Microcrystal Electron Diffraction (MicroED) for Small‐Molecule Structure Determination

The development of new methods to analyze and determine molecular structures parallels the ability to accelerate synthetic research. For many decades, single-crystal analysis by X-ray diffraction (SXRD) has been the definitive tool for structural analysis at the atomic level; the drawback, however, is that a suitable single crystal of the analyte needs to be grown. The recent innovation of the crystalline sponge (CS) method allows the microanalysis of compounds simply soaked in a readily prepared CS crystal, thus circumventing the need to screen crystallization conditions while also using only a trace amount of the sample. In this context, electron diffraction for the structure determination of small molecules is discussed as potentially the next big development in this field.