Revealing the Roles of Desolvation and Molecular Self-Assembly in Crystal Nucleation from Solution: Benzoic and p-Aminobenzoic Acids

Abstract

Abstract. There has been much recent interest in the role of solution chemistry and in particular the importance of molecular self-assembly in the nucleation of crystalline phases.Techniques such as FTIR and NMR have highlighted the existence of solution phase dimers which in many cases mirror the structural synthons found in the resulting macroscopic crystals. However there are no reported examples in which this new insight into the solution phase has been linked directly to the kinetics of crystal nucleation. Here for the first time, using a combination of solution FTIR, computational chemistry and measured crystal nucleation rate data, such a link is demonstrated for p-aminobenzoic (PABA) and benzoic acids nucleating from polar and nonpolar solvents. Solute dimerization and desolvation are found to be rate determining processes in the overall nucleation pathway.

The influence of solution environment on the nucleation kinetics and crystallisability of para-aminobenzoic acid

“…Davey 6 proposed that the de-solvation rates of a solute molecule can be the rate-limiting step for both nucleation and crystal growth; this was recently highlighted by comparing the free energy of solvation of the carboxylic acid dimer of para-aminobenzoic acid (PABA) in various solvents, to attachment frequency calculated from isothermal nucleation studies 7 .…”

“…Recent studies have shown that nucleation kinetic parameters can 4 be derived from the probability distribution of induction times (time taken for a system to crystallise while under non-kinetic supersaturation conditions) as observed from measurements of induction times at a set temperature and hence supersaturation (isothermal method), and these have been related to the mechanisms by which critical nuclei form in supersaturated solutions 9 . The relationship between induction time and supersaturation can be used to calculate nucleation kinetic parameters, such as interfacial tension and the methodology has been successfully applied to organic materials 7,10,11 .…”

“…This suggests that there is a barrier to growth at the (0 1 0) surface in water which is not present or is decreased to a large extent in ethanol and acetonitrile solutions. Sullivan et al 7 have recently indicated the importance of dimer formation as a key step in attachment to the PABA crystal during crystallisation.…”

Measuring induction times and crystal nucleation rates

“…Although also other dependencies of the pre-exponential term on the supersaturation ratio S are known in literature [7,14]. The variables A and B are supersaturation ratio S independent variables and can be referred to as the kinetic factor or preexponential factor A and thermodynamic or exponential factor B.…”

Measurement, modelling, and closed-loop control of crystal shape distribution: Literature review and future perspectives

“…crystal size (diameter) distribution) are largely semi-empirical, and on-line characterisation of nuclei is still difficult. Little work has been done on the prediction and measurement of the nuclei shape distribution [134]. Therefore it requires further research in this area.…”