Electron diffraction determines molecular absolute configuration in a pharmaceutical nanocrystal

Abstract

Dynamical refinement spots a difference For chiral molecules used in drugs, one isomer can have beneficial bioactivity, whereas the others are useless or even harmful. Determining the absolute configuration of molecules with chiral centers is often achieved through x-ray crystallography, but this requires relatively large crystals and high-quality data. Brázda et al. used electron diffraction to determine the absolute structure of an extremely radiation-sensitive crystal with micrometer dimensions (see the Perspective by Xu and Zou). In a strategy analogous to serial crystallography methods, many frames were combined to generate a complete dataset. Refinement incorporating dynamical effects differentiated the correct and incorrect molecular configuration. Science , this issue p. 667 ; see also p. 632