Direct Location of Organic Molecules in Framework Materials by Three-Dimensional Electron Diffraction

[Image: see text] In the study of framework materials, probing interactions between frameworks and organic molecules is one of the most important tasks, which offers us a fundamental understanding of host–guest interactions in gas sorption, separation, catalysis, and framework structure formation. Single-crystal X-ray diffraction (SCXRD) is a conventional method to locate organic species and study such interactions. However, SCXRD demands large crystals whose quality is often vulnerable to, e.g., cracking on the crystals by introducing organic molecules, and this is a major challenge to use SCXRD for structural analysis. With the development of three-dimensional electron diffraction (3D ED), single-crystal structural analysis can be performed on very tiny crystals with sizes on the nanometer scale. Here, we analyze two framework materials, SU-8 and SU-68, with organic molecules inside their inorganic crystal structures. By applying 3D ED, with fast data collection and an ultralow electron dose (0.8–2.6 e(–) Å(–2)), we demonstrate for the first time that each nonhydrogen atom from the organic molecules can be ab initio located from structure solution, and they are shown as distinct and well-separated peaks in the difference electrostatic potential maps showing high accuracy and reliability. As a result, two different spatial configurations are identified for the same guest molecule in SU-8. We find that the organic molecules interact with the framework through strong hydrogen bonding, which is the key to immobilizing them at well-defined positions. In addition, we demonstrate that host–guest systems can be studied at room temperature. Providing high accuracy and reliability, we believe that 3D ED can be used as a powerful tool to study host–guest interactions, especially for nanocrystals.