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Title: Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector

Abstract

A specialized quantum area detector for electron diffraction studies makes it possible to solve the structure of small organic compound nanocrystals in non-cryo conditions by direct methods. Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼0.013 e{sup −} Å{sup −2} s{sup −1}) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS, SHELX) and for electron crystallography (ADT3D/PETS, SIR2014)

Authors:
;  [1];  [2];  [3];  [4];  [1];  [5];  [1];  [3];  [6];  [1];  [3];  [7];  [1];  [2];  [8]
  1. Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden (Netherlands)
  2. (C-CINA), Biozentrum, University of Basel, CH-4058 Basel (Switzerland)
  3. Nanomegas SPRL, Boulevard Edmond Machtens 79, B 1080, Brussels (Belgium)
  4. Department of Physics and Energy, Materials and Surface Science Institute (MSSI), University of Limerick, Limerick (Ireland)
  5. (Netherlands)
  6. (Spain)
  7. Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), 5232 Villigen (Switzerland)
  8. (PSI), 5232 Villigen (Switzerland)
Publication Date:
OSTI Identifier:
22535125
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section A, Foundations and Advances (Online); Journal Volume: 72; Journal Issue: Pt 2; Other Information: PMCID: PMC4770873; PMID: 26919375; PUBLISHER-ID: td5026; OAI: oai:pubmedcentral.nih.gov:4770873; Copyright (c) E. van Genderen et al. 2016; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United Kingdom
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; COMPUTER CODES; ELECTRON DIFFRACTION; MATHEMATICAL SOLUTIONS; NANOSTRUCTURES; RADIATION EFFECTS; SIGNAL-TO-NOISE RATIO; TEMPERATURE RANGE 0273-0400 K; THREE-DIMENSIONAL CALCULATIONS; TRANSMISSION ELECTRON MICROSCOPY; X RADIATION

Citation Formats

Genderen, E. van, Clabbers, M. T. B., Center for Cellular Imaging and NanoAnalytics, Das, P. P., Stewart, A., Nederlof, I., Amsterdam Scientific Instruments, Postbus 41882, 1009 DB Amsterdam, Barentsen, K. C., Portillo, Q., Centres Científics i Tecnològics de la Universitat de Barcelona, University of Barcelona, Carrer de Lluís Solé i Sabaris, 1-3, Barcelona, Pannu, N. S., Nicolopoulos, S., Gruene, T., E-mail: tim.gruene@psi.ch, Abrahams, J. P., E-mail: tim.gruene@psi.ch, Center for Cellular Imaging and NanoAnalytics, and Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institute. Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector. United Kingdom: N. p., 2016. Web. doi:10.1107/S2053273315022500.
Genderen, E. van, Clabbers, M. T. B., Center for Cellular Imaging and NanoAnalytics, Das, P. P., Stewart, A., Nederlof, I., Amsterdam Scientific Instruments, Postbus 41882, 1009 DB Amsterdam, Barentsen, K. C., Portillo, Q., Centres Científics i Tecnològics de la Universitat de Barcelona, University of Barcelona, Carrer de Lluís Solé i Sabaris, 1-3, Barcelona, Pannu, N. S., Nicolopoulos, S., Gruene, T., E-mail: tim.gruene@psi.ch, Abrahams, J. P., E-mail: tim.gruene@psi.ch, Center for Cellular Imaging and NanoAnalytics, & Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institute. Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector. United Kingdom. doi:10.1107/S2053273315022500.
Genderen, E. van, Clabbers, M. T. B., Center for Cellular Imaging and NanoAnalytics, Das, P. P., Stewart, A., Nederlof, I., Amsterdam Scientific Instruments, Postbus 41882, 1009 DB Amsterdam, Barentsen, K. C., Portillo, Q., Centres Científics i Tecnològics de la Universitat de Barcelona, University of Barcelona, Carrer de Lluís Solé i Sabaris, 1-3, Barcelona, Pannu, N. S., Nicolopoulos, S., Gruene, T., E-mail: tim.gruene@psi.ch, Abrahams, J. P., E-mail: tim.gruene@psi.ch, Center for Cellular Imaging and NanoAnalytics, and Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institute. Fri . "Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector". United Kingdom. doi:10.1107/S2053273315022500.
@article{osti_22535125,
title = {Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector},
author = {Genderen, E. van and Clabbers, M. T. B. and Center for Cellular Imaging and NanoAnalytics and Das, P. P. and Stewart, A. and Nederlof, I. and Amsterdam Scientific Instruments, Postbus 41882, 1009 DB Amsterdam and Barentsen, K. C. and Portillo, Q. and Centres Científics i Tecnològics de la Universitat de Barcelona, University of Barcelona, Carrer de Lluís Solé i Sabaris, 1-3, Barcelona and Pannu, N. S. and Nicolopoulos, S. and Gruene, T., E-mail: tim.gruene@psi.ch and Abrahams, J. P., E-mail: tim.gruene@psi.ch and Center for Cellular Imaging and NanoAnalytics and Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institute},
abstractNote = {A specialized quantum area detector for electron diffraction studies makes it possible to solve the structure of small organic compound nanocrystals in non-cryo conditions by direct methods. Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼0.013 e{sup −} Å{sup −2} s{sup −1}) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS, SHELX) and for electron crystallography (ADT3D/PETS, SIR2014)},
doi = {10.1107/S2053273315022500},
journal = {Acta Crystallographica. Section A, Foundations and Advances (Online)},
number = Pt 2,
volume = 72,
place = {United Kingdom},
year = {Fri Feb 05 00:00:00 EST 2016},
month = {Fri Feb 05 00:00:00 EST 2016}
}