scholarly journals Putting MicroED to the Test: An Account of the Evaluation of 30 Diverse Pharmaceutical Compounds

2021 ◽  
Author(s):  
Jessica E. Burch ◽  
Austin G. Smith ◽  
Seb Caille ◽  
Shawn D. Walker ◽  
Ryan Wurz ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Electron Diffraction ◽  
Sample Preparation ◽  
Data Processing ◽  
Diffraction Data ◽  
Structural Data ◽  
Pharmaceutical Compounds ◽  
Electron Diffraction Data ◽  
Transfer Processes ◽  
Minimal Sample

The application of microcrystal electron diffraction (microED) to a variety of pharmaceutical compounds is reported. The examples and work detailed showcase the utility of microED as a routine technique for the rapid collection, analysis, and generation of structural data on a number of pharmaceutically relevant compounds, requiring minimal sample preparation and often without the need for time-consuming vitrification and cryo transfer processes. The development of a scripted data processing workflow allowed for simultaneous collection and processing of electron diffraction data, further expediting structural analysis of fifteen compounds.

Specifics of the data processing of precession electron diffraction tomography data and their implementation in the program PETS2.0

2019 ◽  
Vol 75 (4) ◽  
pp. 512-522 ◽  
Author(s):  
Lukáš Palatinus ◽  
Petr Brázda ◽  
Martin Jelínek ◽  
Jaromíra Hrdá ◽  
Gwladys Steciuk ◽  
...  
Keyword(s):  
Electron Diffraction ◽  
Data Processing ◽  
Diffraction Data ◽  
Crystal Orientation ◽  
Diffraction Method ◽  
Specific Aspect ◽  
Electron Diffraction Data ◽  
Diffraction Tomography ◽  
Profile Fitting ◽  
Precession Electron Diffraction

Electron diffraction tomography (EDT) data are in many ways similar to X-ray diffraction data. However, they also present certain specifics. One of the most noteworthy is the specific rocking curve observed for EDT data collected using the precession electron diffraction method. This double-peaked curve (dubbed `the camel') may be described with an approximation based on a circular integral of a pseudo-Voigt function and used for intensity extraction by profile fitting. Another specific aspect of electron diffraction data is the high likelihood of errors in the estimation of the crystal orientation, which may arise from the inaccuracies of the goniometer reading, crystal deformations or crystal movement during the data collection. A method for the refinement of crystal orientation for each frame individually is proposed based on the least-squares optimization of simulated diffraction patterns. This method provides typical angular accuracy of the frame orientations of less than 0.05°. These features were implemented in the computer program PETS 2.0. The implementation of the complete data processing workflow in the program PETS and the incorporation of the features specific for electron diffraction data is also described.

scholarly journals Electron diffraction data processing with DIALS

2018 ◽  
Vol 74 (6) ◽  
pp. 506-518 ◽  
Author(s):  
Max T. B. Clabbers ◽  
Tim Gruene ◽  
James M. Parkhurst ◽  
Jan Pieter Abrahams ◽  
David G. Waterman
Keyword(s):  
Electron Diffraction ◽  
Data Integration ◽  
Data Processing ◽  
Diffraction Data ◽  
Electron Diffraction Data ◽  
Beam Model ◽  
Detector Distance ◽  
Diffraction Geometry ◽  
Continuous Rotation ◽  
Ewald Sphere

Electron diffraction is a relatively novel alternative to X-ray crystallography for the structure determination of macromolecules from three-dimensional nanometre-sized crystals. The continuous-rotation method of data collection has been adapted for the electron microscope. However, there are important differences in geometry that must be considered for successful data integration. The wavelength of electrons in a TEM is typically around 40 times shorter than that of X-rays, implying a nearly flat Ewald sphere, and consequently low diffraction angles and a high effective sample-to-detector distance. Nevertheless, the DIALS software package can, with specific adaptations, successfully process continuous-rotation electron diffraction data. Pathologies encountered specifically in electron diffraction make data integration more challenging. Errors can arise from instrumentation, such as beam drift or distorted diffraction patterns from lens imperfections. The diffraction geometry brings additional challenges such as strong correlation between lattice parameters and detector distance. These issues are compounded if calibration is incomplete, leading to uncertainty in experimental geometry, such as the effective detector distance and the rotation rate or direction. Dynamic scattering, absorption, radiation damage and incomplete wedges of data are additional factors that complicate data processing. Here, recent features of DIALS as adapted to electron diffraction processing are shown, including diagnostics for problematic diffraction geometry refinement, refinement of a smoothly varying beam model and corrections for distorted diffraction images. These novel features, combined with the existing tools in DIALS, make data integration and refinement feasible for electron crystallography, even in difficult cases.

scholarly journals Single Crystal 3D Rotation Electron Diffraction from Nano-sized Crystals

2014 ◽  
Vol 70 (a1) ◽  
pp. C366-C366
Author(s):  
Xiaodong Zou
Keyword(s):  
Electron Diffraction ◽  
Data Collection ◽  
Data Processing ◽  
Single Crystal ◽  
Diffraction Data ◽  
Structure Determination ◽  
Reciprocal Lattice ◽  
Electron Diffraction Data ◽  
Electron Crystallography ◽  
Structure Solution

Electron crystallography is an important technique for structure analysis of nano-sized materials. Crystals too small or too complicated to be studied by X-ray diffraction can be investigated by electron crystallography. However, conventional TEM methods requires high TEM skills and strong crystallographic knowledge, which many synthetic materials scientists and chemists do not have. We recently developed the software-based Rotation Electron Diffraction (RED) method for automated collection and processing of 3D electron diffraction data. Complete single crystal 3D electron diffraction data can be collected from nano- and micron-sized crystals in less than one hour by combining electron beam tilt and goniometer tilt, which are controlled by the RED – data collection software.3 The unit cell, possible space groups and electron diffraction intensities can be obtained from the RED data using the RED data processing software. The figure below illustrates the data collection and data processing of a zeolite silicalite-1 by RED. 1427 ED frames were collected in less than 1 hour from a crystal of 800 x 400 x 200 nm in size. A 3D reciprocal lattice of silicalite-1 was reconstructed from the ED frames, from which the unit cell parameters and space group were determined (P21/n, a=20.02Å, b=20.25Å, c=13.35Å, alfa=90.130, beta=90.740, gamma=90.030. It was possible to cut the 3D reciprocal lattice perpendicular to any directions and study the reflection conditions. The reflection intensities could be extracted. The structure of the calcined silicalite-1 could be solved from the RED data by routine direct methods using SHELX-97. All 78 unique Si and O atoms could be located and refined to an accuracy better than 0.08 Å. The RED method has been applied for structure solution of a wide range of crystals and shown to be very powerful and efficient. Now a structure determination can be achieved within a few hours, from the data collection to structure solution. We will present several examples including unknown inorganic compounds, metal-organic frameworks and organic structures solved from the RED data. Different parameters that affect the RED data quality and thus the structure determination will be discussed. The methods are general and can be applied to any crystalline materials.

Crystal Structure Determination of Glycerol-Containing Lipids from Electron Diffraction Data. Use of Analog Compounds Based upon Configurational Isomers of Cyclopentane-1, 2, 3-TRIOL

1977 ◽  
Vol 35 ◽  
pp. 24-25
Author(s):  
Douglas L. Dorset ◽  
Anthony J. Hancock
Keyword(s):  
Crystal Structure ◽  
Electron Diffraction ◽  
Diffraction Data ◽  
Structure Determination ◽  
Crystal Surface ◽  
Coherent Scattering ◽  
Crystal Structure Determination ◽  
Electron Diffraction Data ◽  
Polar Group ◽  
Axis Orientation

Lipids containing long polymethylene chains were among the first compounds subjected to electron diffraction structure analysis. It was only recently realized, however, that various distortions of thin lipid microcrystal plates, e.g. bends, polar group and methyl end plane disorders, etc. (1-3), restrict coherent scattering to the methylene subcell alone, particularly if undistorted molecular layers have well-defined end planes. Thus, ab initio crystal structure determination on a given single uncharacterized natural lipid using electron diffraction data can only hope to identify the subcell packing and the chain axis orientation with respect to the crystal surface. In lipids based on glycerol, for example, conformations of long chains and polar groups about the C-C bonds of this moiety still would remain unknown.One possible means of surmounting this difficulty is to investigate structural analogs of the material of interest in conjunction with the natural compound itself. Suitable analogs to the glycerol lipids are compounds based on the three configurational isomers of cyclopentane-1,2,3-triol shown in Fig. 1, in which three rotameric forms of the natural glycerol derivatives are fixed by the ring structure (4-7).

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