21. August 2017

Electron Nanocrystallography

To efficiently develop new active pharmaceutical ingredients and obtain approval, researchers require the exact three-dimensional structure of the substances. If they consist of individual crystals, the spatial structure can be determined using X-ray structural analysis. In many cases, however, scientists have access only to powder, blends of crystalline grains between 10–500 nanometers in size.
The Swiss Nanoscience Institute recently funded the A3EDPI project, lead by Dr. Tim Grüne from the Paul Scherrer Institute (PSI). The project is a multi-disciplinary effort conducted by academic groups from the PSI and Uni Basel (C-CINA), as well as industrial partners such as Hoffman-La Roche and DECTRIS.
DECTRIS is the world leader in Hybrid Photon Counting (HPC) detectors, and it was already involved in a previous SNI-PSI NanoArgovia collaboration to prove the suitability of HPC detectors for micro Electron Diffraction studies.

Since the outcome was very encouraging, the A3EDPI project is a follow-up and the main goal is to investigate whether electron nanocrystallography can be used efficiently to clarify the spatial structure of the different molecules. “As we are expanding into the Electron Microscopy (EM) market, a successful collaboration is a very important step in setting the basis for success, especially since Pharma companies are looking closer to the potential of EM to solve the structure of small medical compounds” says Dr. Clemens Schulze-Briese, DECTRIS Chief Scientific Officer.
In EM, the samples are exposed to a high-energy electron beam. The electrons have wave properties; depending on how the atoms are arranged, a very specific diffraction pattern is produced for each molecule that provides insights into their atomic structure. Initial experiments using a few model substances have already returned data of outstanding   quality. The team is now investigating whether electron nanocrystallography can be further developed into an attractive standard for the pharma and chemical industry, and whether performance and quality requirements for industrial applications can be fulfilled.
Figure 1. Diffraction pattern of a 400-nm crystal of the antibiotic Epicorazine A. The data quality is so high that all hydrogen atoms apart from one (yellow atom) have been allocated automatically and correctly – something that cannot be taken for granted even in X-ray structures with much larger crystals. (Image: Tim Grüne, PSI).