On avoiding negative electron density in Gram-Charlier refinements of anharmonic motion: the example of glutathione

Christian B. Hübschle 1 , Charlotte Ruhmlieb 2 , Anja Burkhardt 3 , Sander van Smaalen 1 ,  and Birger Dittrich 4
  • 1 Laboratory of Crystallography, University of Bayreuth, BGI-Gebäude, 95440 Bayreuth, Germany
  • 2 Institut für Physikalische Chemie der Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
  • 3 Deutsches Elektronensynchrotron DESY, Hamburg, Notkestrasse 85, 22607 Hamburg, Germany
  • 4 Heinrich-Heine Universität Düsseldorf, Institut für Anorganische Chemie und Strukturchemie, Universitätsstraße 1, 40225 Düsseldorf, Germany
Christian B. Hübschle
  • Corresponding author
  • Laboratory of Crystallography, University of Bayreuth, BGI-Gebäude, 95440 Bayreuth, Germany
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, Charlotte Ruhmlieb
  • Institut für Physikalische Chemie der Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
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, Anja Burkhardt
  • Deutsches Elektronensynchrotron DESY, Hamburg, Notkestrasse 85, 22607 Hamburg, Germany
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, Sander van Smaalen
  • Laboratory of Crystallography, University of Bayreuth, BGI-Gebäude, 95440 Bayreuth, Germany
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and Birger Dittrich
  • Corresponding author
  • Heinrich-Heine Universität Düsseldorf, Institut für Anorganische Chemie und Strukturchemie, Universitätsstraße 1, 40225 Düsseldorf, Germany
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Abstract

The structure of glutathione, γ-l-Glutamyl-l-cysteinyl-glycine (C10H17N3O6S), was studied by multi-temperature single-crystal X-ray diffraction. Residual density maps from conventional independent atom model refinement gave indication of anharmonic motion in the molecule. This was further investigated by invariom refinement with anisotropic displacement parameters for all atoms, which described asphericity due to chemical bonding and lone pairs; afterwards only the residual-density signal of anharmonic motion remained. Treating anharmonicity with third-order Gram-Charlier displacement parameters led to regions with unphysical negative electron density. In contrast, a maximum entropy method (MEM) determination of the electron density successfully takes the features into account. Respective difference electron density plots (MEM minus prior and [Invariom+GC] minus invariom) agree well with each other. Challenges in treating and understanding the phenomenon are discussed. A procedure is proposed how unphysical negative electron density can be avoided. It is closely related to the free lunch algorithm.

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