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Electron density, disorder and polymorphism: high‐resolution diffraction studies of the highly polymorphic neuralgic drug carbamazepine
Author(s) -
Sovago Ioana,
Gutmann Matthias J.,
Senn Hans Martin,
Thomas Lynne H.,
Wilson Chick C.,
Farrugia Louis J.
Publication year - 2016
Publication title -
acta crystallographica section b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.604
H-Index - 33
ISSN - 2052-5206
DOI - 10.1107/s2052520615019538
Subject(s) - monoclinic crystal system , orthorhombic crystal system , neutron diffraction , crystallography , crystal structure , polymorphism (computer science) , crystal structure prediction , molecule , atom (system on chip) , chemistry , materials science , biochemistry , organic chemistry , genotype , gene , computer science , embedded system
Analysis of neutron and high‐resolution X‐ray diffraction data on form (III) of carbamazepine at 100 K using the atoms in molecules (AIM) topological approach afforded excellent agreement between the experimental results and theoretical densities from the optimized gas‐phase structure and from multipole modelling of static theoretical structure factors. The charge density analysis provides experimental confirmation of the partially localized π‐bonding suggested by the conventional structural formula, but the evidence for any significant C—N π bonding is not strong. Hirshfeld atom refinement (HAR) gives H atom positional and anisotropic displacement parameters that agree very well with the neutron parameters. X‐ray and neutron diffraction data on the dihydrate of carbemazepine strongly indicate a disordered orthorhombic crystal structure in the space group Cmca , rather than a monoclinic crystal structure in space group P 2 1 / c . This disorder in the dihydrate structure has implications for both experimental and theoretical studies of polymorphism.