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RESEARCH / LITERATURE

Research Literature

Find research, methods, and reviews across our scientific fields.

One collection · Original publication dates · Authors, journals & DOIs

All publications 157

Duplicate DOIs are merged. This is a selected collection, not an exhaustive bibliography.

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Reviews & perspectives
Drug Discovery Today: Technologies

Microcrystal electron diffraction in macromolecular and pharmaceutical structure determination

Max T. B. Clabbers; Hongyi Xu

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.

MicroED structure determination
Read guide →Original paper ↗

DOI: 10.1016/j.ddtec.2020.12.002

Original research
CrystEngComm

Structural analysis of metastable pharmaceutical loratadine form II, by 3D electron diffraction and DFT+D energy minimisation

Grahame R. Woollam; Partha P. Das; Enrico Mugnaioli; Iryna Andrusenko; Athanassios S. Galanis; Jacco van de Streek; Stavros Nicolopoulos; Mauro Gemmi; Trixie Wagner

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.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1039/d0ce01216e

Reviews & perspectives
Natural Product Reports

MicroED in natural product and small molecule research

Emma Danelius; Steve Halaby; Wilfred A. van der Donk; Tamir Gonen

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.

MicroED structure determination
Read guide →Original paper ↗

DOI: 10.1039/d0np00035c

Original research
Nature Nanotechnology

Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing

Qiang Cheng; Tuo Wei; Lukas Farbiak; Lindsay T Johnson; Sean A Dilliard; Daniel J Siegwart

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.

mRNA / LNPIn Vivo Cell Engineering & Gene Editing
Read guide →Original paper ↗

DOI: 10.1038/s41565-020-0669-6

Methods
IUCrJ

Polymorph evolution during crystal growth studied by 3D electron diffraction

Edward T. Broadhurst; Hongyi Xu; Max T. B. Clabbers; Molly Lightowler; Fabio Nudelman; Xiaodong Zou; Simon Parsons

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.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1107/s2052252519016105

Reviews & perspectives
ACS Central Science

3D Electron Diffraction: The Nanocrystallography Revolution

Mauro Gemmi; Enrico Mugnaioli; Tatiana E. Gorelik; Ute Kolb; Lukas Palatinus; Philippe Boullay; Sven Hovmöller; Jan Pieter Abrahams

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.

MicroED structure determination
Read guide →Original paper ↗

DOI: 10.1021/acscentsci.9b00394

Original research
Angewandte Chemie International Edition

The Crystal Structure of Orthocetamol Solved by 3D Electron Diffraction

Iryna Andrusenko; Victoria Hamilton; Enrico Mugnaioli; Arianna Lanza; Charlie Hall; Jason Potticary; Simon R. Hall; Mauro Gemmi

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.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1002/anie.201904564

Original research
Science

Electron diffraction determines molecular absolute configuration in a pharmaceutical nanocrystal

Petr Brázda; Lukáš Palatinus; Martin Babor

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.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1126/science.aaw2560

Reviews & perspectives
Nature Methods

The cryo-EM method microcrystal electron diffraction (MicroED)

Brent L. Nannenga; Tamir Gonen

This review explains MicroED and compares its role with other structure-determination methods. It surveys example structures and practical considerations for prospective users, including the progression from specimen preparation to diffraction acquisition and analysis. Its value for pharmaceutical readers is methodological orientation across sample classes, rather than evidence that a specific API screening workflow has been validated.

MicroED structure determination
Read guide →Original paper ↗

DOI: 10.1038/s41592-019-0395-x

Original research
ACS Central Science

The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination

Christopher G. Jones; Michael W. Martynowycz; Johan Hattne; Tyler J. Fulton; Brian M. Stoltz; Jose A. Rodriguez; Hosea M. Nelson; Tamir Gonen

Researchers demonstrated atomic-resolution structure determination of small organic molecules from nanocrystals present in ordinary powders, using minimal specimen preparation. The study included pharmaceutical and natural-product examples and showed that individual compounds could be analyzed from a mixed specimen. It established a practical route around the need to grow crystals large enough for conventional single-crystal X-ray diffraction.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1021/acscentsci.8b00760

Original research
Angewandte Chemie International Edition

Rapid Structure Determination of Microcrystalline Molecular Compounds Using Electron Diffraction

Tim Gruene et al.

A prototype electron diffractometer combined a transmission electron microscope with a hybrid pixel detector. Researchers determined a methylene blue derivative and identified the crystal structure of paracetamol within a commercial medicine containing crystalline and noncrystalline components. The work demonstrated chemical crystallography from crystals too small for standard X-ray workflows, while emphasizing the need for appropriate structural validation.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1002/anie.201811318

Original research
Organic Process Research & Development

Crystal Structures of Two Important Pharmaceuticals Solved by 3D Precession Electron Diffraction Tomography

Partha P. Das; Enrico Mugnaioli; Stavros Nicolopoulos; Camilla Tossi; Mauro Gemmi; Athanasios Galanis; Gheorghe Borodi; Mihaela M. Pop

Researchers determined crystal structures of ramelteon and tolvaptan using three-dimensional precession electron diffraction tomography on approximately 500-nanometer crystals. Structures from subsequently grown, much larger crystals were measured by single-crystal X-ray diffraction for comparison. Agreement in molecular conformation, packing, and unit-cell parameters supported the electron-diffraction workflow for these two pharmaceutical materials.

MicroED structure determinationPharmaceutical solid state
Read guide →Original paper ↗

DOI: 10.1021/acs.oprd.8b00149

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