Chirality and accurate structure models by exploiting dynamical effects in continuous-rotation 3D ED data

Abstract

Dynamical diffraction effects are usually considered a nuisance for structure analysis from continuous-rotation 3D electron diffraction (3D ED) data like cRED and MicroED. Here we demonstrate that by accounting for these effects during the structure refinement, significantly improved models can be obtained in terms of accuracy and reliability with up to four-fold reduction of the noise level in difference Fourier maps in comparison to the standard structure determination routines that ignore dynamical diffraction. As dynamical diffraction effects break the inversion symmetry of the diffraction, they allow a quick, easy, and reliable determination of the absolute structure of chiral crystals.

Electron Diffraction of 3D Molecular Crystals

“…Nevertheless, the outlook for 3D ED appears promising, as recent work by Klar et al has extended the scope of dynamical refinement to a wide range of data sets collected using continuous rotation. 178 An encouraging experiment reported by Klar et al involves a double-blind comparison against analogous X-ray data collected on a chiral zeolite. In this case, dynamical refinement on 3D ED data returned internally consistent results with an independent assessment of absolute structure made via the Flack parameter.…”

“…In cases where nanocrystals have been milled to thicknesses at or below the elastic mean free path of the material, dynamical scattering is expected to be weak or unobservable. Nevertheless, the outlook for 3D ED appears promising, as recent work by Klar et al has extended the scope of dynamical refinement to a wide range of data sets collected using continuous rotation . An encouraging experiment reported by Klar et al involves a double-blind comparison against analogous X-ray data collected on a chiral zeolite.…”

Design of Active Defects in Semiconductors: 3D Electron Diffraction Revealed Novel Organometallic Lead Bromide Phases Containing Ferrocene as Redox Switches

“…[46,47] In favorable cases it even approaches the accuracy of SCXRD and furthermore enables a robust determination of the absolute structure. [48,49] One challenge that still needs to be overcome is the beam sensitivity of some materials, which can make a structure analysis difficult or impossible. It could be shown that the development of fast acquisition protocols [45,50] allows the use of this technique with various transmission electron microscopes (TEMs) even for very beam sensitive materials.…”

Absolute configuration determination of SMTP-7 via microcrystal electron diffraction (MicroED)

“…[25][26][27] It has been shown with model chiral compounds that dynamical refinement can be used to determine the absolute structure and improve the model accuracy of chiral crystals. 17,18 In this work, we aim to apply this approach to SMTP-7 and SMTP-7D, two relatively large small molecule drug candidates, not only to substantiate the absolute configuration assignments but also to validate the dynamical refinement methodology.…”

“…chiral salt formation) can be used to derive the absolute configuration. 16 Excitingly, computational tools of dynamical refinement on ED data have been recently developed and utilized to directly assign the absolute configuration of model organic molecules, 17,18 although a genuinely unknown example is yet to be explored with this approach. 19…”