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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.
This 2020 study added a SORT component to lipid nanoparticles to alter tissue targeting and deliver mRNA or CRISPR cargoes. It provides preclinical evidence for extrahepatic delivery, rather than proof of human tissue targeting or clinical benefit.
Combining cryogenic specimen preparation with three-dimensional electron diffraction, researchers followed glycine crystallization from water. Different samples captured the sequential appearance of its three ambient-pressure polymorphs, including a short-lived beta form before alpha became dominant. Structures could be obtained from very small crystallites, demonstrating how diffraction can reveal phases missed by slower bulk measurements.
This outlook places three-dimensional electron diffraction within the wider development of nanocrystallography. It discusses acquisition and analysis approaches, the treatment of diffraction from very small crystals, and applications spanning organic, inorganic, and biological materials. Pharmaceutical examples help connect the methodological landscape with molecular crystal analysis, while the article remains a synthesis rather than a new API validation study.
Researchers solved the previously unknown crystal structure of orthocetamol, a pharmaceutical compound that had not yielded single crystals suitable for X-ray diffraction. The approach combined low-dose three-dimensional electron-diffraction acquisition with a single-electron detector. The case illustrates structure determination from challenging small crystals rather than requiring successful growth of larger specimens first.
A complete structure analysis of a sofosbuvir–L-proline pharmaceutical cocrystal used electron diffraction from a highly beam-sensitive nanocrystal. Collecting data at multiple positions and using improved intensity extraction enabled structure solution. Dynamical diffraction effects then distinguished the absolute structure despite the sample containing light atoms, establishing an important route to stereochemical assignment.
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