Nucleation of organic crystals from solution starts from self-assembly of molecules. New and advanced techniques are continuously explored to have an insight into understanding the nucleation mechanism and the local structure in both solution and resulting crystalline forms.
In this thesis, multiple spectroscopic techniques were applied - infrared (IR), Raman, near-edge X-ray absorption fine structure (NEXAFS) and X-ray photoelectron (XPS) - that gave an extensive overview of local interactions between molecules. The nucleation rates were calculated based on probability distributions of induction times using multiple micro-reactor setup and revised methodology.
Solid and solution state characterisation of both polymorphs of p-nitrobenzoic acid (PNBA), Forms I and II, has been performed and they were found to have similar crystal structures and be enantiotropically related. A comparative examination of substituent effects on local interactions and electronic structures of PNBA, p-aminobenzoic acid (PABA), and benzoic acid (BA) has been performed. PNBA has a strong electron withdrawing nitro group, while PABA has a strong electron donating amine group. IR and Raman spectra showed the carbonyl stretching frequency for PNBA is highest, followed by BA and PABA. PNBA has a lower orbital energy for all core 1s levels and lowest unoccupied molecular orbital (1π*), than PABA in the solid state. The substituent effect on the carbonyl stretching frequency and oxygen NEXAFS data of PNBA, BA and PABA in acetonitrile and ethanol were in the same order as the solid state. FTIR data for all compounds indicate that solution speciation in acetonitrile is carboxylic acid dimers and solute-solvent complexes, while in ethanol there are just solute-solvent interactions.
The influences of thermodynamic,B, and pre-exponential kinetic factors,A, on the nucleation rate did not correlate with the spectroscopic data. This raised several questions on the accuracy of the obtained A and B from the induction time measurements and the role of hydrogen bonding in the nucleation pathway.
