Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector

Acta Crystallogr A Found Adv. 2016 Mar;72(Pt 2):236-42. doi: 10.1107/S2053273315022500. Epub 2016 Feb 5.

Abstract

Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼ 0.013 e(-) Å(-2) s(-1)) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS, SHELX) and for electron crystallography (ADT3D/PETS, SIR2014).

Keywords: Timepix quantum area detector; carbamazepine; electron diffraction structure determination; electron nanocrystallography; nicotinic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbamazepine / chemistry*
  • Crystallography, X-Ray
  • Models, Molecular
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Niacin / chemistry*
  • Organic Chemicals / chemistry*
  • Temperature
  • X-Ray Diffraction / methods*

Substances

  • Organic Chemicals
  • Niacin
  • Carbamazepine