Beyond MicroED: ab initio crystal structures using 4D-STEM

Microcrystal electron diffraction (microED) has recently morphed into an increasingly mainstream technique in structural chemistry. Its ability to interrogate nanocrystals orders of magnitude too small for conventional X - ray diffraction has enabled solid -state structure elucidation of several species previously considered impossible to solve using X -ray crystallogr aphy. Nevertheless, selected area aperture-enabled microED remains thwarted by the presence of disordered, overlapping, or otherwise poorly diffracting domains, all of which routinely conspire to diminish data quality. Just as insufficient crystal size histor ically stymied conventional X - ray methods, these nanoscale defects frequently prohibit structure solution using classical microED. To overcome this, we apply 4D scanning transmission electron microscopy (4D - STEM) in conjunction with electron diffraction tomography to interrogate crystal structures spanning a wide gamut of chemical space, including beam-sensitive organometallic complexes and biomolecular organic compounds. 4D - STEM leverages a scanning nanobeam to record ED patterns at an array of real-space points defined by a 2D raster scan across a user -selected region of a crystalline specimen. For instance, within an illuminated area of 500 nm 2, individual diffraction patterns can be collected every 5 nm. Conceptually, therefore, 4D – STEM provides an inherently serial approach to diffraction, simply localized with nanoscale precision onto the canvas of a single crystal. Our results represent the fi rst 4D - STEM structures phased ab initio by direct methods. Unlike standard microED, data acquisition in 4D - STEM is not constrained by the shape or size of the SA aperture. Instead, 4D - STEM enables the ex post facto construction of bespoke virtual apertures, allowing for precise real - space localization of exactly which domains of crystal contributed to pro ductive Bragg diffraction in reciprocal space. We refer to these regions as coherently diffracting zones (CDZs). This empowers us to discard unwanted signal from poorly diffracting domains, rotationally misoriented