Crystal structure solution of hydrogen bonded systems : a validation and an investigation using historical methodologies followed by a review of crystal structure prediction methodologies to date

Abstract

There are many chemicals that crystallize into more than one form. This phenomenon is called polymorphism. In each form or polymorph, inter and intra-molecular binding differ to varying degrees. As a result of this structural variation, the physical properties of the solid phases may also differ. Even the smallest of changes at the molecular level can result in a significant change in the final adopted crystal structure. Polymorphism in crystal structures allows studies of structure-property relationships since it is only the packing motifs that differ between polymorphs. In this thesis, a ‘computationally assisted’ approach to crystal structure solution was taken. X-ray powder diffraction was used to generate unit cell dimensions and space groups while historical in-house molecular modelling methods were used to generate possible trial structures that would be the starting point for refinement.

Finally, a review of the latest methodologies for crystal structure prediction and consideration of polymorphism within the pharmaceutical industry completes this work.