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MICROED / 3D ELECTRON DIFFRACTION

Pharmaceutical structures and polymorphs: the literature library

Explore significant papers from 2018 onward by year, author, DOI, and application. Historical papers retain their original publication dates.

Explore the MicroED literature →
bioRxiv

GROND preprint adds dynamical corrections to standard electron crystallography workflows

An October 27 preprint introduces GROND, an open-source tool that inserts dynamical scattering corrections between conventional electron diffraction processing and refinement. Tests across six structures improved refinement residuals and revealed previously unmodeled hydrogen atoms in small molecules. The work has not been peer reviewed, and performance on pharmaceutical samples needs separate validation.

Zeitschrift für Kristallographie – Crystalline Materials

Organic pigment benchmark evaluates XRPD as a prescreen for 3D electron diffraction

Researchers compared laboratory powder X-ray diffraction with 3D electron diffraction outcomes for 29 samples spanning 17 organic pigments. XRPD-derived domain size was the most useful screening indicator; structure solution succeeded above approximately 31 nanometers and failed below that value in this sample set. The threshold is empirical and should not be generalized to every pharmaceutical solid.

RSC Advances

40 years later: completion of the structural characterization of the anxiolytic drug buspirone HCl and solid-form landscape expansion

Electron diffraction established the previously unresolved structure of buspirone hydrochloride Form 2. The study also prepared 15 multicomponent solids, including cocrystals, an ionic cocrystal, and salts, and compared conformations and thermal behavior. This expands structural knowledge of a long-marketed drug and provides a solid-form exploration example without demonstrating improved clinical performance for the newly prepared materials.

Molecular Pharmaceutics / American Chemical Society

Formulations at the Nanoscale: Multi-dimensional Electron Diffraction of Long-Acting Injectable, Cabotegravir

This study applied multidimensional electron diffraction to cabotegravir nanocrystals within a long-acting injectable formulation. 3D electron diffraction confirmed a structure consistent with the known X-ray model, while imaging and diffraction linked particle shape to crystal structure and revealed dislocations. The results describe nanoscale structural features that may guide formulation work; improved product performance was not demonstrated.

Journal of Medicinal Chemistry

Discovery of a Quinazoline-Based Nav1.7 Inhibitor with MicroED-Confirmed Absolute Configuration and Oral Efficacy in Rodent Models of Neuropathic Pain

A medicinal-chemistry study developed a chiral quinazoline-based Nav1.7 inhibitor and used MicroED to confirm the lead compound’s absolute configuration. The report combined structure–activity studies with pharmacokinetic and pain-model experiments in rodents. Its pharmaceutical relevance is the stereochemical assignment within a drug-discovery program; the animal findings do not establish analgesic efficacy or safety in patients.

ACS Central Science

Room Temperature Structures of Solvated Organic Molecules Enabled by Liquid Cell Electron Diffraction

Liquid cells made from paired carbon grids retained a thin solution layer around microcrystals for room-temperature MicroED. The study obtained atomic structures from solvated organic molecules and pharmaceutical hydrates while using low-dose, rapid, multi-crystal acquisition to limit beam damage. It extends access to hydrated or solvated states, but sample-specific radiation sensitivity and preparation remain important constraints.

Journal of Applied Crystallography

Cryo-EM–microcrystal electron diffraction structural elucidation of cefadroxil: nanocrystallographic and neurotherapeutic insights into a β-lactam antibiotic

The authors reported a cryo-MicroED structure of cefadroxil, characterizing its molecular geometry, stereochemistry, and intermolecular packing. The crystallographic model also supported complementary molecular-dynamics analysis. This is a structural case study of an established beta-lactam antibiotic; the accompanying computational work should not be interpreted as clinical evidence of a new neurotherapeutic benefit or a general performance guarantee.

IUCrJ

High-throughput automated molecular replacement for small-molecule MicroED data

An automated molecular-replacement workflow solved the electron-diffraction structure of corilagin, a macrocyclic gallotannin that resisted ab initio phasing. Validation used known paritaprevir and grazoprevir structures across several resolution cutoffs. The results suggest an alternative route for flexible or lower-quality small-molecule datasets, with the important condition that chemically appropriate trial conformations must be available.

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