A Comparison of Structure Determination of Small Organic Molecules by 3D Electron Diffraction at Cryogenic and Room Temperature

Yang, Taimin; Waitschat, Steve; Inge, Andrew Kentaro; Stock, Norbert; Zou, Xiaodong; Xu, Hongyi

doi:10.3390/sym13112131

“…Three-dimensional electron diffraction (3DED) was used to obtain the unknown crystal structures of the nanoribbons grown at 650 °C for 10 days. 3DED is an emerging technique developed to determine structures from nanocrystals by obtaining a series of electron diffraction patterns from an arbitrary orientation. − It overcomes the challenge for single-crystal X-ray diffraction of large micrometer-sized crystals being needed. Compared to atomic electron tomography (AET), , 3DED can provide global atomic positions for accurate structure determination .…”

Section: Resultsmentioning

confidence: 99%

Thermodynamics and Kinetics in Anisotropic Growth of One-Dimensional Midentropy Nanoribbons

Wang

¹

,

Yang

²

,

Kumar

³

et al. 2023

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One-dimensional (1D) materials demonstrate anisotropic in-plane physical properties that enable a wide range of functionalities in electronics, photonics, valleytronics, optoelectronics, and catalysis. Here, we undertake an in-depth study of the growth mechanism for equimolar midentropy alloy of (NbTaTi)0.33S3 nanoribbons as a model system for 1D transition metal trichalcogenide structures. To understand the thermodynamic and kinetic effects in the growth process, the energetically preferred phases at different synthesis temperatures and times are investigated, and the phase evolution is inspected at a sequence of growth steps. It is uncovered that the dynamics of the growth process occurs at four different stages via preferential incorporation of chemical species at high-surface-energy facets. Also, a sequence of temperature and time dependent nonuniform to uniform phase evolutions has emerged in the composition and structure of (NbTaTi)0.33S3 which is described based on an anisotropic vapor–solid (V–S) mechanism. Furthermore, direct evidence for the 3D structure of the charge density wave (CDW) phase (width less than 100 nm) is provided by three-dimensional electron diffraction (3DED) in individual nanoribbons at cryogenic temperature, and detailed comparisons are made between the phases obtained before and after CDW transformation. This study provides important fundamental information for the design and synthesis of future 1D alloy structures.

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“…3D electron diffraction (3D ED), also known as MicroED, is a crystallographic technique capable of structure determination from micrometre‐sized crystals and has been used to determine a number of small molecule crystal structures [6–26] . Two studies from 2018 highlighted the potential of 3D ED as a phase analysis tool by rapid structure determination and solving numerous small molecule structures from an artificial heterogeneous mixture [10,11] .…”

Section: Introductionmentioning

confidence: 99%

Phase Identification and Discovery of an Elusive Polymorph of Drug‐Polymer Inclusion Complex Using Automated 3D Electron Diffraction

Lightowler,

Li,

Ou

et al. 2024

Angewandte Chemie

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3D electron diffraction (3D ED) has shown great potential in crystal structure determination in materials, small organic molecules, and macromolecules. In this work, an automated, low‐dose and low‐bias 3D ED protocol has been implemented to identify six phases from a multiple‐phase melt‐crystallisation product of an active pharmaceutical ingredient, griseofulvin (GSF). Batch data collection under low‐dose conditions using a widely available commercial software was combined with automated data analysis to collect and process over 230 datasets in three days. Accurate unit cell paramters obtained from 3D ED data allowed direct phase identification of GSF Forms III, I and the known GSF inclusion complex (IC) with polyethylene glycol (PEG) (GSF‐PEG IC‐I), as well as three minor phases, namely GSF Forms II, V and an elusive new phase, GSF‐PEG IC‐II. Their structures were then directly determined by 3D ED. Furthermore, we reveal how the stabilities of the two GSF‐PEG IC polymorphs are closely related to their crystal structures. These results demonstrate the power of automated 3D ED for accurate phase identification and direct structure determination of complex, beam‐sensitive crystallisation products, which is significant for drug development where solid form screening is crucial for the overall efficacy of the drug product.

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“…3D electron diffraction (3D ED), also known as MicroED, is a crystallographic technique capable of structure determination from micrometre‐sized crystals and has been used to determine a number of small molecule crystal structures [6–26] . Two studies from 2018 highlighted the potential of 3D ED as a phase analysis tool by rapid structure determination and solving numerous small molecule structures from an artificial heterogeneous mixture [10,11] .…”

Section: Introductionmentioning

confidence: 99%

Phase Identification and Discovery of an Elusive Polymorph of Drug‐Polymer Inclusion Complex Using Automated 3D Electron Diffraction

Lightowler,

Li,

Ou

et al. 2024

Angew Chem Int Ed

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0

View full text Add to dashboard Cite

3D electron diffraction (3D ED) has shown great potential in crystal structure determination in materials, small organic molecules, and macromolecules. In this work, an automated, low‐dose and low‐bias 3D ED protocol has been implemented to identify six phases from a multiple‐phase melt‐crystallisation product of an active pharmaceutical ingredient, griseofulvin (GSF). Batch data collection under low‐dose conditions using a widely available commercial software was combined with automated data analysis to collect and process over 230 datasets in three days. Accurate unit cell paramters obtained from 3D ED data allowed direct phase identification of GSF Forms III, I and the known GSF inclusion complex (IC) with polyethylene glycol (PEG) (GSF‐PEG IC‐I), as well as three minor phases, namely GSF Forms II, V and an elusive new phase, GSF‐PEG IC‐II. Their structures were then directly determined by 3D ED. Furthermore, we reveal how the stabilities of the two GSF‐PEG IC polymorphs are closely related to their crystal structures. These results demonstrate the power of automated 3D ED for accurate phase identification and direct structure determination of complex, beam‐sensitive crystallisation products, which is significant for drug development where solid form screening is crucial for the overall efficacy of the drug product.

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A Comparison of Structure Determination of Small Organic Molecules by 3D Electron Diffraction at Cryogenic and Room Temperature

Cited by 8 publications

References 48 publications

Thermodynamics and Kinetics in Anisotropic Growth of One-Dimensional Midentropy Nanoribbons

Thermodynamics and Kinetics in Anisotropic Growth of One-Dimensional Midentropy Nanoribbons

Phase Identification and Discovery of an Elusive Polymorph of Drug‐Polymer Inclusion Complex Using Automated 3D Electron Diffraction

Phase Identification and Discovery of an Elusive Polymorph of Drug‐Polymer Inclusion Complex Using Automated 3D Electron Diffraction

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