Yale's MicroED Brings Hidden Hydrogen Into Focus

Hydrogen—the lightest atom—does the heavy lifting when it comes to important chemical reactions. It can be stored and released as clean fuel, and its movements help catalysts build medicines, fertilizers, and materials. One way hydrogen is available for use is through a hydride—a hydrogen (H) atom bound to a metal. Yet with standard tools, this metal‑bound atom can be hard to find in the structure.

In a new study, Yale researchers critically evaluated new methods for pinpointing the hydride location in a cobalt-hydride crystal structure, and one stood out.

“We discovered that a microcrystal electron diffractometer (MicroED) can accurately locate the hydride better than X-ray methods,” said Patrick Holland, senior co-author of the study and the Whitehead Professor of Chemistry.

This work shows a practical path to reliably identifying and measuring locations of hydrides, which could help researchers better understand and design catalysts and other molecules. “The MicroED system has been a boon to our research,” said Holland.

The study appears in ACS Central Science, a journal published by the American Chemical Society.

The hydride in hiding
The challenge with studying hydrides is that the available tools are either ineffective or impractical. With standard X-ray crystallography, which provides a 3D map of a molecule, the large metal atom obscures the view of the tiny H atom. Alternatively, neutron crystallography (the “gold standard” for precise measurements) requires a specialized facility that most scientists can’t access. There are only a handful of them in the world, one being Oak Ridge National Laboratory in Tennessee, which helped validate this study.

Clearly, researchers need a more feasible alternative, and electron diffraction shows promise.

“The advantage of using electrons is that they interact more strongly with samples and diffract through a different mechanism than X-rays, making it more effective at determining the accurate location of the H atom,” said Ryan Donnelly, first author and graduate student in Holland’s lab.

Next, the team put electron diffraction to the test.

Crystal clear mapping
In the study, Donnelly used a cobalt-hydride crystal as a test case to compare several tools, including Yale’s newly acquired MicroED, to determine which could accurately find the hydride. Unlike traditional X-ray crystallography, which requires larger crystals, MicroED works with much smaller crystals, enabling more detailed structural analysis.

In the next step, Donnelly carefully compared the results from his electron diffraction structure to various methods of analyzing X-ray data. He found that the hydride location was closer to the “gold standard” from a neutron crystallography structure. Specifically, MicroED can reliably detect the hydride when the data were high quality and the refinement uses a dynamical scattering model. Under those conditions, the hydride can be discerned in the correct location.

Overall, this study shows that MicroED with dynamical refinement is a practical, broadly deployable approach for detecting metal hydrides, potentially expanding access beyond specialized neutron facilities.

The findings also build on a growing body of Yale work using MicroED to determine structures, including a microcrystalline metal-organic framework, and a natural product derived from total synthesis.

“It’s exciting to have demonstrated another application of this powerful technique,” said Donnelly.

In addition to appearing in a leading chemistry journal, Donnelly’s research won a Best Poster Award at the Bruker-MIT Crystallography Symposium in February 2026.

Yale co-authors of the study are Theodore J. Gerard and Sebastian M. Krajewski. Additional co-authors are Brandon Q. Mercado of Stony Brook University and Xiaoping Wang of Oak Ridge National Laboratory. The research was funded by the Department of Energy.