Understanding the crystal landscape of primary sulfinamides and predicting cocrystallization

This thesis focuses on design principles in crystal engineering, from the development of our knowledge of understudied functional groups, to the synthesis of cocrystals. Chapter one is a brief introduction to the concepts and development of the field of crystal engineering over the past 30 years, including the definition and utilisation of the hydrogen bond in the synthesis of multicomponent materials, and reviewing the cocrystallization literature involving sulfur functional groups. Chapter two describes the various synthetic strategies utilised in the synthesis of a library of primary aryl sulfinamides, an under-studied sulfur functional group from a solid state chemistry perspective. Their solid-state properties are examined, with focus on the robust supramolecular synthons that they exhibit. Finally, this chapter describes their hydrolysis, examining the relationship between their hydrolytic sensitivity and solid state structure. Chapter three outlines the preparation of novel solid forms of the active pharmaceutical material Salsalate. These include the newly observed phenomenon of reactive cocrystallization. Chapter four outlines the development of an experimental data matrix and machine learning algorithm for the computational prediction of cocrystal formation, and the use of this software to rank and compare the probable cocrystals from an external test set. This work was conducted in collaboration with Prof. Richard Cooper and Jerome Wicker of the University of Oxford, UK. The solid-state properties of many of the novel cocrystals identified in the development of the experimental data matrix are described, with focus on the presence of recurring and predictable hydrogen bonding motifs observed in these systems. Chapter five examines the future work that can be envisaged building on the work described in the earlier chapters