Polymorph Identification and Crystal Structure Determination by a Combined Crystal Structure Prediction and Transmission Electron Microscopy Approach
- 16 April 2013
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 19 (24), 7874-7882
- https://doi.org/10.1002/chem.201204368
Abstract
Electron diffraction offers advantages over X-ray based methods for crystal structure determination because it can be applied to sub-micron sized crystallites, and picogram quantities of material. For molecular organic species, however, crystal structure determination with electron diffraction is hindered by rapid crystal deterioration in the electron beam, limiting the amount of diffraction data that can be collected, and by the effect of dynamical scattering on reflection intensities. Automated electron diffraction tomography provides one possible solution. We demonstrate here, however, an alternative approach in which a set of putative crystal structures of the compound of interest is generated by crystal structure prediction methods and electron diffraction is used to determine which of these putative structures is experimentally observed. This approach enables the advantages of electron diffraction to be exploited, while avoiding the need to obtain large amounts of diffraction data or accurate reflection intensities. We demonstrate the application of the methodology to the pharmaceutical compounds paracetamol, scyllo-inositol and theophylline.Keywords
This publication has 56 references indexed in Scilit:
- Spotlights on our sister journals: Chem. Eur. J. 19/2013Chemistry – A European Journal, 2013
- Determination of the Crystal Structure of a New Polymorph of TheophyllineChemistry – A European Journal, 2013
- Automated Diffraction Tomography for the Structure Elucidation of Twinned, Sub‐micrometer Crystals of a Highly Porous, Catalytically Active Bismuth Metal–Organic FrameworkAngewandte Chemie-International Edition, 2012
- Automated Diffraction Tomography for the Structure Elucidation of Twinned, Sub‐micrometer Crystals of a Highly Porous, Catalytically Active Bismuth Metal–Organic FrameworkAngewandte Chemie, 2012
- Towards crystal structure prediction of complex organic compounds – a report on the fifth blind testActa crystallographica Section B, Structural science, crystal engineering and materials, 2011
- Crystal polymorphism in a carbamazepine derivative: OxcarbazepineJournal of Pharmaceutical Sciences, 2010
- Significant progress in predicting the crystal structures of small organic molecules – a report on the fourth blind testActa crystallographica Section B, Structural science, crystal engineering and materials, 2009
- Symmetry-modified charge flippingActa Crystallographica Section A Foundations of Crystallography, 2009
- High-resolution transmission electron microscopy: the ultimate nanoanalytical techniqueChemical Communications, 2004
- Preparation and physical characterization of forms II and III of paracetamolJournal of Thermal Analysis and Calorimetry, 1997