Small Molecule Microcrystal Electron Diffraction for the Pharmaceutical Industry-Lessons Learned From Examining Over...

Area of Science:

• Crystallography and structural biology
• Materials science and solid-state chemistry

Background:

• Microcrystal electron diffraction (MicroED) is a powerful technique for determining high-resolution crystal structures.
• Its potential in drug discovery and development is significant, offering a solution for samples that are difficult to crystallize.
• However, widespread adoption in the pharmaceutical industry has been limited by access to specialized equipment and expertise.

Purpose of the Study:

• To present the development and operational experience of a small molecule MicroED service pipeline tailored for the pharmaceutical industry.
• To share insights into the practical application and outcomes of MicroED for pharmaceutical research.
• To assess the potential for increased adoption of MicroED within the pharmaceutical sector.

Main Methods:

• Established a dedicated service pipeline for small molecule MicroED analysis.
• Processed over fifty small molecule samples from pharmaceutical clients within one year.
• Collected and analyzed diffraction data to determine crystal structures.

Main Results:

• The majority of submitted small molecule samples yielded data suitable for high-resolution structure solution using MicroED.
• Successfully determined multiple small molecule MicroED structures of pharmaceutical relevance.
• Gained practical insights into typical experimental workflows and outcomes for pharmaceutical applications.

Conclusions:

• The developed MicroED service pipeline effectively supports pharmaceutical industry needs for small molecule structure determination.
• MicroED is capable of rapidly providing structural information for compounds that are challenging to analyze by conventional methods.
• Continued growth in MicroED adoption is anticipated within the pharmaceutical industry due to its unique capabilities.