Tuning the sugar‐response of boronic acid block copolymers

Abstract

A detailed study of the pH‐ and sugar‐responsive behavior of poly(3‐acrylamidophenylboronic acid pinacol ester)‐b‐poly(N,N‐dimethylacrylamide) (PAPBAE‐b‐PDMA) block copolymers is presented. Reversible addition‐fragmentation chain transfer (RAFT) polymerization of the pinacol ester of 3‐acrylamidophenylboronic acid resulted in homopolymers with molecular weights between 12,000 and 37,000 g/mol. The resulting homopolymers were employed as macro‐chain transfer agents during the polymerization of N,N‐dimethylacrylamide (DMA). Successful chain extension and removal of the pinacol protecting groups to yield poly(3‐acrylamidophenylboronic acid)‐b‐PDMA (PAPBA‐b‐PDMA) with free boronic acid moieties resulted in pH‐ and sugar‐responsive block copolymers that were subsequently investigated for their behavior in aqueous solution. The PAPBA‐b‐PDMA block copolymers were capable of solution self‐assembly due to the PAPBA block being water‐insoluble below its pKa. The resulting aggregates were demonstrated to solubilize and release model hydrophobic compounds, as demonstrated by fluorescence studies. Dissociation of the aggregates was induced by raising the pH above the pKa of the boronic acid residues or by adding sugars capable of forming boronate esters. Aggregate size, dissociation kinetics, and the effect of various sugars were considered. The critical sugar concentration needed to induce aggregate dissociation was tuned by incorporation of hydrophilic DMA units within the PAPBA responsive segment to yield PDMA‐b‐poly(3‐acrylamidophenylboronic acid‐co‐DMA) block copolymers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

In situsynthesis of ABA triblock copolymer nanoparticles by seeded RAFT polymerization: Effect of the chain length of the third a block on the triblock copolymer morphology

“…From the linear ln([ M ] 0 /[ M ])‐time plot shown in Figure (B), the pseudo‐first‐order kinetics of the seeded RAFT polymerization just like a general homogeneous RAFT polymerization is concluded. This is not surprised, since the monomer of DMA and the newly‐formed third block of PDMA are soluble in the polymerization medium of methanol, and therefore the seeded RAFT polymerization runs similarly with the homogeneous solution RAFT polymerization . Figure (C) shows the GPC traces of the PDMA‐ b ‐PS‐ b ‐PDMA triblock copolymers synthesized at different polymerization time (or monomer conversion), from which the molecular weight M n,GPC and PDI of the triblock copolymer are obtained.…”

Responsive Boronic Acid-Decorated (Co)polymers: From Glucose Sensors to Autonomous Drug Delivery

“…The reversible, glucose-induced dissociation was reported a year later for a P(DMA)- block -P( m APBA) showing uniform micellar like aggregates (D = 35 nm) at a pH of 8.7, which dissociate upon addition of 45 mM of d -Glu as measured by dynamic light scattering (DLS) [18]. The kinetics of the dissociation of these micelles were shown to be dependent on block copolymer structure, pH and the identity of the added sugar [19]. Similar amphiphilic block-copolymers were reported through the use of an mPEG-functionalized macro-chain transfer agent for the RAFT polymerization of 4-VBA [20].…”

“…The addition of d -Glu will release the phenyl boronic acid as a boronate ester, leaving behind a diol on the polymeric backbone, which increases the hydrophilicity of the inner micellar core [43,44,45]. Various other BA-containing block copolymers, for example including PDMA- block -P m APBA, showed the release of physically absorbed Nile Red in the micelle core in response to increasing pH or added glucose/fructose [19]. More complex release structures can be made by fine tuning the copolymer composition.…”

Triple responsive block copolymers combining pH‐responsive, thermoresponsive, and glucose‐responsive behaviors

“…The equilibrium between bound and free glucose is driven by a number of factors, including the p K a of the boronic acid, the p K a of the diol, and the diol dihedral angle, with the ratio of bound to free glucose generally increasing with decreasing p K a of the boronic acid. While phenylboronic acid has a p K a value near 9.0, the acidity of other arylboronic acids depends on the substituents on the aromatic ring, with electron‐withdrawing groups reducing the p K a . In this work, we sought to exploit the diol‐ and pH‐responsive nature of boronic acid moieties to tune the thermal behavior of temperature‐responsive polymers in aqueous solution.…”

“…Boronic acids and esters have been incorporated into a number of different macromolecular architectures, but controlled‐release applications have primarily relied on the synthesis of boronic acid‐containing block copolymers . The solution self‐assembly of such block copolymers allows for the sequestration of materials into the interior of the nanostructures, potentially providing protection from degradation by the surrounding environment or preserving biological activity while simultaneously increasing circulation lifetime in the blood.…”