For many decades, the method to obtain atomic-level descriptions of chemical compounds and materials - be it a drug, a catalyst, or a commodity chemical - has been X-ray crystallography. This method has a known weakness: it requires one single, high-quality and large enough crystal to study. Scientists often couldn’t determine a new substance's structure if it only existed as microscopic dust or was too fragile for X-ray beams.
A fundamental problem in materials chemistry is that the many interesting substances form only as microscopic powders (very tiny crystals). As scientists then use X-rays of increasing intensity to make measurements possible for progressively smaller crystals, this can lead to damaging the crystal studied before a full set of measurements can be made. Although some very small crystals can instead be studied by electron diffraction, these crystals have an upper size limit and there remains a gap between what is too small to study with X-rays but too large for electrons.
Now, a research team led by Professor Lee Brammer, working in collaboration with teams at Diamond Light Source and University of Glasgow, have reported an approach, published in Angewandte Chemie, that bypasses the one-crystal method entirely to address this characterisation gap. The technique, referred to as Multi-Crystal X-ray Diffraction (MCXRD), allows scientists to piece together an atomic map of chemical compounds by combining measurements from many tiny crystals. The approach builds upon one used by structural biologists, who face similar problems in studying the structure of proteins by X-ray diffraction, and now demonstrates the wide applicability to chemistry and materials science.
The MCXRD studies use specialised software and synchrotron radiation (high-intensity X-ray light), to collect many fragments of data from 10s to 1,000s of different crystals. Scientists can hit each individual crystal with a low enough dose of radiation - enough to get a tiny bit of information without destroying the crystal - and then use an algorithm to stitch those many fragments into a single, high-resolution X-ray data set from which a 3D molecular structure model can be obtained.
“We hope that this approach will open up new opportunities for chemists and materials scientists in need of accurate structure characterisation of particularly challenging materials,” Professor Lee Brammer, lead author.
The ability to determine the exact position of atoms in these materials is at the heart of understanding their properties and the key to developing better products. The published study examined Metal-Organic Frameworks (porous materials used for gas capture, catalysis and drug delivery), materials at the centre of the award of the 2025 Nobel Prize in Chemistry. The implications of this study are much broader, however, and could have an impact right across chemistry, speeding up the discovery process in areas such as pharmaceuticals and advanced materials.