Nanocrystalline cellulose/β-casein conjugated nanoparticles prepared by click chemistry

Functionalized nanoparticles are promising building blocks for well-defined nanomaterials with unique properties. Site-specific or regio-selective functionalization of those nanoparticles and organization into high-order assemblies is a major challenge in materials research. Here, we demonstrate site-specific immobilization of a model protein at one tip of nanocrystalline cellulose (NCC), single-crystalline rod-like shaped nanoparticles that are isolated by acid hydrolysis of bulk cellulose. Click reaction between reducing end functionalized NCC bearing azide groups and β-casein micelles bearing acetylene groups results in mushroom-like conjugated nanoparticles in different arrangements. The strategy developed here to design hybrid polysaccharide–protein nanoparticles could be useful for building novel functional self-assembled nanobiomaterials and have potential in nanomedicine, immunoassay and drug delivery applications.     

“Click” coupling between alkyne‐decorated multiwalled carbon nanotubes and reactive PDMA‐PNIPAM micelles

Covalent functionalization of alkyne‐decorated multiwalled carbon nanotubes (MWNTs) with a well‐defined, azide‐derivatized, thermoresponsive diblock copolymer, poly(N,N‐dimethylacrylamide)‐poly(N‐isopropylacrylamide) (PDMA‐PNIPAM) was accomplished by the Cu(I)‐catalyzed [3 + 2] Huisgen cycloaddition. It was found that this reaction could simultaneously increase the molecular size and bonding density of grafted polymers when PDMA‐PNIPAM micelles were employed in the coupling system. On the other hand, attachment of molecularly dissolved unimers of high‐molecular weight onto the nanotube resulted in low‐graft density. The block copolymer bearing azide groups at the PDMA end was prepared by reversible addition–fragmentation transfer polymerization, which formed micelles with a diameter of ～40 nm at temperatures above its critical micelle temperature. Scanning electron microscopy was utilized to demonstrate that the coupling reaction was successfully carried out between copolymer micelles and alkyne‐bearing MWNTs. FTIR spectroscopy was utilized to follow the introduction and consumption of alkyne groups on the MWNTs. Thermogravimetric analysis indicated that the functionalized MWNTs consisted of about 45% polymer. Transmission electron microscopy was utilized to image polymer‐functionalized MWNTs, showing relatively uniform polymer coatings present on the surface of nanotubes. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7187–7199, 2008     

Synthesis of azide‐functionalized nanoparticles by microemulsion polymerization and surface modification by click chemistry in aqueous medium

Stable translucent aqueous suspensions of azide‐functionalized cross‐linked nanoparticles (NPs), with diameters in the 15–20 nm range, were prepared using two synthetic approaches. Copolymerization of azidomethylstyrene (VBN₃), styrene, and divinylbenzene in various oil‐in‐water microemulsions led to NPs with modulable azide contents (0.53–0.78 mmol/g) and surface over volume distributions. Surface modifications of reactive NPs bearing chlorobenzyl groups, produced by microemulsion copolymerization of vinylbenzylchloride, with sodium azide led to azido‐coated NPs with high densities of peripheral groups (0.13–0.45 mmol/g). It is shown that the nature of the surfactant used for the preparation of the microemulsion has an impact on the incorporation of VBN₃ in the polymer particles as well as on the surface reaction yield. The azide‐functionalized NPs were used as clickable polymeric scaffolds for the grafting of sparingly water‐soluble dansyl and fluorescein derivatives through copper(I)‐catalyzed azide‐alkyne cycloaddition in water in the presence of surfactants as solubilizing agents to produce fluorescent NPs. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Preparation of novel photoreactive polycarbazole‐based microparticles: Reactivity features

Four types of innovative benzophenone (BPh)‐ or aryl azide (ArAz)‐containing photoreactive polycarbazole (polyCbz)‐based microparticles (MPs) were prepared using an oxidative liquid phase polymerization system. Their photochemical reactivity was evaluated by their reaction with highly inert poly(2‐chloro‐paraxylelene) (Parylene C) films. Possible mechanisms for the photochemical reaction of those MPs with Parylene C were discussed. The highly photoreactive BPh was found to react more inside the particle causing internal cross‐linking of MP polyCbz chains, fusion between adjoining particles and deformation of their spherical structure. In contrast, the less reactive but more selective ArAz‐containing MPs were found to react much more with Parylene C. The strong reactivity of such photoreactive MPs toward Parylene C films emphasizes a general method for the functionalization of stable nonfunctional polymeric coatings. This paves the way to simple and solvent‐free functionalization of nonfunctional coatings and materials by light. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

“Clickable” and Antifouling Block Copolymer Brushes as a Versatile Platform for Peptide‐Specific Cell Attachment

To tailor cell–surface interactions, precise and controlled attachment of cell‐adhesive motifs is required, while any background non‐specific cell and protein adhesion has to be blocked effectively. Herein, a versatile and highly reproducible antifouling surface modification based on “clickable” groups and hierarchically structured diblock copolymer brushes for the controlled attachment of cells is reported. The polymer brush architecture combines an antifouling bottom block of poly(2‐hydroxyethyl methacrylate) poly(HEMA) and an ultrathin azide‐bearing top block, which can participate in well‐established “click” reactions including the highly selective copper‐catalyzed alkyne‐azide cycloaddition (CuAAC) reaction under mild conditions. This straightforward approach allows the rapid conjugation of a cell‐adhesive, alkyne‐bearing cyclic RGD peptide motif, enabling subsequent specific attachment of NIH 3T3 fibroblasts, their extensive proliferation and confluent cell sheet formation after 48 h of incubation. The generally applicable strategy presented in this report can be employed for surface functionalization with diverse alkyne‐bearing biological moieties via CuAAC or copper‐free alkyne‐azide cycloaddition protocols, making it a versatile functionalization approach and a promising tool for tissue engineering, biomaterial implant design, and other applications that require surfaces supporting highly specific cell attachment.     

Well‐controlled ATRP of 2‐(2‐(2‐azidoethyoxy)ethoxy)ethyl methacrylate for high‐density click functionalization of polymers and metallic substrates

The combination of atom transfer radical polymerization (ATRP) and click chemistry has created unprecedented opportunities for controlled syntheses of functional polymers. ATRP of azido‐bearing methacrylate monomers (e.g., 2‐(2‐(2‐azidoethyoxy)ethoxy)ethyl methacrylate, AzTEGMA), however, proceeded with poor control at commonly adopted temperature of 50 °C, resulting in significant side reactions. By lowering reaction temperature and monomer concentrations, well‐defined pAzTEGMA with significantly reduced polydispersity were prepared within a reasonable timeframe. Upon subsequent functionalization of the side chains of pAzTEGMA via Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) click chemistry, functional polymers with number‐average molecular weights (M_n) up to 22 kDa with narrow polydispersity (PDI < 1.30) were obtained. Applying the optimized polymerization condition, we also grafted pAzTEGMA brushes from Ti6Al4 substrates by surface‐initiated ATRP (SI‐ATRP), and effectively functionalized the azide‐terminated side chains with hydrophobic and hydrophilic alkynes by CuAAC. The well‐controlled ATRP of azido‐bearing methacrylates and subsequent facile high‐density functionalization of the side chains of the polymethacrylates via CuAAC offers a useful tool for engineering functional polymers or surfaces for diverse applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1268–1277     

Prepolymerization and postpolymerization functionalization approaches to fluorescent conjugated carbazole‐based glycopolymers via “click chemistry”

Facile prepolymerization and postpolymerization functionalization approaches to prepare well‐defined fluorescent conjugated glycopolymers through Cu(I)‐catalyzed azide/alkyne “Click” ligation were explored. Two well‐defined carbazole‐based fluorescent conjugated glycopolymers were readily synthesized based on these strategies and characterized by ¹H NMR, ¹³C NMR, IR spectra, and UV‐vis spectra. The “Click” ligation offers a very effective conjugation method to covalently attach carbohydrate residues to fluorescent conjugated polymers. In addition, the studies of carbohydrate–lectin interactions were performed by titration of concanavalin A (Con A) to D ‐glucose‐bearing poly(anthracene‐alt‐carbazole) copolymer P‐2 resulting in significant fluorescence quenching of the polymer due to carbohydrate–lectin interactions. When peanut agglutinin (PNA) was added, no distinct change in the fluorescent properties of P‐2 was observed. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2948–2957, 2009     

Combining cationic ring‐opening polymerization and click chemistry for the design of functionalized polyurethanes

A straightforward strategy for the synthesis and functionalization of polyurethanes (PUs) via the use of alkyne‐functionalized polytetrahydrofuran (PTHF) diols is described. The alkyne groups have been introduced into the PTHF chains by the cationic ring‐opening copolymerization of tetrahydrofuran and glycidyl propargyl ether. These PTHF prepolymers were combined with 1,4‐butanediol and hexamethylene diisocyanate for the synthesis of linear PUs with latent functionalization sites. The polyether segments of the PUs have then been coupled with several types of functionalized azides by the copper‐catalyzed azide‐alkyne “click” chemistry, for example with phosphonium containing azides for their antibacterial properties. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Functionalized poly(oxanorbornene)‐block‐copolymers: Preparation via ROMP/click‐methodology

Block copolymers on basis of poly(oxanorbornenes) bearing functional moieties in their side‐chains are prepared via a combination of ROMP‐methods and 1,3‐dipolar‐“click”‐reactions. Starting from N‐substituted‐ω‐bromoalkyl‐oxanorbornenes and alkyl‐/perfluoroalkyl‐oxanorbornenes, block copolymers with molecular weights up to 25,000 g mol^?1 were generated. Subsequent nucleophilic exchange‐reactions yielded the block‐copolymers functionalized with ω‐azidoalkyl‐moieties in one block. The 1,3‐azide/alkine‐“click” reactions with a variety of terminal alkynes in the presence of a catalyst system consisting of tetrakis(acetonitrile)hexafluorophosphate copper(I) and tris(1‐benzyl‐5‐methyl‐1H‐ [1,2,3]triazol‐4‐ylmethyl)‐amine furnished the substituted block copolymers in high yields, as proven by NMR‐spectroscopy. The resulting polymers were investigated via temperature‐dependent SAXS‐methods, revealing their microphase separated structure as well as their temperature‐dependent behavior. The presented method offers the generation of a large set of different block‐copolymers from only a small set of starting materials because of the high versatility of the “click” reaction, thus enabling a simple and complete functionalization after the initial polymerization reaction. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 485–499, 2007     

Surface‐Grafted conjugated polymers for hybrid cellulose materials

Conjugated polymers were grafted onto cellulose substrates in an effort to create a general method for the synthesis of conjugated polymer/cellulose hybrid materials. In this report, we describe the grafting of poly(fluorene), poly(fluorenevinylene), and a poly(fluorene‐ethynylene‐phenylene) onto modified cellulose paper substrates using Suzuki, Heck, and Sonogashira‐type polymerizations, respectively. The application of these three widely used coupling chemistries to surface‐grafted conjugated polymers on cellulose provides a general route to cellulose‐based hybrid materials tunable with almost any aromatic repeat structure for specific applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Covalent Attachment of Fibronectin onto Emulsion‐Templated Porous Polymer Scaffolds Enhances Human Endometrial Stromal Cell Adhesion,Infiltration, and Function

A novel strategy for the surface functionalization of emulsion‐templated highly porous (polyHIPE) materials as well as its application to in vitro 3D cell culture is presented. A heterobifunctional linker that consists of an amine‐reactive N‐hydroxysuccinimide ester and a photoactivatable nitrophenyl azide, N‐sulfosuccinimidyl‐6‐(4′‐azido‐2′‐nitrophenylamino)hexanoate (sulfo‐SANPAH), is utilized to functionalize polyHIPE surfaces. The ability to conjugate a range of compounds (6‐aminofluorescein, heptafluorobutylamine, poly(ethylene glycol) bis‐amine, and fibronectin) to the polyHIPE surface is demonstrated using fluorescence imaging, FTIR spectroscopy, and X‐ray photoelectron spectroscopy. Compared to other existing surface functionalization methods for polyHIPE materials, this approach is facile, efficient, versatile, and benign. It can also be used to attach biomolecules to polyHIPE surfaces including cell adhesion‐promoting extracellular matrix proteins. Cell culture experiments demonstrated that the fibronectin‐conjugated polyHIPE scaffolds improve the adhesion and function of primary human endometrial stromal cells. It is believed that this approach can be employed to produce the next generation of polyHIPE scaffolds with tailored surface functionality, enhancing their application in 3D cell culture and tissue engineering whilst broadening the scope of applications to a wider range of cell types.     

PET‐RAFT as a facile strategy for preparing functional lipid–polymer conjugates

From readily available starting materials, we report a facile synthesis of lipid–polymer conjugates (LPCs). Easy access to multigram quantities of a dialkyl lipid chain transfer agent allows a range of LPCs to be prepared bearing well‐defined hydrophilic polymer head‐groups, controlled molecular weights and low dispersity by photoelectron transfer RAFT polymerization (PET‐RAFT). As dictated by the lipid packing parameters, the resulting LPCs were suitable for solution‐phase self‐assembly, both independently and in combination with naturally occurring phospholipids, affording micelles, smaller vesicle‐like structures, or stabilized large unilamellar vesicles. Notably, co‐assembly of LPCs and phospholipids bearing mutually orthogonal fluorophores showed negligible phase separation/aggregation. To demonstrate the versatility of these LPCs, the RAFT chain‐end was removed, affording thiol‐terminated LPCs that could be used for the manipulation and stabilization of gold nanoparticle assemblies. Facile access to structurally diverse LPC building blocks enables a variety of biotechnology and biomedical applications, including drug‐delivery, cell engineering, and 3D‐printed biomaterials. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1259–1268     

Bandgap engineering of indenofluorene‐based conjugated copolymers with pendant donor‐π‐acceptor chromophores for photovoltaic applications

Three narrow‐band‐gap conjugated copolymers based on indenofluorene and triphenylamine with pendant donor‐π‐acceptor chromophores were successfully synthesized by post‐functionalization approach. All the polymers have good solubility in common solvents and excellent thermal stability. The photophysical properties, energy levels and band gaps of the polymers were well manipulated by introducing different acceptor groups onto the end of their conjugated side chains. By using different acceptor groups, the band gaps of the polymers were narrowed from 1.86 to 1.53 eV by lowering their lowest unoccupied molecular orbital levels, whereas their relatively deep highest occupied molecular orbital levels of approximately ?5.35 eV were maintained. Bulk‐heterojunction solar cells with these polymers as electron donors and (6,6)‐phenyl‐C₇₁‐butyric acid methyl ester as acceptor showed power conversion efficiencies as high as 3.1% and high open circuit voltages more than 0.88 eV. The relationships between the performance and film morphology, energy levels, charge mobilities were discussed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of stable “gold nanoparticle–polymeric micelle” conjugates: A new class of star “molecular chimera” that self‐assemble into linear arrays of spherical micelles

Stable and aggregation‐free “gold nanoparticle–polymeric micelle” conjugates were prepared using a new and simple protocol enabled by the hydrogen bonding between surface‐capping ligands and polymeric micelles. Individual gold nanoparticles were initially capped using a phosphatidylthio–ethanol lipid and further conjugated with a star poly(styrene‐block‐glutamic acid) copolymer micelle using a one‐pot preparation method. The morphology and stability of these gold–polymer conjugates were characterized using transmission electron microscopy (TEM) and UV–vis spectroscopy. The self‐assembly of this class of polymer‐b‐polypeptide in aqueous an medium to form spherical micelles and further their intermicelle reorganization to form necklace‐like chains was also investigated. TEM and laser light scattering techniques were employed to study the morphology and size of these micelles. Polymeric micelles were formed with diameters in the range of 65–75 nm, and supermicellular patterns were observed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3570–3579, 2007     

A versatile method for cyclic polymers from conjugated and unconjugated vinyl monomers

A versatile method was introduced to prepare cyclic polymers from both conjugated and unconjugated vinyl monomers. It was developed on the combination of the RAFT polymerization and the self‐accelerating double strain‐promoted azide‐alkyne click (DSPAAC) reaction. In this approach, a switchable chain transfer agent 1 was designed to have hydroxyl terminals and a functional pyridinyl group. The protonation and deprotonation of pyridinyl group endowed the chain transfer agent 1 with a switchable control capability to RAFT polymerization of both conjugated and unconjugated vinyl monomers. Based on this, RAFT polymerization and the following hydroxyl end group modification were used to prepare various azide‐terminated linear polymers including polystyrene, poly(N‐vinylcarbazole), and polystyrene‐block‐poly(N‐vinylcarbazole). Using sym‐dibenzo‐1,5‐cyclooctadiene‐3,7‐diyne (DBA) as small linkers, the corresponding cyclic polymers were then prepared via the DSPAAC reaction between DBA and azide terminals of the linear precursors. Due to the self‐accelerating property of DSPAAC reaction, this bimolecular ring‐closing reaction could efficiently produce the pure cyclic polymers using excess molar amounts of DBA to linear polymer precursors. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 1811–1820     

Cyclodextrin-based inclusion complexation bridging supramolecular chemistry and macromolecular self-assembly

Research into macromolecular self-assembly has been progressively developing since the 1970s but with a little affect from the achievements of supramolecular chemistry. In recent years, this situation has changed as more and more factors and concepts in supramolecular chemistry have been introduced into studies of the self-assembly of polymers. In this respect, inclusion complexation based on cyclodextrins plays a remarkable role. In this tutorial review, we address how inclusion complexation has been employed and used to promote the recent developments in macromolecular self-assembly. These include the amphiphilicity adjustment of macromolecules, non-covalent linkages for forming pseudo block copolymers and micelles, surface modification and functionalization of polymeric micelles and vesicles, and the combination of synthetic polymeric assemblies with biological moieties. Furthermore, the realization of the reversible stimuli-responsiveness of polymeric assemblies and materials, particularly hydrogels by means of controllable inclusion complexation is discussed as well.     

Synthesis and two‐photon absorption properties of conjugated polymers with N‐arylpyrrole as conjugated bridge and isolation moieties

Three novel conjugated polymers with N‐arylpyrrole as the conjugated bridge were designed and synthesized, which emitted strong one‐ or two‐photon excitation fluorescence in dilute tetrahydrofuran (THF) solution with high quantum yields. The maximal two‐photon absorption (TPA) cross‐sections of the polymers, measured by the two‐photon‐induced fluorescence method using femtosecond laser pulses in THF, were 752, 1114, and 1869 GM, respectively, indicating that the insertion of electron‐donating or electron‐withdrawing moieties into the polymer backbone could benefit to the increase of the TPA cross‐section. Their large TPA cross‐sections, coupled with the relatively high emission quantum yields, made these conjugated polymers attractive for practical applications, especially two‐photon excited fluorescence. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

A Chemo‐Mechanical Tweezer for Single‐Molecular Characterization of Soft Materials

A new atomic force microscopy (AFM)‐based chemo‐mechanical tweezer has been developed that can measure mechanical properties of individual macromolecules in supramolecular assembly and reveal positions of azide‐containing polymers. A key feature of the new technology is the use of an AFM tip densely modified with 4‐dibenzocyclooctynols (chemo‐mechanical tweezer) that can react with multiple azide containing macromolecules of micelles to give triazole “clicked” compounds, which during retracting phases of AFM imaging are removed from the macromolecular assembly thereby providing a surface topographical image and positions of azide‐containing polymers. The force–distance curves gave mechanical properties of removal of individual molecules from a supramolecular assembly. The new chemo‐mechanical tweezer will make it possible to characterize molecular details of macromolecular assemblies thereby offering new avenues to tailor properties of such assemblies.     

Temperature‐induced self‐assembly and metal‐ion stabilization of histidine functional block copolymers

Histidine functional block copolymers are thermally self‐assembled into polymer micelles with poly‐N‐isopropylacrylamide in the core and the histidine functionality in the corona. The thermally induced self‐assemblies are reversible until treated with Cu²⁺ ions at 50 °C. Upon treatment with 0.5 equivalents of Cu²⁺ relative to the histidine moieties, metal‐ion coordination locks the self‐assemblies. The self‐assembly behavior of histidine functional block copolymers is explored at different values of pH using DLS and ¹H NMR. Metal‐ion coordination locking of the histidine functional micelles is also explored at different pH values, with stable micelles forming at pH 9, observed by DLS and imaged by atomic force microscopy. The thermal self‐assembly of glycine functional block copolymers at pH 5, 7, and 9 is similar to the histidine functional materials; however, the self‐assemblies do not become stable after the addition of Cu²⁺, indicating that the imidazole plays a crucial role in metal‐ion coordination that locks the micelles. The reversibility of the histidine‐copper complex locking mechanism is demonstrated by the addition of acid to protonate the imidazole and destabilize the polymer self‐assemblies. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1964–1973     

Covalent surface functionalization of multiwalled carbon nanotubes through bergman cyclization of enediyne‐containing dendrimers

A method for covalent functionalization of multiwalled carbon nanotubes (MWCNTs) was developed using the free radicals generated through Bergman cyclization of enediyne‐containing compounds. Four enediyne‐bearing Frechet type dendrimers were synthesized in good quantities and characterized. Then, the enediyne‐containing molecules were reacted with MWCNTs in N‐methyl‐2‐pyrrolidinone at 206 °C under nitrogen. The structure and morphology of the resulting products were characterized by thermogravimetric analysis, ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and transmission electron microscopy. The dendrimer‐functionalized MWCNTs showed good solubility/dispersibility in common organic solvents and polymer solutions. They were used in the formation of polymer composites through electrospinning with polycaprolactone. The results confirmed the surface functionalization of MWCNTs. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011