Interplay of self-assembly and sequence formation in irreversible step-growth copolymerization

The phase behavior and material properties of copolymers are intrinsically dependent on their primary comonomer sequences. Achieving precise control over monomer sequence in synthetic copolymerizations is challenging, as sequence is determined not only by the reaction conditions and the properties of the reactants but also by the statistical nature of the copolymerization process itself. Mayo-Lewis reactivity ratios are often used to predict copolymer composition and sequence and are based on ratios of static reactivity constants. However, prior results have demonstrated that in a generic, solution-based step-growth A,B-copolymerization, relatively weak non-bonded attractions between certain monomer pairs can induce emergent microphase separations. Such polymerization-driven separations lead to deviations from standard kinetics due to the emergent heterogeneities in reactant concentrations, which can also cause significant shifts in the resulting copolymer sequences. Previously, these effects were observed in systems where the activation energies were equal for all reaction pathways, that is, between all monomer pair combinations, and all the simulations start from the systems composed of only unbound monomers. In this work, we explored the combined effects of differences in both activation energies and non-bonded attractions between monomers on copolymerization kinetics and sequence formation and examined the sequences produced within this same step-growth copolymerization model. Moreover, we explore the effects of adding pre-formed seed oligomers on copolymerization kinetics and sequence formation, which could alter the nucleation phase of polymerization-driven self-assembly and nematic alignments. We found that the resulting sequences depend on a complex interplay of monomer attractions, activation energies, chain flexibility, solvent viscosity, and the sequences of the added seed oligomers. By carefully tuning those parameters, through comonomer selection, chemical modification, choice of solvent, and the addition of pre-formed seed oligomer, synthetic approaches could be devised to intentionally bias the formation of certain sequences with uniform molecular weights. These findings provide insight into the complex interplay between sequence and nascent oligomer phase behavior, highlighting the potential for exploiting emergent phase properties in the informed design of advanced sequence-biased materials.