Single-Chain Studies Reveal that Neutral Poly(2-ethyl-2-oxazoline) Exhibits Polyelectrolyte-like Behavior in Aqueous...

Poly-(2-ethyl-2-oxazoline) (PEtOx) exhibits excellent water solubility and biocompatibility comparable to polyethylene glycol (PEG). However, the underlying mechanisms behind these properties and its interactions with water molecules remain insufficiently understood, which limits its broader application. In this paper, by employing atomic force microscope-based single-molecule force spectroscopy (AFM-SMFS), the single-chain behaviors of PEtOx in different environments have been investigated, revealing a reduced extensibility observed in deionized (DI) water and KCl solutions of low concentrations (≤ 0.1 M) compared with that in nonane. Gel electrophoresis results indicate that PEtOx is positively charged under these conditions. These findings indicate that PEtOx exhibits polyelectrolyte-like behavior in DI water: (i) an increased stiffness compared to its inherent elasticity; (ii) a directional migration of polymers under the electric field. The possible reason for the polyelectrolyte-like behavior could be that the PEtOx chain is charged due to H-bonding with H₃O⁺. These findings suggest that PEtOx is another pseudo-polyelectrolyte (or supra-polyelectrolyte), similar to PEG. Given that proteins and nucleic acids are polyelectrolytes, it is reasonable to infer that the polyelectrolyte-like behavior of PEtOx may be one of the reasons for its good biocompatibility. It is anticipated that this discovery will lay the groundwork for further applications of PEtOx in biomaterials.