Role of restraints on hydrogen atoms in Hirshfeld atom refinement: the case of tri-aspartic acid trihydrate

Abstract

Two polymorphs of L-Asp-L-Asp-L-Asp (DDD) trihydrate as model compounds for biologically important proton-shuttle reactions were investigated with the quantum-crystallographic refinement technique Hirshfeld atom refinement (HAR). With HAR, hydrogen-atom positions are refined freely against the X-ray diffraction data and yield X—H bond distances close to those from neutron diffraction. However, the X-ray data of DDD trihydrate do not contain sufficient information to refine anisotropic displacement parameters (ADPs) for the hydrogen atoms, although the data quality is comparable to that of typical oligopeptide or protein datasets, including those with disordered fragments. Therefore, the following restraints were tested for the hydrogen-atom ADPs using NoSpherA2/olex2.refine: a restraint that approximates isotropic behaviour (ISOR), a restraint that enforces similar movement in any direction (SIMU), a rigid-bond restraint (DELU) and an advanced rigid-bond restraint (RIGU). Although it was found that there is no significant influence of the restraint weights and corresponding ADP values on the X—H distances, some recommendations on hydrogen-atom ADP restraint weights to be used in HAR are given. For ISOR, the suggested values are 10 times smaller (stricter) than the default values for non-hydrogen atoms in independent atom model (IAM) refinements, whereas those for RIGU are suggested to be less strict.