Most industrial crystallisation processes follow a ‘wet’ chemistry approach, i.e. they involve one or more solvents, but the outcome of a crystallization is not yet possible to predict. In this project, we will focus on the solute–solvent interactions as dominant, but currently neglected, part of intermolecular interactions in solution and a major structure-driving influence.

The Edkins group has experience in gauging solvent–solute interactions with laboratory-based spectroscopic methods (e.g. solution NMR and FTIR), and we will use host–guest titrations with the solvent in question as guest to quantify the binding constant Kbind and the respective Gibbs free binding energy ΔGbind for different stoichiometry of the aggregate.

To get accurate information on the cluster size and stoichiometry, we will use Diffusion-Ordered NMR spectroscopy (DOSY) to gauge the diffusion coefficient, D, of the aggregates, which can further be translated into the hydrodynamic radius and hence the volume and stoichiometry of the diffusing species.

Using a combination of 1H and 13C-NMR, FTIR and UV-visible (UV-vis) spectroscopy for the titrations we will gauge different molecular interaction types ranging from hydrogen bonds to π-stacking, as well as covering a large concentration range and interaction lifetimes from femtosecond to milliseconds. Furthermore, we will use neutron total scattering experiments at the ISIS neutron and muon research facility to gauge the structural model of the solution. This will allow us to reveal connections between the structure of the pre-crystallisation phase, the strength and energy of aggregates and the crystallisation outcome.

Using the complete information, we will categorise the solute-solvent interaction and aim to predict the impact that the solvent has on the crystallization outcome. This outcome could be directly implemented by researchers to ‘dial-in’ the crystallisation solvent to the required outcome and represent a game-changer in crystallisation science.

The successful candidate will have a background in Pharmaceutics, Chemistry, Crystallisation and/or related disciplines. You will have an interest in digging deep into factors guiding crystallization. A background knowledge and practical experience in NMR spectroscopy will be of benefit.