Structural investigations with high pressure techniques and multicomponent systems

Student thesis: Doctoral Thesis

Abstract

This thesis illustrates the use of high pressure crystallography techniques for the discovery and investigation of solid-state forms and probes the relationship between molecular structure and compression of both single and multicomponent systems. As well as investigating a data-driven approach to directing experimental co-crystallisation attempts.Single crystal X-ray diffraction techniques are a highlight in all areas of this study, as well as computational approaches which were used in the evaluation of the interactions of small molecule systems. Data-mining of the Cambridge Structural Database made the comparison of the compression studies richer.The pharmaceutical co-crystal, indomethacin and saccharin was analysed with respect to increasing pressure. The system is an example of a homomolecular synthon co-crystal allowing investigation of the component dimers free of strong interaction with surrounding molecules. The ambient pressure structure remains stable but investigation showed that the saccharin dimer sits in a pocket made by indomethacin allowing the dimer to lie further apart than in the pure compound.To follow, a structural compression study of the single component saccharin using synchrotron radiation lead to the structural characterisation of the first new polymorph of saccharin. The hydrogen bonding pattern of the new phase remains consistent however Pixel calculations revealed that the biggest difference in packing arises due to the reduction of an interlayer distance.To further explore multicomponent systems, two stoichiometric ratios of benzoic acid and isonicotinamide (2:1 & 1:1) were investigated. The rate of compression in these systems are almost identical despite the different molecular packing in each of the stoichiometric ratios. Through the investigation of materials in these initial chapters, the rate of compression in particular supramolecular synthons, e.g. amide-dimers, is demonstrated to be consistent despite the difference in the molecular make-up of the materials under study and their packing arrangements.Lastly, a data-driven approach was applied in directing the discovery of a new solid-state entity. Following previous failed attempts, machine learning was employed to direct experimental co-crystallisations which led to a new co-crystal of Artemisinin and 1-Napthol. Pixel calculations revealed that the largest contribution to crystal stabilisation comes from dispersion energy and enabled the identification of dominant intermolecular interactions in the crystal structures.
Date of Award1 Jul 2018
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorIain Oswald (Supervisor) & Gavin Halbert (Supervisor)

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