Microcrystal Electron Diffraction (MicroED) for Small‐Molecule Structure Determination

Kunde, Tom; Schmidt, Bernd

doi:10.1002/anie.201813215

Cited by 28 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[11][12][13][14] Although used primarily for the backbone structure of biological macromolecules, cryo-EM has recently been applied to small organic compounds with microED (electron diffraction), with atomic-resolution (<1 Å) crystal structures obtained from nanocrystals (∼10 -15 g) in minutes. [15][16] A different technique to obtain sub-atomic resolution of small organic molecules is scanning tunneling microscopy (STM) and atomic force microscopy (AFM). Both are scanning probe microscopy (SPM) technique and will be the focus of discussion in this paper.…”

Section: Overview Of the Molecular Characterization Techniquesmentioning

confidence: 99%

Identify Similarities in Diverse Polycyclic Aromatic Hydrocarbons of Asphaltenes and Heavy Oils Revealed by Noncontact Atomic Force Microscopy: Aromaticity, Bonding, and Implications in Reactivity

Zhang¹

2019

Preprint

View full text Add to dashboard Cite

Heavy oils are enriched with polycyclic (or polynuclear) aromatic hydrocarbons (PAH or PNA), but characterization of their chemical structures has been a great challenge due to their tremendous diversity. Recently, with the advent of molecular imaging with noncontact Atomic Force Microscopy (nc-AFM), molecular structures of petroleum has been imaged and a diverse range of novel PAH structures was revealed. Understanding these structures will help to understand their chemical reactivities and the mechanisms of their formation or conversion. Studies on aromaticity and bonding provide means to recognize their intrinsic structural patterns which is crucial to reconcile a small number of structures from AFM and to predict infinite number of diverse molecules in bulk. Four types of PAH structures can be categorized according to their relative stability and reactivity, and it was found that the most and least stable types are rarely observed in AFM, with most molecules as intermediate types in a subtle balance of kinetic reactivity and thermodynamic stability. Local aromaticity was found maximized when possible for both alternant and nonalternant PAHs revealed by the aromaticity index NICS (Nucleus-Independent Chemical Shift) values. The unique role of five-membered rings in disrupting the electron distribution was recognized. Especially, the presence of partial double bonds in most petroleum PAHs was identified and their implications in the structure and reactivity of petroleum are discussed.

show abstract

Section: Overview Of the Molecular Characterization Techniquesmentioning

confidence: 99%

Identify Similarities in Diverse Polycyclic Aromatic Hydrocarbons of Asphaltenes and Heavy Oils Revealed by Noncontact Atomic Force Microscopy: Aromaticity, Bonding, and Implications in Reactivity

Zhang¹

2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, fs-electron diffraction has also enabled the structural determination of radiation labile organic crystals at room temperature [41]. Low-dose micro-electron diffraction [95,96] (microED) is, in fact, likely to become the most convenient and economical approach for determining the structure of sub-µm crystals. Samples must, however, withstand the high vacuum conditions in the electron column or otherwise be kept at cryogenic temperatures.…”

Section: Serial Fs-x-ray Crystallographymentioning

confidence: 99%

Recent Advances in Ultrafast Structural Techniques

Sciaini

2019

Applied Sciences

View full text Add to dashboard Cite

A review that summarizes the most recent technological developments in the field of ultrafast structural dynamics with focus on the use of ultrashort X-ray and electron pulses follows. Atomistic views of chemical processes and phase transformations have long been the exclusive domain of computer simulators. The advent of femtosecond (fs) hard X-ray and fs-electron diffraction techniques made it possible to bring such a level of scrutiny to the experimental area. The following review article provides a summary of the main ultrafast techniques that enabled the generation of atomically resolved movies utilizing ultrashort X-ray and electron pulses. Recent advances are discussed with emphasis on synchrotron-based methods, tabletop fs-X-ray plasma sources, ultrabright fs-electron diffractometers, and timing techniques developed to further improve the temporal resolution and fully exploit the use of intense and ultrashort X-ray free electron laser (XFEL) pulses.

show abstract

“…It could complement other main techniques of the field, i.e., cryo-electron microscopy (cryo-EM) and X-ray diffraction (XRD), in term of sample requirements and molecular targets. Indeed, MicroED uses crystals too small for single-crystal XRD (Nannenga, 2020), or even for serial crystallography at X-ray freeelectron laser sources (XFEL) (Wolff et al, 2020), and enables the study of small molecules inaccessible to single particle cryo-EM (Jones et al, 2018;Kunde & Schmidt, 2019). Therefore, the development of this emerging approach could greatly benefit drug discovery (Brázda et al, 2019;.…”

Section: Introductionmentioning

confidence: 99%

Redetermination of the first unknown protein MicroED structure by high resolution X-ray diffraction

Zou

Högbom

et al. 2021

Preprint

View full text Add to dashboard Cite

Microcrystal electron diffraction (MicroED) has the potential to considerably impact the field of structural biology. Indeed, the method can solve atomic structures of a wide range of molecules, beyond the reach of single particle cryo-electron microscopy, exploiting crystals too small for X-ray diffraction (XRD) even using X-ray free-electron lasers. However, until the first unknown protein structure – a R2-like ligand binding oxidase from Sulfolobus acidocaldarius (SaR2lox) – was recently solved at 3.0 Å resolution, MicroED had only been used to study known protein structures previously obtained by XRD. Here, after adapting sample preparation protocols, the structure of the SaR2lox protein originally solved by MicroED was redetermined by XRD at 2.1 Å resolution. In light of the higher resolution XRD data and taking into account experimental differences of the methods, the quality of the MicroED structure is examined. The analysis demonstrates that MicroED provided an overall accurate model, revealing biologically relevant information specific to SaR2lox, such as the absence of an ether cross-link, but did not allow to detect the presence of a ligand visible by XRD in the protein binding pocket. Furthermore, strengths and weaknesses of MicroED compared to XRD are discussed in the perspective of this real-life protein example. The study provides fundaments to help MicroED become a method of choice for solving novel protein structures.

show abstract

Microcrystal Electron Diffraction (MicroED) for Small‐Molecule Structure Determination

Cited by 28 publications

References 24 publications

Identify Similarities in Diverse Polycyclic Aromatic Hydrocarbons of Asphaltenes and Heavy Oils Revealed by Noncontact Atomic Force Microscopy: Aromaticity, Bonding, and Implications in Reactivity

Identify Similarities in Diverse Polycyclic Aromatic Hydrocarbons of Asphaltenes and Heavy Oils Revealed by Noncontact Atomic Force Microscopy: Aromaticity, Bonding, and Implications in Reactivity

Recent Advances in Ultrafast Structural Techniques

Redetermination of the first unknown protein MicroED structure by high resolution X-ray diffraction

Contact Info

Product

Resources

About