Branching Architecture Enhances Polyion Complex Formation beyond Overall Charge under Weakly Cationic Conditions

Abstract Branched polyelectrolytes form more stable polyion complexes (PICs) than their linear counterparts, yet whether this reflects an intrinsic effect of architecture or merely the higher overall charge that usually accompanies branching has remained unresolved. Here, we address this question using a series of pH-responsive polyzwitterions, poly(glutamate) derivatives bearing ethylenediamine-based carboxybetaine side chains (PGlu(DET-Car)). Within this platform, the number of arms was designed to be varied while maintaining identical side-chain chemistry and comparable overall charge. The stepwise protonation of the ethylenediamine moieties generates a weakly cationic state over the pH range of 6–7. In this weakly charged regime, the dominant contribution of net charge is minimized, allowing the subtle effects of molecular architecture on electrostatic interactions to be resolved. We find that increasing the number of arms markedly enhances interactions with flexible polyanions, whereas no such enhancement occurs for a rigid low-molecular-weight anionic probe. These results establish that regions of locally elevated charge density, which tend to form within branched architectures, promote cooperative, multivalent interactions that are inaccessible to linear chains of equivalent overall charge. The molecular architecture thus represents an independent design parameter for PIC formation, complementary to overall charge and chain length.