Validation of experimental charge densities: refinement of the macrolide antibiotic roxithromycin

Acta Crystallogr B. 2010 Oct;66(Pt 5):568-77. doi: 10.1107/S0108768110026480. Epub 2010 Sep 4.

Abstract

Multipole refinements of larger organic molecules have so far been limited to a few exceptional cases. We report an investigation of the detailed experimental electron-density distribution (EDD) of roxithromycin, a macrolide antibiotic consisting of 134 atoms. Although the experimental multipole refinement on high-resolution synchrotron data converged smoothly, validation of the electron density by calculation of an `experiment minus invariom' difference density revealed conformational disorder of the H atoms. Hydrogen disorder is shown to affect the EDD, the electrostatic potential and atomic properties as defined by Bader's quantum theory of atoms in molecules. A procedure to obtain the electron density distribution in the presence of disorder is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Electrons
  • Hydrogen Bonding
  • Macrolides / chemistry
  • Roxithromycin / chemistry*
  • X-Ray Diffraction

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • Roxithromycin