Abstract
Rising hypersensitivity to PEG and accelerated blood clearance highlight the need for alternative charge-neutral hydrophilic polymers. Poly(ylide)s represent a class of hydrophilic polymers with biocompatibility and antifouling properties. Here, we explore poly(iminopyridinium ylide) (PIPY) as a versatile nano- and biomedical building block. PIPY is synthesized via post-polymerization modification of poly(pentafluorophenyl acrylate), maintaining a narrow molecular weight distribution. PIPY's structure was confirmed by NMR, FTIR, and SEC. PIPY is soluble in water, saline, MeOH, and DMSO, and remains stable from strongly acidic to physiological pH. Critical aggregation concentration and DOSY NMR measurements indicate an anti-polyelectrolyte effect and minimal responsiveness to apolar environments, respectively. Notably, PIPY exhibits minimal, entropically driven binding to biomolecules such as bovine serum albumin and lysozyme. This low interaction is critical for its ability to prevent insulin fibrillation upon heating, suggesting utility as a protein-stabilizing matrix. These combined properties position PIPY as a promising material for future bio- and nanomedical applications.