Jul 3, 2020

The surface chemistry of a nanocellulose drug carrier unravelled by MAS-DNP #DNPNMR

Kumar, Akshay, Hippolyte Durand, Elisa Zeno, Cyril Balsollier, Bastien Watbled, Cecile Sillard, Sébastien Fort, et al. “The Surface Chemistry of a Nanocellulose Drug Carrier Unravelled by MAS-DNP.” Chemical Science, 2020, 10.1039.C9SC06312A.


Cellulose nanofibrils (CNF) are renewable bio-based materials with high specific area, which makes them ideal candidates for multiple emerging applications including for instance on-demand drug release. However, in-depth chemical and structural characterization of the CNF surface chemistry is still an open challenge, especially for low weight percentage of functionalization. This currently prevents the development of efficient, cost-effective and reproducible green synthetic routes and thus the widespread development of targeted and responsive drug-delivery CNF carriers. We show in this work how we use dynamic nuclear polarization (DNP) to overcome the sensitivity limitation of conventional solid-state NMR and gain insight into the surface chemistry of drug-functionalized TEMPO-oxidized cellulose nanofibrils. The DNP enhanced-NMR data can report unambiguously on the presence of trace amounts of TEMPO moieties and depolymerized cellulosic units in the starting material, as well as coupling agents on the CNFs surface (used in the heterogeneous reaction). This enables a precise estimation of the drug loading while differentiating adsorption from covalent bonding (∼1 wt% in our case) as opposed to other analytical techniques such as elemental analysis and conductometric titration that can neither detect the presence of coupling agents, nor differentiate unambiguously between adsorption and grafting. The approach, which does not rely on the use of 13C/15N enriched compounds, will be key to further develop efficient surface chemistry routes and has direct implication for the development of drug delivery applications both in terms of safety and dosage.

Jul 2, 2020

[NMR] Permanent position for a researcher - staff scientist at CEA Grenoble in DNP-enhanced solid-state NMR #DNPNMR



Permanent position opening for a researcher - staff scientist at CEA Grenoble In the field of DNP-enhanced solid-state NMR


Job description

The Interdisciplinary Research Institute of Grenoble (IRIG) has an open position for a researcher - staff scientist specialist in NMR spectroscopy applied to the chemical sciences. The successful candidate will be affiliated to the Modeling and Exploration of Materials Laboratory (MEM), a joint research unit of CEA and the University Grenoble Alpes. He/she will join the DNP research group led by G. De Paëpe at the IRIG, CEA Grenoble, France.

The successful candidate will participate in the research activities of the group, will build and manage new projects with academic and industrial partners. He/She will also be in charge of the DNP-NMR lab equipment in terms of day-to-day operation, maintenance, hardware troubleshooting and fixing. As such, duties include operation of 2 high-field DNP-NMR spectrometers, a fully automated cryostat for close-loop cryogenic helium sample spinning, developing and testing helium/nitrogen fast MAS DNP probes. A central aspect of the work will consist in setting up established pulse sequences (for spin ½ and quadrupolar nuclei) but also to design and develop innovative sequences, data acquisition and processing protocols, as well as user-friendly post-processing analysis tools. The position implies as well, taking an active part in training and guiding graduate students from the group.

Scientific environment and workplace

The MEM laboratory currently hosts 2 DNP spectrometers, including the first DNP spectrometer installed in France (2011). Since then, the laboratory has gained international recognition in the DNP field. The originality of the Grenoble DNP team lies in the diversity of its research, which encompasses methodological developments (pulse sequences, sample preparation, DNP theory, design of improved polarizing agents, targeted and selective DNP), major instrumental developments (autonomous helium cryostat and fast MAS cryogenic probes operating at very low temperatures << 100 K and fast MAS), but also advanced applications in the field of functional materials and complex biomolecular systems.

The MEM laboratory also hosts 3 other NMR spectrometers (200 / 400 / 500 MHz) equipped with solution, PFG, HRMAS and solid-state NMR probes, including a fast MAS probe and an in operando probe for low field paramagnetic NMR. IRIG gathers 10 laboratories including MEM, with about 1000 researchers, technicians, doctoral and post-doctoral students, covering a large variety of interdisciplinary fields (nanophysics, chemistry for health and energy, cryo-technologies, biology and medicine). Besides, IRIG includes also the IBS NMR groups which are specialized in structural biology and host 6 other NMR instruments (including a 950 MHz spectrometer). This strong environment in NMR is ideally complemented by research teams specialized in EPR, advanced electron microscopy, X-ray (lab equipment and ESRF) and neutron (ILL) diffraction.

Located in the French Alps and surrounded by a stunning natural environment, the international city of Grenoble represents an extremely rich ecosystem formed by public research organizations (CEA, CNRS, ESRF, ILL) and high-tech companies. In addition, the Université Grenoble Alpes attracts a large number of students who can benefit from high-level academic training in a broad range of disciplines.

Qualifications

Candidates should have a PhD in Chemistry / Physical Chemistry / Physics or Engineering with a dissertation awarded from a research group specialized in advanced NMR spectroscopy techniques. The candidate should have hands-on experience in solid-state NMR and dynamic nuclear polarization. Preference will be given to candidates with postdoctoral experience of at least two to three years. The candidate should master NMR acquisition software and have a strong expertise in NMR theory, pulse sequence development and computational analysis. Experience with spectrometer and probe troubleshooting, matlab or equivalent, python scripting etc. is a plus. Excellent communication skills in English and ability to work in a research team is a requirement.

How to Apply

Candidates are requested to send by email a motivation letter and a detailed CV to Gaël De Paëpe at gael.depaepe@cea.fr, deadline for application: August 15th, 2020. Selected candidates will be informed quickly and called for an interview planned in September 2020. Depending on the situation, interviews might be conducted online.

Additional information: This offer corresponds to a tenured position at the French Atomic and Alternative Energy Commission (CEA, www.cea.fr). Salary is commensurate with experience. 

-- Dr Gaël De Paëpe CEA / Univ. Grenoble Alpes DRF/IRIG/MEM/RM email gael.depaepe@cea.fr voice (office) +33 4 38 78 65 70 voice (lab) +33 4 38 78 47 26 fax +33 4 38 78 50 90 Mailing address: CEA Grenoble 17 Avenue des Martyrs Bâtiment 51C Office P.132a / Lab P.138 38054 Grenoble Cedex 9 - France 

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[NMR] PhD thesis proposal (Paris Montpellier, France) - October 2020 #DNPNMR



Dear colleagues,

We are looking for a phD student :

Title: The Observation of low Gyromagnetic ratio nuclei in biomaterial Environments Through Hyperpolarization Enhanced magnetic Resonance

Financing: Agence Nationale de la Recherche

Starting Date: between october and december 2020

Objectives : The proposed Ph.D. thesis aims at optimizing 43Ca DNP NMR for the analysis of Ca environments in synthetic biomaterials, and then extending this new technique to the in-depth study of bones of normal and genetically engineered mice, in view of expanding our understanding of human bone pathologies.
Moreover, the investigation of other poorly-sensitive cations of biological relevance (Mg2+, K+) using these new DNP methods will be looked into, to gain additional information on the structure of biomaterials.

A first part of the work will be dedicated to the synthesis of a variety of model calcium-phosphate samples, starting from purely hydroxyapatite phases (the main inorganic component of bones and teeth) and then switching to surface-grafted compounds and more biologically-relevant and biomimetic hybrids. Each of these compounds will be elaborated by using or adapting previously-published protocols and fully characterized by standard analytical techniques, including “conventional” multinuclear solid state NMR, before moving to DNP analysis. Moreover, for each phase, computational models will be developed, involving first principles calculations of NMR parameters, to ensure a proper interpretation of the DNP spectra.

A second part will be focused on the study of local cation environments in pathological mice bones using DNP NMR experiments. This final objective is to highlight the variability of the calcium environments at the collagen/mineral interface when comparing healthy and impaired tissues, and to establish the link between NMR descriptions at the molecular level and the changes in functional properties in bones of the pathological mice, or, in other words, at determining which are the molecular-level changes that could impact bone density and resistance to fracture.

Environment: This thesis will take place at the Laboratoire de Chimie de la Matière Condensée de Paris in Sorbonne Université (https://lcmcp.upmc.fr/site/smiles/) and the Institut Charles Gerhardt in Montpellier (https://www.icgm.fr/imno). Part of the work will also be performed in strong collaboration with CEA Grenoble for DNP experiments, and the Centre de Physiopathologie Toulouse Purpan for studies on pathological mice bones.

Application: Interested candidates should email their CV an application and recommandation letters to:
Pr Christel GERVAIS (LCMCP, christel.gervais_stary@sorbonne-universite.fr)
Pr Christian BONHOMME (LCMCP, christian.bonhomme@sorbonne-universite.fr)
Dr Danielle Laurencin (ICGM, danielle.laurencin@umontpellier.fr)
-- -------------------------------------- Dr Christel GERVAIS - Professeur Laboratoire de Chimie de la Matiere Condensée de Paris Sorbonne Université Case courrier 174 4 place Jussieu 75252 PARIS cedex 05 Aile 34-44, 4e étage, porte 424 Tel : 33-1-44-27-63-35 e-mail : christel.gervais_stary@sorbonne-universite.fr ------------------------------------------

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Jul 1, 2020

Cryogenic Platforms and Optimized DNP Sensitivity #DNPNMR

Matsuki, Yoh, and Toshimichi Fujiwara. “Cryogenic Platforms and Optimized DNP Sensitivity,” 7:16, 2018.



Modern high-field DNP NMR spectrometers are typically based on a cryogenic magic-angle sample spinning (MAS) capability. Conventionally, sample temperatures of T ∼100 K have been widely used, enabling substantial NMR signal enhancement with DNP at high external field conditions such as B0 =9.4 T. Today, however, the need for performing MAS DNP at much lower temperatures (T ≪100 K) is receiving growing attention for its ability to recover the rapidly degrading efficiency of the cross-effect (CE)-based DNP at even higher magnetic fields, B0 >10 T. In this article, we describe three contemporary cryogenic DNP MAS NMR probe systems: one is N2 based for T ∼100 K, and the other two are helium based for T ≪100 K. Principal requirements important in designing the cryogenic MAS NMR systems include long-term stability, cost efficiency, and readiness of operation. All the described setups incorporated various modifications and novel features to meet these challenges. In particular, the novel closed-cycle helium MAS system realizes all the requirements to a high standard, establishing an efficient and practical platform for ultralow sample temperature (T ∼30 K) MAS DNP. The resulting dramatic increase in sensitivity gain suggests the regained promise for the CE-based DNP at very high-field conditions (B0 >10 T). The experimental DNP data and effective sensitivity gain obtained with the described systems operating at 14.1 and 16.4 T are also discussed.

Jun 29, 2020

Continuous wave electron paramagnetic resonance of nitroxide biradicals in fluid solution

Eaton, Sandra S., Lukas B. Woodcock, and Gareth R. Eaton. “Continuous Wave Electron Paramagnetic Resonance of Nitroxide Biradicals in Fluid Solution.” Concepts in Magnetic Resonance Part A 47A, no. 2 (March 2018): e21426.


Nitroxide biradicals have been prepared with electron-electron spin-spin exchange interaction, J, ranging from weak to very strong. EPR spectra of these biradicals in fluid solution depend on the ratio of J to the nitrogen hyperfine coupling, AN, and the rates of interconversion between conformations with different values of J. For relatively rigid biradicals EPR spectra can be simulated as the superposition of AB splitting patterns arising from different combinations of nitrogen nuclear spin states. For more flexible biradicals spectra can be simulated with a Liouville representation of the dynamics that interconvert conformations with different values of J on the EPR timescale. Analysis of spectra, factors that impact J, and examples of applications to chemical and biophysical problems are discussed.

[NMR] PhD thesis proposal (Marseille, France) - October 2020 #DNPNMR

PhD thesis proposal

Title: Enhancing NMR sensitivity with diamond nitrogen-vacancy centres

Financing: Agence Nationale de la Recherche - Net Remuneration: ~1420 € / month

Starting Date: October 2020

Topic Description: Dynamic nuclear polarization is a powerful method that improves NMR sensitivity by transferring spin polarization from electrons to nuclei, but it is limited because it requires cryogenic temperatures and paramagnetic doping that alter resolution and sensitivity. A more advantageous approach would be to polarize a material directly from a substrate that is itself highly polarizable. In this context, synthetic diamonds containing NV (nitrogen-vacancy) centers appear to be ideal candidates as they allow this operation to be performed under laser illumination at room temperature. These spin polarizations could then be transferred from the diamond to another material, thus offering a general method for increasing NMR sensitivity. This thesis aims to overcome this challenge by combining new instrumentation and optimized diamond synthesis to maximize the spin polarization inside the diamond and to study its transfer from the diamond to an external material.

Environment: At the interface of the physico-chemistry of (nano)materials and spectroscopy, this thesis will take place on the St Jérôme campus in Marseille (France) within the Institut de Chimie Radicalaire (UMR 7273) in close collaboration with the Institut de Recherche de Chimie Paris (UMR 8247), the Laboratoire des Sciences des Procédés et des Matériaux (UPR 3407), and the Laboratoire Charles Coulomb (UMR 5221).

Application: To apply, please send a CV and a cover letter to Pr. Stéphane Viel (s.viel@univ-amu.fr). Please also provide a copy of the results obtained during the Master's course as well as 2 letters of recommendation.
Pr. Stéphane Viel - UFR Sciences, Départ. de Chimie, Institut de Chimie Radicalaire (UMR 7273)
Adresse : Aix-Marseille Université, Campus St Jérôme (case 512), Av. Escadrille Normandie Niemen, 13397 Marseille cedex 20
Tél. : +33 (0)4 91 28 8902 - Mobile : +33 (0)6 68 27 2901 - E-mail : s.viel@univ-amu.fr - Site : http://icr-amu.cnrs.fr/spip.php?article123
Afin de respecter l'environnement, merci de n'imprimer cet email que si nécessaire.

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Jun 26, 2020

Simultaneous T1 and T2 mapping of hyperpolarized 13C compounds using the bSSFP sequence #DNPNMR

Milshteyn, Eugene, Galen D. Reed, Jeremy W. Gordon, Cornelius von Morze, Peng Cao, Shuyu Tang, Andrew P. Leynes, Peder E.Z. Larson, and Daniel B. Vigneron. “Simultaneous T1 and T2 Mapping of Hyperpolarized 13C Compounds Using the BSSFP Sequence.” Journal of Magnetic Resonance 312 (March 2020): 106691.


As in conventional 1H MRI, T1 and T2 relaxation times of hyperpolarized (HP) 13C nuclei can provide important biomedical information. Two new approaches were developed for simultaneous T1 and T2 mapping of HP 13C probes based on balanced steady state free precession (bSSFP) acquisitions: a method based on sequential T1 and T2 mapping modules, and a model-based joint T1/T2 approach analogous to MR fingerprinting. These new methods were tested in simulations, HP 13C phantoms, and in vivo in normal Sprague-Dawley rats. Non-localized T1 values, low flip angle EPI T1 maps, bSSFP T2 maps, and Bloch-Siegert B1 maps were also acquired for comparison. T1 and T2 maps acquired using both approaches were in good agreement with both literature values and data from comparative acquisitions. Multiple HP 13C compounds were successfully mapped, with their relaxation time parameters measured within heart, liver, kidneys, and vasculature in one acquisition for the first time.