Alkyne-functionalized Poly Research Articles

Fabrication of Low-Fouling Surfaces on Alkyne-Functionalized Poly-(p-xylylenes) Using Click Chemistry.

A facial, versatile, and universal method that breaks the substrate limits is desirable for antifouling treatment. Thin films of functional poly-p-xylylenes (PPX) that are deposited using chemical vapor deposition (CVD) provide a powerful platform for surface immobilization of molecules. In this study, we prepared an alkyne-functionalized PPX coating on which poly (sulfobetaine methacrylate-co-Az) could be conjugated via click chemistry. We found that the conjugated polymers were very stable and inhibited cell adhesion and protein adsorption effectively. The same conjugation strategy could also be applied to conjugate azide-containing poly (ethylene glycol) and poly (NIPAAm). The results indicate that our method provides a simple and robust tool for fabricating antifouling surfaces on a wide range of substrates using CVD technology of functionalized poly (p-xylylenes) for biosensor, diagnostics, immunoassay, and other biomaterial applications.

Polyrotaxane-based thin film composite membranes for enhanced nanofiltration performance

An urgent need exists for the development of advanced water purification technologies to meet the increasing global demand being placed on freshwater resources. Membrane-based separation technologies for size-selective contaminant removal represent a promising approach to achieve this goal. Here, a novel thin film composite nanofiltration membrane is prepared via interfacial polymerization of α-cyclodextrin on a commercially available polyacrylonitrile substrate. Subsequent in-situ inclusion complexation of alkyne-functionalized poly(ethylene glycol) (PEG) is then used to tune the polyrotaxane-based pores for size-dependent filtration. The resultant membrane shows excellent size-selective rejection rates for organic dye (e.g. rhodamine B, >99%) as well as heavy-metal ions (e.g. Co(II), >90%), while crucially maintaining high water permeance (e.g. H2O: 7.1 L h−1 m−2 bar−1). The facile and straightforward synthetic approach to the fabrication of polyrotaxane nanofiltration membranes, combined with their strong nanofiltration separation performance, holds significant promise for membrane-based water purification applications.

Well-Defined Diblock Poly(ethylene glycol)-b-Poly(ε-caprolactone)-Based Polymer-Drug Conjugate Micelles for pH-Responsive Delivery of Doxorubicin.

Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC micelles, revealed their improved anticancer efficiency towards MCF-7 cells as compared to free DOX.

Striking Effect of Polymer End-Group on C60 Nanoparticle Formation by High Shear Vibrational Milling with Alkyne-Functionalized Poly(2-oxazoline)s.

Buckminsterfullerene (C60) has a large potential for biomedical applications. However, the main challenge for the realization of its biomedical application potential is to overcome its extremely low water solubility. One approach is the coformulation with biocompatible water-soluble polymers, such as poly(2-oxazoline)s (PAOx), to form water-soluble C60 nanoparticles (NPs). However, uniform and defined NPs have only been obtained via a thin film hydration method or using cyclodextrin-functionalized PAOx. Here, we report the mechanochemical preparation of defined and stable C60:PAOx NPs by the introduction of a simple alkyne group as a polymer end-group. The presence of this alkyne bond is proven to be crucial in the mechanochemical synthesis of stable, defined sub-100 nm C60:PAOx NPs, with high C60 content up to 8.9 wt %.

Post modification of acetylene functional poly(oxindole biphenylylene) by photoinduced CuAAC

A novel strategy to obtain side chain modified poly(oxindole biphenylylene) (POXI) by photoinduced copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction is described. In the first step, an alkyne-functionalized poly(oxindolebiphenylylene) (POXI-alkyne) is synthesized by superacid-catalyzed condensation of isatin with aromatic hydrocarbons. Subsequently, poly(ethylene glycol) methyl ether (Me-PEG), 1-pyrenemethanol (Py-OH) and 1,3-dibromopropane (DBP) are functionalized by azide groups via simple nucleophilic substitution reaction. Visible-light-induced CuAAC reaction between POXI-alkyne and the corresponding azide functionalized click components employing dibenzoyldiethylgermane (DBDEG) as photoactivator resulted in the formation of POXI-PEG, POXI-Py and insoluble network, respectively. Successful modification of POXI was confirmed by the spectral, (1H NMR, FT-IR, Fluorescence), chromatographic (GPC) and thermal (DSC) investigations.

Magnetic Hydrogels from Alkyne/Cobalt Carbonyl-Functionalized ABA Triblock Copolymers.

A series of alkyne-functionalized poly(4-(phenylethynyl)styrene)-block-poly(ethylene oxide)-block-poly(4-(phenylethynyl)styrene) (PPES-b-PEO-b-PPES) ABA triblock copolymers was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. PESn[Co2(CO)6]x-EO800-PESn[Co2(CO)6]x ABA triblock copolymer/cobalt adducts (10-67 wt % PEO) were subsequently prepared by reaction of the alkyne-functionalized PPES block with Co2(CO)8 and their phase behavior was studied by TEM. Heating triblock copolymer/cobalt carbonyl adducts at 120 °C led to cross-linking of the PPES/Co domains and the formation of magnetic cobalt nanoparticles within the PPES/Co domains. Magnetic hydrogels could be prepared by swelling the PEO domains of the cross-linked materials with water. Swelling tests, rheological studies and actuation tests demonstrated that the water capacity and modulus of the hydrogels were dependent upon the composition of the block copolymer precursors.

Synthesis, characterization and chondrocyte culture of polyhedral oligomeric silsesquioxane (POSS)-containing hybrid hydrogels

Polyhedral oligomeric silsesquioxanes (POSS)-based hybrid hydrogels were successfully prepared via a fast azide-alkyne click reaction between octa-azido-functionalized POSS (OAPOSS) and alkyne-functionalized poly(ethylene glycol) (PEG).

Hyperbranched polyisobutylenes for self-healing polymers

Hyperbranched azide- and alkyne-functionalized poly(isobutylene)s (PIBs, Mn = 25 200–35 400 g mol−1) suitable for crosslinking at room temperature via the copper-catalyzed alkyne–azide “click” cycloaddition reaction (CuAAC) are reported, aiming at the design of improved crosslinking reactions for novel self-healing materials. Based on the low glass transition temperature (Tg) the high molecular mobility of the hyperbranched PIBs was linked with an efficient crosslinking chemistry while introducing reactive endgroups into the polymer and tuning molecular architecture via living carbocationic polymerization (LCCP). Hyperbranched PIBs were prepared by inimer-type LCCP followed by direct end quenching of living chain ends with either 3-(bromopropoxy)benzene (BPB) or trimethyl(3-phenoxy-1-propynyl)silane (TMPPS). Optimized quenching time conditions (6 hours quenching with BPB and 20 hours quenching with TMPPS) yielded the fully bromine- and trimethylsilyl-protected alkyne-functionalized hyperbranched PIBs with up to ∼9 endgroups, subsequently being converted into the respective fully azide- and alkyne-functionalized polymers. “Click” reactions between the azide and the alkyne group of hyperbranched PIBs linked the two spherical polymers resulting in fast gelation times of 30 to 50 minutes as investigated via melt rheology. Materials with high network densities were obtained due to the high amount of reactive endgroups and the architecture of the applied polymers. Thus, the concept of crosslinking hyperbranched azide- and alkyne-functionalized PIBs via “click” chemistry at room temperature towards self-healing polymers could be successfully proven.

Barnacle Cement as Surface Anchor for “Clicking” of Antifouling and Antimicrobial Polymer Brushes on Stainless Steel

Barnacle cement (BC) was utilized 'beneficially' as a surface anchor on stainless steel (SS) for coupling of functional polymer brushes via "click" reactions in both "grafting-to" and "grafting-from" processes. Ethylene sulfide (ES), propargyl carbonylimidazole (PPC) and azidoethyl carbonylimidazole (AEC) reacted with amine and/or hydroxyl groups in BC to introduce the corresponding thiol, alkyne, and azide groups on SS surfaces (SS-thiol, SS-alkyne, and SS-azide, respectively). Antifouling zwitterionic SS-PMPC surface was prepared by thiol-ene photopolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) from the SS-thiol surface. Protein-resistant SS-PPEGMA and protein-adsorbing SS-PPFS surfaces were prepared by coupling of the respective azide-functionalized poly(poly(ethylene glycol)methyl ether methacrylate) (azido-PPEGMA) and poly(2,3,4,5,6-pentafluorostyrene) (azido-PPFS) polymer brushes in azide-alkyne "click" reaction. Antifouling alkyne-functionalized poly(N-hydroxyethyl acrylamide) (alkynyl-PHEAA) and antibacterial alkyne-functionalized poly(2-(methacryloyloxy)ethyl trimethylammonium chloride) (alkynyl-PMETA) polymer brushes were clicked on the SS-azide surface. Adsorption of bovine serum albumin and bacteria fouling of Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus epidermidis ( S. epidermidis ) were investigated on the polymer-functionalized SS surfaces. The versatile bioanchor and functional polymer brush coatings are stable in an abiotic aqueous environment for over a month.

Reduction biodegradable brushed PDMAEMA derivatives synthesized by atom transfer radical polymerization and click chemistry for gene delivery

Novel reducible and degradable brushed poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) derivatives were synthesized and evaluated as non-viral gene delivery vectors. First, alkyne-functionalized poly(aspartic acid) with a disulfide linker between the propargyl group and backbone poly([(propargyl carbamate)-cystamine]-α,β-aspartamide) (P(Asp-SS-AL)) was synthesized. Second, linear low molecular weight (LMW) monoazido-functionalized PDMAEMAs synthesized via atom transfer radical polymerization were conjugated to the polypeptide side-chains of P(Asp-SS-AL) via click chemistry to yield high molecular weight (HMW) polyaspartamide-based disulfide-containing brushed PDMAEMAs (PAPDEs). The PAPDEs were able to condense plasmid DNA to form 100 to 200nm polyplexes with positive ζ-potentials. Moreover, in the presence of dithiothreitol the PAPDEs degraded into LMW PDAMEMA, resulting in disintegration of the PAPDE/DNA polyplexes and subsequent release of plasmid DNA. In vitro experiments revealed that the PAPDEs were less cytotoxic and more effective in gene transfection than control 25kDa poly(ethyleneimine) and HMW linear PDMAEMA. In conclusion, reducible and degradable polycations composed of LMW PDMAEMAs coupled to a polypeptide backbone via reduction-sensitive disulfide bonds are effective gene vectors with an excellent cytocompatibility.

Photoinitiated Alkyne–Azide Click and Radical Cross-Linking Reactions for the Patterning of PEG Hydrogels

The photolithographical patterning of hydrogels based solely on the surface immobilization and cross-linking of alkyne-functionalized poly(ethylene glycol) (PEG-tetraalkyne) is described. Photogenerated radicals as well as UV absorption by a copper chelating ligand result in the photochemical redox reduction of Cu(II) to Cu(I). This catalyzes the alkyne-azide click reaction to graft the hydrogels onto an azide-functionalized plasma polymer (N(3)PP) film. The photogenerated radicals were also able to abstract hydrogen atoms from PEG-tetraalkyne to form poly(α-alkoxy) radicals. These radicals can initiate cross-linking by addition to the alkynes and intermolecular recombination to form the PEG hydrogels. Spatially controlling the two photoinitiated reactions by UV exposure through a photomask leads to surface patterned hydrogels, with thicknesses that were tunable from tens to several hundreds of nanometers. The patterned PEG hydrogels (ca. 60 μm wide lines) were capable of resisting the attachment of L929 mouse fibroblast cells, resulting in surfaces with spatially controlled cell attachment. The patterned hydrogel surface also demonstrated spatially resolved chemical functionality, as postsynthetic modification of the hydrogels was successfully carried out with azide-functionalized fluorescent dyes via subsequent alkyne-azide click reactions.

Surface-Functionalized and Surface-Functionalizable Poly(vinylidene fluoride) Graft Copolymer Membranes via Click Chemistry and Atom Transfer Radical Polymerization

Poly(vinylidene fluoride) (PVDF) with azide-functionalized poly(glycidyl methacrylate) (PGMA) side chains (PVDF-g-P[GMA-(N3)(OH)]) were synthesized via free radical-initiated graft copolymerization of glycidyl methacrylate (GMA) from ozone-pretreated PVDF backbone (PVDF-g-PGMA), followed by reaction of the oxirane rings in the GMA side chains with sodium azide. Alkyne-functionalized poly(N-isopropylacrylamide) (alkynyl-PNIPAM), prepared a priori by atom transfer radical polymerization (ATRP), was used for the click reaction with the azido-containing PGMA side chains of the PVDF-g-P[GMA-(N3)(OH)] copolymer to give rise to the thermoresponsive PVDF-g-P[GMA-click-PNIPAM] copolymer. Both the PVDF-g-P[GMA-(N3)(OH)] and PVDF-g-P[GMA-click-PNIPAM] copolymers can be readily cast into microporous membranes by phase inversion in an aqueous medium. The PVDF-g-P[GMA-(N3)(OH)] microporous membranes with azido-containing surfaces could be further functionalized via surface click reaction with alkyne-terminated PNIPAM of controlled chain lengths to obtain the PVDF-g-P[GMA-click-PNIPAM]surface microporous membranes. The surface composition and morphology of the PVDF-g-P[GMA-click-PNIPAM] membranes can be adjusted by the temperature of casting medium, while the flux through both types of membranes exhibits thermoresponsive behavior.

Biodegradable Click Capsules with Engineered Drug-Loaded Multilayers

We report the modular assembly of a polymer-drug conjugate into covalently stabilized, responsive, biodegradable, and drug-loaded capsules with control over drug dose and position in the multilayer film. The cancer therapeutic, doxorubicin hydrochloride (DOX), was conjugated to alkyne-functionalized poly(l-glutamic acid) (PGA(Alk)) via amide bond formation. PGA(Alk) and PGA(Alk+DOX) were assembled via hydrogen bonding with poly(N-vinyl pyrrolidone) (PVPON) on planar and colloidal silica templates. The films were subsequently covalently stabilized using diazide cross-linkers, and PVPON was released from the multilayers by altering the solution pH to disrupt hydrogen bonding. After removal of the sacrificial template, single-component PGA(Alk) capsules were obtained and analyzed by optical microscopy, transmission electron microscopy, and atomic force microscopy. The PGA(Alk) capsules were stable in the pH range between 2 and 11 and exhibited reversible swelling/shrinking behavior. PGA(Alk+DOX) was assembled to form drug-loaded polymer capsules with control over drug dose and position in the multilayer system (e.g., DOX in every layer or exclusively in layer 3). The drug-loaded capsules could be degraded enzymatically, resulting in the sustained release of active DOX over approximately 2 h. Cellular uptake studies demonstrate that the viability of cells incubated with DOX-loaded PGA(Alk) capsules significantly decreased. The general applicability of this modular approach, in terms of incorporation of polymer-drug conjugates in other click multilayer systems, was also demonstrated. Biodegradable click capsules with drug-loaded multilayers are promising candidates as carrier systems for biomedical applications.

Low-Fouling Poly(N-vinyl pyrrolidone) Capsules with Engineered Degradable Properties

We report the assembly of low-fouling polymer capsules with engineered deconstruction properties by using a combination of layer-by-layer (LbL) assembly and click chemistry. Preformed, hydrogen-bonded multilayers of alkyne-functionalized poly(N-vinyl pyrrolidone) (PVPON(Alk)) and poly(methacrylic acid) (PMA) assembled at pH 4 on silica particles were cross-linked with a bisazide linker (containing a disulfide link) through alkyne-azide click chemistry. Following dissolution of the silica template particles, and altering the solution pH to 7.2 to disrupt hydrogen bonding between PVPON(Alk) and PMA to effect removal of PMA, stable, cross-linked PVPON capsules were obtained. The presence of the disulfide bond in the bisazide linker endowed the PVPON capsules with degradable characteristics under model intracellular conditions. The capsules deconstructed within 4 h in the presence of 5 mM glutathione. The cross-linked PVPON(Alk) multilayers (assembled on silica particles) were low-fouling to a range of proteins, including fibrinogen, lysozyme, immunoglobulin G, and bovine serum albumin. Further, MTT assays showed that the PVPON capsules had no effect on the proliferation of cells from a human colon cancer cell line (LIM1899), indicating negligible cytotoxicity toward the LIM1899 cells. The low-fouling, degradable, and low cytotoxicity characteristics of the PVPON capsules makes them attractive as a platform for the development of advanced therapeutic delivery systems.

Synthesis of Poly(benzyl ether) Dendrimer Containing Tetra(ethyleneoxide) at Core Using Click Chemistry

The convergent synthetic strategy for the poly(benzyl ether) dendrimers having the tetraethyleneoxide at core via the copper-catalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide was described. Tetraethyleneglycol diazide, designed to serve as the core in dendrimer, was stitched with the alkyne-functionalized poly(benzyl ether) dendrons by the click chemistry leading to the formation of triblock dendritic polymers in high yields. The absorption and emission of the dendrimers were investigated. The structure of the dendrimers was characterized with 1H NMR, 13C NMR, and IR spectroscopies, mass spectra, and gel-permeation chromatography.

Synthesis and Characterization of Poly(benzyl ether) Dendrimer Containing Fluorene as a Core Chromophore

The convergent synthetic strategy for the emissive poly(benzyl ether) dendrimers having the chromophore at core via the copper-catalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide was described. 2,7-Diazido-9H-fluorene, designed to serve as the core in dendrimer, was stitched with the alkyne-functionalized poly(benzyl ether) dendrons by the click chemistry leading to the formation of fluorescent poly(benzyl ether) dendrimers in high yields. The absorption and emission of the dendrimers were investigated. Their photophysical studies indicated that 2,7-diazido-9H-fluorene showed no fluorescence due to the quenching effect from the electron-rich α-nitrogen of the azido group but the dendrimers fluoresced due to the elimination of the quenching through the formation of the triazole ring.

Para-Hydrogenation of unsaturated moieties on poly(lysine) derived substrates for the development of novel hyperpolarized MRI contrast agents

Four alkyne-functionalized poly(lysine) derivatives have been synthesized and characterized by 1H and 13C NMR spectroscopy. In the first poly(lysine) derivative, phenylpropiolate moieties are directly bound to the aminic arms, whereas in the other derivatives, propargylamine moieties are bound to the aminic poly(lysine) arms through glucaric acid and diethylene glycol (DG) chains, respectively. para-Hydrogenation of the alkyne-functionalized poly(lysine) compounds has been investigated and the results have been discussed in terms of spin lattice relaxation properties of the hydrogenated products. It is shown that the longer the mobile chain separating the unsaturation from the poly(lysine) backbone, the more intense the polarized signals when para-hydrogenation is carried out. This is due to (a) the maintenance of short reorientational times on the unsaturated ends, and therefore a sufficiently long T(1) of the protons added during hydrogenation, and (b) the minor effect of steric hindrance by the poly(lysine) backbone that decreases interaction of the unsaturation with the catalyst, allowing higher hydrogenation rates.