMR spectroscopy Centre de Résonance Magnétique des Systèmes Biologiques Bordeaux, France

Position description

A short-term (6 months) postdoctoral position is available at the Center for Magnetic Resonance of Biological Systems located in Bordeaux, France. The position will focus on hyperpolarized carbon-13 spectroscopy and imaging.

Qualifications

Due to the short duration of the contract, the candidate will ideally have a previous experience in the field of MRS/MRI of hyperpolarized media and Dynamic Nuclear Polarization techniques. 

Facilities

The RMSB Center operates a dissolution DNP polarizer dedicated to MRI/MRS biomedical applications, two small animal Bruker MRI system (4.7 T and 7 T) and two high-resolution NMR spectrometer (400 and 500 MHz). The RMSB Center is composed of 40 scientists involved in development and applications of biomedical MRS/MRI. The Center is located on the Life Sciences and hospital campus at 10 minutes from the city center with public transportation.

Environment

Bordeaux is a 1-million urban area and hosts one of the largest university and research community in France. Located in South west of France in close proximity of the Atlantic Ocean, the city, part of the World Heritage List, offers a wide range of cultural and outdoors activities.

Conditions of employment

The duration of the position is 6 months with a net monthly salary of ~2100 euros.
The position is open from 1st November 2014
For more information and application please contact:

Yannick Crémillieux, yannick.cremillieux@u-bordeaux.fr

-- 
Yannick Crémillieux
PhD, DR CNRS
CRMSB, UMR 5536
Université Bordeaux 2
146, rue Léo-Saignat
33076 BORDEAUX Cedex

Tél: +33 (0)547304253
Fax: +33 (0)557574556

====================================
This is the AMPERE MAGNETIC RESONANCE mailing list:

NMR web database:

Radical-free dynamic nuclear polarization using electronic defects in silicon


Cassidy, M.C., et al., Radical-free dynamic nuclear polarization using electronic defects in silicon. Physical Review B, 2013. 87(16): p. 161306.


Direct dynamic nuclear polarization of 1H nuclei in frozen water and water-ethanol mixtures is demonstrated using silicon nanoparticles as the polarizing agent. Electron spins at dangling-bond sites near the silicon surface are identified as the source of the nuclear hyperpolarization. This polarization method opens avenues for the fabrication of surface engineered nanostructures to create high nuclear spin polarized solutions without introducing contaminating radicals, and for the study of molecules adsorbed onto surfaces.

Wednesday, September 17, 2014

Spectral editing through laser-flash excitation in two-dimensional photo-CIDNP MAS NMR experiments


Sai Sankar Gupta, K.B., et al., Spectral editing through laser-flash excitation in two-dimensional photo-CIDNP MAS NMR experiments. J Magn Reson, 2014. 246C(0): p. 9-17.


In solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) MAS NMR experiments, strong signal enhancement is observed from molecules forming a spin-correlated radical pair in a rigid matrix. Two-dimensional 13C-13C dipolar-assisted rotational resonance (DARR) photo-CIDNP MAS NMR experiments have been applied to obtain exact chemical shift assignments from those cofactors. Under continuous illumination, the signals are enhanced via three-spin mixing (TSM) and differential decay (DD) and their intensity corresponds to the electron spin density in pz orbitals. In multiple-13C labelled samples, spin diffusion leads to propagation of signal enhancement to all 13C spins. Under steady-state conditions, direct signal assignment is possible due to the uniform signal intensity. The original intensities, however, are inaccessible and the information of the local electron spin density is lost. Upon laser-flash illumination, the signal is enhanced via the classical radical pair mechanism (RPM). The obtained intensities are related to isotropic hyperfine interactions aiso and both enhanced absorptive and emissive lines can be observed due to differences in the sign of the local isotropic hyperfine interaction. Exploiting the mechanism of the polarization, selectivity can be increased by the novel time-resolved two-dimensional dipolar-assisted rotational resonance (DARR) MAS NMR experiment which simplifies the signal assignment compared to complex spectra of the same RCs obtained by continuous illumination. Here we present two-dimensional time-resolved photo-CIDNP MAS NMR experiments providing both directly: signal assignment and spectral editing by sign and strength of aiso. Hence, this experiment provides a direct key to the electronic structure of the correlated radical pair.

Monday, September 15, 2014

Long-lived localization in magnetic resonance imaging


Dumez, J.N., et al., Long-lived localization in magnetic resonance imaging. J Magn Reson, 2014. 246C(0): p. 27-30.


The longitudinal nuclear relaxation time, T1, sets a stringent limit on the range of information that can be obtained from magnetic resonance imaging (MRI) experiments. Long-lived nuclear spin states provide a possibility to extend the timescale over which information can be encoded in magnetic resonance. We introduce a strategy to localize an ensemble of molecules for a significantly extended duration ( approximately 30 times longer than T1 in this example), using a spatially selective conversion between magnetization and long-lived singlet order. An application to tagging and transport is proposed.

Friday, September 12, 2014

Achieving 1% NMR polarization in water in less than 1min using SABRE


Zeng, H., et al., Achieving 1% NMR polarization in water in less than 1min using SABRE. J Magn Reson, 2014. 246C(0): p. 119-121.


The development of biocompatible hyperpolarized media is a crucial step towards application of hyperpolarization in vivo. This article describes the achievement of 1% hyperpolarization of 3-amino-1,2,4-triazine protons in water using the parahydrogen induced polarization technique based on signal amplification by reversible exchange (SABRE). Polarization was achieved in less than 1min.

Wednesday, September 10, 2014

Dipolar Induced Para-Hydrogen-Induced Polarization


Buntkowsky, G., et al., Dipolar Induced Para-Hydrogen-Induced Polarization. Solid State Nuclear Magnetic Resonance, 2014(0).


Analytical expressions for the signal enhancement in solid-state PHIP NMR spectroscopy mediated by homonuclear dipolar interactions and single pulse or spin-echo excitation are developed and simulated numerically. It is shown that an efficient enhancement of the proton NMR signal in solid-state NMR studies of chemisorbed hydrogen on surfaces is possible. Employing typical reaction efficacy, enhancement-factors of ca. 30–40 can be expected both under ALTADENA and under PASADENA conditions. This result has important consequences for the practical application of the method, since it potentially allows the design of an in-situ flow setup, where the para-hydrogen is adsorbed and desorbed from catalyst surfaces inside the NMR magnet.

Monday, September 8, 2014

Overhauser effects in insulating solids


Can, T.V., et al., Overhauser effects in insulating solids. J Chem Phys, 2014. 141(6): p. 064202.


We report magic angle spinning, dynamic nuclear polarization (DNP) experiments at magnetic fields of 9.4 T, 14.1 T, and 18.8 T using the narrow line polarizing agents 1,3-bisdiphenylene-2-phenylallyl (BDPA) dispersed in polystyrene, and sulfonated-BDPA (SA-BDPA) and trityl OX063 in glassy glycerol/water matrices. The (1)H DNP enhancement field profiles of the BDPA radicals exhibit a significant DNP Overhauser effect (OE) as well as a solid effect (SE) despite the fact that these samples are insulating solids. In contrast, trityl exhibits only a SE enhancement. Data suggest that the appearance of the OE is due to rather strong electron-nuclear hyperfine couplings present in BDPA and SA-BDPA, which are absent in trityl and perdeuterated BDPA (d21-BDPA). In addition, and in contrast to other DNP mechanisms such as the solid effect or cross effect, the experimental data suggest that the OE in non-conducting solids scales favorably with magnetic field, increasing in magnitude in going from 5 T, to 9.4 T, to 14.1 T, and to 18.8 T. Simulations using a model two spin system consisting of an electron hyperfine coupled to a (1)H reproduce the essential features of the field profiles and indicate that the OE in these samples originates from the zero and double quantum cross relaxation induced by fluctuating hyperfine interactions between the intramolecular delocalized unpaired electrons and their neighboring nuclei, and that the size of these hyperfine couplings is crucial to the magnitude of the enhancements. Microwave power dependent studies show that the OE saturates at considerably lower power levels than the solid effect in the same samples. Our results provide new insights into the mechanism of the Overhauser effect, and also provide a new approach to perform DNP experiments in chemical, biophysical, and physical systems at high magnetic fields.

Training School on Hyperpolarization Techniques


Dear All,

The next COST Training School on Hyperpolarization techniques will be held on 20-24th October 2014, nearby Marseille.

The topics will include Dissolution DNP, MAS ssNMR / DNP, liquid DNP, Theory of polarization mechanisms (SE, CE, OE, static and MAS DNP, TM), High-field EPR, CIDNP, ONP, Hyperpolarized gas, Para Hydrogen Induced Polarization and application of DNP techniques.

This is a unique occasion to meet and discuss with leading actors involved in DNP breakthroughs in the frame of a training school.

The school is limited to 30 participants! 

Grants will be offered by EuroHyperPol COST Action program (TD1103) and the grant will be delivered after the School.


Looking forward to see you on the seaside !
Olivier Ouari and Paul Tordo

------------------------------------------------
Aix-Marseille Universite / CNRS
Faculte ed Saint Jerome case 521
13013 Marseille, France.

Friday, September 5, 2014

Dynamic Nuclear Polarization of 1H, 13C, and 59Co in a Tris(ethylenediamine)cobalt(III) Crystalline Lattice Doped with Cr(III)


Corzilius, B., et al., Dynamic Nuclear Polarization of 1H, 13C, and 59Co in a Tris(ethylenediamine)cobalt(III) Crystalline Lattice Doped with Cr(III). J. Am. Chem. Soc., 2014. 136(33): p. 11716-11727.


The study of inorganic crystalline materials by solid-state NMR spectroscopy is often complicated by the low sensitivity of heavy nuclei. However, these materials often contain or can be prepared with paramagnetic dopants without significantly affecting the structure of the crystalline host. Dynamic nuclear polarization (DNP) is generally capable of enhancing NMR signals by transferring the magnetization of unpaired electrons to the nuclei. Therefore, the NMR sensitivity in these paramagnetically doped crystals might be increased by DNP. In this paper we demonstrate the possibility of efficient DNP transfer in polycrystalline samples of [Co(en)3Cl3]2·NaCl·6H2O (en = ethylenediamine, C2H8N2) doped with Cr(III) in varying concentrations between 0.1 and 3 mol %. We demonstrate that 1H, 13C, and 59Co can be polarized by irradiation of Cr(III) with 140 GHz microwaves at a magnetic field of 5 T. We further explain our findings on the basis of electron paramagnetic resonance spectroscopy of the Cr(III) site and analysis of its temperature-dependent zero-field splitting, as well as the dependence of the DNP enhancement factor on the external magnetic field and microwave power. This first demonstration of DNP transfer from one paramagnetic metal ion to its diamagnetic host metal ion will pave the way for future applications of DNP in paramagnetically doped materials or metalloproteins.