Chemical crystallography by serial femtosecond X-ray diffraction

Abstract

Inorganic–organic hybrid materials represent a large share of newly reported structures, owing to their simple synthetic routes and customizable properties1. This proliferation has led to a characterization bottleneck: many hybrid materials are obligate microcrystals with low symmetry and severe radiation sensitivity, interfering with the standard techniques of single-crystal X-ray diffraction2,3 and electron microdiffraction4–11. Here we demonstrate small-molecule serial femtosecond X-ray crystallography (smSFX) for the determination of material crystal structures from microcrystals. We subjected microcrystalline suspensions to X-ray free-electron laser radiation12,13 and obtained thousands of randomly oriented diffraction patterns. We determined unit cells by aggregating spot-finding results into high-resolution powder diffractograms. After indexing the sparse serial patterns by a graph theory approach14, the resulting datasets can be solved and refined using standard tools for single-crystal diffraction data15–17. We describe the ab initio structure solutions of mithrene (AgSePh)18–20, thiorene (AgSPh) and tethrene (AgTePh), of which the latter two were previously unknown structures. In thiorene, we identify a geometric change in the silver–silver bonding network that is linked to its divergent optoelectronic properties20. We demonstrate that smSFX can be applied as a general technique for structure determination of beam-sensitive microcrystalline materials at near-ambient temperature and pressure.

Layered Organic Metal Chalcogenides (OMCs): From Bulk to Two‐Dimensional Materials

“…Crystal structure of AgTePh from smSFX. [18] Copyright 2022 Springer Nature. [16] Copyright 2019 Springer Nature.…”

“…The structure of AgSPh (Figure 8) was resolved with the latest technological development in analysis, smSFX; [18] it [15] Copyright 2018 Royal Society of Chemistry. [13] Copyright 2016 Royal Society of Chemistry.…”

SDPD-SX: combining a single crystal X-ray diffraction setup with advanced powder data structure determination for use in early stage drug discovery

“…This is unfortunate, because 3D-structural information has significant potential to inform design (especially conformational design) earlier in the drug discovery process. Several groups have developed specialised diffraction approaches for dealing with very small single crystals 1–3 or for collecting single-crystal data from oriented powder samples 4–7 and electron crystallography is now poised to have a significant impact. 8–10 Collecting PXRD data using SX instrumentation is well-established 11 and has found applications in phase identification, QPA and structure refinement, 12 but reports of its use for structure determination are extremely rare.…”

Acoustic Focusing of Protein Crystals for In-Line Monitoring and Up-Concentration during Serial Crystallography

“…The development of serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs) has pushed structural biology to unprecedented time resolution. − It is based on delivering a continuously replenishing sample of protein crystals to the X-ray interaction region, where elastic scattering results in a diffraction pattern of the instantaneous structure prior to radiation damage according to the diffraction before destruction principle. , By indexing individual diffraction patterns and merging the resulting still frames, a 3D structure of the electron density in the unit cell can be obtained with atomic resolution for radiation-sensitive photoenzymes , or metal–organic chalcogenolates at room temperature.…”