The advanced treatment of hydrogen bonding in quantum crystallography

Although hydrogen bonding is one of the most important motifs in chemistry and biology, H-Atom parameters are especially problematic to refine against X-ray diffraction data. New developments in quantum crystallography offer a remedy. This article reports how hydrogen bonds are treated in three different quantum-crystallographic methods: Hirshfeld atom refinement (HAR), HAR coupled to extremely localized molecular orbitals and X-ray wavefunction refinement. Three different compound classes that form strong intra-or intermolecular hydrogen bonds are used as test cases: hydrogen maleates, the tripeptide l-Alanyl-glycyl-l-Alanine co-crystallized with water, and xylitol. The differences in the quantum-mechanical electron densities underlying all the used methods are analysed, as well as how these differences impact on the refinement results.