Novel Approaches to the formation of metastable polymorphs of organic molecules

  • Charlie Hall

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Control of the internal structure of organic crystals is paramount in producing materials
functionalised in a predictable, practical and reproducible manner. This thesis explores and
builds upon the current knowledge of organic crystal growth, intending to expand the tools
available to crystallographers, along with testing our ability to predict the properties that crystalline materials exhibit. The first section of this work looks at developing a new tool for the crystallisation of organic materials. The first chapter highlights how the use of volatile deep eutectic solvents affords an element of crystallographic control in a variety of pharmaceuticals, including the production of the
elusive form II paracetamol at room temperature and pressure, without the use of additives. Following this, the second chapter looks at the structural and thermodynamic properties of the volatile deep eutectic solvents during thermal cycling. These data were collected using the concurrent techniques of synchrotron powder X-ray diffraction and differential scanning calorimetry, which was carried out using the I12 beamline at Diamond Light Source. This analysis is the first of its type to be carried out on deep eutectic systems, allowing an insight into the fundamental structure that these mixtures
exhibit at different temperatures. In particular, the formation of metastable crystalline phases during the thermal cycles is revealed, strongly supporting the hypothesis that intermediary phases can direct the crystallographic pathway of organic molecules during their formation from the volatile deep eutectic solvent medium.

The final chapter of this thesis looks at the crystallographic case study of two functionalised
chalcones, which exhibit polymorphism of crystals ranging in colour across the optical spectrum. A variety of crystallographic techniques are used to acquire structural control, to analyse the crystals in terms of structural, optical and thermodynamic properties. Theoretical modelling is applied to
these structures, demonstrating our current ability to predict crystalline properties using quantum chemical calculations. In particular, a new method for determining optical properties is established, which gives information about the relative shifts in absorption spectra between crystals, while also indicating the most optically-relevant bonding motifs within each structure.
Date of Award28 Sept 2021
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorSimon R Hall (Supervisor) & Sean A Davis (Supervisor)

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