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Three-dimensional electron diffraction and scanning transmission electron microscopy resolved the layered structure and stacking variations of bismuth subsalicylate, a long-used pharmaceutical ingredient. Clustering compatible diffraction datasets helped obtain the ordered structural model, while imaging exposed disorder. The paper shows why complementary electron-crystallography techniques can be valuable when small crystals and structural defects obstruct conventional characterization.
The authors determined the absolute configuration of a preclinical API by forming a salt with a chiral reference and analyzing its microcrystalline powder using MicroED. This approach transfers known stereochemical information from the salt former to the API. It addresses situations where large crystals cannot be obtained, but depends on a suitable, well-characterized chiral reference.
The 2022 study delivered CAR-encoding mRNA with CD5-targeted lipid nanoparticles, generating transient CAR T cells in mice. The abstract reports reduced cardiac fibrosis and improved function after injury. This is preclinical evidence, not human efficacy.
Three-dimensional electron diffraction showed that solution-grown and melt-grown materials previously grouped as delta-indomethacin have different crystal structures. The authors retained delta for the solution-grown form and proposed theta for the melt-grown form. Both displayed plastic bending associated with molecular slip. This case demonstrates how structural measurements can resolve longstanding ambiguity in polymorph identity.
Researchers solved a previously unresolved indomethacin form by three-dimensional electron diffraction and related its packing to infrared and Raman observations. They measured faster dissolution than the better-characterized alpha and gamma forms and observed a solid-state transition to alpha. This is a solid-form structure–property study; laboratory dissolution results do not by themselves establish improved human bioavailability.
Researchers described a pharmaceutical MicroED service workflow after examining more than fifty client-submitted small-molecule samples. Most yielded diffraction data suitable for structure solution, and validation examples included common reference compounds and teniposide. The paper documents preparation, collection, processing, and typical obstacles; its selected service cohort does not establish a universal success rate.
This review introduces the development and scope of MicroED, from small molecules and peptides to proteins and larger complexes. It explains how nanocrystalline samples extend crystallographic opportunities and summarizes the method’s trajectory. Its value for pharmaceutical materials is conceptual orientation; readers should use dedicated API studies to evaluate solid-form identification and industrial performance.
This study combined MicroED with crystal structure prediction to support solid-form selection for remdesivir. Experimentally determined structural information was evaluated alongside computational crystal-energy analysis, demonstrating a joint experimental and modeling approach when conventional large-crystal growth is difficult. The work concerns solid-state characterization and selection, not a new assessment of antiviral efficacy or clinical performance.
MicroED analysis of lomaiviticin C prompted revision of its molecular connectivity and stereochemical assignments. High-field NMR and computational analysis supported the revised interpretation, with implications for related lomaiviticins. This is a natural-product structure-elucidation landmark rather than a pharmaceutical-polymorph study, demonstrating the value of complementary methods when complex, sparsely protonated molecules resist confident NMR assignment.
Clabbers and Xu review the properties of electron diffraction and early MicroED developments relevant to pharmaceutical chemistry and structural biology. The discussion spans small-molecule structure determination, fragment screening, and structure-guided discovery. It is a historical perspective on opportunities and limitations, rather than new experimental proof of performance across a pharmaceutical sample collection.
Researchers combined room-temperature, limited-resolution three-dimensional electron diffraction with density-functional energy minimization to determine metastable loratadine Form II. Direct methods were insufficient because of resolution, disorder, and possible beam-induced amorphization. Simulated annealing generated candidate models, and computational validation selected the correct structure, illustrating a complementary experimental and computational workflow for challenging pharmaceutical polymorphs.
Covering work from 2013 through 2020, this highlight reviews how MicroED expanded from protein crystallography into natural products and small organic molecules. It discusses examples obtained from extremely small crystals and outlines progress in specimen handling, data collection, and structural analysis. The article offers historical context and practical possibilities, not a prospective pharmaceutical success-rate benchmark.
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