Molecular Self-Assembly, Nucleation Kinetics and Cluster Formation Associated with Solution Crystallisation

The structural pathway from a single molecule to clustering through to nucleation during a crystallisation process is not fully understood. As such the solution state structure, nucleation kinetics and phase transformation kinetics of p-Aminobenzoic (PABA) acid are probed using a combination of in-situ crystallisation characterisation techniques and nucleation kinetic analysis methods.
The solubility of alpha PABA is measured in a number of solvents where van’t Hoff analysis shows that solute-solute interactions are probable in all solvents. Solution state FTIR studies reveal the presence of a distribution of solvated monomer and carboxylic acid dimer species in acetonitrile solutions. This provides a link between solution state structural synthons and the carboxylic acid dimer structural synthon of the alpha PABA solid phase.
Isothermal nucleation kinetic analysis reveals that calculated interfacial tension, γeff, values are found to be low for an organic material; where γeff values are 0.85 – 1.31 mJ/m2 in ethanol and 2.36 – 2.60 mJ/m2 in water. Due to this the critical cluster sizes are in the region of 0.48 – 1.98 nm. Poly-thermal kinetic analysis reveals a nucleation mechanism change from instantaneous to progressive as a function of decreasing solubility in ethanol, acetonitrile and water. This is caused by an increase in attachment frequency due to decreasing de-solvation free energy of PABA found from molecular dynamics simulations, this in combination with increasing γeff causes the thermodynamic component of the nucleation rate to become limiting.
Isothermal and poly-thermal X-ray scattering studies of PABA nucleation reveal the formation of large liquid-like clusters of PABA, >40nm, in the under-saturated state. These Nano-scale assemblies increase in size and structural ordering, indicated by an increase in fractal dimensionality from 1 – 2 as a function of driving force. The Guinier region of the high q structures is found to increase from Rg = 0.46nm to 0.53 nm which indicates a population of monomers and dimers of PABA in the supersaturated state. This was confirmed as the carboxylic acid dimer structure from form factor fitting of known structural synthons of the alpha phase.In-situ XRD studies of the polymorphic phase transformation of the beta-alpha phase, indicates that the dissolution and growth processes are consistent with zero order nucleation kinetics and first and zero order kinetics respectively with the latter seemingly temperature dependant. UV/Vis analysis in combination with the XRD data reveal the transformation is a dissolution controlled process explained by particle morphology. The transformation temperature was also estimated from the growth and dissolution rate constants as 22.8 – 23.6 °C.