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Applications of Electron Nanocrystallography for Organic and Macromolecular Structure Determination

English title Applications of Electron Nanocrystallography for Organic and Macromolecular Structure Determination
Applicant Grüne Tim
Number 169258
Funding scheme Project funding (Div. I-III)
Research institution Paul Scherrer Institut
Institution of higher education Paul Scherrer Institute - PSI
Main discipline Condensed Matter Physics
Start/End 01.04.2017 - 31.03.2021
Approved amount 261'208.00
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All Disciplines (2)

Discipline
Condensed Matter Physics
Other disciplines of Physics

Keywords (4)

Nanocrystals; Electron diffraction; Catalyst characterisation; Structural chemistry

Lay Summary (German)

Lead
Die Struktur eines chemischen Stoffes, also dreidimensionale Anordnung der Atome, ist ein grundlegender Baustein für die viele Forschungsgebiete wie Chemie, Materialwissenschaften, und der Medikamentenentwicklung. Eine der mächtigsten Methode, die Struktur zu bestimmen, ist die Kristallographie: wenn der Stoff kristallisiert werden kann, führt eine Untersuchung mit Röntgenstrahlen zu seiner Struktur. Die Schweizer Lichtquelle, SLS am Paul Scherrer Institut, produziert so starke Röntgenstrahlen, dass winzige Kristalle mit bis zu einem hundertstel Millimeter Kantenlänge untersucht werden können. Haufig müssen jedoch noch kleiner Kristalle untersucht werden. In diesen Fällen kann man Elektronenstrahlen statt Röntgenstrahlen für die Untersuchung benutzen. Allerdings ist die Handhabung und Analyse von Elektronenkristalldaten bislang nur Spezialisten vorbehalten.
Lay summary
Ziel dieses Projektes ist es, die Technik der Elektronenbeugung so weit zu entwickeln, dass sie jedem Labor, das Röntgenstrukturanalyse durchführt, als Erweiterung zur Verfügung steht. Somit können al jene Proben untersucht werden, bei denen derzeit keine ausreichend grosse Kristalle hergestellt werden können. Ein erster Schritt ist dabei die Installation der Detektoren der Firma Dectris Ltd. aus Baden AG an herkömmlichen Elektronenmikroskopen. Die Detektoren von Dectris sind seit über 10 Jahren marktführend zur Messung von Röntgenstrahlen. In einem ersten Experiment konnten wir ihre Ueberlegenheit ebenso bei der Messung von Elektronen unter Beweis stellen. Sie sind mehr als 40 mal so empfindlich wie herkömmliche Detektoren. Dadurch wird die Messung von strahlempfindlichen Proben überhaupt erst ermöglicht. Bisher waren die Proben bereits zerstört, noch ehe das erste Signal gemessen werden konnte. Darüber hinaus verbessern wir die Durchführung der Experimente und die Datenanalyse, damit schon bald in jedem Labor, dass ein Röntgenmessgerät nutzt, ebenso ein Elektronenmessgerät stehen kann.
Direct link to Lay Summary Last update: 01.05.2018

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
Heterogeneity of nano-sized zeolite crystals
Wennmacher Julian T.C., Li Teng, Zaubitzer Christian, Gemmi Mauro, Mugnaioli Enrico, Gruene Tim, van Bokhoven Jeroen A. (2020), Heterogeneity of nano-sized zeolite crystals, in Microporous and Mesoporous Materials, 294, 109897-109897.
3D-structured supports create complete data sets for electron crystallography
Wennmacher Julian T. C., Zaubitzer Christian, Li Teng, Bahk Yeon Kyoung, Wang Jing, van Bokhoven Jeroen A., Gruene Tim (2019), 3D-structured supports create complete data sets for electron crystallography, in Nature Communications, 10(1), 3316-3316.
Design guidelines for an electron diffractometer for structural chemistry and structural biology
Heidler Jonas, Pantelic Radosav, Wennmacher Julian T. C., Zaubitzer Christian, Fecteau-Lefebvre Ariane, Goldie Kenneth N., Müller Elisabeth, Holstein Julian J., van Genderen Eric, De Carlo Sacha, Gruene Tim (2019), Design guidelines for an electron diffractometer for structural chemistry and structural biology, in Acta Crystallographica Section D Structural Biology, 75(5), 458-466.
Rapid structure determination of microcrystalline molecular compounds using electron diffraction
Gruene Tim, Wennmacher Julian T. C., Zaubitzer Christian, Holstein Julian J., Heidler Jonas, Fecteau-Lefebvre Ariane, De Carlo Sacha, Müller Elisabeth, Goldie Kenneth N., Regeni Irene, Li Teng, Santiso-Quinones Gustavo, Steinfeld Gunther, Handschin Stefan, van Genderen Eric, van Bokhoven Jeroen A., Clever Guido H., Pantelic Radosav (2018), Rapid structure determination of microcrystalline molecular compounds using electron diffraction, in Angewandte Chemie International Edition, 57, 16313-16317.

Datasets

Rapid structure determination of microcrystalline molecular compounds using electron diffraction (nanoArgovia Project A3EDPI)

Author Gruene, Tim
Publication date 22.08.2018
Persistent Identifier (PID) 10.5281/zenodo.1297083
Repository Zenodo.org


3D-structured Supports create complete Data Sets for Electron Crystallography

Author Wennmacher, Julian T. C.; Zaubitzer, Christian; Li, Teng; Bahk, Yeon Kyoung; Wang, Jing; van Bokhoven, Jeroen A.; Gruene, Tim
Publication date 25.07.2019
Persistent Identifier (PID) 10.5281/zenodo.2553377
Repository Zenodo


Collaboration

Group / person Country
Types of collaboration
van Bokhoven, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Detector group, Paul Scherrer Institute Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
C-Cina, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
SLS, Paul Scherrer Institute Switzerland (Europe)
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Vienna BioCentre, Cryo-EM Symposium Poster Instrumentation for the Collection of Electron Diffraction Data 14.02.2020 Wien, Austria Grüne Tim;
Invited talk at the Netherlands Centre for Electron Nanoscopy (NeCen) Individual talk An EIGER X 1M detector turns a Transmission Electron Microscope into an Electron Diffractometer 12.06.2019 Leiden, Netherlands Grüne Tim;
iNEXT meeting Talk given at a conference Structure Determination with Electron Crystallography 29.05.2019 Brno, Czech Republic Grüne Tim;
Invited Talk at Boehringer Ingelheim Individual talk Organic and macromolecular crystallography with electrons 09.04.2019 Vienna, Austria Grüne Tim;
6th Ringberg Workshop on Structural Biology Individual talk An EIGER X 1M detector turns a Transmission Electron Microscope into an Electron Diffractometer for Chemistry and Biology 27.02.2019 Schloss Ringberg, Bavaria, Germany Grüne Tim;
Invited Talk at Roche Individual talk Organic and macromolecular crystallography with electrons 31.01.2019 Basel, Switzerland Grüne Tim;
Dectris Webinar Individual talk Applicability of 3D electron diffraction for the pharmaceutical industry 22.01.2019 Baden Daettwil, Switzerland Grüne Tim;
Regiomeeting 2018 Talk given at a conference DIY - How an EIGER detector turns a TEM into an electron diffractometer 27.09.2018 Emmetten, Switzerland Grüne Tim;
Invited Talk at BASF Individual talk Turning Powder into Single Crystals: Electron Crystallography for Structural Chemistry and Structural Biology 25.09.2018 Ludwigshafen, Germany Grüne Tim;
Annual Meeting of the Swiss Nanoscience Institute Talk given at a conference The EIGER X 1M Detector and a TEM make a Synchrotron 13.09.2018 Lenzerheide, Switzerland Grüne Tim;
INTERNATIONAL SCHOOL of CRYSTALLOGRAPHY Poster 3D structures support complete data sets for electron crystallography 01.06.2018 Erice, Italy Wennmacher Julian;
CCPEM Spring Symposium 2018 Talk given at a conference Collecting diffraction data with an electron microscope 11.04.2018 Keele University, Great Britain and Northern Ireland Grüne Tim;
British Crystallographic Association Spring Meeting 2018 Talk given at a conference Application of 3D Electron Diffraction to Organic and Macromolecular Crystallography 28.03.2018 University of Warwick, Great Britain and Northern Ireland Grüne Tim;


Self-organised

Title Date Place
3D Electron Crystallography for Macromolecular Compounds 18.09.2017 Paul Scherrer Institute, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Nano-Tech Apéro Talk 14.11.2018 Kaiseraugst, Switzerland Grüne Tim;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media CONVERSATIONS WITH SCIENTISTS Tim Gruene: Advancing Electron Crystallography Today's Science International 2019
Media relations: print media, online media Electron Crystallography: A Better Way to See Small Molecules Today's Science International 2019
Media relations: print media, online media Electron crystallography could be a powerful tool for organic chemists Chemical & Engineering News International 2018
New media (web, blogs, podcasts, news feeds etc.) MicroED: From Powder to Structure in a Half-Hour NIH Director's Blog International 2018
Media relations: print media, online media Zapping substances with electrons can quickly map chemical structures ScienceNews International 2018

Patents

Title Date Number Inventor Owner

Abstract

Structural information at atomic detail is important for research related bothto organic and macromolecular compounds. Pharmaceutically active organiccompounds can be modified to improve efficiency and reduce side effects.Structural information of macromolecular compounds can reveal domain movements,binding pockets for ligands and thus help understand e.g. enzymatic reactionmechanisms or mechanistic functioning of large complexes like the polymerase,the ribosome, or ion channels.Electron microscopy, nuclear magnetic resonance, and crystallography are themajor methods for structure determination of macromolecular compounds. thestructure of organic compounds is mainly determined with X-ray diffraction. Thecombination of electron microscopes with crystal diffraction leads to electronnanocrystallography: electrons interact very strongly with matter, and perdiffracted quantum they deposit three orders of magnitude less damaging energyin the crystal than X-rays. For these two properties, electron diffraction datacan be collected from crystals with nanometre dimensions. Even for veryradiation sensitive compounds like macromolecules, one to five crystals aresufficient for complete data. The possibility to determine a structure from onlyvery few nanocrystals carries at least two important advantages. Firstly itproduces reliable data and structures that can be determined and validated withestablished methods from the well matured field of X-ray crystallography.Secondly and more importantly, data collection from nanocrystals providesinformation from samples that have failed X-ray diffraction because of too smallor too few crystals. Especially for small molecule compounds,nanocrystallography can sometimes distinguish between intrinsic disorder andsamples composed of several types of crystals, which is important, e.g. for thepurity and thus efficiency of drugs.If all this is true, why are there so few organic and macromolecular structuresdetermined with electron diffraction from three dimensional nanocrystals? Themethod has only become possible with very recent detector developments.Currently data processing may take several weeks and requires highly experiencedand expert knowledge. This makes it little attractive for researchers to becomefamiliar with a new technique no matter its prospects.This project will pave way for electron diffraction to become a competitivemethod for structure determination: Reliable and fast determination ofexperimental parameters and new methods for structure solution from electrondiffraction data will encourage laboratories with access to electron microscopesto collect diffraction data on their own. This also connects with free electronlasers like the SwissFEL: using electron diffraction for structure determinationleaves more room to the SwissFEL for its unique strength, namely time-resolvedstudies at atomic detail.The project goal will be pursued with an interdisciplinary approach combiningaspects of electron microscopy with crystallography, and by developinginnovative methods for instrument calibration compatible with state-of-the-artelectron microscopes
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