Continuous-rotation 3D electron diffraction methods are increasingly popular for the structure analysis of very small organic molecular crystals and crystalline inorganic materials. Dynamical diffraction effects cause non-linear deviations from kinematical intensities that present issues in structure analysis. Here, a method for structure analysis of continuous-rotation 3D electron diffraction data is presented that takes multiple scattering effects into account. Dynamical and kinematical refinements of 12 compounds-ranging from small organic compounds to metal-organic frameworks to inorganic materials-are compared, for which the new approach yields significantly improved models in terms of accuracy and reliability with up to fourfold reduction of the noise level in difference Fourier maps. The intrinsic sensitivity of dynamical diffraction to the absolute structure is also used to assign the handedness of 58 crystals of 9 different chiral compounds, showing that 3D electron diffraction is a reliable tool for the routine determination of absolute structures.

Department of Geosciences University of Bremen Bremen Germany

Department of Materials and Environmental Chemistry Stockholm University Stockholm Sweden

Institute of Inorganic Chemistry Leibniz University Hannover Hannover Germany

Institute of Physics Czech Academy of Sciences Prague Czech Republic

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Sheldrick GM. A short history of SHELX. Acta Crystallogr. A. 2008;64:112–122. doi: 10.1107/S0108767307043930. PubMed DOI

Mugnaioli E, Gorelik T, Kolb U. ‘Ab initio’ structure solution from electron diffraction data obtained by a combination of automated diffraction tomography and precession technique. Ultramicroscopy. 2009;109:758–765. doi: 10.1016/j.ultramic.2009.01.011. PubMed DOI

Palatinus L, et al. Specifics of the data processing of precession electron diffraction tomography data and their implementation in the program PETS2.0. Acta Crystallogr. B. 2019;75:512–522. doi: 10.1107/S2052520619007534. PubMed DOI

Gruene, T., Holstein, J. J., Clever, G. H. & Keppler, B. Establishing electron diffraction in chemical crystallography. Nat. Rev. Chem.5, 660–668 (2021). PubMed

Gemmi M, et al. 3D electron diffraction: the nanocrystallography revolution. ACS Central Sci. 2019;5:1315–1329. doi: 10.1021/acscentsci.9b00394. PubMed DOI PMC

Prince, E. International Tables for Crystallography Volume C: Mathematical, Physical and Chemical Tables (International Union of Crystallography, 2006); 10.1107/97809553602060000103

Bethe, H. Theorie der Beugung von Elektronen an Kristallen. Ann. Phys.392, 55–129 (1928).

Zuo, J. M. & Spence, J. C. H. Electron Microdiffraction (Springer, 1992).

Own CS, Marks LD, Sinkler W. Precession electron diffraction 1: multislice simulation. Acta Crystallogr. A. 2006;62:434–443. doi: 10.1107/S0108767306032892. PubMed DOI

Oleynikov P, Hovmöller S, Zou X. Precession electron diffraction: observed and calculated intensities. Ultramicroscopy. 2007;107:523–533. doi: 10.1016/j.ultramic.2006.04.032. PubMed DOI

Spence JCH, Zuo JM, O’Keeffe M, Marthinsen K, Hoier R. On the minimum number of beams needed to distinguish enantiomorphs in X-ray and electron diffraction. Acta Crystallogr. A. 1994;50:647–650. doi: 10.1107/S0108767394002850. DOI

Inui H, Fujii A, Tanaka K, Sakamoto H, Ishizuka K. New electron diffraction method to identify the chirality of enantiomorphic crystals. Acta Crystallogr. B. 2003;59:802–810. doi: 10.1107/S010876810302411X. PubMed DOI

Ma Y, Oleynikov P, Terasaki O. Electron crystallography for determining the handedness of a chiral zeolite nanocrystal. Nat. Mater. 2017;16:755–759. doi: 10.1038/nmat4890. PubMed DOI

Brazda P, Palatinus L, Babor M. Electron diffraction determines molecular absolute configuration in a pharmaceutical nanocrystal. Science. 2019;364:667–669. doi: 10.1126/science.aaw2560. PubMed DOI

Palatinus L, Petříček V, Corrêa CA. Structure refinement using precession electron diffraction tomography and dynamical diffraction: theory and implementation. Acta Crystallogr. A. 2015;71:235–244. doi: 10.1107/S2053273315001266. PubMed DOI

Wang B, et al. A porous cobalt tetraphosphonate metal-organic framework: accurate structure and guest molecule location determined by continuous-rotation electron diffraction. Chemistry. 2018;24:17429–17433. doi: 10.1002/chem.201804133. PubMed DOI

Rojas A, Arteaga O, Kahr B, Camblor MA. Synthesis, structure, and optical activity of HPM-1, a pure silica chiral zeolite. J. Am. Chem. Soc. 2013;135:11975–11984. doi: 10.1021/ja405088c. PubMed DOI

Tang L, et al. A zeolite family with chiral and achiral structures built from the same building layer. Nat. Mater. 2008;7:381–385. doi: 10.1038/nmat2169. PubMed DOI

Frojdh, E. et al. Discrimination of aluminum from silicon by electron crystallography with the JUNGFRAU detector. Crystals10, 1148 (2020).

Nakane T, et al. Single-particle cryo-EM at atomic resolution. Nature. 2020;587:152–156. doi: 10.1038/s41586-020-2829-0. PubMed DOI PMC

Gruza B, Chodkiewicz ML, Krzeszczakowska J, Dominiak PM. Refinement of organic crystal structures with multipolar electron scattering factors. Acta Crystallogr. A. 2020;76:92–109. doi: 10.1107/S2053273319015304. PubMed DOI PMC

Wang B, et al. Absolute configuration determination of pharmaceutical crystalline powders by MicroED via chiral salt formation. Chem. Commun. 2022;58:4711–4714. doi: 10.1039/D2CC00221C. PubMed DOI PMC

Le Page Y, Gabe EJ, Gainsford GJ. A robust alternative to η refinement for assessing the hand of chiral compounds. J. Appl. Cryst. 1990;23:406–411. doi: 10.1107/S0021889890005775. DOI

Broadhurst ET, et al. Polymorph evolution during crystal growth studied by 3D electron diffraction. IUCrJ. 2020;7:5–9. doi: 10.1107/S2052252519016105. PubMed DOI PMC

Dong Z, Ma Y. Atomic-level handedness determination of chiral crystals using aberration-corrected scanning transmission electron microscopy. Nat. Commun. 2020;11:1588. doi: 10.1038/s41467-020-15388-5. PubMed DOI PMC

Gruene T, et al. Rapid structure determination of microcrystalline molecular compounds using electron diffraction. Angew. Chem. Int. Ed. 2018;57:16313–16317. doi: 10.1002/anie.201811318. PubMed DOI PMC

Gemmi M, La Placa MGI, Galanis AS, Rauch EF, Nicolopoulos S. Fast electron diffraction tomography. J. Appl. Crystallogr. 2015;48:718–727. doi: 10.1107/S1600576715004604. DOI

Parsons S, Flack HD, Wagner T. Use of intensity quotients and differences in absolute structure refinement. Acta Crystallogr. B. 2013;69:249–259. doi: 10.1107/S2052519213010014. PubMed DOI PMC

Escudero-Adán EC, Benet-Buchholz J, Ballester P. The use of Mo Kα radiation in the assignment of the absolute configuration of light-atom molecules; the importance of high-resolution data. Acta Crystallogr. B. 2014;70:660–668. doi: 10.1107/S2052520614014498. PubMed DOI

Latychevskaia T, Abrahams JP. Inelastic scattering and solvent scattering reduce dynamical diffraction in biological crystals. Acta Crystallogr. B. 2019;75:523–531. doi: 10.1107/S2052520619009661. PubMed DOI PMC

Cichocka MO, Angstrom J, Wang B, Zou X, Smeets S. High-throughput continuous rotation electron diffraction data acquisition via software automation. J. Appl. Crystallogr. 2018;51:1652–1661. doi: 10.1107/S1600576718015145. PubMed DOI PMC

Jones CG, et al. The CryoEM method MicroED as a powerful tool for small molecule structure determination. ACS Cent. Sci. 2018;4:1587–1592. doi: 10.1021/acscentsci.8b00760. PubMed DOI PMC

Allen FH, Bruno IJ. Bond lengths in organic and metal-organic compounds revisited: X-H bond lengths from neutron diffraction data. Acta Crystallogr. B. 2010;66:380–386. doi: 10.1107/S0108768110012048. PubMed DOI

Yanagisawa, H., Yamashita, K., Nureki, O. & Kikkawa, M. MicroED datasets of hemin and biotin collected on Ceta camera. Zenodo10.5281/zenodo.3366892 (2019).

Thompson, E. & Jenkins, H. T. 3DED/microED datasets of biotin (Glacios/Ceta-D). Zenodo10.5281/zenodo.4895412 (2021).

Bruhn JF, et al. Small molecule microcrystal electron diffraction for the pharmaceutical industry–lessons learned from examining over fifty samples. Front. Mol. Biosci. 2021;8:354. doi: 10.3389/fmolb.2021.648603. PubMed DOI PMC

Pastero L, Turci F, Leinardi R, Pavan C, Monopoli M. Synthesis of α-quartz with controlled properties for the investigation of the molecular determinants in silica toxicology. Cryst. Growth Des. 2016;16:2394–2403. doi: 10.1021/acs.cgd.6b00183. DOI

Palatinus L, et al. Hydrogen positions in single nanocrystals revealed by electron diffraction. Science. 2017;355:166–169. doi: 10.1126/science.aak9652. PubMed DOI

Zaarour M, et al. Synthesis of new cobalt aluminophosphate framework by opening a cobalt methylphosphonate layered material. CrystEngComm. 2017;19:5100–5105. doi: 10.1039/C7CE01129F. DOI

Zhou H, et al. Programming conventional electron microscopes for solving ultrahigh-resolution structures of small and macro-molecules. Anal. Chem. 2019;91:10996–11003. doi: 10.1021/acs.analchem.9b01162. PubMed DOI

Plana-Ruiz S, et al. Fast-ADT: a fast and automated electron diffraction tomography setup for structure determination and refinement. Ultramicroscopy. 2020;211:112951. doi: 10.1016/j.ultramic.2020.112951. PubMed DOI

Roslova M, et al. InsteaDMatic: towards cross-platform automated continuous rotation electron diffraction. J. Appl. Crystallogr. 2020;53:1217–1224. doi: 10.1107/S1600576720009590. PubMed DOI PMC

Bortolini, C. et al. Atomic structure of amyloid crystals. Zenodo10.5281/zenodo.5303223 (2022).

Clabbers MTB, Gruene T, van Genderen E, Abrahams JP. Reducing dynamical electron scattering reveals hydrogen atoms. Acta Crystallogr. A. 2019;75:82–93. doi: 10.1107/S2053273318013918. PubMed DOI PMC

Knudsen EB, Sørensen HO, Wright JP, Goret G, Kieffer J. FabIO: easy access to two-dimensional X-ray detector images in Python. J. Appl. Cryst. 2013;46:537–539. doi: 10.1107/S0021889813000150. DOI

Palatinus L, Chapuis G. SUPERFLIP – a computer program for the solution of crystal structures by charge flipping in arbitrary dimensions. J. Appl. Cryst. 2007;40:786–790. doi: 10.1107/S0021889807029238. DOI

Petříček V, Dušek M, Palatinus L. Crystallographic computing system JANA2006: general features. Z. Kristallogr. Cryst. Mater. 2014;229:345–352. doi: 10.1515/zkri-2014-1737. DOI

Palatinus L, et al. Structure refinement using precession electron diffraction tomography and dynamical diffraction: tests on experimental data. Acta Crystallogr. B. 2015;71:740–751. doi: 10.1107/S2052520615017023. PubMed DOI

Palatinus L, et al. Structure refinement from precession electron diffraction data. Acta Crystallogr. A. 2013;69:171–188. doi: 10.1107/S010876731204946X. PubMed DOI

Klar, P. B. et al. Data for accurate structure models and absolute configuration determination using dynamical effects in continuous-rotation 3D ED data. Zenodo10.5281/zenodo.5579792 (2021). PubMed PMC

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