An integrated workflow for the structure elucidation of nanocrystalline powders.

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.

SUBMITTER: Sabena C 

PROVIDER: S-EPMC12920802 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature