Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED

Area of Science:

• Crystallography
• Electron Diffraction
• Drug Discovery

Background:

• Microcrystal electron diffraction (microED) is a rapidly developing technique for analyzing micro- and nanocrystals.
• Its application to pharmaceutical compounds is an area of active investigation.

Purpose of the Study:

• To evaluate the utility of microED for the crystallographic analysis of pharmaceutical compounds.
• To assess the capability of microED in determining the absolute stereochemistry of chiral drug molecules.

Main Methods:

• Analysis of 30 diverse pharmaceutical samples using microcrystal electron diffraction (microED).
• Structure elucidation of micro- and nanocrystals obtained from process and medicinal chemistry groups.
• Application of dynamical refinement to continuous rotation electron diffraction data for stereochemistry assignment.

Main Results:

• 15 out of 30 crystal structures were successfully elucidated within 40 hours of microscope time.
• The absolute stereochemistry of all chiral compounds was correctly assigned using dynamical refinement.
• MicroED proved effective for rapid structure determination of pharmaceutical compounds.

Conclusions:

• Microcrystal electron diffraction (microED) is a highly applicable technique for the rapid analysis of pharmaceutical compounds.
• Dynamical refinement of microED data is a reliable method for determining the absolute stereochemistry of chiral drug candidates.
• This technique holds significant promise for accelerating drug discovery and development processes.