Host perturbation in a β-hydroquinone clathrate studied by combined X-ray/neutron charge-density analysis: Implications for molecular inclusion in supramolecular entities

Article abstract of DOI:10.1002/chem.201400129

X-ray/neutron (X/N) diffraction data measured at very low temperature (15 K) in conjunction with ab initio theoretical calculations were used to model the crystal charge density (CD) of the host-guest complex of hydroquinone (HQ) and acetonitrile. Due to pseudosymmetry, information about the ordering of the acetonitrile molecules within the HQ cavities is present only in almost extinct, very weak diffraction data, which cannot be measured with sufficient accuracy even by using the brightest X-ray and neutron sources available, and the CD model of the guest molecule was ultimately based on theoretical calculations. On the other hand, the CD of the HQ host structure is well determined by the experimental data. The neutron diffraction data provide hydrogen anisotropic thermal parameters and positions, which are important to obtain a reliable CD for this light-atom-only crystal. Atomic displacement parameters obtained independently from the X-ray and neutron diffraction data show excellent agreement with a |ΔU| value of 0.00058 A² indicating outstanding data quality. The CD and especially the derived electrostatic properties clearly reveal increased polarization of the HQ molecules in the host-guest complex compared with the HQ molecules in the empty HQ apohost crystal structure. It was found that the origin of the increased polarization is inclusion of the acetonitrile molecule, whereas the change in geometry of the HQ host structure following inclusion of the guest has very little effect on the electrostatic potential. The fact that guest inclusion has a profound effect on the electrostatic potential suggests that nonpolarizable force fields may be unsuitable for molecular dynamics simulations of host-guest interaction (e.g., in protein-drug complexes), at least for polar molecules. Electron-density analysis by low-temperature X-ray/neutron diffraction and ab initio calculations revealed that inclusion of acetonitrile in a hydroquinone clathrate leads to substantial polarization of the host structure (see figure). Thus, doubt is cast on the accuracy of nonpolarizable force fields used in molecular dynamics simulations.