Transformation of RAFT Polymer End Groups into Nitric Oxide Donor Moieties: En Route to Biochemically Active...

Polymers with a terminal S-nitrosothiol moiety were synthesized by modifying the thiocarbonylthio end group formed by reversible addition-fragmentation chain transfer polymerization. Specifically, benzodithioate-terminated poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) was first synthesized by polymerizing OEGMA in the presence of 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid. Sequential treatment with hydrazine hydrate and a stoichiometric amount of nitrous acid resulted in the formation of S-nitrosothiol-terminated polymers. A similar approach was applied to block copolymers of POEGMA incorporating a domain of poly[(N,N-diisopropylamino)ethyl methacrylate], thus, enabling the preparation of pH responsive nitric oxide (NO)-releasing micelles. The micelles possessed substantially modified S-nitrosothiol loss kinetics compared to the hydrophilic homopolymer analogue. Moreover, thiol-triggered degradation of the S-nitrosothiol was significantly slower when the S-nitrosothiol was embedded in a micellar structure. These results demonstrate that it is possible to incorporate nitric oxide donor moieties directly onto a polymer chain end, enabling simple synthesis of biochemically active nanostructures.