Electron density, disorder and polymorphism: high-resolution diffraction studies of the highly polymorphic neuralgic drug carbamazepine

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 P2₁/c. This disorder in the dihydrate structure has implications for both experimental and theoretical studies of polymorphism.An experimental charge density study on polymorph (III) of carbamazepine is in excellent agreement with theory and a Hirshfeld atom refinement based on the X-ray data provides positional and anisotropic displacement parameters for the H atoms closely similar to those obtained from the neutron diffraction data. X-ray and neutron diffraction data on the dihydrate of carbamazepine strongly indicate a disordered orthorhombic crystal structure in Cmca, rather than a monoclinic crystal structure in P2₁/c.