3D electron diffraction for structure determination of small-molecule nanocrystals: A possible breakthrough for the pharmaceutical industry

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2022 Sep;14(5):e1810. doi: 10.1002/wnan.1810. Epub 2022 May 20.

Abstract

Nanomedicine is among the most fascinating areas of research. Most of the newly discovered pharmaceutical polymorphs, as well as many new synthesized or isolated natural products, appear only in form of nanocrystals. The development of techniques that allow investigating the atomic structure of nanocrystalline materials is therefore one of the most important frontiers of crystallography. Some unique features of electrons, like their non-neutral charge and their strong interaction with matter, make this radiation suitable for imaging and detecting individual atoms, molecules, or nanoscale objects down to sub-angstrom resolution. In the recent years the development of three-dimensional (3D) electron diffraction (3D ED) has shown that electron diffraction can be successfully used to solve the crystal structure of nanocrystals and most of its limiting factors like dynamical scattering or limited completeness can be easily overcome. This article is a review of the state of the art of this method with a specific focus on how it can be applied to beam sensitive samples like small-molecule organic nanocrystals. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Keywords: 3D electron diffraction; electron crystallography; pharmaceutics; small-molecule organics; structure solution.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Industry
  • Electrons*
  • Nanoparticles* / chemistry