(259f) Solvent Structuring and Viscosity Effects on Thermodynamics and Kinetics of Crystallization

The structuring of the solvent at the crystal-solvent interface largely regulates the activation barrier for incorporation of solute into the crystal. Depending on the groups exposed on the crystal surface, the solvent at the interface may be ordered or disordered ^1,2. In general, the consequences of solvent structuring on the molecular level interactions comprising crystallization are poorly understood. Organic solvents, in which the bonds that could support a defined fluid structure are weak and varied present a particular challenge to understand the effect of solvent structuring on thermodynamics and kinetics of crystallization.

We explore the thermodynamic parameters of crystallization of a group of supramolecules known as porphyrins in organic solvents. Thermodynamic characteristics of crystallization were used as probes for the presence of solvent structuring which reveals that the interactions that govern the enthalpy and entropy of crystallization are dominated by the van der Waals contact between the solvent aliphatic tails and the non-polar groups of the etioporphyrin I (a free base porphyrin).

Time-resolved in situ atomic force microscopy monitoring of the step dynamics on (010) face of etioporphyrin I in two types of solvents, alcohols (octanol, butanol and hexanol) and DMSO, of varying aliphatic chain length and subsequent solvent viscosity demonstrates the impact of solvent structuring, solute-solvent interactions and solvent viscosity on the barrier of solute incorporation into kinks. The relation between step kinetic coefficient and solvent viscosity reveals that the crystallization of organic small molecules is not governed by diffusion limitation but rather by solute-solvent interaction at the kinks. The correlation between the step velocity and the solute concentration on the (010) face of etioporphyrin I for different solvents reveal that for solvents belonging to the same homologous series, solute incorporation scales with the solute diffusion coefficient. All-atom MD simulation for solvent structuring at the crystal interface emphasizes the importance of solute-solvent binding at the crystal interface.These emerging insights offer guidance for polymorph selection, chiral separations, structure design and numerous other open questions relevant to myriad crystallization systems in the pharmaceutical and chemical industries.

References

1. Vácha, R., Zangi, R., Engberts, J. B. F. N. & Jungwirth, P. Water Structuring and Hydroxide Ion Binding at the Interface between Water and Hydrophobic Walls of Varying Rigidity and van der Waals Interactions. The Journal of Physical Chemistry C (2008) 112, 7689-7692.

2. Meister, K., Strazdaite, S., DeVries, A. L., Lotze, S., Olijve, L. L. C., Voets, I. K., & Bakker, H. J. Observation of ice-like water layers at an aqueous protein surface. Proceedings of the National Academy of Sciences (2014) 111, 17732-17736.