(334a) Solvent -solute interaction and viscosity effects on thermodynamics and kinetics of crystallization

The structuring of 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, solvent at the interface may be ordered or disordered. In general, 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 and solvent-solute interactions on thermodynamics and kinetics of crystallization.

We explore the thermodynamic parameters of crystallization for etioporphyrin I (a planar free base porphyrin) in a range of organic solvents from alcohols (octanol, hexanol and butanol), through a polar aprotic solvent (DMSO), to a carboxylic derivative (caprylic acid). Thermodynamic characteristics of crystallization along with absorption spectroscopy were used as probes to decipher the presence of solvent structuring and solute-solvent interactions for non-solvate crystals crystallizing from different organic solvents.

Time-resolved in situ atomic force microscopy monitoring of the step dynamics on (010) face of etioporphyrin in two types of solvent, alcohols (octanol, butanol and hexanol) and DMSO, having varying aliphatic chain lengths and subsequent solvent viscosities demonstrate the impact of solute-solvent interactions and solvent viscosity on the barrier for solute incorporation into kinks. The relationship 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 interaction 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.