Author Archives: tmaly

Dehydration entropy drives liquid-liquid phase separation by molecular crowding

Park, Sohee, Ryan Barnes, Yanxian Lin, Byoung-jin Jeon, Saeed Najafi, Kris T. Delaney, Glenn H. Fredrickson, Joan-Emma Shea, Dong Soo Hwang, and Songi Han. “Dehydration Entropy Drives Liquid-Liquid Phase Separation by Molecular Crowding.” Communications Chemistry 3, no. 1 (December 2020): 83.

https://doi.org/10.1038/s42004-020-0328-8

Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)—a widely used molecular crowder—in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.

From nano-seggregation to mesophases: probing the liquid structure of perfluoroalkylalkanes with 129Xe NMR spectroscopy

Morgado, Pedro. “From Nano-Seggregation to Mesophases: Probing the Liquid Structure of Perfluoroalkylalkanes with 129Xe NMR Spectroscopy.” Phys. Chem. Chem. Phys., 2020, 12.

https://doi.org/10.1039/D0CP02123G

In this work we demonstrate that pure perfluoroalkylalkane diblock molecules are not isotropic liquids and self organize forming domains at the nanometric scale. 129Xe NMR spectra were obtained as a function of temperature for seven liquid perfluoroalkylalkanes, covering a range of relative lengths of the hydrogenated and fluorinated segments. The results support the presence of domains richer in the hydrogenated groups, in which xenon is preferentially dissolved. The average local concentration within the xenon coordination sphere is estimated to be 0.05 mole fraction higher in hydrogenated groups than the stoichiometric proportion. Atomistic molecular dynamics simulations support this analysis and allow a detailed analysis of the liquid structure. Furthermore, 129Xe NMR spectra in perfluorohexylhexane (F6H6) and perfluorohexyloctane (F6H8) obtained as a function of temperature, clearly detect the existence of two distinct environments in the fluid, one richer in hydrogenated groups and another richer in fluorinated groups, consistent with the formation of mesophases. It is important to stress that nano-segregation is this case observed in liquids interacting exclusively through dispersion forces, unlike most common examples of segregation which are determined by hydrogen bonding and polarity. Given the simple molecular structure and interactions of the studied PFAA, we believe that the present results can have a general impact in understanding the early mechanisms of segregation, phase separation and self-assembly.

Parahydrogen‐Induced Hyperpolarization of Gases #DNPNMR

Kovtunov, Kirill V., Igor V. Koptyug, Marianna Fekete, Simon B. Duckett, Thomas Theis, Baptiste Joalland, and Eduard Y. Chekmenev. “Parahydrogen‐Induced Hyperpolarization of Gases.” Angewandte Chemie International Edition 59, no. 41 (October 5, 2020): 17788–97.

https://doi.org/10.1002/anie.201915306

Imaging of gases is a major challenge for any modality including MRI. NMR and MRI signals are directly proportional to the nuclear spin density and the degree of alignment of nuclear spins with applied static magnetic field, which is called nuclear spin polarization. The level of nuclear spin polarization is typically very low, i.e., one hundred thousandth of the potential maximum at 1.5 T and a physiologically relevant temperature. As a result, MRI typically focusses on imaging highly concentrated tissue water. Hyperpolarization methods transiently increases nuclear spin polarizations up to unity, yielding corresponding gains in MRI signal level of several orders of magnitude that enable the 3D imaging of dilute biomolecules including gases. Parahydrogen-induced polarization is a fast, highly scalable, and low-cost hyperpolarization technique. The focus of this Minireview is to highlight selected advances in the field of parahydrogen-induced polarization for the production of hyperpolarized compounds, which can be potentially employed as inhalable contrast agents.

Design of Nuclear Magnetic Resonance Molecular Probes for Hyperpolarized Bioimaging

Kondo, Yohei, Hiroshi Nonaka, Yoichi Takakusagi, and Shinsuke Sando. “Design of Nuclear Magnetic Resonance Molecular Probes for Hyperpolarized Bioimaging.” Angewandte Chemie International Edition, May 6, 2020, anie.201915718.

https://doi.org/10.1002/anie.201915718

Nuclear hyperpolarization has emerged as a method to dramatically enhance the sensitivity of NMR. By applying this powerful tool, small molecules with stable isotopes have been subjected to highly sensitive biomedical molecular imaging. The recent development of molecular probes for hyperpolarized in vivo analysis has demonstrated the ability of this technique to provide unique metabolic and physiological information. This review presents a brief introduction of hyperpolarization technology, approaches to rational design of molecular probes for hyperpolarized analysis, and examples of molecules that have met with in vitro or in vivo success.

[NMR] Senior MRS Scientist position at Synex Medical, Toronto/Boston/Remote

Senior Magnetic Resonance Scientist

Apply here:https://synex.breezy.hr/p/01e875623b57-senior-magnetic-resonance-scientist

Synex Medical is developing the next generation of non-invasive health sensors to allow for continuous monitoring at the molecular level. Our technology is based on novel techniques in magnetic resonance that allow us to accurately measure critical blood-metabolites completely non-invasively and in highly miniaturized form-factors. We want people to have access to their own metabolism and to make predictive healthcare the norm.

We are an incredibly driven team that are working with the leading experts in our field. We’re looking for a person with experience in magnetic resonance spectroscopy who’s ambitious to tackle hard and exciting problems. 

As a Senior Magnetic Resonance Scientist, you will:

  • Work closely with the NMR team and leading academic collaborators to develop and optimize highly advanced pulse sequences for in vivo measurements.
  • Translate existing pulse sequences from high-field spectrometers to use on benchtop and custom systems.
  • Build and work with ultra compact, low-field (< 1 Tesla) NMR systems.
  • Work with a team of some of the leading electrical engineers, embedded firmware and FPGA designers, and machine learning & signal processing engineers to produce creative solutions to complex scientific challenges.
  • Stay up to date on state-of-the-art NMR techniques and come up with innovative ways of applying them to our technology.

We are looking for someone with:

  • 3+ years of experience working on NMR or MRI platforms.
  • A Ph.D. with an emphasis on applied Magnetic Resonance. M.Sc with significant and highly relevant experience will also be considered.
  • Pulse sequence development experience will be a significant asset.
  • Thorough understanding of magnetic resonance theory and NMR/MRI experimental techniques.
  • Experience with complex sample and/or biological MR techniques.
  • Familiarity with common NMR/MR softwares and pulse sequence programming (e.g. Topspin). Should be able to understand and translate pulse sequences from major NMR/MRI vendors.
  • An ambition and drive to tackle hard problems.

Nice to haves:

  • Experience with permanent magnet NMR, signal processing and analysis, and NMR hardware.
  • Experience with low field NMR (< 1 Tesla) and/or MRI.
  • Experience with in vivo MRS techniques.
  • Experience with modeling NMR experiments and spin dynamics using Hamiltonian and Bloch equation simulations.

Perks: 

  • Competitive salary and company ownership opportunities.
  • A diverse and accepting work atmosphere.
  • Minimum three (3) weeks of vacation entitlement for all new employees.
  • Employee training and development initiatives and support for career advancement (through financial assistance and flexible scheduling).
  • Flexibility in working schedule.

Rudraksha “Rudy” Majumdar, Ph.D.Senior NMR Scientist www.synexmedical.comC:+1 (647) 573-33962 Bloor Street E, Suite 310 Toronto, ON M4W 1A8

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[NMR] Postdoctoral Position on Biophysical NMR at Merck & Co, Inc. (US)

Yongchao SU yongchaosu@gmail.com via listes.univ-paris-diderot.fr Tue, Jan 12, 4:23 PM (19 hours ago)
to nmr

Dear NMR Colleagues,

I’d like to share a three-year-term postdoc opening at Merck & Co, Inc. in the United States. It is a great opportunity for those who would like to pursue an industrial career and utilize this powerful and lovely tool to advance biopharmaceutical characterization for drug product developments.

The proposed study is to investigate molecular mechanisms to understand (in-)stability of oligonucleotide, protein and mAb therapeutics in biological formulations. All junior researchers with solution NMR and/or solid-state NMR training are welcome to apply. Research experiences on biomacromolecules using NMR are appreciated. 

Many thanks if you could share with your group and networks. Interested candidates can forward CVs to me at yongchao.su@merck.com .

Postdoctoral Research Fellow – Biophysical NMR of Protein Therapeutics job in Rahway, New Jersey, United States of America | Research & Development jobs at Merck

Thanks,

Yongchao Su

Principal Scientist

Head of Biopharmaceutical NMR Lab (BNL)

Pharmaceutical Sciences | Preclinical Development

Merck & Co. Inc, Rahway, NJ 07065

Google Scholar | LinkedIn
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Parahydrogen‐Induced Radio Amplification by Stimulated Emission of Radiation

Joalland, Baptiste, Nuwandi M. Ariyasingha, Sören Lehmkuhl, Thomas Theis, Stephan Appelt, and Eduard Y. Chekmenev. “Parahydrogen‐Induced Radio Amplification by Stimulated Emission of Radiation.” Angewandte Chemie International Edition 59, no. 22 (May 25, 2020): 8654–60.

https://doi.org/10.1002/anie.201916597

Radio amplification by stimulated emission of radiation (RASER) was recently discovered in a low-field NMR spectrometer incorporating a highly specialized radiofrequency resonator, where a high degree of proton-spin polarization was achieved by reversible parahydrogen exchange. RASER activity, which results from the coherent coupling between the nuclear spins and the inductive detector, can overcome the limits of frequency resolution in NMR. Here we show that this phenomenon is not limited to low magnetic fields or the use of resonators with high-quality factors. We use a commercial bench-top 1.4 T NMR spectrometer in conjunction with pairwise parahydrogen addition producing protonhyperpolarized molecules in the Earth s magnetic field (ALTADENA condition) or in a high magnetic field (PASADENA condition) to induce RASER without any radio-frequency excitation pulses. The results demonstrate that RASER activity can be observed on virtually any NMR spectrometer and measures most of the important NMR parameters with high precision.

Analysis of the electronic structure of the primary electron donor of photosystem I of Spirodela oligorrhiza by photochemically induced dynamic nuclear polarization (photo-CIDNP) solid-state nuclear magnetic resonance (NMR)

Janssen, Geertje J., Patrick Eschenbach, Patrick Kurle, Bela E. Bode, Johannes Neugebauer, Huub J. M. de Groot, Jörg Matysik, and Alia Alia. “Analysis of the Electronic Structure of the Primary Electron Donor of Photosystem I of Spirodela Oligorrhiza by Photochemically Induced Dynamic Nuclear Polarization (Photo-CIDNP) Solid-State Nuclear Magnetic Resonance (NMR).” Magnetic Resonance 1, no. 2 (November 13, 2020): 261–74.

https://doi.org/10.5194/mr-1-261-2020

The electron donor in photosystem I (PSI), the chlorophyll dimer P700, is studied by photochemically induced dynamic nuclear polarization (photo-CIDNP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) on selectively 13C and uniformly 15N labeled PSI core preparations (PSI-100) obtained from the aquatic plant duckweed (Spirodela oligorrhiza). Light-induced signals originate from the isotope-labeled nuclei of the cofactors involved in the spin-correlated radical pair forming upon light excitation. Signals are assigned to the two donor cofactors (Chl a and Chl a’) and the two acceptor cofactors (both Chl a). Light-induced signals originating from both donor and acceptor cofactors demonstrate that electron transfer occurs through both branches of cofactors in the pseudo-C2 symmetric reaction center (RC). The experimental results supported by quantum chemical calculations indicate that this functional symmetry occurs in PSI despite similarly sized chemical shift differences between the cofactors of PSI and the functionally asymmetric special pair donor of the bacterial RC of Rhodobacter sphaeroides. This contributes to converging evidence that local differences in time-averaged electronic ground-state properties, over the donor are of little importance for the functional symmetry breaking across photosynthetic RC species.

SLIM: A Short‐Linked, Highly Redox‐Stable Trityl Label for High‐Sensitivity In‐Cell EPR Distance Measurements

Fleck, Nico, Caspar A. Heubach, Tobias Hett, Florian R. Haege, Pawel P. Bawol, Helmut Baltruschat, and Olav Schiemann. “SLIM: A Short‐Linked, Highly Redox‐Stable Trityl Label for High‐Sensitivity In‐Cell EPR Distance Measurements.” Angewandte Chemie International Edition 59, no. 24 (June 8, 2020): 9767–72.

https://doi.org/10.1002/anie.202004452

The understanding of biomolecular function is coupled to knowledge about the structure and dynamics of these biomolecules, preferably acquired under native conditions. In this regard, pulsed dipolar EPR spectroscopy (PDS) in conjunction with site-directed spin labeling (SDSL) is an important method in the toolbox of biophysical chemistry. However, the currently available spin labels have diverse deficiencies for in cell applications, e.g. low radical stability or long bioconjugation linkers. In this work, a synthesis strategy is introduced for the derivatization of trityl radicals with a maleimide functionalized methylene group. The resulting trityl spin label SLIM yields narrow distance distributions, enables highly sensitive distance measurements down to concentrations of 90 nM and shows high stability against reduction. Using this label, the GDI domain of YopO is shown to change its conformation within eukaryotic cells.

[NMR] Postdoc position on DNP/RF instrumentation at ENS Paris #DNPNMR

Hi all,
There is a postdoc position available in Kong Ooi Tan’s team at ENS Paris starting in spring 2021. Initial contract is for one year, and renewable at the end of each contract year. The main goal of the project is to develop rf and microwave instrumentation for Dynamic Nuclear Polarization (DNP) techniques at high magnetic fields, i.e., ≥ 9.4 T/ 400 MHz/ 263 GHz. The candidate needs to build a DNP NMR probe with optimized rf & microwave delivery from the source to the sample at a cryogenic condition. The array of instruments that has to be built includes microwave waveguides, resonant cavity, and rf resonance circuitry. Hence, candidates with experience in assembling rf and microwave components is highly desirable. Besides, we will build a low-cost EPR circuitry in the same probe to allow the characterization of the DNP polarizing agents using EPR spectroscopy. Our lab houses an 800 MHz/ 527 GHz MAS-DNP spectrometer, a 600 MHz, a 400 MHz, and two dissolution-DNP polarizers (a Bruker prototype at 6.7 T/ 188 GHz and a home-built cryogen-free system at 9.4 T/ 263 GHz).
More details are available at https://euraxess.ec.europa.eu/jobs/590039Group website: http://www.paris-en-resonance.fr
Feel free to circulate the advertisement to whoever might be interested in this position.
Thank you for your time and happy holidays!
Regards,Kong

Prof. Kong Ooi Tan
Junior ProfessorLaboratoire des Biomolécules UMR 7203 
Département de Chimie
École Normale Supérieure 24 Rue Lhomond 
75231 Paris CEDEX 05
Université PSLhttp://www.paris-en-resonance.fr

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