Synthesis, aqueous solution behavior and self-assembly of a dual pH/thermo-responsive fluorinated diblock terpolymer

Abstract

The synthesis of fluorinated dual-responsive block terpolymers via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization is presented. The resulting block terpolymers consist of a hydrophobic block which comprises an alternating copolymer of tert-butyl-2-trifluoromethacrylate (MAF-TBE) and vinyl acetate (VAc) (M_n = 9,800 g mol⁻¹, Đ = 1.31) and a hydrophilic block of temperature-responsive poly(N-isopropylacrylamide) (PNIPAM). Two P(VAc-alt-MAF-TBE)-b-PNIPAM block terpolymers, containing 37 and 61 mol% of NIPAM (with M_n = 16 600 g mol⁻¹, Đ = 1.13 and M_n = 22 400 g mol⁻¹, Đ = 1.28, respectively), were synthesized in good yields. Subsequent hydrolysis of the ester groups in the P(MAF-TBE-alt-VAc) segments resulted in the formation of double hydrophilic pH and temperature-responsive diblock terpolymers which demonstrated remarkable solution properties. The impact of the trifluoromethyl groups on the aqueous solution behavior of the diblock terpolymers was studied by monitoring the lower critical solution temperature (LCST) using UV/vis spectroscopy at different pH values (ranging from 9.5 to 2.5). This study revealed that the fluorinated moieties dictate the solvation of the terpolymers inducing attractive hydrophobic interactions which drove the system to phase separation. Additionally, other amphiphilic diblock terpolymers were prepared by extension of the P(VAc-alt-MAF-TBE) macromolecular chain transfer agent with hydrophilic poly(N,N-dimethylacrylamide) (PDMA) (M_n = 14 000 g mol⁻¹, Đ = 1.21 for 52 mol% PDMA and M_n = 19 000 g mol⁻¹, Đ = 1.45 for 79 mol% PDMA). Transmission electron microscopy measurements showed that the diblock terpolymers can self-assemble in aqueous solution to form various micellar or vesicular morphologies depending on the terpolymer composition and solution pH, rendering them attractive for drug delivery and in other biomedical applications.