• 2-oxazine
• 2-oxazoline
• curcumin
• drug
• gradient copolymers

Poly(2-oxazoline)s and, recently, also poly(2-oxazine)s have gained increasing attention for biomedical applications. The homopolymerization of these two cyclic imino ether monomers through cationic ring-opening polymerization have been extensively reported. On the other side not so much data have been published about the copolymerization of these two different monomers. We demonstrate with this study that the statistical copolymerization of 2-oxazines with 2oxazolines monomers can lead with a single step reaction to the synthesis of amphiphilic gradient copolymers. We report for the first time the statistical copolymerization of 2-npropyl-2-oxazine (nPrOzi) and 2-nbutyl-2-oxazine (nBuOzi) with 2-methyl-2-oxazoline (MeOx) or 2-ethyl-2-oxazoline (EtOx). These resulting gradient copolymers are the combination of the structural modularity of poly(2-oxazoline)s with the surprisingly biological properties of poly(2-oxazine)s. In all copolymerizations was found that nPrOzi and nBuOzi showed a higher interaction in the copolymeritazion than in the homopolymerization. This behavior was explained on the basis of a kinetic study revealing that a combination of electronic and steric effects reverse the monomer incorporation in the statistical copolymerization compared to the homopolymerizations. For all gradient copolymers, prepared with different molar ratios, we studied the self-assembly properties in an aqueous environment as well as the thermoresponsive characteristics, as a confirmation of their potential as stimuli-responsive nonionic surfactants for various applications, especially biomedical.