Professor Lee Brammer and his research team at the University of Sheffield are addressing a long-standing limitation in chemical and materials characterization by rethinking how X-ray diffraction data are collected. Working with collaborators at Diamond Light Source and the University of Glasgow, the group has demonstrated a technique that reconstructs atomic structures by combining data from many microscopic crystals rather than relying on a single, high-quality specimen.
Smith, J. P., Smith, R., Roseveare, T. M., Bara, D., Thom, A. J. R., Forgan, R. S., Warren, M. R., Warren, A. J., Owen, R. L., & Brammer, L. (2026). Multi‐Crystal X‐Ray Diffraction (MCXRD) Bridges the Crystallographic Characterisation Gap in Chemistry and Materials Science: Application to MOFs. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.202523233
For decades, X-ray crystallography has been the primary tool for determining atomic arrangements in molecules and materials. Its precision is well established, but the technique depends on growing a crystal large and stable enough to survive prolonged exposure to X-ray beams. In practice, many compounds of interest never reach that size. They form as powders, fracture easily, or degrade before a complete dataset can be collected. This has left a gap between what can be studied with conventional X-ray methods and what is too large for electron diffraction but too small for standard crystallography.
Professor Lee Brammer and his research team at the University of Sheffield stated,
“We hope that this approach will open up new opportunities for chemists and materials scientists in need of accurate structure characterization of particularly challenging materials.”
The approach developed by Brammer’s team, known as multi-crystal X-ray diffraction, sidesteps that constraint. Instead of extracting all structural information from a single crystal, the method gathers partial diffraction data from tens to thousands of individual microcrystals. Each crystal is exposed to a low radiation dose, minimizing damage. Computational tools then assemble the fragments into a complete, high-resolution structural model.
The idea draws on strategies used in structural biology, where proteins are often studied using serial crystallography because large crystals are difficult to obtain. What distinguishes this work is its application to small-molecule chemistry and materials science, areas where microcrystalline powders are common but have traditionally been difficult to analyze at atomic resolution.
Synchrotron radiation plays a key role in enabling the technique. High-intensity X-ray sources allow extremely short exposures, capturing usable diffraction patterns before radiation damage accumulates. Advances in detector speed and data processing software make it possible to align and merge datasets collected from crystals with slightly different orientations and imperfections.
In their study, the researchers applied the method to metal-organic frameworks, porous materials widely studied for gas storage, catalysis, and drug delivery. These materials often crystallize as fine powders, making them challenging targets for conventional crystallography. Using the multi-crystal approach, the team resolved atomic positions that had previously been inaccessible, providing a clearer view of how the framework components assemble and interact.
The implications extend beyond a single class of materials. Accurate structural information underpins nearly every stage of chemical design, from understanding catalytic activity to predicting mechanical or electronic behavior. When structures cannot be solved, development slows or proceeds by trial and error. By reducing the dependence on ideal crystals, multi-crystal diffraction lowers a practical barrier that has limited progress in many areas of materials research.
Related work at synchrotron facilities worldwide has been moving in a similar direction, combining large datasets from imperfect samples to extract reliable structural information. What distinguishes the Sheffield team’s contribution is demonstrating that these ideas can be generalized across chemistry and materials science, not just biology.
The technique does not replace single-crystal diffraction, which remains the most straightforward option when suitable crystals exist. Instead, it fills a gap between existing methods, offering a viable route when traditional approaches fail. As computational tools improve and synchrotron access expands, multi-crystal diffraction could become a standard option for characterizing materials that were previously considered structurally inaccessible.
For engineers and chemists working on new compounds, catalysts, or functional materials, the ability to determine atomic structure without perfect crystals could shorten development cycles and reduce uncertainty. In that sense, the work represents less a dramatic breakthrough than a practical shift in how difficult samples are approached, one that aligns experimental reality more closely with the demands of modern materials research.
Adrian graduated with a Masters Degree (1st Class Honours) in Chemical Engineering from Chester University along with Harris. His master’s research aimed to develop a standardadised clean water oxygenation transfer procedure to test bubble diffusers that are currently used in the wastewater industry commercial market. He has also undergone placments in both US and China primarely focused within the R&D department and is an associate member of the Institute of Chemical Engineers (IChemE).
