Quantification of enantiomorphs in chiral crystalline powders through three-dimensional electron diffraction

Chirality in crystalline materials is a fundamental feature that has a dramatic influence on their properties. Yet, the quantitative determination of the ratio between two enantiomorphic crystals in chiral solids remains challenging. Here we present the quantitative analysis of chiral nanocrystals through a method based on three-dimensional electron diffraction. We developed a dual tilt-scan protocol for tomography data collection in both real and reciprocal space, determining the absolute structure and estimating the crystal volume. Combined with automated serial data collection from hundreds of nanocrystals, this strategy allows high-throughput chirality determination, as well as the overall enantiomorphic excess. The successful application of this method to chiral inorganic nanocrystals reveals the role of chiral ligands in the bias of two enantiomorphic structures. We further demonstrated the robustness of this method on one chiral drug, cinchonine, offering a transformative approach to studying chiral organic materials when they are not enantiopure.