pH‐Responsive Non‐Ionic Diblock Copolymers: Ionization of Carboxylic Acid End‐Groups Induces an Order–Order Morphological Transition

Abstract

A carboxylic acid based reversible additionfragmentation transfer (RAFT) agent is used to prepare gels composed of worm-like diblock copolymers using two non-ionic monomers, glycerol monomethacrylate (GMA) and 2-hydroxypropyl methacrylate (HPMA). Ionization of the carboxylic acid end-group on the PGMA stabilizer block induces a worm-to-sphere transition, which in turn causes immediate degelation. This morphological transition is fully reversible as determined by TEM and rheology studies and occurs because of a subtle change in the packing parameter for the copolymer chains. A control experiment where the methyl ester derivative of the RAFT agent is used to prepare the same diblock copolymer confirms that no pH-responsive behavior occurs in this case. This end-group ionization approach is important for the design of new pH-responsive copolymer nano-objects as, unlike polyacids or polybases, only a minimal amount of added base (or acid) is required to drive the morphological transition.

Characterization of Diblock Copolymer Order-Order Transitions in Semidilute Aqueous Solution Using Fluorescence Correlation Spectroscopy

“…Again, this indicates a worm-to-sphere transition, in this case caused by a rather subtle end-group ionization effect. [ 27 ] The critical pH observed for this worm-to-sphere transition (pH 4.2) is in good agreement with that indicated for closely related HOOC-PGMA 56 -block -PHPMA 155 diblock copolymer nanoparticles by rheology measurements [ 27 ] and also dynamic light scattering (DLS) studies of the HOOC-PGMA 43 -block -P(HPMA 119 -co -GlyMA 1 ) nanoparticles (see Figure S4 in the Supporting Information). When considering the selfconsistency of the observed thermoresponsive behavior, it should be noted that the solution pH for the latter formulation was pH 3.9.…”

“…[ 27 ] This nearuniform water-soluble macro-CTA was then chain-extended via RAFT aqueous dispersion copolymerization of HPMA and GlyMA (targeting approximately one epoxy group per copolymer chain) at 70 °C at approximately pH 3.5. 1 H NMR studies confi rmed that a very high HPMA conversion (>99%) was achieved at 10% solids, while gel permeation chromatography analysis ( N , N ′-dimethylformamide eluent) indicated a relatively high blocking effi ciency (>90%) and a relatively low copolymer disper-…”

“…[ 9 ] However, very recently it was reported that end-group chemistry can be exploited in order to introduce pH-dependent behavior in addition to such thermoresponsive behavior (Figure 1 b). [ 27 ] More specifi cally, a carboxylic acid-based RAFT chain transfer agent (CTA) was utilized in the preparation of the hydrophilic PGMA block in order to confer pH-dependent behavior on the nonionic diblock copolymer chains. [ 27 ] Thus raising the solution pH above the pK a of 4.7 causes ionization of the terminal carboxylic acid group and hence introduces anionic charge, which in turn leads to a pH-induced worm-to-sphere transition ( Figure 2 ).…”

“…[ 27 ] More specifi cally, a carboxylic acid-based RAFT chain transfer agent (CTA) was utilized in the preparation of the hydrophilic PGMA block in order to confer pH-dependent behavior on the nonionic diblock copolymer chains. [ 27 ] Thus raising the solution pH above the pK a of 4.7 causes ionization of the terminal carboxylic acid group and hence introduces anionic charge, which in turn leads to a pH-induced worm-to-sphere transition ( Figure 2 ). [ 27 ] Spherical diblock copolymer nanoparticles produce a low-viscosity, freefl owing solution that can be readily sterilized via ultrafi ltration, which has important biomedical implications.…”

“…[ 27 ] Thus raising the solution pH above the pK a of 4.7 causes ionization of the terminal carboxylic acid group and hence introduces anionic charge, which in turn leads to a pH-induced worm-to-sphere transition ( Figure 2 ). [ 27 ] Spherical diblock copolymer nanoparticles produce a low-viscosity, freefl owing solution that can be readily sterilized via ultrafi ltration, which has important biomedical implications. [ 9 ] Aqueous dispersions of worms are much more viscous, with freestanding gels being formed in semidilute aqueous solution as a result of multiple inter-worm contacts.…”