The Chemistry of Poly(2‐oxazoline)s

Abstract

Research in the field of poly(2‐alkyl/aryl‐2‐oxazoline)s (PAOx) is rapidly expanding as this polymer class combines high synthetic versatility with good biocompatibility, opening up the way to highly functional (bio)materials. PAOx are prepared by living cationic ring‐opening polymerization (CROP) of 2‐oxazolines. The variety of 2‐oxazoline monomers that are readily available or can easily be synthesized allows for tuning of polymer properties and introduction of diverse functionalities. Moreover, thanks to the living nature of the CROP, well‐defined polymers with narrow molar mass distribution and high end‐group fidelity can be obtained. This article covers all aspects of PAOx ranging from the synthesis of 2‐oxazoline monomers, via an in‐depth discussion of the CROP mechanism to the synthesis and properties of functional PAOx (co)polymers. The presented research demonstrates that due to their structural adaptability and so‐called “stealth” behavior, PAOx are well‐suited for a range of biomedical applications, including polymer therapeutics, scaffolds for three‐dimensional cell culture, surface modification, matrix excipient for solid dispersions, and antimicrobial agents.The goal of this article is not to review all applications of PAOx, but to highlight key examples illustrating the numerous possibilities, broad application range and the general state‐of‐art use.

Chain and Step Growth Polymerizations of Cyclic Imino Ethers: From Poly(2‐oxazoline)s to Poly(ester amide)s

“…The access to tailor‐made macromolecular engineered polymers and their beneficial biomedical properties are two main reasons that POx have received significant attention in the last decade. From a chemistry point of view, the optimization of the polymerization conditions including temperature and solvents, and the synthesis of new initiators, terminating agents and monomers have been subject of numerous studies . The straightforward tuning of the polymer properties by changing the side chains of the polymers is one of the main advantages of this polymer class.…”

“…Nucleophiles such as carboxylic acids, amines, thiols, alcohols are also capable of ring‐opening Oxs/Ozs via a nucleophilic attack on the 5‐position of the Oxs/Ozs. This reaction does not only allow to terminate the living cationic ring‐opening polymerization (see Scheme A, termination step) but can also be used to form primary amides when reacting the CIE and the nucleophilic compound in an equimolar ratio (Scheme D). By using multifunctional CIEs and nucleophilic compounds, these reactions can also lead to a polyaddition (Scheme C).…”

Synthesis of Linear ABC Triblock Copolymers and Their Self‐Assembly in Solution

“…Cationic ring‐opening polymerization (CROP) enables to polymerize different monomers including cyclic amines and cyclic ethers. It is notably used to produce polyoxazolines . Like AROP, CROP is very sensitive to impurities and limited to specific solvents like acetonitrile, chlorobenzene, and nitromethane.…”

Poly(2-isopropenyl-2-oxazoline) Hydrogels for Biomedical Applications

“…37,46 They can be regarded as interesting new hydrogels for biomedical applications, as PAOx exhibit good biocompatibility, hydrophilicity, and enable orthogonal functionalization possibilities, which has been well documented in recent years. 18,35,37,[47][48][49][50][51][52] Nevertheless, up to date there is no polymer that fulfills all the requirements for an ideal hydrogel with respect to its chemical nature, biocompatibility and biodegradability, and the chemical bond forming events to create covalent cross-links. Consequently, finding and investigating other alternative polymers represent the focus of the ongoing research.…”