Wednesday, April 25, 2018

Effect of heavy atoms on photochemically induced dynamic nuclear polarization in liquids

Okuno, Y. and S. Cavagnero, Effect of heavy atoms on photochemically induced dynamic nuclear polarization in liquids. Journal of Magnetic Resonance, 2018. 286: p. 172-187.


Given its short hyperpolarization time (∼10−6 s) and mostly non-perturbative nature, photo-chemically induced dynamic nuclear polarization (photo-CIDNP) is a powerful tool for sensitivity enhancement in nuclear magnetic resonance. In this study, we explore the extent of 1H-detected 13C nuclear hyperpolarization that can be gained via photo-CIDNP in the presence of small-molecule additives containing a heavy atom. The underlying rationale for this methodology is the well-known external-heavy-atom (EHA) effect, which leads to significant enhancements in the intersystem-crossing rate of selected photosensitizer dyes from photoexcited singlet to triplet. We exploited the EHA effect upon addition of moderate amounts of halogen-atom-containing cosolutes. The resulting increase in the transient triplet-state population of the photo-CIDNP sensitizer fluorescein resulted in a significant increase in the nuclear hyperpolarization achievable via photo-CIDNP in liquids. We also explored the internal-heavy-atom (IHA) effect, which is mediated by halogen atoms covalently incorporated into the photosensitizer dye. Widely different outcomes were achieved in the case of EHA and IHA, with EHA being largely preferable in terms of net hyperpolarization.



Monday, April 23, 2018

Magnetic-Field-Dependent Lifetimes of Hyperpolarized 13C Spins at Cryogenic Temperature

Niedbalski, P., et al., Magnetic-Field-Dependent Lifetimes of Hyperpolarized 13C Spins at Cryogenic Temperature. The Journal of Physical Chemistry B, 2018. 122(6): p. 1898-1904.


Using a home-built cryogen-free dynamic nuclear polarization (DNP) system with a variable magnetic field capability, 13C spin–lattice T1 relaxation times of hyperpolarized [1-13C] carboxylates (sodium acetate, glycine, sodium pyruvate, and pyruvic acid) doped with trityl OX063 free radical were systematically measured for the first time at different field strengths up to 9 T at T = 1.8 K. Our data reveal that the 13C T1 values of these frozen hyperpolarized 13C samples vary drastically with the applied magnetic field B according to an apparent empirical power-law dependence (13C T1 ∝ Bα, 2.3 < α < 3.1), with relaxation values ranging from a few hundred seconds at 1 T to over 200,000 s at fields close to 9 T. This low temperature relaxation behavior can be ascribed approximately to a model that accounts for the combined effect of 13C–1H intramolecular dipolar interaction and the relaxation contribution from the paramagnetic impurities present in the DNP sample. Since the lifetime or T1 storage of the hyperpolarized state is intimately linked to DNP efficiency, these 13C relaxation data at cryogenic temperature have important theoretical and experimental implications as the DNP of 13C-labeled biomolecules is pushed to higher magnetic fields.

Friday, April 20, 2018

Primary Transfer Step in the Light-Driven Ion Pump Bacteriorhodopsin: An Irreversible U-Turn Revealed by Dynamic Nuclear Polarization-Enhanced Magic Angle Spinning NMR #DNPNMR

Ni, Q.Z., et al., Primary Transfer Step in the Light-Driven Ion Pump Bacteriorhodopsin: An Irreversible U-Turn Revealed by Dynamic Nuclear Polarization-Enhanced Magic Angle Spinning NMR. J. Am. Chem. Soc., 2018. 140(11): p. 4085-4091.


Despite much attention, the path of the highly consequential primary proton transfer in the light-driven ion pump bacteriorhodopsin (bR) remains mysterious. Here we use DNP-enhanced magic angle spinning (MAS) NMR to study critical elements of the active site just before the Schiff base (SB) deprotonates (in the L intermediate), immediately after the SB has deprotonated and Asp85 has become protonated (in the Mo intermediate), and just after the SB has reprotonated and Asp96 has deprotonated (in the N intermediate). An essential feature that made these experiments possible is the 75-fold signal enhancement through DNP. (15)N(SB)-(1)H correlations reveal that the newly deprotonated SB is accepting a hydrogen bond from an alcohol and (13)C-(13)C correlations show that Asp85 draws close to Thr89 before the primary proton transfer. Concurrently, (15)N-(13)C correlations between the SB and Asp85 show that helices C and G draw closer together just prior to the proton transfer and relax thereafter. Together, these results indicate that Thr89 serves to relay the SB proton to Asp85 and that creating this pathway involves rapprochement between the C and G helices as well as chromophore torsion.

Wednesday, April 18, 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.

Postdoc position at Utrecht University: solid-state NMR-based design of membrane-active peptide-antibiotics


A 2.5 years postdoc position in the structural characterisation and design of novel peptide-antibiotics is available in the Weingarth group at Utrecht University, the Netherlands. 

The project is set within the context of the rapid development of antimicrobial resistance that urgently calls for novel antibiotics with unexploited mechanisms. 

We aim to structurally characterise a highly promising class of membrane-binding peptide-antibiotics that can kill the most refractory pathogens at nanomolecular concentrations and that are robust to antimicrobial resistance. Together with collaborators from Utrecht pharmacy department, we eventually aim to rationally develop novel and improved antibiotics. For the structural characterisation of membrane-binding peptide-antibiotics, our team uses recombinant expression techniques and sensitivity-enhanced solid-state NMR methods such as 1H-detection and DNP. 

We are embedded within the excellently-equipped Utrecht NMR facility (solid state NMR: 950, 800, 700, 500 MHz // 800 & 400 MHz DNP // 900 MHz solution NMR magnet). A 1.2 GHz magnet will be installed in the near future. 

The ideal candidate should be experienced in recombinant expression techniques and solid-state OR solution NMR. Experience in NMR structure calculation is a plus. Experience in other biophysical techniques (ITC, spectroscopic techniques) would also be valuable. 

Applicants with strong knowledge in molecular biology and a further, alternative background could also be considered. 

The NWO-funded position is to be filled asap, and the selected candidate will be part of several antibiotics characterisation/design projects that have been successfully implemented in my lab. Applications are accepted until 01.06.2018. 

To apply, and for further inquiries, please contact m.h.weingarth@uu.nl


Recent publications: 

2. Medeiros-Silva, J. et al, (2016) Angew. Chem. 55, 13606, 1H-detected solid-state NMR of water-inaccessible proteins in vitro and in situ


Conditions of employment: The candidate is offered a full/part-time position for 2.5 years. 
Salary: The gross salary is in the range between € 3.111- , and maximum € 4.084- per month. 

The salary is supplemented with a holiday bonus of 8% and an end-of-year bonus of 8,3% per year. In addition, we offer: a pension scheme, a partially paid parental leave, flexible employment conditions. Conditions are based on the Collective Labour Agreement Dutch Universities. The research group will provide the candidate with necessary support on all aspects of the project. More information: http://www.uu.nl/EN/informationfor/jobseekers/Working-for-Utrecht-University/terms-of-employment/Pages/default.aspx

Friday, April 13, 2018

Discovery of Intermediates of lacZ beta-Galactosidase Catalyzed Hydrolysis Using dDNP NMR

Kjeldsen, C., J.H. Ardenkjaer-Larsen, and J.O. Duus, Discovery of Intermediates of lacZ beta-Galactosidase Catalyzed Hydrolysis Using dDNP NMR. J. Am. Chem. Soc., 2018. 140(8): p. 3030-3034.


Using dissolution dynamic nuclear polarization, the sensitivity of single scan solution state (13)C NMR can be improved up to 4 orders of magnitude. In this study, the enzyme lacZ beta-galactosidase from Escherichia coli was subjected to hyperpolarized substrate, and previously unknown reaction intermediates were observed, including a 1,1-linked disaccharide. The enzyme is known for making 1,6-transglycosylation, producing products like allolactose, that are also substrates. To analyze the kinetics, a simple kinetic model was developed and used to determine relative transglycosylation and hydrolysis rates of each of the intermediates, and the novel transglycosylation intermediates were determined as better substrates than the 1,6-linked one, explaining their transient nature. These findings suggest that hydrolysis and transglycosylation might be more complex than previously described.

Wednesday, April 11, 2018

3D hyperpolarized C-13 EPI with calibrationless parallel imaging

Gordon, J.W., et al., 3D hyperpolarized C-13 EPI with calibrationless parallel imaging. J Magn Reson, 2018. 289: p. 92-99.


With the translation of metabolic MRI with hyperpolarized (13)C agents into the clinic, imaging approaches will require large volumetric FOVs to support clinical applications. Parallel imaging techniques will be crucial to increasing volumetric scan coverage while minimizing RF requirements and temporal resolution. Calibrationless parallel imaging approaches are well-suited for this application because they eliminate the need to acquire coil profile maps or auto-calibration data. In this work, we explored the utility of a calibrationless parallel imaging method (SAKE) and corresponding sampling strategies to accelerate and undersample hyperpolarized (13)C data using 3D blipped EPI acquisitions and multichannel receive coils, and demonstrated its application in a human study of [1-(13)C]pyruvate metabolism.

Friday, April 6, 2018

High-power sub-terahertz source with a record frequency stability at up to 1 Hz #DNPNMR

Fokin, A., et al., High-power sub-terahertz source with a record frequency stability at up to 1 Hz. Sci Rep, 2018. 8(1): p. 4317.


Many state-of-the-art fundamental and industrial projects need the use of terahertz radiation with high power and small linewidth. Gyrotrons as radiation sources provide the desired level of power in the sub-THz and THz frequency range, but have substantial free-running frequency fluctuations of the order of 10(-4). Here, we demonstrate that the precise frequency stability of a high-power sub-THz gyrotron can be achieved by a phase-lock loop in the anode voltage control. The relative width of the frequency spectrum and the frequency stability obtained for a 0.263 THz/100 W gyrotron are 4 x 10(-12) and 10(-10), respectively, and these parameters are better than those demonstrated so far with high-power sources by almost three orders of magnitude. This approach confirms its potential for ultra-high precision spectroscopy, the development of sources with large-scale radiating apertures, and other new projects.

Wednesday, April 4, 2018

Low-temperature magnetic resonance imaging with 2.8 μm isotropic resolution

Chen, H.-Y. and R. Tycko, Low-temperature magnetic resonance imaging with 2.8 μm isotropic resolution. Journal of Magnetic Resonance, 2018. 287: p. 47-55.



We demonstrate the feasibility of high-resolution 1H magnetic resonance imaging (MRI) at low temperatures by obtaining an MRI image of 20 μm diameter glass beads in glycerol/water at 28 K with 2.8 μm isotropic resolution. The experiments use a recently-described MRI apparatus (Moore and Tycko, 2015) with minor modifications. The sample is contained within a radio-frequency microcoil with 150 μm inner diameter. Sensitivity is additionally enhanced by paramagnetic doping, optimization of the sample temperature, three-dimensional phase-encoding of k-space data, pulsed spin-lock detection of 1H nuclear magnetic resonance signals, and spherical sampling of k-space. We verify that the actual image resolution is 2.7 ± 0.3 μm by quantitative comparisons of experimental and calculated images. Our imaging approach is compatible with dynamic nuclear polarization, providing a path to significantly higher resolution in future experiments.

Monday, April 2, 2018

Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate #DNPNMR

Cavallari, E., et al., Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate. J Magn Reson, 2018. 289: p. 12-17.


The use of [1-(13)C]pyruvate, hyperpolarized by dissolution-Dynamic Nuclear Polarization (d-DNP), in in vivo metabolic studies has developed quickly, thanks to the imaging probe's diagnostic relevance. Nevertheless, the cost of a d-DNP polarizer is quite high and the speed of hyperpolarization process is relatively slow, meaning that its use is limited to few research laboratories. ParaHydrogen Induced Polarization Side Arm Hydrogenation (PHIP-SAH) (Reineri et al., 2015) is a cost effective and easy-to-handle method that produces (13)C-MR hyperpolarization in [1-(13)C]pyruvate and other metabolites. This work aims to identify the main determinants of the hyperpolarization levels observed in C13-pyruvate using this method. By dissecting the various steps of the PHIP-SAH procedure, it has been possible to assess the role of several experimental parameters whose optimization must be pursued if this method is to be made suitable for future translational steps. The search for possible solutions has led to improvements in the polarization of sodium [1-(13)C]pyruvate from 2% to 5%. Moreover, these results suggest that observed polarization levels could be increased considerably by an automatized procedure which would reduce the time required for the work-up passages that are currently carried out manually. The results reported herein mean that the attainment of polarization levels suitable for the metabolic imaging applications of these hyperpolarized substrates show significant promise.

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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Wednesday, February 28, 2018

Analysis of Molecular Orientation in Organic Semiconducting Thin Films Using Static Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy #DNPNMR

Suzuki, K., et al., Analysis of Molecular Orientation in Organic Semiconducting Thin Films Using Static Dynamic Nuclear Polarization Enhanced Solid-State NMR Spectroscopy. Angew. Chem. Int. Ed., 2017. 56(47): p. 14842-14846.


Molecular orientation in amorphous organic semiconducting thin-film devices is an important issue affecting device performance. However, to date it has not been possible to analyze the “distribution” of the orientations. Although solid-state NMR (ssNMR) spectroscopy can provide information on the “distribution” of molecular orientations, the technique is limited because of the small amount of sample in the device and the low sensitivity of ssNMR. Here, we report the first application of dynamic nuclear polarization enhanced ssNMR (DNP-ssNMR) spectroscopy for the orientational analysis of amorphous phenyldi(pyren-1-yl)phosphine oxide (POPy2). The 31P DNP-ssNMR spectra exhibited a sufficient signal-to-noise ratio to quantify the distribution of molecular orientations in amorphous films: the P=O axis of the vacuum-deposited and drop-cast POPy2 shows anisotropic and isotropic distribution, respectively. The different molecular orientations reflect the molecular origin of the different charge transport behaviors.

Tuesday, February 27, 2018

[NMR] POSTDOCTORAL POSITION: Nuclear Spin Singlet States and PHIP, New York University



POSTDOCTORAL POSITION: Nuclear Spin Singlet States and PHIP
New York University

DESCRIPTION:

A postdoctoral position is available immediately for the study of nuclear spin singlet state life times and singlet relaxation mechanisms, the development of efficient singlet/triplet conversion pulse sequences and methodology, as well as para-hydrogen induced polarization (PHIP) in the laboratory of Alexej Jerschow at New York University (NYU). The lab is located in newly renovated facilities of the Molecular Nanoscience Center at NYU’s Washington Square Campus in the heart of Manhattan.

Applicants should have an advanced degree (Ph.D) in Physics, Chemistry, or a related field, and should have experience with NMR/MRI theory and experiment. Knowledge of relaxation theory and computer programming and simulation skills would be a plus, as well as prior experience any of the specific research areas. Remuneration is competitive and commensurate with experience and will be based on New York University guidelines. Women and minorities are encouraged to apply.

CONTACT: 
To be considered, the application has to be submitted via the following link: https://apply.interfolio.com/49106.

Preliminary inquiries can be sent to
Alexej Jerschow
Department of Chemistry
100 Washington Square East
New York University
New York, NY 10003.

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Monday, February 26, 2018

Best Practices for Scientific Computing

Ever since I started in Magnetic Resonance Spectroscopy I did a lot of programming in Matlab, C, C++, LabVIEW, html,  and more recently Python. All of it is picked along the way, without ever having a class in programming. With that a lot of bad habits evolve over the years. No matter what programming language is your currently choice, take a look at this very nice article. If you don't want to read through the whole thing take a look at Box 1 on page 2 to get an idea of the basics.



Wilson G, Aruliah DA, Brown CT, Chue Hong NP, Davis M, Guy RT, et al. (2014) Best Practices for Scientific Computing. PLoS Biol 12(1): e1001745. https://doi.org/10.1371/journal.pbio.1001745


Scientists spend an increasing amount of time building and using software. However, most scientists are never taught how to do this efficiently. As a result, many are unaware of tools and practices that would allow them to write more reliable and maintainable code with less effort. We describe a set of best practices for scientific software development that have solid foundations in research and experience, and that improve scientists' productivity and the reliability of their software.

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.

[NMR] PhD position on solid-state NMR of materials at the University of Lille, France #DNPNMR



Please forward to potential candidates.

Project title: Development of high-field (DNP)-NMR methods for the observation of quadrupolar nuclei in hybrid materials.

A three-year PhD position in solid-state NMR spectroscopy of advanced materials is available at the University of Lille, Lille, France. It can start from July 2018.

Project description: Hybrid materials are promising for numerous applications, such as catalysis, gas storage or drug delivery. Solid-state NMR provides unique information about the atomic-level structure of defects and surfaces in hybrid materials. Nevertheless, a major limitation is the lack of sensitivity of solid-state NMR, which limits the observation of defects and surfaces, particularly for insensitive isotopes with low gyromagnetic ratio, low natural abundance or subject to large quadrupolar interaction. Recent instrumental developments, such as high-magnetic field and Dynamic Nuclear Polarization (DNP), can boost the sensitivity of solid-state NMR. This project aims at developing and applying novel solid-state NMR methods to probe the local environment of quadrupolar nuclei in hybrid materials. The structural information obtained by solid-state NMR will be useful to improve the performances of hybrid materials.

Host and research infrastructure: Lille is a vibrant and handsome city, imbued with a rich history, located in the middle of northwestern Europe (only 30 min by high-speed trains from Brussels, 1h from Paris and 1h30 from London). Lille is one of France’s top student cities and the university of Lille is a leading center for magnetic resonance. Lille NMR facility includes 800 and 900 MHz NMR spectrometers and has been selected to host the first 1.2 GHz NMR spectrometer to be installed in France. Our research group is internationally known for the development of solid-state NMR methods, notably for quadrupolar nuclei, and the characterization of hybrid materials. We have an expertise in high-field solid-state NMR spectroscopy and were among the pioneers of high-field DNP-NMR of hybrid and inorganic materials. 

The person: We seek application from national and international students who have graduated in physics or chemistry, preferably with a background in material sciences or NMR spectroscopy. The successful applicant will be given the opportunity to work in an exciting environment with national and international collaborations.

Contact: Applications and informal queries about the lab and research projects should be directed by email to olivier.lafon@univ-lille1.fr

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Friday, February 23, 2018

Optimal sample formulations for DNP SENS: The importance of radical-surface interactions #DNPNMR

Perras, F.A., et al., Optimal sample formulations for DNP SENS: The importance of radical-surface interactions. Current Opinion in Colloid & Interface Science, 2018. 33: p. 9-18.


The efficacy of dynamic nuclear polarization (DNP) surface-enhanced NMR spectroscopy (SENS) is reviewed for alumina, silica, and ordered mesoporous carbon (OMC) materials, with vastly different surface areas, as a function of the biradical concentration. Importantly, our studies show that the use of a “one-size-fits-all” biradical concentration should be avoided when performing DNP SENS experiments and instead an optimal concentration should be selected as appropriate for the type of material studied as well as its surface area. In general, materials with greater surface areas require higher radical concentrations for best possible DNP performance. This result is explained with the use of a thermodynamic model wherein radical-surface interactions are expected to lead to an increase in the local concentration of the polarizing agent at the surface. We also show, using plane-wave density functional theory calculations, that weak radical-surface interactions are the cause of the poor performance of DNP SENS for carbonaceous materials.

Wednesday, February 21, 2018

A quasi-optical and corrugated waveguide microwave transmission system for simultaneous dynamic nuclear polarization NMR on two separate 14.1 T spectrometers #DNPNMR

Gyrotrons typically generate much more microwave power than needed in a DNP-NMR experiment. This article describes a very nice way how to share the microwave power generated by a single gyrotron between two NMR experiments.


Dubroca, T., et al., A quasi-optical and corrugated waveguide microwave transmission system for simultaneous dynamic nuclear polarization NMR on two separate 14.1 T spectrometers. J. Magn. Reson., 2018.


Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with Boltzmann distributions of nuclear spin states on the order of parts per million in conventional magnetic fields. To overcome this limitation, dynamic nuclear polarization (DNP) can be used to gain up to three orders of magnitude in signal enhancement, which can decrease experimental time by up to six orders of magnitude. In DNP experiments, nuclear spin polarization is enhanced by transferring the relatively larger electron polarization to NMR active nuclei via microwave irradiation. Here, we describe the design and performance of a quasi-optical system enabling the use of a single 395 GHz gyrotron microwave source to simultaneously perform DNP experiments on two different 14.1 T (1H 600 MHz) NMR spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the other configured for solution state NMR experiments. In particular, we describe how the high power microwave beam is split, transmitted, and manipulated between the two spectrometers. A 13C enhancement of 128 is achieved via the cross effect for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at 110K, while a 31P enhancement of 160 is achieved via the Overhauser effect for triphenylphosphine using the monoradical BDPA under solution NMR conditions at room temperature. The latter result is the first demonstration of Overhauser DNP in the solution state at a field of 14.1 T (1H 600 MHz). Moreover these results have been produced with large sample volumes (∼100 µL, i.e. 3 mm diameter NMR tubes).

Tuesday, February 20, 2018

[NMR] AMPERE NMR SCHOOL 2018

Dear NMR Community, 

On behalf of the Organizing Committee it’s my great pleasure to invite you to attend the next AMPERE NMR School 2018, an annual event organized since earlier 90th in Zakopane under auspices of the Groupment AMPERE, will be organized from June 10 th to 16 th 2018 in Zakopane, Poland ( www. zakopane .pl). 

The traditional topics given in the School: 
· solid state and soft matter NMR
· NMR diffusometry and relaxometry
· application of NMR in biology and medicine
· magnetic resonance imaging and spectroscopy
· NMR and quantum information
· theoretical and experimental aspects of dynamic nuclear spin polarization
· NMR methodology and techniques.

The School is addressed to PhD students of various fields of physics, chemistry, biology and medicine and is focused on theoretical and experimental aspects of NMR methods and their applications. The lectures are expected to contain a basic (tutorial) introduction and the research of your interest. 

The conference fee (450 Euro) includes full board, accommodation and the conference proceedings. We will be able to provide a financial support for the students you will recommend up to 200 Euro. More detailed information you will find on the conference website. 




With my best wishes

Stefan Jurga

……………………………………………………..
Prof. Stefan Jurga
Director
NanoBioMedical Centre
Adam Mickiewicz University
Ul. Umultowska 85
61-614 Poznań, Poland
Ph. +48 61 829 67 04

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[NMR] Open NMR Position at MPI Kohlenforschung in Mülheim an der Ruhr

A new position in the area NMR applied to catalysis research is now open in Mülheim an der Ruhr, Germany. Please distribute. (Basic German knowledge required ;)


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Christophe Farès, Ph.D.
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NMR Department/NMR Abteilung
Max-Planck Insitut für Kohlenforschung/ Max-Planck Insitute for Coal Research
Kaiser-Wilhelm Platz 1
45470 Mülheim an der Ruhr
Tel: +49 208 306 2130 
E-mail: fares [a] mpi-muelheim [.] mpg [.] de
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Monday, February 19, 2018

Sensitivity-enhanced detection of non-labile proton and carbon NMR spectra on water resonances #DNPNMR

Novakovic, M., et al., Sensitivity-enhanced detection of non-labile proton and carbon NMR spectra on water resonances. Phys. Chem. Chem. Phys., 2017. 20(1): p. 56-62.


Chemical exchange saturation transfer (CEST) experiments enhance the NMR signals of labile protons by continuously transferring these protons' saturation to an abundant solvent pool like water. The present study expands these principles by fusing into these experiments homonuclear isotropic mixing sequences, enabling the water-enhanced detection of non-exchangeable species. Further opportunities are opened by the addition of coupling-mediated heteronuclear polarization transfers, which then impose on the water resonance a saturation stemming from non-labile heteronuclear species like (13)C. To multiplex the ensuing experiments, these relayed approaches are combined with time-domain schemes involving multiple Ramsey-labeling experiments imparting the frequencies of the non-labile sites on the water resonance, via chemical exchange. (13)C and (1)H NMR spectra were detected in this fashion with about two-fold SNR amplification vis-a-vis conventionally detected spectroscopies. When combined with non-uniform sampling principles, this methodology thus becomes a sensitive alternative to detect non-exchangeable species in biomolecules. Still, multiple parameters including the scalar couplings and solvent exchange rates, will affect the efficiency and consequently the practicality of the overall experiment.

Friday, February 16, 2018

NMR Signal Quenching from Bound Biradical Affinity Reagents in DNP Samples #DNPNMR #NMR


Rogawski, R., et al., NMR Signal Quenching from Bound Biradical Affinity Reagents in DNP Samples. J Phys Chem B, 2017. 121(48): p. 10770-10781.


We characterize the effect of specifically bound biradicals on the NMR spectra of dihydrofolate reductase from E. coli. Dynamic nuclear polarization methods enhance the signal-to-noise of solid state NMR experiments by transferring polarization from unpaired electrons of biradicals to nuclei. There has been recent interest in colocalizing the paramagnetic polarizing agents with the analyte of interest through covalent or noncovalent specific interactions. This experimental approach broadens the scope of dynamic nuclear polarization methods by offering the possibility of selective signal enhancements and the potential to work in a broad range of environments. Paramagnetic compounds can have other effects on the NMR spectroscopy of nearby nuclei, including broadening of nuclear resonances due to the proximity of the paramagnetic agent. Understanding the distance dependence of these interactions is important for the success of the technique. Here we explore paramagnetic signal quenching due to a bound biradical, specifically a biradical-derivatized trimethoprim ligand of E. coli dihydrofolate reductase. Biradical-derivatized trimethoprim has nanomolar affinity for its target, and affords strong and selective signal enhancements in dynamic nuclear polarization experiments. In this work, we show that, although the trimethoprim fragment is well ordered, the biradical (TOTAPOL) moiety is disordered when bound to the protein. The distance dependence in bleaching of NMR signal intensity allows us to detect numerous NMR signals in the protein. We present the possibility that static disorder and electron spin diffusion play roles in this observation, among other contributions. The fact that the majority of signals are observed strengthens the case for the use of high affinity or covalent radicals in dynamic nuclear polarization solid state NMR enhancement.

[NMR] PhD position at the CNRS/University of Marseille #DNPNMR


ERC-funded PhD position is available in Marseille on the structural investigation of functional organic materials by DNP and NMR

Project title: “Structural investigation of polymorphic organic powders at natural isotopic abundance”

A 3-year PhD position is available at the CNRS/University of Aix-Marseille on the development of new experimental and theoretical approaches in dynamic nuclear polarization (DNP) NMR for the structural investigation of functional organic powders at natural isotopic abundance.

Context: Functional organic materials have been successfully used as active components in many applications, going from light emitters to optical devices, flexible photovoltaic devices, printed electronic inks, molecular machines, pigments, pharmaceuticals, etc. Such compounds can be used to produce low-cost, easily manufacturable, and lightweight materials that can replace traditional inorganic functional materials in energy-related applications (e.g. as semiconductors in solar cells or light emitter diodes), bringing significant economic and practical benefits. Moreover, they can be easily chemically modified to respond to specific application requirements (e.g. as active principle ingredients in pharmacy). In view of obtaining new functional materials with tailored properties, the true challenge in this field is the ability to establish a clear two-way relationship between the structure and the properties of the functional material in its end-use solid form. Because, in their end-use form, materials for the mentioned applications generally form particles with nanometer to micrometer-size dimensions, the main actual limitation to the rational development of new functional materials is the lack of a widely applicable methodology able to characterize fully and unambiguously the structure of functional organic powders lacking long-range order. 

Aim and job description: The aim of the thesis is to devise new analytical routes for accessing ab initio the structure of polymorphic organic microcrystalline powders at natural isotopic abundance through a combination of DNP NMR experiments and computational methods. The selected candidate will actively develop and optimize new NMR experiments for accessing dipolar and scalar couplings on functional materials for energy or pharmaceutical applications at natural isotopic abundance. The candidate will also use first principle calculations of NMR observables (in collaboration with the University of Oxford), as well as analytical (Mathematica, MatLab) or numerical (SIMPSON) simulations to help interpretation of experimental data.

Practical details: The PhD project will be performed at the Institut de Chimie Radicalaire (ICR UMR7273). Located in the south of France in Marseille, ICR is internationally recognized for its double expertise in i) the development of new DNP approaches for the characterization of organic solids and ii) the synthesis of radical species currently used as the most effective polarizing agents for solid DNP. Through the analytical facility Spectropole, ICR has access to a vast range of instrumentation for X-ray diffraction, mass spectrometry, IR, elemental analysis, as well as several NMR spectrometers for liquids and solids with fields ranging from 300 to 600 MHz. Notably, the candidate will access two 400 MHz wide-bore NMR spectrometers equipped with the latest hardware and numerous solid-state probes for spinning speeds up to 60 kHz. 

The PhD studentship will be funded by a European contract (ERC Starting grant, STRUCTURE project, G. Mollica) for a duration of 3 years, starting October 1st 2018. In the framework of ongoing collaborations, the candidate will be in contact with researchers from other European groups. He/she is expected to communicate the results of his/her work at international conferences.



Profile: The candidate should have a Master degree in Chemistry or Physics. Previous experience in NMR spectroscopy and/or computational methods is an advantage. Skills in organic chemistry are not required, but experience with crystallization procedures will be a plus. He/she is expected to be a motivated, imaginative, independent hard worker, with an interest in understanding fundamental aspects of NMR and polymorphism. He/she should have no issues with mobility and demonstrate excellent communication skills in English (knowledge of French is not required).

Application procedure: The candidate should send a motivation letter, at least two names for recommendation, CV (with list of publications and communications) and Master grades (with ranking) to:


&

Stephane Viel s.viel@univ-amu.fr

Application deadline: 15th March 2018.
--------------------------------


(EURAXESS Job Offer id: 279201)
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