ORGANICS & PHARMACEUTICALS/PROTEINS
Polymorphism is very important in the pharmaceutical industry where it also occurs very frequently in other organic materials like pigments and proteins. Physical properties of organic compounds (specially for drug design) depend on their precise crystal structure. 3D electron diffraction tomography sheds light to the crystal structure of organic compounds and proteins.
Trace analysis with TEM high resolution imaging and electron diffraction
High Resolution Virtual Dark Field (VDF) in TEM is a technique that enables detection of very small trace of crystalline material; in the example shown above, trace crystals of very small sizes (eg 10nm) can be observed at very low quantity (< 0.01%). Structure characterization (like phase confirmation) of such small crystals can be done using Electron Diffraction on individual crystallites.
Drug polymorph structure analysis with TEM 3D electron diffraction tomography
Electron Crystallography is considered as the method of choice for structure determination of nanocrystalline compounds (crystals as small as 20 nm to several microns). Such nano-crystallites reveal typically “X‐Ray amorphous” powder diffraction patterns (for sizes & 10nm) where is very difficult to identify and characterize their structures using X-Ray diffraction techniques.
Use of precession 3D electron diffraction (PED) with TEM makes possible unit cell and structure determination on individual nanocrystals. Using 3D diffraction tomography, a 3D reconstruction of the reciprocal space can be performed by tilting the sample and recording ED patterns (Fig. 1) (typically ±45° every 1°). Collected electron diffraction (ED) patterns can be processed to precisely determine the unit cell and reveal the space group symmetry of the API crystal. Full atomic crystal structure can also be performed after collection and precise measurement of ED intensities.
Structural Characterization in TEM by 3D Electron Diffraction / Micro-ED
Dr. Partha Das Application Scientist NanoMEGAS Belgium
In recent years there has been a huge interest in characterization for various materials where more than 300 structures have been solved (minerals, zeolites, MOFS, aperiodic crystals, archaeological artefacts, functional materials, organic pharmaceuticals, proteins etc.) using 3D Electron Diffraction from nanometer size crystals in TEM. The principle of acquiring TEM 3D-ED data consists of focusing the electron beam on a nanometer size crystal (50-500 nm), while sampling thereciprocal/diffraction space in small steps using beam precession or continuous crystal rotation (with or without beam PED, technique known as 3D Electron Diffraction Tomography/Micro-ED). ED intensities can be registered using CCD cameras or ultra- sensitive pixelated detectors. Acquired 3D-ED data can be used to determine ab-initio crystal unit cell, space group and atomic positions. Further dynamical refinement can also be performed using PED to detect H atoms, refine occupancies an improve reliability of the structural model down to 1-3 pm accuracy. In this webinar various examples will be shown how 3D-ED method has been applied successfully to solve structures of a big variety of nanocrystalline materials.
3D ELECTRON DIFFRACTION TOMOGRAPHY – ORGANICS-PHARMACEUTICALS
Schmidt, M. U., et al. “Electron Diffraction, X-Ray Powder Diffraction and Pair-Distribution- Function Analyses to Determine the Crystal Structures of Pigment Yellow 213, C23H21N5O9.” Acta Crystallographica Section B: Structural Science, vol. 65, no. 2, 2009, pp. 189–99, doi:10.1107/S0108768109003759.