# Hydrophilic Poly(Iminopyridinium Ylide)s: Defining a New Chemical Space for Poly(ylide)s

## TL;DR

This paper introduces a new type of water-loving polymer that is stable and interacts minimally with biomolecules, making it useful for biomedical applications.

## Contribution

The paper introduces poly(iminopyridinium ylide) as a novel charge-neutral hydrophilic polymer with unique biomedical properties.

## Key findings

- PIPY is soluble in water and stable across a wide pH range.
- PIPY shows minimal binding to biomolecules like bovine serum albumin and lysozyme.
- PIPY prevents insulin fibrillation, indicating its potential as a protein-stabilizing material.

## 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.

Poly(iminopyridinium ylide) (PIPY) is reported as an overall charge‐neutral hydrophilic polymer with good water‐solubility, stability across physiologically relevant pH levels, and minimal biomolecular interactions. PIPY shows prevention of insulin fibrillation, which highlights its protein‐stabilizing capacity. Synthesized via post‐polymerization modification, PIPY emerges as a versatile polymer platform for nanomedical and biomedical applications.