The advanced treatment of hydrogen atoms in quantum crystallography

Crystal structure determination using X-ray diffraction has become a routine technique for life and materials sciences, chemistry, biology, physics, etc. since its discovery 106 years ago. Despite its long existence, the most widely used model for crystal structure refinement is still the hundred-years old Independent Atom Model (IAM), which neglects chemical information present in the experimental data, such as bonding densities and densities due to lone electron pair regions. Over the past decades, new models have been developed to include this chemical information via aspherical description of atoms either using multipole-based techniques, maximum entropy methods or wavefunction-based techniques. The latter constitute the recently emerged field of quantum crystallography, combining quantum theory and crystallography to provide advanced structure refinements and wavefunctions with embedded information from experiment, giving access to experimental electron density distributions.
In this thesis, we show the different models that allow access to these chemical information present in the experimental data, explaining the theory behind the atomic scattering factors, and their different sources according to each different model. These are employed and tested thoroughly for cases where the spherical approach (independent atom model) using X-ray diffraction data fails most dramatically: hydrogen atoms.
We show how to obtain accurate atomic parameters for hydrogen atoms in unusual bonding situations using X-ray diffraction data only. These include hydrogen atoms in tautomeric equilibrium (Chapter 8), involved in bridging positions within strong intramolecular hydrogen bonds (Chapters 9, 9.2 and Section 10.2), involved in agostic interactions, bonded to heavy elements (Chapter 11) and in proteins (Chapter 12). Correlations between hydrogen atoms displacement parameters and their positions are evaluated through their congruent refinement using state of the art methods for the estimation of anisotropic displacement parameters (Chapter 10.2). We compare derived X-H bond lengths and ADPs to those obtained from neutron diffraction data as reference. We demonstrate that the effects of the electric field imposed by the crystal environment for ionic systems plays an important role on the location of the mobile hydrogen atom inside strong intramolecular hydrogen bonds for the hydrogen maleate class of compounds (Chapter 9.2).
The results obtained here lead to the development of a software (lamaGOET) and a new method, namely the HAR-ELMO method (Chapter 12). Successful applications of Hirshfeld Atom Refinement and HAR-ELMO for systems including transition metal hydrides and proteins are presented for the first time using the developed software and method (Chapter 11 and 12), where quantum crystallography’s powerful tools are tested to obtain properties for molecules which are dependent on accurate determination of their hydrogen atom parameters such as agostic interactions.