title: Electron density, disorder and polymorphism: high-resolution diffraction studies of the highly polymorphic neuralgic drug carbamazepine.
abstract: 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 P2(1)/c. This disorder in the dihydrate structure has implications for both experimental and theoretical studies of polymorphism.
authors.affiliation: WESTChem School of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland.
authors.forename: Ioana
authors.initials: I
authors.lastname: Sovago
authors.affiliation: ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Science and Innovation Campus, Chilton, Didcot, Oxfordshire OX11 0QX, England.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Gutmann
authors.affiliation: WESTChem School of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland.
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Senn
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, England.
authors.forename: Lynne H
authors.initials: LH
authors.lastname: Thomas
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, England.
authors.forename: Chick C
authors.initials: CC
authors.lastname: Wilson
authors.affiliation: WESTChem School of Chemistry, University of Glasgow, Glasgow G12 8QQ, Scotland.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Farrugia
mesh_terms: D002220:Carbamazepine / Q000032:analysis* / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D004583:Electrons; D006860:Hydrogen Bonding; D008958:Models, Molecular; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002220:Carbamazepine
keywords: Hirshfeld atom refinement; carbamazepine; electron density; polymorph