The crystallization of decanoic acid/dopamine supramolecular self-assemblies in the presence of coacervates

Hypothesis: Supramolecular self-assemblies involving non-covalent interactions play important roles in material science as well as living systems as they result in unique properties and/or functions. However, understanding of their self-assembly mechanism and crystallization has remained rudimentary. Experiment: Here, we focus on biomolecular fatty acid and dopamine, which commonly exist in biological systems and closely related to neurodegenerative diseases, and investigate their self-assembly pathway by optical and fluorescence microscopy, DLS, SAXS, TEM, 2D-NMR, etc. Findings: It is found that they could form the crystalline plates in solution or via a metastable liquid − liquid phase separation (LLPS). The nucleation and growth of crystalline plates observed occurs in solution or the dilute phase of LLPS, and not within the concentrated coacervate phase. This is because in coacervate, dopamine intercalates into fatty acid through hydrophobic and electrostatic interaction, which hinders the rearrangement of molecules and nucleation process, whereas in solution or dilute phase, they have the mobility to arrange into ordered structures to maximize electrostatic, hydrogen bonding and π-π interactions, leading to nucleation and crystallization. Moreover, the transitions between the coacervates and crystalline phase can be realized by adjusting the temperature. Our results shed light on the multistep nucleation in the presence of LLPS, as well as molecular mechanisms involved, thus further extending the nucleation–growth mechanisms.