The University of ManchesterRachel A SullivanFor the degree of Doctor of PhilosophyMolecules, Clusters and Crystals: The Crystallisation of p-aminobenzoic acid from SolutionJanuary 2015Nucleation is a key step in the crystallisation process, where a new crystalline solid phase is created from a supersaturated solution. The applications of crystallisation as a purification and separation technique span many industries, yet still no definitive molecular mechanism for nucleation exists. This PhD is part of a critical mass research project involving researchers from both the Universities of Manchester and Leeds. The aim is to reveal the relationship between structural components of the nucleation transition state, solution phase molecular self-assembly and nano cluster formation, through to critically sized crystalline nuclei which then grow to crystals. All work has been carried out on a small organic molecule, p-aminobenzoic acid (PABA). This PhD has delivered successful characterisation of PABA in the solid and solution state, along with a detailed understanding of its nucleation kinetics and growth rates from a range of solvents. PABA has two enantiotropically related polymorphs, alpha and β, with the former constructed of carboxylic acid dimers and the latter of a hydrogen bonded tetramer network linking alternate acid and amine functionalities. New determinations of the crystal structures of both forms were submitted to the CCDC with Ref codes of AMBNAC07 and 08 for alpha and β PABA respectively.A detailed morphological study on both forms of PABA employing modelling and experimental methods has revealed the effect of solvent on the growth habit. In all polar solvents, alpha PABA displays a more important or slower growing (002) face than the calculated morphology implies. In water, β PABA has a much smaller (101 ̅) face in comparison to β PABA grown from alcohols. Crystallisation experiments demonstrate a clear solvent effect on the appearance of the two polymorphs. From organic solvents only alpha PABA is obtained, from water both alpha and β PABA are crystallised. A database search (CCDC) suggests that water may play an important role in the stabilisation of the nucleation transition state for both alpha and β PABA. This is not possible in organic solvents.Detailed nucleation and crystal growth kinetics have been measured for alpha PABA at 20°C in water, acetonitrile, ethyl acetate and 2-propanol. A clear solvent trend was observed in both the derived rates of molecular attachment and crystal growth. These were fastest in water, followed by acetonitrile, then ethyl acetate and finally slowest, in 2-propanol. This can be explained by the solvation of the carboxylic acid functional group, where 2-propanol is deemed the most effective solvator of building units in solution and on a crystal surface. This conclusion is supported by the solution FTIR spectroscopy, which clearly confirms strong solvation.