Regulation of self-assembly evolution pathway of block copolymers with crystalline side chains via liquid-liquid...

Liquid-liquid phase separation (LLPS) plays a fundamental role in orchestrating biomolecular condensation and the formation of membraneless organelles. Inspired by this biological principle, there is growing interest in exploiting LLPS as a strategic pathway to guide the self-assembly of synthetic polymers into well-defined nanostructures. Herein, we investigate the LLPS-guided self-assembly of C₁₈H₃₇-substituted poly(ε-caprolactone)-b-poly(N,N-dimethylacrylamide) (C₁₈PCL-b-PDMA) block copolymers (BCPs), where the core-forming block PCL bears octadecyl side chains at different substitution sites (ε, β/δ, γ). Using εC₁₈PCL₅₂-b-PDMA₂₆₀ as a primary model, we demonstrate that the self-assembly pathway and final morphology can be strategically manipulated by controlling the phase-separation kinetics. After applying a heating-cooling-aging process, the experimental results show that slow cooling rate leads to a multi-step nucleation-growth process involving various metastable intermediates, whereas accelerated cooling rate directly induces the formation of polymer-rich droplets that act as nucleation precursors, effectively lowering the energy barrier toward stable cylinders. Furthermore, precise control over LLPS can be achieved via a solvent-exchange method, where the solvent quality dictates droplet stability and the subsequent transformation kinetics into cylinders. Comparative studies with β/δ- and γ-substituted analogues reveal that the substitution position critically influences the chain mobility to undergo conformational ordering, thereby affecting the assembly rate and structural outcome. This work underscores LLPS as a versatile and powerful strategy for regulating the self-assembly pathways of BCPs, providing fundamental insights into non-equilibrium assembly processes and offering a robust platform for the design of functional polymeric nanomaterials with tailored hierarchical structures.