Poly(2‐Hydroxymethyl‐2‐oxazoline) as Super‐hydrophilic Antifouling Polymer

Non-ionic "super-hydrophilic" polymers generally possess non-fouling characteristics and can suppress non-specific interactions with blood proteins. Here, we revitalized a protected alcohol functionalized 2-oxazoline monomer, 2-acetoxymethyl-2-oxazoline and explored the possibility of making "super-hydrophilic" poly(2-oxazoline)s for biomedical applications. The synthesis of the 2-acetoxymethyl-2-oxazoline monomer and its cationic ring-opening homopolymerization and copolymerization kinetics are reported. The monomer showed unanticipated and intriguing reactivity during homopolymerization as it very slowly polymerizes at low temperature while the polymerization rate constant at high temperature is amongst the highest known values. Additionally, first order kinetic plots for the copolymerisation of AcOMeOx with EtOx at high temperature revealed that AcOMeOx is incorporated slower than EtOx confirming its lower nucleophilicity, while EtOx was accelerated in the copolymerization indicating chain-end activation by the ester side-chains. Subsequently, controlled hydrolysis of the resulting poly(2-acetoxymethyl-2-oxazoline) (PAcOMeOx) generates the alcohol (-OH) side chain functional poly(2-hydroxymethyl-2-oxazoline) (PHOMeOx). The PHOMeOx was found to be the most hydrophilic poly(2-oxazoline) reported to date revealing strong anti-fouling properties against serum protein during the cell association studies. Hence, the "super-hydrophilic" and anti-fouling PHOMeOx might be an interesting candidate to be explored in the area of polymeric drug and gene delivery as well as anti-fouling surfaces.