Azlactone-functionalized Polymer Research Articles

Photo-controlled organocatalyzed radical polymerization synthesis of well-defined azlactone-functionalized polymers and its (bio)conjugated application

Well-defined azlactone-functionalized polymers have emerged as highly valuable precursors for the synthesis of (bio)molecules-conjugated materials. The development of polymerization process working at moderate temperature or ambient temperature and without use of metal catalysts or odorous agents for the synthesis of azlactone-functionalized polymers would be attractive, particularly in biomedical applications. In the present study, we have successfully copolymerized 2-vinyl-4,4-dimethylazlactone (VDM) and methacrylate monomers such as methyl methacrylate and poly(ethylene glycol) methyl ether methacrylate (mPEGMA) by photoinduced reversible complexed mediated polymerization (photo-RCMP). The polymerization was conducted at a wavelength of 365 nm and was well controlled with an initial ratio of VDM as high as of 20 mol%. The copolymer molecular weight and its dispersity (Ð < 1.3) was well controlled during the whole process and the system was perfectly a photo-switchable “on/off” system with no polymerization took place when the system was not irradiated. In addition, the ability of the resulting amine-reactive copolymer to be engaged in post-polymerization modifications was demonstrated using furfurylamine and l-carnosine.

Protein-Polymer Conjugates Synthesized Using Water-Soluble Azlactone-Functionalized Polymers Enable Receptor-Specific Cellular Uptake toward Targeted Drug Delivery.

Conjugation of proteins to drug-loaded polymeric structures is an attractive strategy for facilitating target-specific drug delivery for a variety of clinical needs. Polymers currently available for conjugation to proteins generally have limited chemical versatility for subsequent drug loading. Many polymers that do have chemical functionality useful for drug loading are often insoluble in water, making it difficult to synthesize functional protein-polymer conjugates for targeted drug delivery. In this work, we demonstrate that reactive, azlactone-functionalized polymers can be grafted to proteins, conjugated to a small-molecule fluorophore, and subsequently internalized into cells in a receptor-specific manner. Poly(2-vinyl-4,4-dimethylazlactone), synthesized using reversible addition-fragmentation chain transfer polymerization, was modified post-polymerization with substoichiometric equivalents of triethylene glycol monomethyl ether to yield reactive water-soluble, azlactone-functionalized copolymers. These reactive polymers were then conjugated to proteins holo-transferrin and ovotransferrin. Protein gel analysis verified successful conjugation of proteins to polymer, and protein-polymer conjugates were subsequently purified from unreacted proteins and polymers using size exclusion chromatography. Internalization experiments using a breast cancer cell line that overexpresses the transferrin receptor on its surface showed that the holo-transferrin-polymer conjugate was successfully internalized by cells in a mechanism consistent with receptor-mediated endocytosis. Internalization of protein-polymer conjugate demonstrated that the protein ligand maintained its overall structure and function following conjugation to polymer. Our approach to protein-polymer conjugate synthesis offers a simple, tailorable strategy for preparing bioconjugates of interest for a broad range of biomedical applications.

Layer-by-Layer Assembly of Amine-Reactive Multilayers Using an Azlactone-Functionalized Polymer and Small-Molecule Diamine Linkers.

We report the reactive layer-by-layer assembly of amine-reactive polymer multilayers using an azlactone-functionalized polymer and small-molecule diamine linkers. This approach yields cross-linked polymer/linker-type films that can be further functionalized, after fabrication, by treatment with functional primary amines, and provides opportunities to incorporate other useful functionality that can be difficult to introduce using other polyamine building blocks. Films fabricated using poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) and three model nondegradable aliphatic diamine linkers yielded reactive thin films that were stable upon incubation in physiologically relevant media. By contrast, films fabricated using PVDMA and varying amounts of the model disulfide-containing diamine linker cystamine were stable in normal physiological media, but were unstable and eroded rapidly upon exposure to chemical reducing agents. We demonstrate that this approach can be used to fabricate functionalized polymer microcapsules that degrade in reducing environments, and that rates of erosion, extents of capsule swelling, and capsule degradation can be tuned by control over the relative concentration of cystamine linker used during fabrication. The polymer/linker approach used here expands the range of properties and functions that can be designed into reactive PVDMA-based coatings, including functionality that can degrade, erode, and undergo triggered destruction in aqueous environments. We therefore anticipate that these approaches will be useful for the functionalization, patterning, and customization of coatings, membranes, capsules, and interfaces of potential utility in biotechnical or biomedical contexts and other areas where degradation and transience are desired. The proof of concept strategies reported here are likely to be general, and should prove useful for the design of amine-reactive coatings containing other functional structures by judicious control of the structures of the linkers used during assembly.

Amine-Reactive Azlactone-Containing Nanofibers for the Immobilization and Patterning of New Functionality on Nanofiber-Based Scaffolds.

We report the design of amine-reactive polymer nanofibers and nonwoven reactive nanofiber mats fabricated by the electrospinning of azlactone-functionalized polymers. We demonstrate that randomly oriented nanofibers fabricated using a random copolymer of methyl methacrylate and 2-vinyl-4,4-dimethylazlactone contain intact and reactive azlactone groups that can be used to introduce new chemical functionality and modulate important interfacial properties of these materials (e.g., wetting behaviors) by postfabrication treatment with primary amine-based nucleophiles. The facile and "click-like" nature of these reactions permits functionalization under mild conditions without substantial changes to nanofiber or mat morphologies. This approach also enables the patterning of new functionality on mat-coated surfaces by treatment with bulk solutions of primary amines or by using methods such as microcontact printing. Further, these reactive mats can also, themselves, be contact-transferred or "printed" onto secondary surfaces by pressing them into contact with other amine-functionalized objects. Finally, we demonstrate that functionalization with hydrophobic amines can increase the stability of these materials in aqueous environments and yield hydrophobic nanofiber scaffolds useful for the design of "slippery" liquid-infused materials. The approaches reported here enable the introduction of new properties to reactive polymer mats after fabrication and, thus, reduce the need to synthesize individual functional polymers prior to electrospinning to achieve new properties. The azlactone chemistry used here broadens the scope of reactions that can be used to functionalize polymer nanofibers and is likely to prove general. We anticipate that this approach can be used with a range of amines or other nucleophiles (e.g., alcohols or thiols) to design nanofibers and reactive nanofiber-based materials with new physical properties, surface features, and behaviors that may be difficult to achieve by the direct electrospinning of conventional materials or other functional polymers.

Degradable Amine-Reactive Coatings Fabricated by the Covalent Layer-by-Layer Assembly of Poly(2-vinyl-4,4-dimethylazlactone) with Degradable Polyamine Building Blocks.

We report the fabrication of reactive and degradable cross-linked polymer multilayers by the reactive/covalent layer-by-layer assembly of a non-degradable azlactone-functionalized polymer [poly(2-vinyl-4,4-dimethylazlactone), PVDMA] with hydrolytically or enzymatically degradable polyamine building blocks. Fabrication of multilayers using PVDMA and a hydrolytically degradable poly(β-amino ester) (PBAE) containing primary amine side chains yielded multilayers (∼100 nm thick) that degraded over ∼12 days in physiologically relevant media. Physicochemical characterization and studies on stable films fabricated using PVDMA and an analogous non-degradable poly(amidoamine) suggested that erosion occurred by chemical hydrolysis of backbone esters in the PBAE components of these assemblies. These degradable assemblies also contained residual amine-reactive azlactone functionality that could be used to impart new functionality to the coatings post-fabrication. Cross-linked multilayers fabricated using PVDMA and the enzymatically degradable polymer poly(l-lysine) were structurally stable for prolonged periods in physiological media, but degraded over ∼24 h when the enzyme trypsin was added. Past studies demonstrate that multilayers fabricated using PVDMA and non-degradable polyamines [e.g., poly(ethylenimine)] enable the design and patterning of useful nano/biointerfaces and other materials that are structurally stable in physiological media. The introduction of degradable functionality into PVDMA-based multilayers creates opportunities to exploit the reactivity of azlactone groups for the design of reactive materials and functional coatings that degrade or erode in environments that are relevant in biomedical, biotechnological, and environmental contexts. This "degradable building block" strategy should be general; we anticipate that this approach can also be extended to the design of amine-reactive multilayers that degrade upon exposure to specific chemical triggers, selective enzymes, or contact with cells by judicious design of the degradable polyamine building blocks used to fabricate the coatings.

Synthesis and Characterization of Backbone Degradable Azlactone-Functionalized Polymers

We report the design of reactive and degradable copolymers that contain both azlactone side chain functionality and hydrolyzable backbone ester groups. Copolymerization of the vinyl monomer 2-vinyl-4,4-dimethylazlactone (VDMA) and the cyclic ketene acetal 2-methylene-1,3-dioxepane (MDO) using conventional or reversible-deactivation radical polymerization techniques yielded copolymers and block copolymers that exhibit amine reactivity associated with poly(vinyl azlactone)s but also hydrolytic degradability associated with conventional polyesters. Our results demonstrate that control over monomer feed ratios and other parameters can be used to tune both copolymer composition (e.g., the number/ratio of azlactone and ester repeat units) and the physical properties of the resulting materials (e.g., glass transition temperatures and ability to self-assemble into nanoscale structures). Post-fabrication functionalization of reactive azlactone groups in MDO-co-VDMA copolymers by treatment with primary amines proce...

One-Step Synthesis of Azlactone-Functionalized SG1-Based Alkoxyamine for Nitroxide-Mediated Polymerization and Bioconjugation

The one-step synthesis of azlactone-functionalized SG1-based alkoxyamine (AzSG1) for the design of functional polymers by nitroxide-mediated polymerization (NMP) is reported. At 347.7 K, its dissociation rate constant, kd, was determined to be 2.72 × 10–4 s–1, leading to an activation energy, Ea, of 119.5 kJ mol–1, which represents the lowest value ever reported for a secondary SG1-based alkoxyamine without any activation by an external stimulus. This was ascribed to enhanced stabilization of the released radical compared to other secondary alkyl radicals. The AzSG1 alkoxyamine was successfully used for the NMP for styrene, n-butyl acrylate, and methyl methacrylate with the addition of a small amount of acrylonitrile as a comonomer, without the need for free SG1. In all cases, first-order kinetics, good control with low dispersities (Đ = 1.2–1.4), and high living chain fractions (LF ∼90%) were obtained. As a proof of concept, the conjugation of azlactone-functionalized polymers to benzylamine and lysozyme was successfully demonstrated. This work may be of high interest for conjugation as the azlactone functionality is also known to react with other nucleophiles such as alcohols or thiols.

Thermoresponsive block copolymers containing reactive azlactone groups and their bioconjugation with lysozyme

Thermoresponsive block copolymers based on poly(ethylene oxide) (PEO) and poly(N-isopropyl acrylamide) (PNIPAM) containing azlactone groups along the backbone and at the chain-end of the macromolecular chain were synthesized by statistically reversible addition–fragmentation chain transfer (RAFT) copolymerization and by using a combination of RAFT polymerization and thiol–ene Michael addition. Well-defined poly(ethylene oxide)-b-poly(2-vinyl-4,4-dimethylazlactone-co-N-isopropyl acrylamide) (PEO-b-P(VDM-co-NIPAM)) block copolymers and azlactone-terminated poly(ethylene oxide)-b-poly(N-isopropyl acrylamide) (PEO-b-PNIPAM-VDM) diblock copolymers with low polydispersity indices (PDIs ≤ 1.10) were prepared and fully characterized by 1H NMR spectroscopy, FT-IR spectroscopy, and SEC. Such PEO-b-P(VDM-co-NIPAM) block copolymers and azlactone-terminated PEO-b-PNIPAM block copolymers present tunable lower critical solution temperature (LCST) depending on PEO, PNIPAM, and PVDM molar ratios. The reactivity of the PEO44-b-P(VDM20-co-NIPAM80) copolymer (Mn,NMR = 14 200 g mol−1, PDI = 1.08) and of the PEO44-b-PNIPAM101-VDM copolymer (Mn,NMR = 13 700 g mol−1, PDI = 1.08) was studied with lysozyme as a model protein. A bioconjugate with a higher apparent molecular weight was obtained with the PEO44-b-P(VDM20-co-NIPAM80) copolymer in comparison with the one obtained using the PEO44-b-PNIPAM101-VDM copolymer as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The results suggest promising applications of azlactone-functionalized polymers within the field of bioconjugation.

Fabrication of oligonucleotide and protein arrays on rigid and flexible substrates coated with reactive polymer multilayers.

We report a top-down approach to the fabrication of oligonucleotide and protein arrays on surfaces coated with ultrathin, amine-reactive polymer multilayers fabricated by the covalent "layer-by-layer" (LbL) assembly of polyethyleneimine (PEI) and the amine-reactive, azlactone-functionalized polymer poly(2-vinyl-4,4-dimethylazlactone) (PVDMA). Manual spotting of amine-terminated oligonucleotide probe sequences on planar glass slides coated with PEI/PVDMA multilayers (~35 nm thick) yielded arrays of immobilized probes that hybridized fluorescently labeled complementary sequences with high signal intensities, high signal-to-noise ratios, and high sequence specificity. Treatment of residual azlactone functionality with the nonfouling small-molecule amine d-glucamine resulted in regions between the features of these arrays that resisted adsorption of protein and permitted hybridization in complex media containing up to 10 mg/mL protein. The residual azlactone groups in these films were also exploited to immobilize proteins on film-coated surfaces and fabricate functional arrays of proteins and enzymes. The ability to deposit PEI/PVDMA multilayers on substrates of arbitrary size, shape, and composition permitted the fabrication of arrays of oligonucleotides on the surfaces of multilayer-coated sheets of poly(ethylene terephthalate) and heat-shrinkable polymer film. Arrays fabricated on these flexible plastic substrates can be bent, cut, resized, and manipulated physically in ways that are difficult using more conventional rigid substrates. This approach could thus contribute to the development of new assay formats and new applications of biomolecule arrays. The methods described here are straightforward to implement, do not require access to specialized equipment, and should also be compatible with automated liquid-handling methods used to fabricate higher-density arrays of oligonucleotides and proteins on more traditional surfaces.

Azlactone-Functionalized Polymers as Reactive Platforms for the Design of Advanced Materials: Progress in the Last Ten Years.

Polymers functionalized with azlactone (or oxazolone) functionality have become increasingly useful for the rapid and modular design of functional materials. Because azlactones can react via ring-opening reactions with a variety of different nucleophilic species (e.g., primary amines, hydroxyl groups, and thiol functionality), azlactone-functionalized materials can serve as convenient 'reactive' platforms for the post-synthesis or post-fabrication introduction of a broad range of chemical functionality to soluble polymers, insoluble supports, and surfaces/interfaces. The last decade has seen an increase in both the number and the variety of reports that exploit the properties and the reactivities of azlactone-functionalized polymers. Here, we highlight recent work from several different laboratories, including our own, toward the design and characterization of azlactone-functionalized polymers, with a particular emphasis on: (i) new synthetic approaches for the preparation of well-defined azlactone-functionalized polymers using living/controlled methods of polymerization, (ii) the design and modular synthesis of side-chain functionalized polymers and block copolymers via post-polymerization modification of azlactone-functionalized polymers, (iii) the development of reactive polymeric supports useful in the contexts of separations and catalysis, and (iv) methods for the fabrication of reactive thin films and other approaches to the immobilization of azlactone functionality on surfaces and interfaces. Examples discussed herein reveal a growing awareness of azlactone functionality as a useful tool for polymer chemists, and highlight several ways that the unique reactivity of these materials can both complement and provide useful alternatives to other reactive polymers currently used to design functional materials.

In situ Synthesis of Oligonucleotide Arrays on Surfaces Coated with Crosslinked Polymer Multilayers

We report an approach to the in situ synthesis of oligonucleotide arrays on surfaces coated with crosslinked polymer multilayers. Our approach makes use of methods for the 'reactive' layer-by-layer assembly of thin, amine-reactive multilayers using branched polyethyleneimine (PEI) and the azlactone-functionalized polymer poly(2-vinyl-4,4'-dimethylazlactone) (PVDMA). Post-fabrication treatment of film-coated glass substrates with d-glucamine or 4-amino-1-butanol yielded hydroxyl-functionalized films suitable for the Maskless Array Synthesis (MAS) of oligonucleotide arrays. Glucamine-functionalized films yielded arrays of oligonucleotides with fluorescence intensities and signal-to-noise ratios (after hybridization with fluorescently labeled complementary strands) comparable to those of arrays fabricated on conventional silanized glass substrates. These arrays could be exposed to multiple hybridization-dehybridization cycles with only moderate loss of hybridization density. The versatility of the layer-by-layer approach also permitted synthesis directly on thin sheets of film-coated poly(ethylene terephthalate) (PET) to yield flexible oligonucleotide arrays that could be readily manipulated (e.g., bent) and cut into smaller arrays. To our knowledge, this work presents the first use of polymer multilayers as a substrate for the multi-step synthesis of complex molecules. Our results demonstrate that these films are robust and able to withstand the ~450 individual chemical processing steps associated with MAS (as well as manipulations required to hybridize, image, and dehybridize the arrays) without large-scale cracking, peeling, or delamination of the thin films. The combination of layer-by-layer assembly and MAS provides a means of fabricating functional oligonucleotide arrays on a range of different materials and substrates. This approach may also prove useful for the fabrication of supports for the solid-phase synthesis and screening of other macromolecular or small-molecule agents.

Functionalization of reactive polymer multilayers with RGD and an antifouling motif: RGD density provides control over human corneal epithelial cell–substrate interactions

Our study demonstrates that substrates fabricated using a "reactive" layer-by-layer approach promote well-defined cell-substrate interactions of human corneal epithelial cells. Specifically, crosslinked and amine-reactive polymer multilayers were produced by alternating "reactive" deposition of an azlactone-functionalized polymer [poly(2-vinyl-4,4-dimethylazlactone)] (PVDMA) and a primary amine-containing polymer [branched poly(ethylene imine)] (PEI). Advantages of our system include a 5- to 30-fold decrease in deposition time compared to traditional polyelectrolyte films and direct modification of the films with peptides. Our films react with mixtures of an adhesion-promoting peptide containing Arg-Gly-Asp (RGD) and the small molecule D-glucamine, a chemical motif which is nonfouling. Resulting surfaces prevent protein adsorption and promote cell attachment through specific peptide interactions. The specificity of cell attachment via immobilized RGD sequences was verified using both a scrambled RDG peptide control as well as soluble-RGD competitive assays. Films were functionalized with monotonically increasing surface densities of RGD which resulted in both increased cell attachment and the promotion of a tri-phasic proliferative response of a human corneal epithelial cell line (hTCEpi). The ability to treat PEI/PVDMA films with peptides for controlled cell-substrate interactions enables the use of these films in a wide range of biological applications.

Fabrication and Selective Functionalization of Amine-Reactive Polymer Multilayers on Topographically Patterned Microwell Cell Culture Arrays

We report an approach to the fabrication and selective functionalization of amine-reactive polymer multilayers on the surfaces of 3-D polyurethane-based microwell cell culture arrays. "Reactive" layer-by-layer assembly of multilayers using branched polyethyleneimine (BPEI) and the azlactone-functionalized polymer poly(2-vinyl-4,4'-dimethylazlactone) (PVDMA) yielded film-coated microwell arrays that could be chemically functionalized postfabrication by treatment with different amine-functionalized macromolecules or small molecule primary amines. Treatment of film-coated arrays with the small molecule amine d-glucamine resulted in microwell surfaces that resisted the adhesion and proliferation of mammalian fibroblast cells in vitro. These and other experiments demonstrated that it was possible to functionalize different structural features of these arrays in a spatially resolved manner to create dual-functionalized substrates (e.g., to create arrays having either (i) azlactone-functionalized wells, with regions between the wells functionalized with glucamine or (ii) substrates with spatially resolved regions of two different cationic polymers). In particular, spatial control over glucamine functionalization yielded 3-D substrates that could be used to confine cell attachment and growth to microwells for periods of up to 28 days and support the 3-D culture of arrays of cuboidal cell clusters. These approaches to dual functionalization could prove useful for the long-term culture and maintenance of cell types for which the presentation of specific and chemically well-defined 3-D culture environments is required for control over cell growth, differentiation, and other important behaviors. More generally, our approach provides methods for the straightforward chemical functionalization of otherwise unreactive topographically patterned substrates that could prove to be useful in a range of other fundamental and applied contexts.

Superhydrophobic Thin Films Fabricated by Reactive Layer-by-Layer Assembly of Azlactone-Functionalized Polymers.

We report an approach to the fabrication of superhydrophobic thin films that is based on the 'reactive' layer-by-layer assembly of azlactone-containing polymer multilayers. We demonstrate that films fabricated from alternating layers of the azlactone functionalized polymer poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) and poly(ethyleneimine) (PEI) exhibit micro- and nanoscale surface features that result in water contact angles in excess of 150º. Our results reveal that the formation of these surface features is (i) dependent upon film thickness (i.e., the number of layers of PEI and PVDMA deposited) and (ii) that it is influenced strongly by the presence (or absence) of cyclic azlactone-functionalized oligomers that can form upon storage of the 2-vinyl-4,4-dimethylazlactone (VDMA) used to synthesize PVDMA. For example, films fabricated using polymers synthesized in the presence of these oligomers exhibited rough, textured surfaces and superhydrophobic behavior (i.e., advancing contact angles in excess of 150º). In contrast, films fabricated from PVDMA polymerized in the absence of this oligomer (e.g., using freshly distilled monomer) were smooth and only moderately hydrophobic (i.e., advancing contact angles of ~75º). The addition of authentic, independently synthesized oligomer to samples of distilled VDMA at specified and controlled concentrations permitted reproducible fabrication of superhydrophobic thin films on the surfaces of a variety of different substrates. The surfaces of these films were demonstrated to be superhydrophobic immediately after fabrication, but they became hydrophilic after exposure to water for six days. Additional experiments demonstrated that it was possible to stabilize and prolong the superhydrophobic properties of these films (e.g., advancing contact angles in excess of 150° even after complete submersion in water for at least six weeks) by exploiting the reactivity of residual azlactones to functionalize the surfaces of the films using hydrophobic amines (e.g., aliphatic or semi-fluorinated aliphatic amines). Our results demonstrate a straightforward and substrate-independent approach to the design of superhydrophobic and reactive polymer-based coatings of potential use in a broad range of fundamental and applied contexts.

Free-standing and reactive thin films fabricated by covalent layer-by-layer assembly and subsequent lift-off of azlactone-containing polymer multilayers.

We report an approach to the fabrication of free-standing and amine-reactive thin films that is based on the reactive layer-by-layer assembly and subsequent lift-off of azlactone-containing polymer multilayers. We demonstrate that covalently cross-linked multilayers fabricated using the azlactone-functionalized polymer poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) and a primary amine-containing polymer [poly(ethyleneimine) (PEI)] can be delaminated from planar glass and silicon surfaces by immersion in mildly acidic aqueous environments to yield flexible freestanding membranes. These free-standing membranes are robust and can withstand exposure to strong acid, strong base, or incubation in high ionic strength solutions that typically lead to the disruption and erosion of polymer multilayers assembled by reversible weak interactions (e.g., "polyelectrolyte multilayers" assembled by electrostatic interactions or hydrogen bonding). We demonstrate further that these PEI/PVDMA assemblies contain residual reactive azlactone functionality that can be exploited to chemically modify the films (either directly after fabrication or after they have been lifted off of the substrates on which they were fabricated) using a variety of amine-functionalized small molecules. These free-standing membranes can also be transferred readily onto other objects (for example, onto the surfaces of planar substrates containing holes or pores) to fabricate suspended polymer membranes and other film-functionalized interfaces. In addition to planar, two-dimensional free-standing films, this approach can be used to fabricate and isolate three-dimensional free-standing membranes (e.g., curved films or tubes) by layer-by-layer assembly on, and subsequent lift-off from, the surfaces of topologically complex substrates (e.g., the curved ends of glass tubing, etc.). The results of this investigation, when combined, suggest the basis of methods for the fabrication of stable, chemically reactive, and flexible polymer thin films and membranes of potential utility in a variety of fundamental and applied contexts.

Functionalization of fibers using azlactone-containing polymers: layer-by-layer fabrication of reactive thin films on the surfaces of hair and cellulose-based materials.

We report an approach to the functionalization of fibers and fiber-based materials that is based on the deposition of reactive azlactone-functionalized polymers and the "reactive" layer-by-layer assembly of azlactone-containing thin films. We demonstrate (i) that the azlactone-functionalized polymer poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) can be used to modify the surfaces of a model protein-based fiber (horsehair) and cellulose-based materials (e.g., cotton and paper), and (ii) that fibers functionalized in this manner can be used to support the fabrication of covalently cross-linked and reactive polymer multilayers assembled using PVDMA and poly(ethyleneimine) (PEI). The growth, chemical reactivity, and uniformity of films deposited on these substrates were characterized using fluorescence microscopy, confocal microscopy, and scanning electron microscopy (SEM). In addition to the direct functionalization of fibers, we demonstrate that the residual azlactone functionality in PVDMA-treated or film-coated fibers can be exploited to chemically modify the surface chemistry and physicochemical properties of fiber-based materials postfabrication using amine functionalized molecules. For example, we demonstrate that this approach permits control over the surface properties of paper (e.g., absorption of water) by simple postfabrication treatment of film-coated paper with the hydrophobic amine n-decylamine. The azlactone functionality present in these materials provides a platform for the modification of polymer-treated and film-coated fibers with a broad range of other chemical and biological species (e.g., enzymes, peptides, catalysts, etc.). The results of this investigation thus provide a basis for the functionalization of fibers and fiber-based materials (e.g., textile fabrics or nonwoven mats) of potential utility in a broad range of consumer, industrial, and biomedical contexts.

Azlactone-functionalized polymers as reactive templates for parallel polymer synthesis: synthesis and screening of a small library of cationic polymers in the context of DNA delivery

Azlactone-functionalized polymers are used as reactive templates for the synthesis of a library of amine-functionalized polymers of interest in the context of DNA delivery and other applications.

Well-Defined Azlactone-Functionalized (Co)polymers on a Solid Support: Synthesis via Supported Living Radical Polymerization and Application as Nucleophile Scavengers

Wang resin has been converted to a supported initiator for transition metal-mediated living radical polymerization often called atom-transfer radical polymerization (ATRP) of 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) and styrene (S). Several "Rasta" resins with well-defined macromolecular architectures, including homopolymers PVDM, PS, statistical P(S-stat-VDM), block P(S-b-VDM), and P[S-b-(S-stat-VDM)] copolymers, have been elaborated. For the homopolymerization of VDM and S, a sacrificial initiator, benzyl 2-bromoisobutyrate (BBI), has been introduced to monitor the evolution of molar masses and polydispersity indexes (PDIs) of PS and PVDM onto the Wang resin support without cleavage. After 6 h, 86.7% conversion of VDM is reached, with the isolated PVDM chains having a molar mass of 18 000 g mol(-1) and a PDI value of 1.22. Block copolymers have been synthesized in two steps, involving the synthesis of the PS block isolated at low conversions (<15%) to maintain the bromine end-chain functionality and the subsequent synthesis of the second PVDM or P(S-stat-VDM) block. Polydispersity indexes of the cleaved (co)polymers were low (PDI = 1.11-1.44), and high azlactone loadings have been reached (loading = 6.0 mmol g(-1)). Such azlactone-functionalized Wang resins have shown high efficiency during the scavenging process of benzylamine as monitored by HPLC. Moreover, grafted statistical copolymers have shown the best behavior for removing benzylamine because of an improvement of the accessibility of azlactone rings by the dilution with styrene units.