# An integrated workflow for the structure elucidation of nanocrystalline powders

## TL;DR

This paper introduces a new workflow to determine the atomic structures of powders when traditional methods fail, using a combination of advanced techniques.

## Contribution

The novel contribution is a modular workflow integrating multiple analytical methods for structure elucidation of nanocrystalline powders.

## Key findings

- The workflow successfully resolved structures of a pyridoxine-N-acetyl-L-cysteine salt and a bacterial chemoattractant peptide.
- The approach identifies molecular components, crystal packing, atom assignments, and hydrogen positions in complex powders.
- The method is scalable and suitable for materials like pigments and pharmaceuticals where conventional crystallography is ineffective.

## Abstract

Structural characterization of powder materials, including those synthesized by mechanochemical methods, remains challenging due to the lack of single crystals suitable for X-ray diffraction. Microcrystal-Electron Diffraction (MicroED) enables structure determination from sub-micrometer crystallites but faces limitations, particularly in locating hydrogen atoms and distinguishing light atoms (C, N, O). We present a general workflow that integrates MicroED with high-resolution mass spectrometry, database mining, solution and solid-state NMR, and DFT-D/GIPAW calculations to resolve atomic structures of complex powders, even with unknown composition. The approach is demonstrated on a pyridoxine-N-acetyl-L-cysteine salt, a mechanochemically synthesized adduct for which large single crystals could not be obtained, and on N-formyl-methionyl-leucyl-phenylalanine (fMLF), a bacterial chemoattractant peptide. This strategy enables comprehensive structure resolution, including identification of molecular components, crystal packing, atom assignments and hydrogen positions. Its modularity and scalability make it suitable for a wide range of powder materials, e.g., pigments, pharmaceutical compounds, etc., especially when conventional crystallography fails.

The structural characterization of powder materials often remains challenging due to the lack of single crystals suitable for X-ray diffraction. Here, the authors present a workflow that integrates microcrystal electron diffraction with high-resolution mass spectrometry, database mining, solution and solid-state NMR, and DFT-D/GIPAW calculations to resolve atomic structures of complex powders, demonstrating the approach on a pyridoxine-N-acetyl-L-cysteine salt, a mechanochemically synthesized adduct for which large single crystals could not be obtained, and on N-formyl-methionyl-leucylphenylalanine, a bacterial chemoattractant peptide.