(472f) The Influence of Solution Conditions on the Self-Assembly of Pre-Nucleation Clusters

The concept of pre-nucleation clusters has been established to, successfully, explain phenomena, in nucleation kinetics, that they were inconsistent with the classical nucleation theory.¹ The key idea is that pre-nucleation clusters are formed providing a comfortable niche for nuclei to be formed.² Phenomenological theories exist describing this two-step nucleation process.³ However, there is a lack of qualitative understanding of the fundamental phenomena underpinning the formation of pre-nucleation clusters both in a supersaturated and an understaturated environment.

Using the models proposed in more recent works is being shown that bigger pre-nucleation clusters provides an environment giving more chances of survival to the nucleus inside it. These findings were tested experimentally using a number of industrially relevant molecules (arginine, glycine, glutamic acid). These molecules are particularly attractive as they have relatively large nucleation times. In addition the formation of pre-nucleation clusters as nucleation precursors for them has been reported in literature. Using DLS it was shown that in aqueous systems, the size of the pre-nucleation clusters scales with the supersaturation. These findings are in accordance with the findings proposed from previous works. Upon filtration, both in a supersaturated and an undersaturated regime, the pre-nucleation clusters recover their initial size in a few hours, in the absence of any agitation.

Experiments were conducted in systems containing water and ethanol to investigate the influence of solution’s chemical potential on the size of the pre-nucleation clusters. It is shown that, in both the undersaturated and the supersaturated regime, the formation of the pre-nucleation clusters follows the fundamentals of self-assembly in solution.⁴ The findings suggest that the influence of the solvent can overcome that of supersaturation, for example an aqueous system containing arginine at S≈0.5 (0.8 g of L-Arginine) gives bigger pre-nucleation clusters than a solution containing 30 % v/v ethanol at S≈0.9.

The findings of this work verify the majority of the findings reported in literature. However, it reports different kinetics of recovery of the pre-nucleation clusters size upon filtration. It highlights the applicability of the fundamentals of self-assembly in solution. The findings suggest that in depth understanding of the self-assembly phenomena are required for the development of efficient strategies for the control of crystallization kinetics via stirring⁵ and for the formulation of amorphous solid dispersions.

References

1. P.G. Vekilov. Nucleation. Crystal Growth & Design. 2010, 10, 5007.
2. B. Peters. On the coupling between slow diffusion transport and barrier crossing in nucleation. The Journal of Chemical Physics. 2011, 135, 044107.
3. W. Pan, A.B. Kolomeisky, P.G. Vekilov. Nucleation of ordered solid phases of proteins via a disordered high-density state: Phenomenological approach. The Journal of Chemical Physics. 2005, 122, 174905.
4. J.N. Israelachvili. Intermolecular and Surface Forces. 3rd ed. Oxford, Academic Press; 2011.
5. A. Jawor-Baczynska, B.D. Moore, H.S. Lee, A.V. McCormick, J. Sefcick. Population and size distribution of solute-rich mesospecies within mesostructured aqueous amino acid solutions. Faraday Discussions, 2013, 167, 425.]
6. M. Diwan, H. Li, F. Nordstrom. Primary Nucleation Under High Shear Conditions. AICHE Conference Proceedings, 2015