Role of Sequence-Length Distribution in Primary Crystal Nucleation of Poly[( <i>S</i> )-3-hydroxybutyrate- <i>co</i> -( <i>S</i> )-3-hydroxyvalerate)] Random Copolymers

Primary crystal nucleation is pivotal in polymer crystallization, dictating the semicrystalline morphology. Yet, the impact of sequence irregularities in random copolymers on this initial step is not fully understood due to challenges in probing nanoscale, transient nucleation events. Utilizing fast-scanning calorimetry (FSC) and polarized optical microscopy (POM), we probed how sequence-length distribution affects the thermodynamic barrier to primary crystal nucleation kinetics and nucleation density in cocrystallizable poly[(S)-3-hydroxybutyrate-co-(S)-3-hydroxyvalerate] (PHBV) random copolymers with about 14–25 mol % 3HV counits. Thermal analysis reveals that 3HV counits partially incorporate as defects into the 3HB crystal lattice (average defect free energy ≈ 2.08 kJ·mol–1). Kinetic analysis further demonstrates that the nucleation rate at higher incorporation of 3HV counits is governed by the competition between this heightened thermodynamic penalty and reduced diffusion constraints from the low glass transition temperature. The switch in nucleation kinetics from short-range diffusion-dominated to thermodynamically controlled behavior with increasing temperature, leads to a notable reduction in the b-axis lattice parameter. Meanwhile, the increasing 3HV counit incorporation expands the crystal lattice, elevates the thermodynamic free energy barrier to nucleation (ΔG*), and enlarges the requisite critical nucleus size (r*). Consequently, temperature-dependent spherulite density observations confirm a sequence-length selection mechanism: only sequences exceeding the critical length can nucleate, with the population of such effective sequences directly determining the final nucleation density. These results connect molecular-scale sequence-length distribution with nanoscale early-stage nucleation, offering mechanistic insight into random copolymer crystallization.