Anionic Oligo(ethylene glycol)-Based Molecular Brushes: Thermo- and pH-Responsive Properties

Anionic thermo- and pH-responsive copolymers were synthesized by photoiniferter reversible addition-fragmentation chain transfer polymerization (PI-RAFT). The thermo-responsive properties were provided by oligo(ethylene glycol)-based macromonomer units containing hydrophilic and hydrophobic moieties. The pH-responsive properties were enabled by the addition of 5-20 mol% of strong (2-acrylamido-2-methylpropanesulfonic) and weak (methacrylic) acids. Upon initiation by visible light at 470 nm and in the absence of radical initiators, yields from the ternary copolymers reached 94% in 2.5 h when the process was carried out in continuous flow mode using 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid as a light-sensitive RAFT agent. The polymers were characterized using size exclusion chromatography, IR and NMR spectroscopy, and differential scanning calorimetry. The copolymers featured a sufficiently high molecular weight (93-146 kDa) consistent with theoretical values and satisfactory dispersities in the range of 1.18-1.45. The pH-responsive properties were studied in deionized water, saline, and buffer solutions. Dramatic differences in LCST behavior were observed in strong and weak acid-based polyelectrolytes. The introduction of sulfonic acid units, even in very small amounts, completely suppressed the LCST transition in deionized water while maintaining it in the saline and buffer solutions, with a negligible LCST dependence on the pH. In contrast, the incorporation of weak methacrylic acid demonstrated a pronounced pH dependence. The peculiarities of micelle formation in aqueous solutions were investigated and critical micelle concentrations and their ability to retain pyrene, a hydrophobic drug model, were determined. It was observed that anionic molecular brushes formed small micelles with aggregation numbers of 1-2 at concentrations in the order of 10^-4 mg/mL. These micelles have a high ability to entrap pyrene, which makes them a promising tool for targeted drug delivery.