Friday, December 29, 2017

Characterizing Thermal Mixing Dynamic Nuclear Polarization via Cross-Talk between Spin Reservoirs #DNPNMR

Guarin, D., et al., Characterizing Thermal Mixing Dynamic Nuclear Polarization via Cross-Talk between Spin Reservoirs. The Journal of Physical Chemistry Letters, 2017. 8(22): p. 5531-5536.


Dynamic nuclear polarization (DNP) embraces a family of methods to increase signal intensities in nuclear magnetic resonance (NMR) spectroscopy. Despite extensive theoretical work that allows one to distinguish at least five distinct mechanisms, it remains challenging to determine the relative weights of the processes that are responsible for DNP in state-of-the-art experiments operating with stable organic radicals like nitroxides at high magnetic fields and low temperatures. Specifically, determining experimental conditions where DNP involves thermal mixing, which denotes a spontaneous heat exchange between different spin reservoirs, remains challenging. We propose an experimental approach to ascertain the prevalence of the thermal mixing regime by monitoring characteristic signature properties of the time evolution of the hyperpolarization. We find that thermal mixing is the dominant DNP mechanism at high nitroxide radical concentrations, while a mixture of different mechanisms prevails at lower concentrations.

Friday, December 22, 2017

Aqueous, Heterogeneous para-Hydrogen-Induced 15N Polarization


Bales, L.B., et al., Aqueous, Heterogeneous para-Hydrogen-Induced 15N Polarization. The Journal of Physical Chemistry C, 2017. 121(28): p. 15304-15309.


The successful transfer of para-hydrogen-induced polarization to 15N spins using heterogeneous catalysts in aqueous solutions was demonstrated. Hydrogenation of a synthesized unsaturated 15N-labeled precursor (neurine) with parahydrogen (p-H2) over Rh/TiO2 heterogeneous catalysts yielded a hyperpolarized structural analogue of choline. As a result, 15N polarization enhancements of over 2 orders of magnitude were achieved for the 15N-labeled ethyltrimethylammonium ion product in deuterated water at elevated temperatures. Enhanced 15N NMR spectra were successfully acquired at 9.4 and 0.05 T. Importantly, long hyperpolarization lifetimes were observed at 9.4 T, with a 15N T1 of ∼6 min for the product molecules, and the T1 of the deuterated form exceeded 8 min. Taken together, these results show that this approach for generating hyperpolarized species with extended lifetimes in aqueous, biologically compatible solutions is promising for various biomedical applications.

Thursday, December 21, 2017

[NMR] NMR position at the University of Florida


The lab of Dr. Matthew Merritt has an immediate opening for a post-doctoral research associate in NMR and metabolism. The position is funded through a newly awarded NIH P41 grant (Project title: National Resource for Advanced NMR Technology, 1P41GM122698) with pay according to the NIH scale. 

Project Description

High Temperature Superconducting (HTS) cold probes provide gains in signal to noise ratio that exceed current cold probe technology by a factor of two at least. In collaboration with Dr. Bill Brey at the NHMFL, the research team will commission newly built HTS probes at 600 and 800 MHz. The probes will focus on X-detection, with potential applications in 13C and 2H based methods for studying intermediary metabolism. Other possible applications include 15N detected methods for structural biology. In addition to these goals, the Merritt lab has an active program in hyperpolarization for the study of metabolic turnover in perfused organs and in vivo. Synchronization of hyperpolarization and traditional isotope methods for measuring metabolic flux is part of a long term strategy for developing new insights into metabolic control and intermediary metabolism.

The NHMFL

The University of Florida (Gainesville) is part of the National High Magnetic Field Laboratory, and hosts a diverse array of state of the art MR and MRI equipment. The site includes 2 horizontal bore imaging systems operating at 4.7 T and 11 T. The 11 T is a 40 cm bore system, and was recently upgraded to the latest Bruker imaging console. We also host multiple vertical bore NMR systems, including a widebore 750 MHz system for imaging and spectroscopy, three 600 MHz NMR systems, and 2 dynamic nuclear polarization instruments operating at 3.35 T (HyperSense) and 5 T (a homebuilt system). An 800 MHz NMR system will be commissioned this year; this system will serve as a primary instrument for development of the new HTS probes.

Candidates with a background in chemistry, physics, or experience in NMR or MRI will be considered. A strong interest in hardware development and troubleshooting ability is strongly encouraged in the applicant.

For applications, please send a CV and a letter of motivation to matthewmerritt@ufl.edu

Matthew E. Merritt
Associate Professor
Department of Biochemistry and Molecular Biology
University of Florida
PO Box 100245
Gaineville, FL 32610-0245
(352) 294-8397


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Wednesday, December 20, 2017

[NMR] Position: Researcher or Senior Researcher in hyperpolarized Magnetic Resonance



Dear colleagues

We have an open position as researcher or senior researcher in hyperpolarized magnetic resonance.

The main responsibility will be to manage the NMR laboratory and related equipment. This means maintaining NMR spectrometers, instrumentation and other infrastructure, and developing and provide NMR training to group members as needed, development and implementation of new NMR experiments and hardware, data analysis and presentation of results for users, supervision of and assistance to internal users and students and supporting the research on hyperpolarization in collaboration with colleagues and external collaborators.

You will also contribute to the common research goals of the Center. Since hyperpolarization is a complex method that requires interdisciplinary skills, the conducted research at HYPERMAG is a team effort. Specifically, it is expected that the successful candidate will conduct research on fundamental questions related to hyperpolarization, and contribute to e.g. the study and understanding of the physics involved in hyperpolarization by dissolution DNP, technological and methodological challenges related to the interface between hyperpolarization and NMR.

The position may involve research-based teaching including guidance and supervision of postdocs and PhD students. The candidate is expected to contribute to developing the research portfolio within the above area and to be service-minded, show team spirit and contribute to a good work atmosphere and a thriving environment is essential.



Best regards,

Jan Henrik Ardenkjær-Larsen
Professor, Center Leader

Technical University of Denmark 
Department of Electrical Engineering
Ørsted Plads, bldg 349, office 126
DK - 2800 Kgs. Lyngby

Phone +45 45253918
Mobile +45 40272775


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Instrumentation for cryogenic magic angle spinning dynamic nuclear polarization using 90L of liquid nitrogen per day #DNPNMR


Albert, B.J., et al., Instrumentation for cryogenic magic angle spinning dynamic nuclear polarization using 90L of liquid nitrogen per day. J. Magn. Reson., 2017. 283(Supplement C): p. 71-78.


Cryogenic sample temperatures can enhance NMR sensitivity by extending spin relaxation times to improve dynamic nuclear polarization (DNP) and by increasing Boltzmann spin polarization. We have developed an efficient heat exchanger with a liquid nitrogen consumption rate of only 90L per day to perform magic-angle spinning (MAS) DNP experiments below 85K. In this heat exchanger implementation, cold exhaust gas from the NMR probe is returned to the outer portion of a counterflow coil within an intermediate cooling stage to improve cooling efficiency of the spinning and variable temperature gases. The heat exchange within the counterflow coil is calculated with computational fluid dynamics to optimize the heat transfer. Experimental results using the novel counterflow heat exchanger demonstrate MAS DNP signal enhancements of 328±3 at 81±2K, and 276±4 at 105±2K.

Monday, December 18, 2017

Anisotropic longitudinal electronic relaxation affects DNP at cryogenic temperatures #DNPNMR


Weber, E.M.M., et al., Anisotropic longitudinal electronic relaxation affects DNP at cryogenic temperatures. Phys. Chem. Chem. Phys., 2017. 19(24): p. 16087-16094.


We report the observation of anisotropic longitudinal electronic relaxation in nitroxide radicals under typical dynamic nuclear polarization conditions. This anisotropy affects the efficiency of dynamic nuclear polarization at cryogenic temperatures of 4 K and high magnetic fields of 6.7 T. Under our experimental conditions, the electron paramagnetic resonance spectrum of nitroxides such as TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) is only partly averaged by electronic spectral diffusion, so that the relaxation times T1e(omega) vary across the spectrum. We demonstrate how the anisotropy of T1e(omega) can be taken into account in simple DNP models.

Friday, December 15, 2017

Uniform field loop-gap resonator and rectangular TEU02 for aqueous sample EPR at 94GHz


Sidabras, J.W., et al., Uniform field loop-gap resonator and rectangular TEU02 for aqueous sample EPR at 94GHz. J. Magn. Reson., 2017. 282(Supplement C): p. 129-135.


In this work we present the design and implementation of two uniform-field resonators: a seven-loop–six-gap loop-gap resonator (LGR) and a rectangular TEU02 cavity resonator. Each resonator has uniform-field-producing end-sections. These resonators have been designed for electron paramagnetic resonance (EPR) of aqueous samples at 94GHz. The LGR geometry employs low-loss Rexolite end-sections to improve the field homogeneity over a 3mm sample region-of-interest from near-cosine distribution to 90% uniform. The LGR was designed to accommodate large degassable Polytetrafluorethylen (PTFE) tubes (0.81mm O.D.; 0.25mm I.D.) for aqueous samples. Additionally, field modulation slots are designed for uniform 100kHz field modulation incident at the sample. Experiments using a point sample of lithium phthalocyanine (LiPC) were performed to measure both the uniformity of the microwave magnetic field and 100kHz field modulation, and confirm simulations. The rectangular TEU02 cavity resonator employs over-sized end-sections with sample shielding to provide an 87% uniform field for a 0.1×2×6mm3 sample geometry. An evanescent slotted window was designed for light access to irradiate 90% of the sample volume. A novel dual-slot iris was used to minimize microwave magnetic field perturbations and maintain cross-sectional uniformity. Practical EPR experiments using the application of light irradiated rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) were performed in the TEU02 cavity. The implementation of these geometries providing a practical designs for uniform field resonators that continue resonator advancements towards quantitative EPR spectroscopy.

Wednesday, December 13, 2017

Perspectives on paramagnetic NMR from a life sciences infrastructure


Ravera, E., G. Parigi, and C. Luchinat, Perspectives on paramagnetic NMR from a life sciences infrastructure. J Magn Reson, 2017. 282(Supplement C): p. 154-169.


The effects arising in NMR spectroscopy because of the presence of unpaired electrons, collectively referred to as "paramagnetic NMR" have attracted increasing attention over the last decades. From the standpoint of the structural and mechanistic biology, paramagnetic NMR provides long range restraints that can be used to assess the accuracy of crystal structures in solution and to improve them by simultaneous refinements through NMR and X-ray data. These restraints also provide information on structure rearrangements and conformational variability in biomolecular systems. Theoretical improvements in quantum chemistry calculations can nowadays allow for accurate calculations of the paramagnetic data from a molecular structural model, thus providing a tool to refine the metal coordination environment by matching the paramagnetic effects observed far away from the metal. Furthermore, the availability of an improved technology (higher fields and faster magic angle spinning) has promoted paramagnetic NMR applications in the fast-growing area of biomolecular solid-state NMR. Major improvements in dynamic nuclear polarization have been recently achieved, especially through the exploitation of the Overhauser effect occurring through the contact-driven relaxation mechanism: the very large enhancement of the (13)C signal observed in a variety of liquid organic compounds at high fields is expected to open up new perspectives for applications of solution NMR.

Monday, December 11, 2017

Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNP NMR Spectroscopy #DNPNMR


Ragavan, M., et al., Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNP NMR Spectroscopy. Angew Chem Int Ed Engl, 2017. 56(25): p. 7070-7073.


The kinase inhibitory domain of the cell cycle regulatory protein p27(Kip1) (p27) was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D-DNP). While intrinsically disordered in isolation, p27 adopts secondary structural motifs, including an alpha-helical structure, upon binding to cyclin-dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with hyperpolarization enable the real-time observation of (13) C NMR signals during p27 folding upon binding to Cdk2/cyclin A on a time scale of several seconds. Time-dependent intensity changes are dependent on the extent of folding and binding, as manifested in differential spin relaxation. The analysis of signal decay rates suggests the existence of a partially folded p27 intermediate during the timescale of the D-DNP NMR experiment.

Friday, December 8, 2017

In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR #DNPNMR


Ni, Q.Z., et al., In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR. The Journal of Physical Chemistry B, 2017. 121(34): p. 8132-8141.


A principal advantage of magic angle spinning (MAS) NMR spectroscopy lies in its ability to determine molecular structure in a noninvasive and quantitative manner. Accordingly, MAS should be widely applicable to studies of the structure of active pharmaceutical ingredients (API) and formulations. However, the low sensitivity encountered in spectroscopy of natural abundance APIs present at low concentration has limited the success of MAS experiments. Dynamic nuclear polarization (DNP) enhances NMR sensitivity and can be used to circumvent this problem provided that suitable paramagnetic polarizing agent can be incorporated into the system without altering the integrity of solid dosages. Here, we demonstrate that DNP polarizing agents can be added in situ during the preparation of amorphous solid dispersions (ASDs) via spray drying and hot-melt extrusion so that ASDs can be examined during drug development. Specifically, the dependence of DNP enhancement on sample composition, radical concentration, relaxation properties of the API and excipients, types of polarizing agents and proton density, has been thoroughly investigated. Optimal enhancement values are obtained from ASDs containing 1% w/w radical concentration. Both polarizing agents TOTAPOL and AMUPol provided reasonable enhancements. Partial deuteration of the excipient produced 3× higher enhancement values. With these parameters, an ASD containing posaconazole and vinyl acetate yields a 32-fold enhancement which presumably results in a reduction of NMR measurement time by ∼1000. This boost in signal intensity enables the full assignment of the natural abundance pharmaceutical formulation through multidimensional correlation experiments.

Wednesday, December 6, 2017

A sub-Kelvin cryogen-free EPR system


This article has nothing to do with DNP. However, the article nicely describes an impressive piece of isntrumentation to reach very low temperatures.


Melhuish, S.J., et al., A sub-Kelvin cryogen-free EPR system. J. Magn. Reson., 2017. 282(Supplement C): p. 83-88.


We present an EPR instrument built for operation at Q band below 1K. Our cryogen-free Dewar integrates with a commercial electro-magnet and bridge. A description of the cryogenic and RF systems is given, along with the adaptations to the standard EPR experiment for operation at sub-Kelvin temperatures. As a first experiment, the EPR spectra of powdered Cr12O9(OH)3(O2CCMe3)15 were measured. The sub-Kelvin EPR spectra agree well with predictions, and the performance of the sub-Kelvin system at 5K is compared to that of a commercial spectrometer.

Tuesday, December 5, 2017

[NMR] HYP18 meeting, Southampton Sep 2-5, 2018 #DNPNMR

This is advance notice of an international meeting on hyperpolarization, HYP18, which will be held in Southampton, UK on Sep 2-5, 2018

The program will cover a wide range of hyperpolarization techniques and their applications, including DNP in both liquids and solids, parahydrogen-based techniques, optical pumping, quantum rotor polarization, and other methods. We hope that the meeting will promote comparison, discussion, and cross-fertilisation between the different techniques. 

Confirmed speakers include:

Stephan Appelt, Aachen, Germany
Peter Blümler, Mainz, Germany
Kevin Brindle, Cambridge, UK
Arnaud Comment, Cambridge, UK
Bob Griffin, MIT, USA
Meghan Halse, York, UK
Sami Jannin, Lyon, France
Fedor Jelezko, Ulm, Germany
John Kurhanewicz, San Francisco, USA
Mathilde Lerche, Copenhagen, Denmark
Anne Lesage, Lyon, France
Gaël de Paëpe, Grenoble, France
Marek Pruski, Iowa, USA
Leif Schröder, Berlin, Germany
Thomas Theis, North Carolina, USA

Registration will open in january. 
So bookmark the link: www.southampton.ac.uk/hyp18
and pencil the dates in your diaries!

Malcolm Levitt and Giuseppe Pileio

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HYP18
Hyperpolarized Magnetic Resonance
Southampton UK, Sep 2-5 2018
——————————————————
Prof Malcolm Levitt
School of Chemistry
Room 27:2026
University of Southampton
Southampton SO17 1BJ
England.
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Monday, December 4, 2017

Photo-induced radical polarization and liquid-state dynamic nuclear polarization with fullerene nitroxide derivatives

DNP without microwave radiation? A very interesting approach.


Liu, G., et al., Photo-induced radical polarization and liquid-state dynamic nuclear polarization with fullerene nitroxide derivatives. Phys. Chem. Chem. Phys., 2017.


We report on radical polarization and optically-driven liquid DNP with nitroxide radicals functionalized by photoexcitable fullerene derivatives. Pulse laser excitation of the fullerene moiety leads to a transient nitroxide radical polarization that is one order of magnitude larger than at Boltzmann equilibrium. Life time of radical polarization increases with size of the fullerene derivative and correlates with the electronic spin lattice relaxation time T1e. Overhauser NMR signal enhancements of toluene solvent protons were observed under steady-state illumination, which replaced microwave irradiation.