Architecture-Dependent Interplay between Self-Assembly and Crystallization in Discrete Block Co-Oligomers

Access to versatile and stable nanostructures formed by the self-assembly of block copolymers in water is essential for biomedical applications. These applications require control over the stability, morphology, and size of the formed nanostructures. Here, we study the self-assembly in water of a library of fully discrete and sequence-controlled AB-type block co-oligomers (BCOs) of oligo(L-lactic acid)-b-oligo(ethylene glycol). In this series, we eliminate all the inherent uncertainty associated with molar mass, ratio, and compositional dispersity, but vary the ratio between the water-soluble and water-insoluble parts. The BCO library is designed in such a way that vesicles, spherical micelles, and cylindrical micelles are generated in solution, hereby covering a variety of common morphologies. With the help of self-consistent field (SCF) computations, the thermodynamic structures in water are predicted for all structures. The morphologies formed were experimentally analyzed using a combination of calorimetry and scattering techniques. When comparing the experimentally found structures with those predicted, we find an excellent agreement. Intriguingly, calorimetry showed the presence of crystallized L-lactic acid (LLA) units in the bilayer of the lamellar forming BCO. Despite this crystallinity, there is no mismatch between the predicted and observed bilayer thicknesses upon self-assembly in water. In this case, phase separation driven by the hydrophobic LLA block coincides with crystallization, resulting in stable morphologies. Thus, SCF guided library design and sample preparation can lead toward robust formulations of nanoparticles.