Avoiding compositional drift during the RAFT copolymerization of N-(2-hydroxypropyl)methacrylamide and N-acryloxysuccinimide: towards uniform platforms for post-polymerization modification

Controlled radical polymerization techniques such as RAFT allow fine control over polymer molecular weight and architecture. These techniques, however, do not eliminate compositional drifts in copolymerizations, which are the consequence of differences in monomer reactivity and can lead to compositionally non-uniform polymers that may hamper establishing structure-property relationships. One way to avoid compositional drifts is to use controlled monomer feeding techniques. Using the N-(2-hydroxypropyl)methacrylamide/N-acryloxysuccinimide (HMPA/NAS) comonomer pair for a first proof-of-concept, this manuscript reports an alternative approach to avoid compositional drifts and generate uniform copolymers by judicious selection of the initial monomer feed composition and controlling monomer conversion. Screening the copolymerization kinetics and copolymer composition of HPMA/NAS copolymers generated under various reaction conditions revealed that RAFT copolymerization of HPMA and NAS in DMF with an initial feed of 30 mol% NAS only resulted in a minimal compositional drift. While these reaction conditions are specific to the NAS/HPMA comonomer pair studied here, this approach may be applied to other comonomer pairs as well. The reactive NAS groups in a poly(HPMA-stat-NAS) copolymer obtained via this strategy could be post-modified with near-quantitative conversion with a amine-functionalized crown ether, which illustrates the versatility of this protocol to generate uniform reactive scaffolds for further post-polymerization modification.