Realising the potential of cryogenic magic-angle spinning nuclear magnetic resonance

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

Progress in the development of new medicines and materials requires knowledge of molecular structures, i.e. the precise arrangment of atoms within molecules. For example, if one knows the precise shape of a malfunctioning protein molecule, one can try to design other molecules which bind to it, so as to prevent it from doing too much damage. Scientists only have a few methods available for finding out about the structures of large molecules like proteins. The most successful method is X-ray crystallography. However, this powerful method requires crystals, which are difficult to produce for many very important biomolecules, especially the type of receptor proteins which sit inside cell membranes ( membrane proteins ).Another promising method is called solid-state NMR (nuclear magnetic resonance), which uses the fact that many of the nuclei at the centres of hydrogen, carbon and nitrogen atoms are weakly magnetic, and behave as small bar magnets. In NMR, radiowaves are used together with a strong magnetic field to probe the interactions between these magnets, allowing one to build up a picture of the molecular structure. Solid-state NMR has been used to obtain structural information from large biomolecules such as membrane proteins, without the need to form crystals. Unfortunately, the NMR signals are very weak. Rather large amounts of sample are often required. This greatly limits the application of this method, since many of the most interesting and important molecules are only available in very small quantities. In the current project we have designed and constructed equipment to perform solid-state NMR at very low temperatures, approaching the boiling point of liquid Helium (4.2 Kelvin, or -269 degrees C). The NMR signal is much stronger at these temperatures. This will allow biologists and chemists to obtain the vital molecular structural information using at least 10 times less sample than was possible before. The project is technically demanding because one must not only keep the sample very cold, but also rotate it very rapidly at a certain angle to the applied magnetic field (this is called magic-angle-spinning, or MAS). This rapid sample rotation is necessary to obtain the most informative NMR signals. Cryogenic magic-angle-spinning NMR is a major technical challenge, and our project combines leading expertise in sample spinning, electronics and cryogenics, in order to overcome these difficulties. In the translation grant we will develop the equipment further so as to allow the samples to be exchanged rapidly and conveniently. We will also invite external users to run their samples on our equipment, in order to develop and strengthen scientific collaborations both within the UK and internationally. We will perform experiments on two different sets of biomolecules produced in Southampton and Leeds, in order to elucidate their molecular structure and functional mechanism. We will also study conducting materials of great technological importance, such as organic conductors, semiconductors and superconductors. The cryoMAS-NMR experiments will allow visualization of the electronic conduction properties with sub-molecular resolution. This will greatly assist the development of new materials with applications in computing, communications, solar energy, and fuel cells.

Publications

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Beduz C (2012) Quantum rotation of ortho and para-water encapsulated in a fullerene cage. in Proceedings of the National Academy of Sciences of the United States of America

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Concistrè M (2013) Anisotropic nuclear spin interactions in H2O@C60 determined by solid-state NMR. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

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Concistrè M (2013) Magic-angle spinning NMR of cold samples. in Accounts of chemical research

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Concistrè M (2014) Freezing of Molecular Motions Probed by Cryogenic Magic Angle Spinning NMR. in The journal of physical chemistry letters

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Ge M (2011) Interaction potential and infrared absorption of endohedral H2 in C60. in The Journal of chemical physics

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Ge M (2011) Infrared spectroscopy of endohedral HD and D2 in C60. in The Journal of chemical physics

 
Description Cryogenic magic-angle-spinning NMR equipment was optimized and stabilized. The technology was applied to the study of molecular rotor systems.
Exploitation Route academic;

exploitation of patents for the cryogenic magic-angle-spinning technology
Sectors Chemicals,Energy,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description EPSRC
Amount £605,877 (GBP)
Funding ID EP/I029451/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2011 
End 09/2014
 
Description EPSRC Platform Grant
Amount £1,784,689 (GBP)
Funding ID EP/P009980/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 03/2017 
End 02/2022
 
Description Endofullerenes
Amount £605,877 (GBP)
Funding ID EP/I029451/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2011 
End 09/2014
 
Description European Research Council
Amount £2,415,690 (GBP)
Funding ID 291044 - HYPERSINGLET 
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 02/2012 
End 03/2016
 
Description Endofullerene collaboration 
Organisation Brown University
Country United States 
Sector Academic/University 
PI Contribution NMR and theory
Collaborator Contribution Synthesis, physical techniques, and theory
Impact Too complex to report here.
Start Year 2006
 
Description Endofullerene collaboration 
Organisation Columbia University
Country United States 
Sector Academic/University 
PI Contribution NMR and theory
Collaborator Contribution Synthesis, physical techniques, and theory
Impact Too complex to report here.
Start Year 2006
 
Description Endofullerene collaboration 
Organisation Institut Laue–Langevin
Country France 
Sector Public 
PI Contribution NMR and theory
Collaborator Contribution Synthesis, physical techniques, and theory
Impact Too complex to report here.
Start Year 2006
 
Description Endofullerene collaboration 
Organisation National institute of Chemical Physics, Tallinn
Country Estonia 
Sector Public 
PI Contribution NMR and theory
Collaborator Contribution Synthesis, physical techniques, and theory
Impact Too complex to report here.
Start Year 2006
 
Description Endofullerene collaboration 
Organisation University of Kyoto
Country Japan 
Sector Academic/University 
PI Contribution NMR and theory
Collaborator Contribution Synthesis, physical techniques, and theory
Impact Too complex to report here.
Start Year 2006
 
Description Endofullerene collaboration 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR and theory
Collaborator Contribution Synthesis, physical techniques, and theory
Impact Too complex to report here.
Start Year 2006
 
Description Hyperpolarization collaboration 
Organisation Cambridge Cancer Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation Swiss Federal Institute of Technology in Lausanne (EPFL)
Country Switzerland 
Sector Public 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation University of Pennsylvania
Country United States 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010
 
Description Hyperpolarization collaboration 
Organisation École normale supérieure de Lyon (ENS Lyon)
Country France 
Sector Academic/University 
PI Contribution NMR techniques, materials, theory, simulations
Collaborator Contribution MRI techniques, materials, methodology
Impact Too complex to report here.
Start Year 2010