Structure of the active pharmaceutical ingredient bismuth subsalicylate

Structure determination of pharmaceutical compounds is invaluable for drug development but is challenging for those that form as small crystals with defects. Bismuth subsalicylate (BSS), among the most commercially significant bismuth compounds, is an active ingredient in over-the-counter medications such as Pepto-Bismol, used to treat dyspepsia and H. pylori infections. Despite its century-long history, the structure has remained unknown. Three-dimensional electron diffraction and hierarchical clustering analysis were applied on select data from ordered crystals, revealing a layered structure. In other less ordered crystals, high-resolution scanning transmission electron microscopy revealed variations in the stacking of layers. Together, these modern electron crystallography techniques provide a new toolbox for structure determination of active pharmaceutical ingredients and drug discovery, demonstrated by this study of BSS.

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High-Efficiency Three-Dimensional Visualization of Complex Microstructures via Multidimensional STEM Acquisition and Reconstruction

Microscopy and Microanalysis ◽

10.1017/s1431927620000173 ◽

2020 ◽

Vol 26 (2) ◽

pp. 240-246 ◽

Cited By ~ 1

Author(s):

Kevin G. Field ◽

Benjamin P. Eftink ◽

Chad M. Parish ◽

Stuart A. Maloy

Keyword(s):

High Efficiency ◽

3D Visualization ◽

Accurate Determination ◽

Three Dimensional ◽

High Energy ◽

Scanning Transmission Electron Microscope ◽

Chromium Steel ◽

Transmission Electron ◽

Scanning Transmission

AbstractComplex material systems in which microstructure and microchemistry are nonuniformly dispersed require three-dimensional (3D) rendering(s) to provide an accurate determination of the physio-chemical nature of the system. Current scanning transmission electron microscope (STEM)-based tomography techniques enable 3D visualization but can be time-consuming, so only select systems or regions are analyzed in this manner. Here, it is presented that through high-efficiency multidimensional STEM acquisition and reconstruction, complex point cloud-like microstructural features can quickly and effectively be reconstructed in 3D. The proposed set of techniques is demonstrated, analyzed, and verified for a high-chromium steel with heterogeneously situated features induced using high-energy neutron bombardment.

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Crystal structure determination of the Γ2 phase in the Fe–Zn–Al system by single-crystal synchrotron X-ray diffraction combined with scanning transmission electron microscopy

Journal of Alloys and Compounds ◽

10.1016/j.jallcom.2015.04.119 ◽

2015 ◽

Vol 644 ◽

pp. 287-296 ◽

Cited By ~ 10

Author(s):

Norihiko L. Okamoto ◽

Haruyuki Inui ◽

Akira Yasuhara ◽

Shu Yamaguchi

Keyword(s):

Crystal Structure ◽

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Structure Determination ◽

Scanning Transmission Electron Microscopy ◽

X Ray Diffraction ◽

X Ray ◽

Transmission Electron ◽

Scanning Transmission

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3D Observation of Elemental Distribution of Si-Device using a Dedicated FIB/STEM System

ISTFA 2005: Conference Proceedings from the 31st International Symposium for Testing and Failure Analysis ◽

10.31399/asm.cp.istfa2005p0382 ◽

2005 ◽

Author(s):

T. Yaguchi ◽

M. Konno ◽

T. Kamino ◽

M. Ogasawara ◽

K. Kaji ◽

...

Keyword(s):

Focused Ion Beam ◽

Ion Beam ◽

Three Dimensional ◽

Elemental Distribution ◽

Multivariate Statistical ◽

X Ray ◽

Sample Rotation ◽

Transmission Electron ◽

Scanning Transmission ◽

Elemental Maps

Abstract A technique for preparation of a pillar shaped sample and its multi-directional observation of the sample using a focused ion beam (FIB) / scanning transmission electron microscopy (STEM) system has been developed. The system employs an FIB/STEM compatible sample rotation holder with a specially designed rotation mechanism, which allows the sample to be rotated 360 degrees [1-3]. This technique was used for the three dimensional (3D) elemental mapping of a contact plug of a Si device in 90 nm technology. A specimen containing a contact plug was shaped to a pillar sample with a cross section of 200 nm x 200 nm and a 5 um length. Elemental analysis was performed with a 200 kV HD-2300 STEM equipped with the EDAX genesis Energy dispersive X-ray spectroscopy (EDX) system. Spectrum imaging combined with multivariate statistical analysis (MSA) [4, 5] was used to enhance the weak X-ray signals of the doped area, which contain a low concentration of As-K. The distributions of elements, especially the dopant As, were successfully enhanced by MSA. The elemental maps were .. reconstructed from the maps.

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Three Dimensional Structure Determination of Botulinum Neurotoxin

10.21236/ada368202 ◽

1999 ◽

Author(s):

Raymond C. Stevens

Keyword(s):

Structure Determination ◽

Botulinum Neurotoxin ◽

Three Dimensional ◽

Dimensional Structure ◽

Three Dimensional Structure

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Meso-Scale Transmission Electron Microscope Tomography Applied for Wax Distribution in Toner Particles

Microscopy and Microanalysis ◽

10.1017/s1431927613012336 ◽

2013 ◽

Vol 19 (S5) ◽

pp. 58-61 ◽

Cited By ~ 1

Author(s):

Mino Yang ◽

Jun-Ho Lee ◽

Hee-Goo Kim ◽

Euna Kim ◽

Young-Nam Kwon ◽

...

Keyword(s):

Electron Microscope ◽

Transmission Electron Microscope ◽

Three Dimensional ◽

Chromatic Aberration ◽

Laser Printer ◽

Medium Voltage ◽

Transmission Electron ◽

Z Contrast ◽

Contrast Image

AbstractDistribution of wax in laser printer toner was observed using an ultra-high-voltage (UHV) and a medium-voltage transmission electron microscope (TEM). As the radius of the wax spans a hundred to greater than a thousand nanometers, its three-dimensional recognition via TEM requires large depth of focus (DOF) for a volumetric specimen. A tomogram with a series of the captured images would allow the determination of their spatial distribution. In this study, bright-field (BF) images acquired with UHV-TEM at a high tilt angle prevented the construction of the tomogram. Conversely, the Z-contrast images acquired by the medium-voltage TEM produced a successful tomogram. The spatial resolution for both is discussed, illustrating that the image degradation was primarily caused by beam divergence of the Z-contrast image and the combination of DOF and chromatic aberration of the BF image from the UHV-TEM.

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Fast Throughput Low Voltage Scanning Transmission Electron Microscope Imaging of Nano-Resolution Three Dimensional Tissue

Microscopy and Microanalysis ◽

10.1017/s1431927609092435 ◽

2009 ◽

Vol 15 (S2) ◽

pp. 642-643

Author(s):

M Bolorizadeh ◽

HF Hess

Keyword(s):

Electron Microscope ◽

Transmission Electron Microscope ◽

Low Voltage ◽

Three Dimensional ◽

Scanning Transmission Electron Microscope ◽

Transmission Electron ◽

Scanning Transmission ◽

Microscope Imaging ◽

Electron Microscope Imaging ◽

Voltage Scanning

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

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Synthesis, characterization and structure determination of a three-dimensional hydrated potassium zinc divanadate: K[Zn2.5V2O7(OH)2]⋅H2O

Solid State Sciences ◽

10.1016/j.solidstatesciences.2005.02.004 ◽

2005 ◽

Vol 7 (5) ◽

pp. 616-621 ◽

Cited By ~ 5

Author(s):

Dora Hoyos ◽

Jean-Louis Paillaud ◽

Angélique Simon-Masseron ◽

Jean-Louis Guth

Keyword(s):

Structure Determination ◽

Three Dimensional

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Measuring the Autocorrelation Function of Nanoscale Three-Dimensional Density Distribution in Individual Cells Using Scanning Transmission Electron Microscopy, Atomic Force Microscopy, and a New Deconvolution Algorithm

Microscopy and Microanalysis ◽

10.1017/s1431927617000447 ◽

2017 ◽

Vol 23 (3) ◽

pp. 661-667 ◽

Cited By ~ 3

Author(s):

Yue Li ◽

Di Zhang ◽

Ilker Capoglu ◽

Karl A. Hujsak ◽

Dhwanil Damania ◽

...

Keyword(s):

Electron Microscopy ◽

Density Distribution ◽

Scanning Transmission Electron Microscopy ◽

Mass Density ◽

Three Dimensional ◽

Force Microscopy ◽

Statistical Measures ◽

Atomic Force ◽

Transmission Electron ◽

Scanning Transmission

AbstractEssentially all biological processes are highly dependent on the nanoscale architecture of the cellular components where these processes take place. Statistical measures, such as the autocorrelation function (ACF) of the three-dimensional (3D) mass–density distribution, are widely used to characterize cellular nanostructure. However, conventional methods of reconstruction of the deterministic 3D mass–density distribution, from which these statistical measures can be calculated, have been inadequate for thick biological structures, such as whole cells, due to the conflict between the need for nanoscale resolution and its inverse relationship with thickness after conventional tomographic reconstruction. To tackle the problem, we have developed a robust method to calculate the ACF of the 3D mass–density distribution without tomography. Assuming the biological mass distribution is isotropic, our method allows for accurate statistical characterization of the 3D mass–density distribution by ACF with two data sets: a single projection image by scanning transmission electron microscopy and a thickness map by atomic force microscopy. Here we present validation of the ACF reconstruction algorithm, as well as its application to calculate the statistics of the 3D distribution of mass–density in a region containing the nucleus of an entire mammalian cell. This method may provide important insights into architectural changes that accompany cellular processes.

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