Jacob G. Ray

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.

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.

Stimuli-Responsive Peptide-Based ABA-Triblock Copolymers: Unique Morphology Transitions With pH

We report the synthesis and solution characterization of poly(L-lysine)-b-poly(propylene oxide)-b-poly(L-lysine) (KPK) triblock copolymers with high lysine weight fractions (>75 wt%). In contrast to PK diblock copolymers in this composition range, KPK triblock copolymers exhibit morphology transitions as a function of pH. Using a combination of light-scattering and microscopy techniques, we demonstrate spherical micelle-vesicle and spherical micelle-disk micelle transitions for different K fractions. We interpret these morphology changes in terms of the energy penalty associated with folding the core P block to form a spherical micelle in relation to the interfacial curvature associated with different charged states of the K block.

Peptide-Based Lipid Mimetics With Tunable Core Properties via Thiol-Alkyne Chemistry

Thiol–alkyne chemistry is utilized to produce peptide-based A2B star polymers. This topography resembles a phospholipid where the polypeptide B block represents a functional, polar head group and the A blocks represent lipophilic units. We utilize a convergent, modular approach to produce lipid mimetics through conjugation of poly(L-glutamic acid) with three different lipophilic moieties (octadecane, cholesterol and polyhedral oligomeric silsesquioxane). All samples are shown to self-assemble in aqueous solution into pH-responsive vesicles. The self-assembly and pH-responsiveness were characterized using circular dichroism spectroscopy and light scattering. Detailed light scattering experiments determined that the aggregation number of the vesicles remains nearly constant as a function of pH, suggesting that the pH-responsiveness is a result of both the helix–coil transition as well as a change in chain packing at the vesicle interface.

Temperature-induced ordering and gelation of star micelles based on ABA triblocks synthesized via aqueous RAFT polymerization

The reversible formation of ordered physical gels from stimuli-responsive ABA [A = poly(N,N-dimethylacrylamide) (PDMA), B = poly(N-isopropylacrylamide) (PNIPAM)] triblock copolymers is investigated utilizing dynamic light scattering, small angle X-ray scattering, and low-shear rheometry. As the temperature is increased above the phase transition temperature of the PNIPAM segment, triblock copolymers under a critical molecular weight are capable of packing into body-centered cubic arrays. Rheometric tests indicate that the storage moduli of the gels at 50 °C are inversely related to the molecular weight of the polymer.

Endolytic, pH-Responsive HPMA-b-(L-Glu) Copolymers Synthesized via Sequential Aqueous RAFT and Ring-Opening Polymerizations

A facile synthetic pathway for preparing block copolymers with pH-responsive L-glutamic acid segments for membrane disruption is reported. Aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization was first used to prepare biocompatible, nonimmunogenic poly[N-(2-hydroxypropyl)methacrylamide]. This macro chain transfer agent (CTA) was then converted into a macroinitiator via simultaneous aminolysis and thiol-ene Michael addition using the primary amine substituted N-(3-aminopropyl)methacrylamide. This macroinitiator was subsequently utilized in the ring-opening polymerization of the N-carboxyanhydride monomer of γ-benzyl-L-glutamate. After deprotection, the pH-dependent coil-to-helix transformations of the resulting HPMA-b-(L-Glu) copolymers were monitored via circular dichroism spectroscopy. HPMA segments confer water solubility and biocompatibility while the L-glutamic acid repeats provide reversible coil-to-helix transitions at endosomal pH values (~5-6). The endolytic properties of these novel [HPMA-b-(L-Glu)] copolymers and their potential as modular components in drug carrier constructs was demonstrated utilizing red blood cell hemolysis and fluorescein release from POPC vesicles.