<i>Ab initio</i>structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector

Genderen, Eric Van; Clabbers, Max T. B.; Das, Partha P.; Stewart, Andrew; Nederlof, Igor; Barentsen, K. C.; Portillo, Q.; Pannu, Navraj S.; Nicolopoulos, Stavros; Gruene, Tim; Abrahams, Jan Pieter

doi:10.1107/s2053273315022500

Cited by 138 publications

(119 citation statements)

References 35 publications

(32 reference statements)

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“…18 Another option to minimize the radiation damage is the use of highly sensitive direct electron detection cameras that allow reducing the electron dose on the sample. 19 Very recently, a novel fast data collection methodology has been proposed in which the crystal is continuously rotated during sequential pattern acquisition avoiding intermediate stops for relocation of the crystal. 20 By applying this method, the total collection time is considerably reduced from 30–60 min down to 3–6 min for a data set that makes it possible to determine the structure of the sample under study.…”

mentioning

confidence: 99%

Ultrafast Electron Diffraction Tomography for Structure Determination of the New Zeolite ITQ-58

Simancas

Bereciartua

et al. 2016

J. Am. Chem. Soc.

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In this work a new ultrafast data collection strategy for electron diffraction tomography is presented that allows reducing data acquisition time by one order of magnitude. This methodology minimizes the radiation damage of beam-sensitive materials, such as microporous materials. This method, combined with the precession of the electron beam, provides high quality data enabling the determination of very complex structures. Most importantly, the implementation of this new electron diffraction methodology is easily affordable in any modern electron microscope. As a proof of concept, we have solved a new highly complex zeolitic structure named ITQ-58, with a very low symmetry (triclinic) and a large unit cell volume (1874.6 Å3), containing 16 silicon and 32 oxygen atoms in its asymmetric unit, which would be very difficult to solve with the state of the art techniques.

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mentioning

confidence: 99%

Ultrafast Electron Diffraction Tomography for Structure Determination of the New Zeolite ITQ-58

Simancas

Bereciartua

et al. 2016

J. Am. Chem. Soc.

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“…To obtain theoretical structure factors, the experimental geometry of the carbamazepine crystal (van Genderen et al, 2016) was optimized by applying periodic DFT calculations implemented in CRYSTAL14 (Dovesi et al, 2014(Dovesi et al, , 2016.Optimization was performed by the B3LYP-D* method, in which B3LYP was augmented with an empirical dispersion term as proposed by Grimme (Grimme et al, 2006) and modified for molecular crystals (Civalleri et al, 2008). The DZP basis set (Dunning, 1970) was used.…”

Section: Methodsmentioning

confidence: 99%

Refinement of Organic Crystal Structure with Multipolar Electron Scattering Factors

Gruza¹,

Chodkiewicz²,

Krzeszczakowska³

et al. 2019

Preprint

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A revolution in resolution is occurring now in electron microscopy arising from the development of methods for imaging single particles at cryogenic temperatures and obtaining electron diffraction data from nanocrystals of small organic molecules or macromolecules. Near- atomic or even atomic resolution of molecular structures can be achieved. The basis of these methods is the scattering of an electron beam due to the electrostatic potential of the sample. To analyze this high-quality experimental data, it is necessary to use appropriate atomic scattering factors. The independent atomic model (IAM) is commonly used although various more advanced models, already known from X-ray diffraction, can also be applied to enhance the analysis.<br>In this study we present a comparison of IAM and TAAM (Transferable Aspherical Atom Model), the latter with the parameters of the Hansen-Coppens multipole model transferred from the University at Buffalo Databank (UBDB). By this method, TAAM takes into account the fact that atoms in molecules are partially charged and are not spherical. We performed structure refinements on a carbamazepine crystal using electron structure factor amplitudes determined experimentally (Jones et al., 2018) or modeled with theoretical quantum-mechanical methods. The results show the possibilities and limitations of the TAAM method when applied to electron diffraction. Among others, the method clearly improves model fitting statistics, when compared to IAM, and allows for reliable refinement of atomic thermal parameters. The improvements are more pronounced with poorer resolution of diffraction data.<br>

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“…Over one hundred macromolecular structures have now been deposited in the PDB, determined by electron diffraction since 1990 ( Figure 1). Nearly half of these are determined from 3D protein crystals, and add to a growing number of small molecule structures [64][65][66][67].…”

Section: Advances In Electron Diffractionmentioning

confidence: 99%

“…Each improvement in detector technology has grown data output, facilitating not only improved speed and accuracy of data collection but also more efficient data archival and processing [77]. While the readout rates of several electron detectors are now in the kilohertz range [65,74,76], most experiments are not performed in this regime. Fast readout is instead used to preserve resolution in electron microscopy images by limiting the influence of motion induced artifacts [78].…”

Section: The Role Of Detectors In Big Data Gatheringmentioning

confidence: 99%

Data-driven challenges and opportunities in crystallography

Glynn

Rodríguez

2019

Emerging Topics in Life Sciences

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Structural biology is in the midst of a revolution fueled by faster and more powerful instruments capable of delivering orders of magnitude more data than their predecessors. This increased pace in data gathering introduces new experimental and computational challenges, frustrating real-time processing and interpretation of data and requiring long-term solutions for data archival and retrieval. This combination of challenges and opportunities is driving the exploration of new areas of structural biology, including studies of macromolecular dynamics and the investigation of molecular ensembles in search of a better understanding of conformational landscapes. The next generation of instruments promises to yield even greater data rates, requiring a concerted effort by institutions, centers and individuals to extract meaning from every bit and make data accessible to the community at large, facilitating data mining efforts by individuals or groups as analysis tools improve.

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Ab initiostructure 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.

Cited by 138 publications

References 35 publications

Ultrafast Electron Diffraction Tomography for Structure Determination of the New Zeolite ITQ-58

Ultrafast Electron Diffraction Tomography for Structure Determination of the New Zeolite ITQ-58

Refinement of Organic Crystal Structure with Multipolar Electron Scattering Factors

Data-driven challenges and opportunities in crystallography

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