Synthesis of Poly(N-isopropylacrylamide)−Poly(ethylene glycol) Miktoarm Star Copolymers via RAFT Polymerization and Aldehyde−Aminooxy Click Reaction and Their Thermoinduced Micellization

Abstract

A facile synthetic pathway to poly(N-isopropylacrylamide) (PNIPAM)−poly(ethylene glycol) (PEG) miktoarm star copolymers with multiple arms has been developed by combining reversible addition−fragmentation chain transfer (RAFT) polymerization and aldehyde−aminooxy “click” coupling reaction. Star PNIPAM with aldehyde functionalized core was initially prepared by the RAFT arm-first technique via cross-linking of the preformed linear macro-RAFT agents using a newly designed aldehyde-containing divinyl compound 6,6′-(ethane-1,2-diylbis(oxy))bis(3-vinylbenzaldehyde) (EVBA). It was then used as a multifunctional coupling agent for the subsequent formation of the second-generation PEG arms via the click coupling reaction between its aldehyde groups and aminooxy-terminated PEGs. The thermoresponsive micellization behavior of PNIPAM−PEG miktoarm star copolymer with different PEG arm numbers in water was also investigated. Opportunities are open for thermoinduced intermolecular or intramolecular micellization of PNIPAM−PEG miktoarm star copolymers via controlling the content ratio of PNIPAM and PEG, forming multimolecular micelles and unimolecular micelles, respectively.

Rapid UV Light‐Triggered Macromolecular Click Conjugations via the Use of o‐Quinodimethanes

“…The numerous applications of orthogonal conjugation chemistries especially in macromolecular science, bio-hybrid chemistry, and materials science have been reviewed by Hawker and coworkers, [1] Sumerlin and Vogt, [2] Schubert and co-workers [3] and by our group. [4] Examples include the copper catalyzed azide-alkyne cycloaddition, [5] thiol-ene [6] and thiol-yne chemistries, [7] oxime formation, [8] and Diels-Alder. [9] The rising interest and developments in ultra-rapid and biocompatible conjugation approaches, including copperfree azide-alkyne cycloadditions, [10] and inverse electron demand Diels-Alder, [11] have also been documented.…”

Synthesis of Star Polymers by RAFT Polymerization as Versatile Nanoparticles for Biomedical Applications

“…Specifically, the formation of pH-sensitive bonds between aldehyde and aminooxy groups has been explored to fabricate miktoarm star polymers. [38,39] Star polymers have also been used to deliver the ubiquitous cellular signalling molecule nitric oxide (NO) and so prevent biofilm formation. [40] To this end, a novel NO delivery agent was synthesized via the integration of NO donor molecules into star polymers.…”

Water-Soluble Stimuli Responsive Star-Shaped Segmented Macromolecules

“…Double hydrophilic PNIPAM n -PEG m miktoarm star copolymers, were synthesized by combining reversible addition fragmentation chain transfer (RAFT) arm-first technique and aldehyde-aminooxy click reaction [32]. The synthetic method allowed the control of the second generation of PEG arms by varying the feed ratio of the aldehyde-aminooxy click reaction.…”

“…PEG and PNIPAM arms are denoted with magenta and light blue colors, respectively. The scheme was inspired by [32].…”

“…A novel amphiphilic block-random star terpolymer bearing 32 arms consisted of MMA blocks close to the star core and DEAEMA/MAA outer random copolymer blocks, core[MMA 48 -b-(DEAEMA 31 co-MAA 26 ) 32 , was prepared by group transfer polymerization (GTP) and studied in aqueous solutions as a function of pH [63]. Due to the high number of arms and the polyampholyte character of the outer blocks, DEAEMA 31 -co-MAA 26 , the star terpolymer formed unimolecular micelles with changeable charge density and sign, simply by varying pH.…”