Reversible Addition-Fragmentation Chain Transfer Aqueous Dispersion Polymerization of 4-Hydroxybutyl Acrylate Produces Highly Thermoresponsive Diblock Copolymer Nano-Objects

Abstract

The reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) using a poly(glycerol monomethacrylate) (PGMA) precursor is an important prototypical example of polymerization-induced self-assembly. 4-Hydroxybutyl acrylate (HBA) is a structural isomer of HPMA, but the former monomer exhibits appreciably higher aqueous solubility. For the two corresponding homopolymers, PHBA is more weakly hydrophobic than PHPMA. Moreover, PHBA has a significantly lower glass transition temperature (T _g) so it exhibits much higher chain mobility than PHPMA at around ambient temperature. In view of these striking differences, we have examined the RAFT aqueous dispersion polymerization of HBA using a PGMA precursor with the aim of producing a series of PGMA_57-300-PHBA_100-1580 diblock copolymer nano-objects by systematic variation of the mean degree of polymerization of each block. A pseudo-phase diagram is constructed using transmission electron microscopy to assign the copolymer morphology after employing glutaraldehyde to cross-link the PHBA chains and hence prevent film formation during grid preparation. The thermoresponsive character of the as-synthesized linear nano-objects is explored using dynamic light scattering and temperature-dependent rheological measurements. Comparison with the analogous PGMA _x -PHPMA _y formulation is made where appropriate. In particular, we demonstrate that replacing the structure-directing PHPMA block with PHBA leads to significantly greater thermoresponsive behavior over a much wider range of diblock copolymer compositions. Given that PGMA-PHPMA worm gels can induce stasis in human stem cells (see Canton et al., ACS Central Science, 2016, 2, 65-74), our findings are likely to have implications for the design of next-generation PGMA-PHBA worm gels for cell biology applications.

Scheme 1. Reaction Scheme for the RAFT Aqueous Solution Polymerization of GMA Using a PGMA₅₇ Precursor to Produce a Longer PGMA_x (x = 70–300) Stabilizer Block, Followed Immediately by the RAFT Aqueous Dispersion Polymerization of HBA at 30 °C to Obtain a Series of PGMA_x-PHBA_y Diblock Copolymer Nano-Objects

Figure 1

Conversion vs time curve (blue circles) and the corresponding semilogarithmic plot (red squares) obtained for the RAFT aqueous dispersion polymerization of HBA using a KPS/AsAc redox initiator at 30 °C when targeting PGMA₁₀₀-PHBA₆₅₀ diblock copolymer nano-objects at 20% w/w solids at a [PGMA₁₀₀]/[KPS] molar ratio of 10.

Figure 2

Evolution in z-average diameter and polydispersity determined by DLS studies during the synthesis of PGMA₁₀₀-PHBA₆₅₀ diblock copolymer nano-objects via RAFT aqueous dispersion polymerization of HBA using a KPS/AsAc redox initiator at 30 °C when targeting 20% w/w solids. Aliquots were extracted periodically over 60 min. [N.B. C, S, W, M, and V denote chains, spheres, worms, a mixed phase comprising worms and vesicles, and vesicles, respectively].

Figure 3

Representative TEM images obtained for aliquots extracted over 60 min during the synthesis of PGMA₁₀₀-PHBA₆₅₀ vesicles via RAFT aqueous dispersion polymerization of HBA, illustrating the progressive evolution in the copolymer morphology from spheres to worms to vesicles. In each case, the nano-object morphology was covalently stabilized at 0.1% w/w solids using excess GA cross-linker at 30 °C (to mimic the PISA synthesis conditions).

Figure 4

Evolution in diblock copolymer M_p and M_w/M_n with HBA conversion determined by DMF GPC (expressed against a series of poly(methyl methacrylate) calibration standards) during the RAFT aqueous dispersion polymerization of HBA using a KPS/AsAc redox initiator at 30 °C when targeting PGMA₁₀₀-PHBA₆₅₀ vesicles at 20% w/w solids using a [PGMA₁₀₀]/[KPS] molar ratio of 10. The dashed black line corresponds to the theoretical molecular weight for the PGMA₁₀₀-PHBA_x diblock copolymer chains.

Figure 5

(a) Master pseudo-phase diagram constructed for a series of PGMA_x-PHBA_y nano-objects after covalent stabilization at 20 °C using GA as a cross-linker. All syntheses involved the RAFT aqueous dispersion polymerization of HBA at 20% w/w solids at 30 °C. Each point represents the copolymer morphology assigned on the basis of DLS and TEM studies. Green circles indicate spheres, red triangles indicate worms, blue squares indicate vesicles, black filled diamonds indicate mixed sphere/worms, and gray circles indicate macroscopic precipitation. Representative TEM images obtained for (b) GA-cross-linked PGMA₁₀₀-PHBA₁₇₅ spheres, (c) GA-cross-linked PGMA₁₀₀-PHBA₃₀₀ worms, and (d) GA-cross-linked PGMA₁₂₅-PHBA₆₂₅ vesicles.

Figure 6

Variation in z-average diameter and polydispersity determined via DLS studies of a series of kinetically-trapped PGMA₃₀₀-PHBA_x spheres prepared at 30 °C when targeting a PHBA DP (x) ranging from 660 to 1580 at 20% w/w solids. [N.B. Targeting even higher PHBA DPs merely resulted in substantially incomplete HBA conversions (<90%) under the same conditions].

Figure 7

Temperature-dependent rheology studies of a 10% w/w aqueous dispersion of linear PGMA₁₀₀-PHBA₃₂₅ nano-objects recorded at an applied strain of 1.0% and an angular frequency of 1.0 rad s^–1: (a) storage (G′; green diamonds) and loss (G″; purple triangles) moduli; (b) complex viscosity (heating ramp = red data; cooling ramp = blue data). For each measurement, 2.0 min was allowed for thermal equilibration.

Figure 8

Temperature-dependent rheology studies of 20% w/w aqueous dispersions recorded at an applied strain of 1.0% and an angular frequency of 1.0 rad s^–1. Storage (G′ = green circles) and loss (G″ = purple squares) moduli observed during a heating ramp from 20 to 37 °C for the following linear nano-objects: (a) PGMA₇₀-PHBA₁₅₀, (b) PGMA₁₀₀-PHBA₂₁₀, and (c) PGMA₁₃₀-PHBA₂₇₀. (d) G′ values observed for PGMA₁₃₀-PHBA₂₇₀ nano-objects during heating (red diamonds) and cooling (blue triangles) cycles between 20 and 37 °C. For each measurement, 2 min was allowed for thermal equilibration.