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Updated: Oct 25, 2025

$Microcrystal Electron Diffraction of Small Molecules$

Microcrystal Electron Diffraction of Small Molecules

Published on: March 15, 2021

Structure Solution of Nano-Crystalline Small Molecules Using MicroED and Solid-State NMR Dipolar-Based Experiments.

Nghia Tuan Duong¹, Yoshitaka Aoyama², Katsumi Kawamoto³

¹RIKEN-JEOL Collaboration Center, RIKEN, Yokohama, Kanagawa 230-0045, Japan.

Molecules (Basel, Switzerland)

|August 7, 2021

Summary

Three-dimensional electron diffraction crystallography (microED) and solid-state NMR (ssNMR) combined to validate crystal structures. This approach overcomes microED

Keywords:

1H-14N PM-S-RESPDOR 1H-1H SERP GIPAW calculations NMR crystallography microED

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Last Updated: Oct 25, 2025

$Microcrystal Electron Diffraction of Small Molecules$

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Published on: March 15, 2021

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy

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Methods of Ex Situ and In Situ Investigations of Structural Transformations: The Case of Crystallization of Metallic Glasses

Methods of Ex Situ and In Situ Investigations of Structural Transformations: The Case of Crystallization of Metallic Glasses

Published on: June 7, 2018

Area of Science:

Crystallography and Spectroscopy
Materials Science
Structural Biology

Background:

Three-dimensional electron diffraction crystallography (microED) enables structure determination of sub-micrometer crystals, but high R factors due to dynamic scattering limit reliability.
Ambiguities in locating hydrogens and assigning nuclei with similar atomic numbers (e.g., C, N, O) persist in microED-based structures.

Purpose of the Study:

To develop and validate a hybrid method combining microED with solid-state NMR (ssNMR) dipolar-based experiments for accurate crystal structure determination.
To address the limitations of microED, particularly concerning R factor reliability and atomic number assignment.

Main Methods:

Utilized microED for initial structure solution of sub-micrometer crystals.
Employed ssNMR dipolar-based experiments, including 1H-14N PM-S-RESPDOR and 1H-1H SERP, to probe specific nuclear interactions.
Performed spin dynamics numerical simulations to analyze NMR data and validate the microED structure.

Main Results:

Successfully validated a microED-determined structure by comparing experimental and calculated dipolar-based NMR results.
Demonstrated the method's applicability to natural abundance samples by performing measurements on 1H and 14N.
Conducted the entire validation procedure at 293 K, contrasting with conventional low-temperature chemical shift calculations.

Conclusions:

The combined microED and ssNMR approach provides a robust method for validating crystal structures, overcoming limitations of each technique alone.
This integrated strategy enhances the reliability of structural analysis for small crystals, particularly for resolving ambiguities in atomic assignments and hydrogen locations.
The method's operation at near-ambient temperature and suitability for natural abundance samples broaden its applicability in structural studies.