Crystal and Electron Properties of Carbamazepine–Aspirin Co-crystal

Carbamazepine (CBZ) and aspirin (ASP) drug molecules in their 1:1 cocrystal interact by relatively strong hydrogen bonds and aromatic–aromatic contacts. The crystal structure and the experimental electron density in the CBZ:ASP cocrystal were derived from a high resolution X-ray diffraction experiment at 100 K, and the results are compared to those previously obtained for the CBZ form III. The isobaric thermal expansion tensor appears to be much more anisotropic for the cocrystal than for CBZ form III. The thermal expansion coefficients αV are found equal to 1.3 for CBZ III and 1.5 × 10–4 K–1 for the CBZ:ASP cocrystal. The interactions in the CBZ:ASP cocrystal have also been analyzed through the electrostatic properties derived from both experimental and theoretical electron densities: topological features, atomic charges, and electrostatic potential. A very good agreement was found for the values of the electron density at the critical points ρ(rCP) obtained from both experiment and theory. This is not, however, true for the Laplacian values which are systematically weaker in the theoretical approach. In contrast, the integrated atomic charges have higher magnitudes for the theoretical density. Additionally, it is shown here that the total molecular energies can be obtained from the electrostatic potential at the nuclei (EPN) within the Thomas–Fermi approximation. The best agreement with the conventional quantum calculations (Restricted Hartree–Fock RHF or Density Functional Theory DFT) was surprisingly obtained for the promolecule (superposition of Independent Atomic Model, IAM) density and not from the multipole model which overestimates or underestimates the energies.