Abhijeet P. Bapat

Dynamic-Covalent Macromolecular Stars with Boronic Ester Linkages

Macromolecular stars containing reversible boronic ester linkages were prepared by an arm-first approach by reacting well-defined boronic acid-containing block copolymers with multifunctional 1,2/1,3-diols. Homopolymers of 3-acrylamidophenylboronic acid (APBA) formed macroscopic dynamic-covalent networks when cross-linked with multifunctional diols. On the other hand, adding the diol cross-linkers to block copolymers of poly(N,N-dimethylacrylamide (PDMA))-b-poly(APBA) led to nanosized multiarm stars with boronic ester cores and PDMA coronas. The assembly of the stars under a variety of conditions was considered. The dynamic-covalent nature of the boronic ester cross-links allowed the stars to reconfigure their covalent structure in the presence of monofunctional diols that competed for bonding with the boronic acid component. Therefore, the stars could be induced to dissociate via competitive exchange reactions. The star formation-dissociation process was shown to be repeatable over multiple cycles.

Protein conjugation of thermoresponsive amine -reactive polymers prepared by RAFT

Reversible addition–fragmentation chain transfer (RAFT) of N-isopropylacrylamide with a chain transfer agent containing an activated-ester moiety was employed to prepare well-defined temperature-responsive polymers for conjugation to amine-containing proteins. Bioconjugation efficiency of the polymers with lysozyme was investigated as a function of stoichiometry, polymer molecular weight, and reaction pH. The resulting polymer–protein conjugates retained the temperature-responsive nature of the original polymers.

Dynamic-covalent nanostructures prepared by Diels–Alder reactions of styrene-maleic anhydride-derived copolymers obtained by one-step cascade block copolymerization

Macromolecular star formation by Diels–Alder chemistry resulted in dynamic nanomaterials capable of reversibly demonstrating the properties of both linear and highly branched macromolecules. Well-defined block copolymers of maleic anhydride (MAn) and styrene [poly(styrene-alt-MAn)-b-polystyrene (P(S-alt-MAn)-b-PS)] were prepared via a one-pot cascade approach by reversible addition–fragmentation chain transfer (RAFT) polymerization. Subsequent ring opening of the anhydride groups in the P(S-alt-MAn) segments by amidation with furfurylamine led to the formation of block copolymers with pendant furan functionality. Diels–Alder reactions of the furan-functional block copolymer with a bismaleimide crosslinker resulted in core-crosslinked stars by an arm-first approach. Star-like structures were also prepared by first allowing the furan-functional block copolymers to pre-assemble into polymeric micelles in a solvent selective for the polystyrene block. Subsequent addition of a bismaleimide and heating to allow the Diels–Alder reaction resulted in core-crosslinked micelles with similar structures to the polymeric stars prepared by the arm-first approach. Regardless of the synthetic approach employed, the thermoreversibility of the Diels–Alder linkages within the cores rendered the stars/crosslinked micelles dynamic-covalent, as demonstrated by their ability to reversibly dissociate back to the individual arms on heating.

Oximes as reversible links in polymer chemistry: dynamic macromolecular stars

We demonstrate the formation of oxime-functional macromolecular stars that are able to dissociate and reconstruct themselves upon application of a stimulus. The reversible nature of the oxime bond in the presence of externally added alkoxyamines or carbonyl compounds enables reconfiguration via competitive exchange. Reversible addition–fragmentation chain transfer (RAFT) polymerization was utilized to prepare well-defined amphiphilic block copolymers in which a hydrophobic keto-functional block allowed self-assembly into micelles in water. Adding a difunctional alkoxyamine small molecule to these solutions resulted in crosslinking of the micelles to yield macromolecular stars. The reversible nature of the O-alkyl oxime linkages was demonstrated via competitive exchange with excess of carbonyl compounds or monofunctional alkoxyamine under acidic conditions and at elevated temperatures to result in dissociation of the stars to unimolecular oxime-functional polymer chains.

Switchable 19F MRI polymer theranostics: towards in situ quantifiable drug release

A switchable polymeric 19F magnetic resonance imaging (MRI) contrast agent was synthesised whereby the transverse (T2) relaxation times increased as a therapeutic was released from a hyperbranched polymer (HBP) scaffold. The HBP comprised of poly(ethyleneglycol) monomethyl ether methacrylate (PEGMA), a fluorinated monomer (trifluoroethyl acrylate), and a suitable monomer for post-conjugation of a drug molecule. Three different hydrophobic drugs were investigated during design of the theranostic; doxorubicin (DOX) and docetaxel (DTX) were conjugated to the HBPs through an acid-cleavable hydrazone linkage, while camptothecin (CPT) was integrated into the HBP via polymerisation of a self-immolative disulphide-linked monomer. 19F NMR relaxometry measurements showed that the increase in hydrophobicity caused by the incorporation of the therapeutic drug led to a decrease in 19F T2 relaxation times and decrease in image intensity. However, upon drug release, the hydrophobicity of the HBP decreased which in turn led to improved mobility of the fluorinated moieities. This was manifest in a restoration of longer 19F T2 relaxation times and an increased image intensity compared to the drug-loaded polymer. This work provides a basis for a MRI contrast agent capable of quantifying in situ drug release.