RESUMEN
For about the last ten years, poly(2-oxazoline)s have attracted significant attention as potential material for biomedical applications in, e.g., drug delivery systems, tissue engineering and more. Commonly, the synthesis of poly(2-oxazoline)s involves problematic organic solvents that are not ideal from a safety and sustainability point of view. In this study, we investigated the cationic ring-opening polymerization of 2-ethyl-2-oxazoline and 2-butyl-2-oxazoline using a variety of initiators in the recently commercialized "green" solvent dihydrolevoglucosenone (DLG). Detailed 1H NMR spectroscopic analysis was performed to understand the influence of the temperature and concentration on the polymerization process. Size exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were performed to determine the molar mass of the resulting polymers. Our work shows clearly that the solvent is not inert under the conditions typically used for the cationic ring-opening polymerization, as evidenced by side products and limited control over the polymerization. However, we could establish that the use of the 2-ethyl-3-methyl-2-oxazolinium triflate salt as an initiator at 60 °C results in polymers with a relatively narrow molar mass distribution and a reasonable control over the polymerization process. Further work will be necessary to establish whether a living polymerization can be achieved by additional adjustments.
RESUMEN
Poly(2-oxazoline)s have been investigated for decades as biomaterials. Pioneering early work suggested that hydrophilic poly(2-oxazoline)s are comparable to poly(ethylene glycol) regarding their potential as biomaterials, but the ready commercial availability of the latter has led to its meteoric rise to become the gold standard of hydrophilic synthetic biomaterials. In contrast, poly(2-oxazoline)s almost fell into oblivion. However, in the last decade, this family of polymers has gained much more interest in general and as biomaterials in particular. The rich chemistry and comparably straightforward synthesis of poly(2-oxazoline)s gives many opportunities for tailoring the properties of the resulting biomaterials, allowing the chemist to explore new conjugation chemistry, and to fine-tune the molar mass, hydrophilic-lipophilic balance as well as architecture. Thus, the wide range of demands for various applications of biomaterials can be suitably addressed. This review aims to give a comprehensive and critical update of the development of poly(2-oxazoline) based biomaterials, focusing on the last 5 years, which have seen an explosive increase of interest. We believe that the research regarding this diverse family of polymers will remain strong and will keep growing, in particular after the promising first-in-human studies of a poly(2-oxazoline) drug conjugate. This review aims at researchers and students new to this polymer family and seasoned poly(2-oxazoline) experts alike and attempts to showcase how the chemical diversity of poly(2-oxazoline)s allows a relatively facile and broad access to biomaterials of all kinds.