Absolute Structure Determination of Chiral Organic Nanocrystals Using Zone-Axis Electron Diffraction

Enantiomorphic identification of chiral molecules is essential in organic chemistry and the pharmaceutical industry, as two enantiomorphic structures can show distinctively different properties. Here, we illustrate the absolute structural determination of organic nanocrystals using zone-axis electron diffraction by taking advantage of electron multiple scattering. Two enantiomorphs are distinguished by comparing the reflection intensities of Friedel pairs in the zone-axis electron diffraction pattern, after confirming the absolute indices of reflections by locating relative positions of diffraction spots from two patterns that deviate from a certain angle. We demonstrate the protocol with successful applications in two chiral drug nanocrystals.