Friday, March 30, 2018

Liquid-State 13C Polarization of 30% through Photo-Induced Non-Persistent Radicals #DNPNMR

Capozzi, A., et al., Liquid-State 13C Polarization of 30% through Photo-Induced Non-Persistent Radicals. The Journal of Physical Chemistry C, 2018.


Hyperpolarization via dissolution Dynamic Nuclear Polarization (dDNP) is crucial to significantly increase the magnetic resonance imaging (MRI) sensitivity, opening up for in vivo real-time MRI using in particular 13C-labelled substrates. The range of applications is however limited by the relatively fast decay of the nuclear spin polarization together with the constraint of having to polarize the spins near the MRI magnet. As recently demonstrated, the employment of UV-induced non-persistent radicals represents an elegant solution to tackle these drawbacks. Nevertheless, since its introduction, the spread of the technique has been prevented by the relatively low achievable polarization, slow buildup time and time-consuming sample preparation. In the present work, thanks to a thorough investigation of the radical generation step, we provide a robust protocol to enhance the efficiency and performance of the UV-radical technique. Under optimal conditions, it was possible to produce up to 60 mM radical in less than 5 min, and reach maximum DNP enhancement with a buildup time constant of approx. 25 min, at 6.7 T and 1 K, resulting in 30% 13C liquid-state polarization.

Thursday, March 29, 2018

[NMR] Post-doc position in low-field SABRE hyperpolarisation


Post-doctoral position in low-field SABRE Hyperpolarisation

A fixed-term postdoctoral appointment in magnetic resonance is available to work with Dr Meghan Halse in the Centre for Hyperpolarisation in Magnetic Resonance (https://www.york.ac.uk/chym/) at the University of York to develop low-field NMR instrumentation and methods to study the signal amplification by reversible exchange (SABRE) hyperpolarisation method in situ – that is under the conditions of weak magnetic field where the polarisation transfer effect takes place.

Department

The Department of Chemistry is one of the largest and most successful academic departments at York. The Department was placed in the top ten UK universities for Research Power by the 2014 Research Excellence Framework exercise (REF). As a Department we strive to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel. We are proud of our Athena SWAN Gold Award. 

The University of York is a member of the Russell Group of research-intensive UK universities. The recent Research Excellence Framework (REF) confirmed the position of the University among the leading institutions in the UK for research. 


Role

You will join a team lead by Dr Meghan Halse (http://www.york.ac.uk/chemistry/staff/academic/h-n/mhalse/) and in addition to research responsibilities, you will be expected to assist with the supervision of more junior group members. 

You will design and construct NMR instrumentation for in situ SABRE detection in the micro-to-millitesla regime and implement methods for exploring and controlling the SABRE polarisation transfer process in these fields. You will use appropriate research techniques and methods for the acquisition and analysis of experimental data. You will write-up and disseminate research results, coordinate publications and further contribute to the identification of possible new areas of research. You will be expected to participate in seminar and conference presentations and support supervision of PhD and project students as well as outreach activities 

You are expected to have a first degree in Chemistry, Physics, Engineering or related subject and a PhD in Chemistry, Physics or Engineering or equivalent experience. You will have significant knowledge and experience of a range of research techniques and methodologies relating to magnetic resonance. You should have experience in magnetic resonance methodology and/or instrumentation development and application. Experience in low-field NMR and hyperpolarisation is desirable. You will have an understanding of the operation of a research laboratory and an awareness of health and safety issues.

You will also have:
Highly developed communication skills including competency to make presentations at conferences
Ability and experience of developing research projects and objectives, conducting research projects and working in a harmonious team
Highly developed self-motivation with good time management and IT skills
Ability to write up research work for publication in high profile journals and engage in public dissemination.

The post is fixed-term for a period of 24 months and will be available from 1 July 2018 or as soon as possible thereafter.

Salary from £31,604 - £35,550 a year on grade 6 of the University’s salary scales.

Informal enquiries may be made to Dr Meghan Halse (meghan.halse@york.ac.uk).



Closing date: 29 April 2018

The Department of Chemistry values all employees for the qualities and skills they bring to the workplace and aims to be a diverse and egalitarian community in which all can thrive.

The University is committed to promoting a diverse and inclusive community – a place where we can all be ourselves and succeed on merit. We offer a range of family friendly, inclusive employment policies, flexible working arrangements, staff engagement forums, campus facilities and services to support staff from different backgrounds.





A place where we can ALL be ourselves #EqualityatYork-- Dr Meghan E. Halse Lecturer Department of Chemistry University of York Heslington York YO10 5DD Email: meghan.halse@york.ac.uk Tel: +44 (0)1904 322853 



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Wednesday, March 28, 2018

DNP enhanced NMR with flip-back recovery #DNPNMR

Bjorgvinsdottir, S., et al., DNP enhanced NMR with flip-back recovery. J Magn Reson, 2018. 288: p. 69-75.


DNP methods can provide significant sensitivity enhancements in magic angle spinning solid-state NMR, but in systems with long polarization build up times long recycling periods are required to optimize sensitivity. We show how the sensitivity of such experiments can be improved by the classic flip-back method to recover bulk proton magnetization following continuous wave proton heteronuclear decoupling. Experiments were performed on formulations with characteristic build-up times spanning two orders of magnitude: a bulk BDPA radical doped o-terphenyl glass and microcrystalline samples of theophylline, l-histidine monohydrochloride monohydrate, and salicylic acid impregnated by incipient wetness. For these systems, addition of flip-back is simple, improves the sensitivity beyond that provided by modern heteronuclear decoupling methods such as SPINAL-64, and provides optimal sensitivity at shorter recycle delays. We show how to acquire DNP enhanced 2D refocused CP-INADEQUATE spectra with flip-back recovery, and demonstrate that the flip-back recovery method is particularly useful in rapid recycling regimes. We also report Overhauser effect DNP enhancements of over 70 at 592.6GHz/900MHz.

Tuesday, March 27, 2018

[NMR] PostDoc position

Dear colleagues
I would greatly appreciate if you could bring this advertisement to the attention of suitable canidates!
Sincerely
Dieter Suter

Postdoctoral Position at Technische Universität Dortmund : Microresonators for EPR

A postdoctoral position is available at the Technical University of Dortmund for a motivated and qualified scientist who is interested to continue the development of miniaturised resonators for EPR. These microresonators are optimised for detecting small samples (down to the nanometer range) with high sensitivity. Candidates should have a firm background and proven track record in the field of magnetic resonance and an interest in numerical simulations of the resonators.
The development of these resonator is a central project in the priority program 1601 of the DFG “New Frontierts in Sensitivity for EPR Spectroscopy: From Biological Cells to Nano Materials” (http://spp1601.de): the resoantors are developed in Dortmund and shared with other members of the SPP for a range of different applications. Additional information on the project is available at http://e3.physik.tu-dortmund.de/~suter/research/EPR_Microresonators.pdf
Applications and requests for additional information should be sent to Dieter.Suter@tu-dortmund.de

____________________________________________________________________________
Dieter Suter | Tel: (+49 231) 755 3512
Fakultät Physik | Fax: (+49 231) 755 3509
Technische Universität Dortmund |
D-44221 Dortmund | e-mail: Dieter.Suter@tu-dortmund.de
____________________________________________________________________________

Monday, March 26, 2018

DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients #DNPNMR

Zhao, L., et al., DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients. Magn. Reson. Chem., 2017. 0(0).


Solid-state NMR spectroscopy has become a valuable tool for the characterization of both pure and formulated active pharmaceutical ingredients (APIs). However, NMR generally suffers from poor sensitivity that often restricts NMR experiments to nuclei with favorable properties, concentrated samples, and acquisition of one-dimensional (1D) NMR spectra. Here, we review how dynamic nuclear polarization (DNP) can be applied to routinely enhance the sensitivity of solid-state NMR experiments by one to two orders of magnitude for both pure and formulated APIs. Sample preparation protocols for relayed DNP experiments and experiments on directly doped APIs are detailed. Numerical spin diffusion models illustrate the dependence of relayed DNP enhancements on the relaxation properties and particle size of the solids and can be used for particle size determination when the other factors are known. We then describe the advanced solid-state NMR experiments that have been enabled by DNP and how they provide unique insight into the molecular and macroscopic structure of APIs. For example, with large sensitivity gains provided by DNP, natural isotopic abundance, (13) C-(13) C double-quantum single-quantum homonuclear correlation NMR spectra of pure APIs can be routinely acquired. DNP also enables solid-state NMR experiments with unreceptive quadrupolar nuclei such as (2) H, (14) N, and (35) Cl that are commonly found in APIs. Applications of DNP-enhanced solid-state NMR spectroscopy for the molecular level characterization of low API load formulations such as commercial tablets and amorphous solid dispersions are described. Future perspectives for DNP-enhanced solid-state NMR experiments on APIs are briefly discussed.

Friday, March 23, 2018

Direct hyperpolarization of micro- and nanodiamonds for bioimaging applications - Considerations on particle size, functionalization and polarization loss

Kwiatkowski, G., et al., Direct hyperpolarization of micro- and nanodiamonds for bioimaging applications - Considerations on particle size, functionalization and polarization loss. J Magn Reson, 2018. 286: p. 42-51.


Due to the inherently long relaxation time of (13)C spins in diamond, the nuclear polarization enhancement obtained with dynamic nuclear polarization can be preserved for a time on the order of about one hour, opening up an opportunity to use diamonds as a new class of long-lived contrast agents. The present communication explores the feasibility of using (13)C spins in directly hyperpolarized diamonds for MR imaging including considerations for potential in vivo applications.

Wednesday, March 21, 2018

Sample Ripening through Nanophase Separation Impacts the Performance of Dynamic Nuclear Polarization

Weber, E., et al., Sample Ripening through Nanophase Separation Impacts the Performance of Dynamic Nuclear Polarization. Angew. Chem., 2018: p. n/a-n/a.


Mixtures of water and glycerol provide popular matrices for low-temperature spectroscopy of vitrified samples. However, they involve counterintuitive physicochemical properties, such as spontaneous nanoscopic phase separations (NPS) in solutions that appear macroscopically homogeneous. We demonstrate that such phenomena can substantially impact the efficiency of dynamic nuclear polarization (DNP) by factors up to 20% by causing fluctuations in local concentrations of polarization agents (radicals). Thus, a spontaneous NPS of water/glycerol mixtures that takes place on time scales on the order of 30-60 min results in a confinement of polarization agents in nanoscopic water-rich vesicles, which in return affects the DNP. Such effects were found for three common polarization agents, TEMPOL, AMUPol and Trityl.


Monday, March 19, 2018

New NMR tools for protein structure and function: Spin tags for dynamic nuclear polarization solid state NMR #DNPNMR

Rogawski, R. and A.E. McDermott, New NMR tools for protein structure and function: Spin tags for dynamic nuclear polarization solid state NMR. Arch. Biochem. Biophys., 2017. 628: p. 102-113.


Magic angle spinning solid state NMR studies of biological macromolecules [1-3] have enabled exciting studies of membrane proteins [4,5], amyloid fibrils [6], viruses, and large macromolecular assemblies [7]. Dynamic nuclear polarization (DNP) provides a means to enhance detection sensitivity for NMR, particularly for solid state NMR, with many recent biological applications and considerable contemporary efforts towards elaboration and optimization of the DNP experiment. This review explores precedents and innovations in biological DNP experiments, especially highlighting novel chemical biology approaches to introduce the radicals that serve as a source of polarization in DNP experiments.

Friday, March 16, 2018

Quantitative biosensor detection by chemically exchanging hyperpolarized 129Xe

Korchak, S., et al., Quantitative biosensor detection by chemically exchanging hyperpolarized 129Xe. PCCP, 2018. 20(3): p. 1800-1808.


Chemical sensors informing about their local environment are of widespread use for chemical analysis. A thorough understanding of the sensor signaling is fundamental to data analysis and interpretation, and a requirement for technological applications. Here, sensors explored for the recognition and display of biomolecular and cellular markers by magnetic resonance and composed of host molecules for xenon atoms are considered. These host-guest systems are analytically powerful and also function as contrast agents in imaging applications. Using nuclear spin hyperpolarization of 129Xe and chemical exchange saturation transfer the detection sensitivity is orders of magnitude enhanced in comparison to conventional 1H NMR. The sensor signaling reflects this rather complex genesis, furthering the mere qualitative interpretation of biosensing data; to harvest the potential of the approach, however, a detailed numerical account is desired. To this end, we introduce a comprehensive expression that maps the sensor detection quantitatively by integration of the hyperpolarization generation and relaxation with the host-xenon exchange dynamics. As demonstrated for the host molecule and well-established biosensor cryptophane-A, this model reveals a distinguished maximum in sensor signaling and exerts control over experimentation by dedicated adjustments of both the amount of xenon and the duration of the saturation transfer applied in a measurement, for example to capitalize on investigations at the detection limit. Furthermore, usage of the model for data analysis makes the quantification of the sensor concentration in the nanomolar range possible. The approach is readily applicable in investigations using cryptophane-A and is straightaway adaptable to other sensor designs for extension of the field of xenon based biosensing.

Wednesday, March 14, 2018

Re-polarization of nuclear spins using selective SABRE-INEPT

Knecht, S., et al., Re-polarization of nuclear spins using selective SABRE-INEPT. Journal of Magnetic Resonance, 2018. 287: p. 10-14.


A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH2, the H2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes “re-polarization”, i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε. For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε≈260 for 15N nuclei, whereas SABRE-INEPT with re-polarization yields ε>2000. We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques.

Monday, March 12, 2018

Testing signal enhancement mechanisms in the dissolution NMR of acetone

Alonso-Valdesueiro, J., et al., Testing signal enhancement mechanisms in the dissolution NMR of acetone. Journal of Magnetic Resonance, 2018. 286: p. 158-162.


In cryogenic dissolution NMR experiments, a substance of interest is allowed to rest in a strong magnetic field at cryogenic temperature, before dissolving the substance in a warm solvent, transferring it to a high-resolution NMR spectrometer, and observing the solution-state NMR spectrum. In some cases, negative enhancements of the 13C NMR signals are observed, which have been attributed to quantum-rotor-induced polarization. We show that in the case of acetone (propan-2-one) the negative signal enhancements of the methyl 13C sites may be understood by invoking conventional cross-relaxation within the methyl groups. The 1H nuclei acquire a relative large net polarization through thermal equilibration in a magnetic field at low temperature, facilitated by the methyl rotation which acts as a relaxation sink; after dissolution, the 1H magnetization slowly returns to thermal equilibrium at high temperature, in part by cross-relaxation processes, which induce a transient negative polarization of nearby 13C nuclei. We provide evidence for this mechanism experimentally and theoretically by saturating the 1H magnetization using a radiofrequency field pulse sequence before dissolution and comparing the 13C magnetization evolution after dissolution with the results obtained from a conventional 1H-13C cross relaxation model of the CH3 moieties in acetone.

Friday, March 9, 2018

The effect of Ho3+ doping on 13C dynamic nuclear polarization at 5 T

Sirusi, A.A., et al., The effect of Ho3+ doping on 13C dynamic nuclear polarization at 5 T. PCCP, 2018. 20(2): p. 728-731.


Dissolution dynamic nuclear polarization was introduced in 2003 as a method for producing hyperpolarized 13C solutions suitable for metabolic imaging. The signal to noise ratio for the imaging experiment depends on the maximum polarization achieved in the solid state. Hence, optimization of the DNP conditions is essential. To acquire maximum polarization many parameters related to sample preparation can be modulated. Recently, it was demonstrated that Ho3+, Dy3+, Tb3+, and Gd3+ complexes enhance the polarization at 1.2 K and 3.35 T when using the trityl radical as the primary paramagnetic center. Here, we have investigated the influence of Ho-DOTA on 13C solid state DNP at 1.2 K and 5 T. We have performed 13C DNP on [1-13C] sodium acetate in 1 : 1 (v/v) water/glycerol with 15 mM trityl OX063 radicals in the presence of a series of Ho-DOTA concentrations (0, 0.5, 1, 2, 3, 5 mM). We have found that adding a small amount of Ho-DOTA in the sample preparation not only enhances the 13C polarization but also decreases the buildup time. The optimum Ho-DOTA concentration was 2 mM. In addition, the microwave sweep spectrum changes character in a manner that suggests both the cross effect and thermal mixing are active mechanisms for trityl radical at 5 T and 1.2 K.

Thursday, March 8, 2018

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

The HYP18 conference on hyperpolarization in Southampton is now open for registration and abstract submission at hyp18.com.

This conference will cover the main areas of nuclear hyperpolarization and some other methods for sensitivity enhancement in NMR and MRI, including:
  • dynamic nuclear polarization (DNP), both in solids and in solution
  • optical pumping 
  • quantum-rotor-induced polarization 
  • parahydrogen-induced polarization 
  • diamond magnetometry 
and key applications such as clinical imaging, materials science, and molecular structure determination. As far as we know, a meeting of this kind has not taken place before. It is a unique opportunity to hear the latest news from this exciting frontier. 
The confirmed plenary speakers are:
The confirmed invited speakers are:
Welcome to Southampton in September!
Malcolm and Peppe

——————————————————
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.
tel. +44 23 8059 6753
fax: +44 23 8059 3781
iPhone: +44 77 7078 2024
email: malcolmhlevitt@mac.com
http://www.southampton.ac.uk/magres/about/staff/levitt.page?
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Wednesday, March 7, 2018

High-resolution hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE

Wespi, P., et al., High-resolution hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE. NMR Biomed., 2018. 31(2): p. e3876-n/a.


The purpose of this work was to increase the resolution of hyperpolarized metabolic imaging of the rat heart with accelerated imaging using k–t principal component analysis (k–t PCA) and k–t compressed sensing (k–t SPARSE). Fully sampled in vivo datasets were acquired from six healthy rats after the injection of hyperpolarized [1-13C]pyruvate. Data were retrospectively undersampled and reconstructed with either k–t PCA or k–t SPARSE. Errors of signal–time curves of pyruvate, lactate and bicarbonate were determined to compare the two reconstruction algorithms for different undersampling factors R. Prospectively undersampled imaging at 1 × 1 × 3.5-mm3 resolution was performed with both methods in the same animals and compared with the fully sampled acquisition. k–t SPARSE was found to perform better at R < 3, but was outperformed by k–t PCA at R ≥ 4. Prospectively undersampled data were successfully reconstructed with both k–t PCA and k–t SPARSE in all subjects. No significant difference between the undersampled and fully sampled data was found in terms of signal-to-noise ratio (SNR) performance and metabolic quantification. Accelerated imaging with both k–t PCA and k–t SPARSE allows an increase in resolution, thereby reducing the intravoxel dephasing of hyperpolarized metabolic imaging of the rat heart.



Monday, March 5, 2018

Mechanism of spontaneous polarization transfer in high-field SABRE experiments

Knecht, S., et al., Mechanism of spontaneous polarization transfer in high-field SABRE experiments. Journal of Magnetic Resonance, 2018. 287: p. 74-81.


We propose an explanation of the previously reported SABRE (Signal Amplification By Reversible Exchange) effect at high magnetic fields, observed in the absence of RF-excitation and relying only on “spontaneous” polarization transfer from parahydrogen (pH2, the H2 molecule in its nuclear singlet spin state) to a SABRE substrate. We propose a detailed mechanism for spontaneous polarization transfer and show that it is comprised of three steps: (i) Generation of the anti-phase Î1zÎ2z spin order of catalyst-bound H2; (ii) spin order conversion Î1zÎ2z→(Î1z+Î2z) due to cross-correlated relaxation, leading to net polarization of H2; (iii) polarization transfer to the SABRE substrate, occurring due to NOE. Formation of anti-phase polarization is due to singlet-to-T0 mixing in the catalyst-bound form of H2, while cross-correlated relaxation originates from fluctuations of dipole–dipole interactions and chemical shift anisotropy. The proposed mechanism is supported by a theoretical treatment, magnetic field-dependent studies and high-field NMR measurements with both pH2 and thermally polarized H2.

Friday, March 2, 2018

Proton and Carbon-13 Dynamic Nuclear Polarization of Methylated β-Cyclodextrins #DNPNMR

Caracciolo, F., et al., Proton and Carbon-13 Dynamic Nuclear Polarization of Methylated β-Cyclodextrins. The Journal of Physical Chemistry B, 2018. 122(6): p. 1836-1845.


1H and 13C dynamic nuclear polarizations have been studied in 13C-enriched β-cyclodextrins doped with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl free radical. 1H and 13C polarizations raised above 7.5 and 7%, respectively, and for both nuclear species, the transfer of polarization from the electron spins appears to be consistent with a thermal mixing scenario for a concentration of 9 13C nuclei per molecule. When the concentration is increased to 21 13C nuclei per molecule, a decrease in the spin–lattice relaxation and polarization buildup rates is observed. This reduction is associated with the bottleneck effect induced by the decrease in the number of electron spins per nucleus when both the nuclear spin–lattice relaxation and the polarization occur through the electron non-Zeeman reservoir. 13C nuclear spin–lattice relaxation has been studied in the 1.8–340 K range, and the effects of internal molecular motions and of the free radicals on the relaxation are discussed. 13C hyperpolarization performances and room-temperature spin–lattice relaxation times show that these are promising materials for future biomedical applications.

Thursday, March 1, 2018

[NMR] Charles P. Slichter, 1924-2018 #DNPNMR



From the Ampere Magnetic Resonance List:

The magnetic resonance community mourns the loss of Charlie Slichter, who passed away on February 19 at age 94. 

Charlie was one of the early developers and proponents of magnetic resonance methods and their many applications in physics and chemistry. He was one of the truly great physical scientists of our time. He was also an unusually warm, generous, and unpretentious human being. 

A full obituary, prepared by David Ailion and including selected links to descriptions of Charlie's life and accomplishments, can be found at:

Robert Tycko 
ISMAR President 

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2013 memories, with a nice picture:

His famous book: Principles of Magnetic Resonance

His Wikipedia page:

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