Absolute Configuration Determination of Pharmaceutical Crystalline Powders by MicroED Via Chiral Salt Formation

Chem. Commun., 2022,58, 4711-4714

Bo Wang,   Jessica F. Bruhn,   Asmerom Weldeab,   Timothy S. Wilson,   Philip T. McGilvray,   Michael Mashore,  Qiong Song,   Giovanna Scapin  and  Yiqing Lina 

OUR PERSPECTIVE:

• Determining the absolute configuration, or the arrangement of all stereocenters in a chiral molecule, is extremely important in drug development.
• Single crystal X-ray crystallography (scXRD) has long been the gold standard method for determining absolute configuration.
• Growing crystals large enough for scXRD can be quite challenging, especially for large compounds.
• An exciting new method for absolute configuration determination is presented in this paper involving MicroED and the incorporation of a chiral probe.
• MicroED uses a transmission electron microscope to determine crystal structures and has been used in recent years to determine the structures of many pharmaceutical compounds. Excitingly, this technique can work with powdered samples and crystals orders of magnitude smaller than those required for scXRD.

Read this paper, published in The Royal Society of Chemistry’s Chemical Communications Journal to find out how MicroED (performed by NanoImaging Services) can be used to determine the absolute configuration of pharmaceutical compounds.

• Absolute configuration determination of chiral APIs by MicroED via chiral salt formation
• This approach can serve as a powerful tool in a pharmaceutical scientist’s toolbox to determine the absolute configuration of a new API early in drug development and to ensure the quality of drug products.