Comparison of Facially Amphiphilic versus Segregated Monomers in the Design of Antibacterial Copolymers

A direct comparison of two strategies for designing antimicrobial polymers is presented. Previously, we published several reports on the use of facially amphiphilic (FA) monomers which led to polynorbornenes with excellent antimicrobial activities and selectivities. Our polymers obtained by copolymerization of structurally similar segregated monomers, in which cationic and non‐polar moieties reside on separate repeat units, led to polymers with less pronounced activities. A wide range of polymer amphiphilicities was surveyed by pairing a cationic oxanorbornene with eleven different non‐polar monomers and varying the comonomer feed ratios. Their properties were tested using antimicrobial assays and copolymers possessing intermediate hydrophobicities were the most active. Polymer‐induced leakage of dye‐filled liposomes and microscopy of polymer‐treated bacteria support a membrane‐based mode of action. From these results there appears to be profound differences in how a polymer made from FA monomers interacts with the phospholipid bilayer compared with copolymers from segregated monomers. We conclude that a well‐defined spatial relationship of the whole polymer is crucial to obtain synthetic mimics of antimicrobial peptides (SMAMPs): charged and non‐polar moieties need to be balanced locally, for example, at the monomer level, and not just globally. We advocate the use of FA monomers for better control of biological properties. It is expected that this principle will be usefully applied to other backbones such as the polyacrylates, polystyrenes, and non‐natural polyamides.     

Using Chemoattractants to Lure Bacteria to Contact‐Killing Surfaces

Antimicrobial surfaces with covalently attached biocidal functionalities only kill microbes that come into direct contact with the surfaces (contact‐killing surfaces). Herein, the activity of contact‐killing surfaces is shown to be enhanced by using gradients in the concentration of soluble chemoattractants (CAs) to attract bacteria to the surfaces. Two natural and nonbiocidal CAs (aspartate and glucose) were used to attract bacteria to model surfaces decorated with quaternary ammonium groups (known to kill bacteria that come into contact with them). These results demonstrate the killing of Escherichia coli and Salmonella typhimurium, two common pathogens, at levels 10‐ to 20‐times greater than that of the native surfaces alone. This approach is general and provides new strategies for the design of active or dynamic contact‐killing surfaces with enhanced antimicrobial activities.     

Bacteria‐Assisted Activation of Antimicrobial Polypeptides by a Random‐Coil to Helix Transition

The application of antimicrobial peptides (AMPs) is largely hindered by their non‐specific toxicity against mammalian cells, which is usually associated with helical structure, hydrophobicity, and charge density. A random coil‐to‐helix transition mechanism has now been introduced into the design of AMPs, minimizing the toxicity against mammalian cells while maintaining high antimicrobial activity. By incorporating anionic phosphorylated tyrosine into the cationic polypeptide, the helical structure of AMPs was distorted owing to the side‐chain charge interaction. Together with the decreased charge density, the AMPs exhibited inhibited toxicity against mammalian cells. At the infectious site, the AMPs can be activated by bacterial phosphatase to restore the helical structure, thus contributing to strong membrane disruptive capability and potent antimicrobial activity. This bacteria‐activated system is an effective strategy to enhance the therapeutic selectivity of AMPs.     

2,3,4,5‐Tetraphenylsilole‐Based Conjugated Polymers: Synthesis,Optical Properties,and as Sensors for Explosive Compounds

A series of linear 2,5‐tetraphenylsilole‐vinylene‐type polymers were successfully synthesized for the first time. The tetraphenylsilole moieties were linked at their 2,5‐positions through a vinylene bridge with p‐dialkoxybenzenes to obtain polymer PSVB and with 3,6‐carbazole to obtain polymer PSVC . For comparison, 2,5‐tetraphenylsilole‐ethyne‐type polymer PSEB was also synthesized, in which the vinylene bridge of PSVB was replaced with an ethyne bridge. Very interestingly, the bridging group (vinylene or ethyne) had a significant effect on the photophysical properties of the corresponding polymers. The fluorescence peak of PSEB at 504 nm in solution originated from the emission of its silole moieties, whereas PSVB and PSVC emitted yellow light and no blueish–green emission from the silole moieties was observed, thus demonstrating that the emissions of PSVB and PSVC were due to their polymer backbones. More importantly, the 2,5‐tetraphenylsilole‐ethyne polymer exhibited a pronounced aggregation‐enhanced emission (AEE) effect but the 2,5‐tetraphenylsilole‐vinylene polymer was AEE‐inactive. Moreover, both AEE‐active 2,5‐tetraphenylsilole‐ethyne polymer and AEE‐inactive 2,5‐tetraphenylsilole‐vinylene polymers were successfully applied as fluorescent chemosensors for the detection of explosive compounds.     

Eradication of Gram‐Positive and Gram‐Negative Bacteria by Photosensitizers Immobilized in Polystyrene

Immobilization of photosensitizers in polymers opens prospects for their continuous and reusable application. Methylene blue (MB) and Rose Bengal were immobilized in polystyrene by mixing solutions of the photosensitizers in chloroform with a polymer solution, followed by air evaporation of the solvent. This procedure yielded 15–140 μm polymer films with a porous surface structure. The method chosen for immobilization ensured 99% enclosure of the photosensitizer in the polymer. The antimicrobial activity of the immobilized photosensitizers was tested against Gram‐positive and Gram‐negative bacteria. It was found that both immobilized photosensitizers exhibited high antimicrobial properties, and caused by a 1.5–3 log₁₀ reduction in the bacterial concentrations to their total eradication. The bactericidal effect of the immobilized photosensitizers depended on the cell concentration and on the illumination conditions. Scanning electron microscopy was used to prove that immobilized photosensitizers excited by white light caused irreversible damage to microbial cells. Photosensitizers immobilized on a solid phase can be applied for continuous disinfection of wastewater bacteria.     

Nano‐Star‐Shaped Polymers for Drug Delivery Applications

With the advancement of polymer engineering, complex star‐shaped polymer architectures can be synthesized with ease, bringing about a host of unique properties and applications. The polymer arms can be functionalized with different chemical groups to fine‐tune the response behavior or be endowed with targeting ligands or stimuli responsive moieties to control its physicochemical behavior and self‐organization in solution. Rheological properties of these solutions can be modulated, which also facilitates the control of the diffusion of the drug from these star‐based nanocarriers. However, these star‐shaped polymers designed for drug delivery are still in a very early stage of development. Due to the sheer diversity of macromolecules that can take on the star architectures and the various combinations of functional groups that can be cross‐linked together, there remain many structure–property relationships which have yet to be fully established. This review aims to provide an introductory perspective on the basic synthetic methods of star‐shaped polymers, the properties which can be controlled by the unique architecture, and also recent advances in drug delivery applications related to these star candidates.     

Selective Control of Cell Activity with Hydrophilic Polymer‐Covered Cationic Nanoparticles

Cationic polymers exhibit high cytotoxicity via strong interaction with cell membranes. To reduce cell membrane damage, a hydrophilic polymer is introduced to the cationic nanoparticle surface. The hydrophilic polymer coating of cationic nanoparticles resulted in a nearly neutral nanoparticle. These particles are applied to mouse fibroblast (3T3) and human cervical adenocarcinoma (Hela) cells. Interestingly, nanoparticles with a long cationic segment decrease cell activity regardless of cell type, while those with a short segment only affect 3T3 cell activity at lower concentrations less than 500 µg mL^?1. Most nanoparticles are located inside 3T3 cells but on the cell membrane of Hela cells. The short cationic nanoparticle shows negligible cell membrane damage despite its high accumulation on Hela cell membranes. Cell activity changed by hydrophilic polymer‐coated cationic nanoparticles is caused by incorporated nanoparticle accumulation in the cells, not cell membrane damage. To suppress the cytotoxicity from the cationic polymer, cationic nanoparticle needs to completely cover with hydrophilic polymer so as not to exhibit the cationic effect and applies to cell with low concentrations to reduce the nonselective cytotoxicity from the cationic polymer.     

Single step synthesis of poly(3‐octylthiophene)/multi‐walled carbon nanotube composites and their characterizations

The transport properties of conducting polymers are known to be greatly influenced by the chemical unsaturation surrounding the polymer backbone, besides favorable conformation of the side chains present. Polymeric composites with multi‐walled carbon nanotubes (MWNT) can provide a good conductive path at relatively low carbon contents, as these have high aspect ratio, specific surfaces and are cost effective. Hence their use in various applications such as organic LED, solar cells and supercapacitors are very much anticipated. In this respect poly(3‐octylthiophene)/MWNT composites have been prepared by an “insitu” polymerization process in chloroform medium with FeCl₃ oxidant at room temperature. The composites were characterized by Fourier Transfer Infrared spectroscopy (FT‐IR), Raman, work function and X‐ray diffraction (XRD) measurements. The results indicate only a weak π‐π interaction between the moieties, in the absence of a strong covalent bonding. The ultraviolet–visible (UV–Vis) measurements also support this view. The photoluminescence (PL) quenching indicates the effectiveness of the interface in the formation of the donor–acceptor type composite. The conductivity of the composites is followed by a four probe technique to understand the conduction mechanism. The Hall voltage measurement is followed to monitor carrier concentrations and mobilities. The impressive conductivity and mobility values encourage the utility of the composites as photovoltaic material. Copyright © 2008 John Wiley & Sons, Ltd.     

Bioinspired,Size‐Tunable Self‐Assembly of Polymer–Lipid Bilayer Nanodiscs

Polymer‐based nanodiscs are valuable tools in biomedical research that can offer a detergent‐free solubilization of membrane proteins maintaining their native lipid environment. Herein, we introduce a novel ca. 1.6 kDa SMA‐based polymer with styrene:maleic acid moieties that can form nanodiscs containing a planar lipid bilayer which are useful to reconstitute membrane proteins for structural and functional studies. The physicochemical properties and the mechanism of formation of polymer‐based nanodiscs are characterized by light scattering, NMR, FT‐IR, and TEM. A remarkable feature is that nanodiscs of different sizes, from nanometer to sub‐micrometer diameter, can be produced by varying the lipid‐to‐polymer ratio. The small‐size nanodiscs (up to ca. 30 nm diameter) can be used for solution NMR spectroscopy studies whereas the magnetic‐alignment of macro‐nanodiscs (diameter of > ca. 40 nm) can be exploited for solid‐state NMR studies on membrane proteins.     

Star‐Shaped Polyaromatic Ethers Coordinated to Redox‐Active Cyclopentadienyliron Moieties

This communication is focused on the controlled design of star‐shaped aromatic ethers with pendent cyclopentadienyliron moieties. A trimetallic core was prepared, which was then reacted with a number of oligomeric ether complexes to give star‐shaped polymers with six, nine, twelve and fifteen pendent cationic cyclopentadienyliron moieties. Cyclic voltammetric studies showed reduction of the iron centers between –0.99 and –1.41 V. Thermogravimetric analysis showed that loss of the metallic moieties occurred between 225 and 284°C.     

Polymer Acceptor Based on B←N Units with Enhanced Electron Mobility for Efficient All‐Polymer Solar Cells

We demonstrate that polymer electron acceptors with excellent all‐polymer solar‐cell (all‐PSC) device performance can be developed from polymer electron donors by using B←N units. By alleviating the steric hindrance effect of the bulky pendant moieties on the conjugated polymers that contain B←N units, the π–π stacking distance of polymer backbones is decreased and the electron mobility is consequently enhanced by nearly two orders of magnitude. As a result, the power conversion efficiency of all‐PSCs with the polymer acting as the electron acceptor is greatly improved from 0.12 % to 5.04 %. This PCE value is comparable to that of the best all‐PSCs with state‐of‐the‐art polymer acceptors.     

Iron‐Catalysed Radical Polymerisation by Living Bacteria

The ability to harness cellular redox processes for abiotic synthesis might allow the preparation of engineered hybrid living systems. Towards this goal we describe a new bacteria‐mediated iron‐catalysed reversible deactivation radical polymerisation (RDRP), with a range of metal‐chelating agents and monomers that can be used under ambient conditions with a bacterial redox initiation step to generate polymers. Cupriavidus metallidurans, Escherichia coli, and Clostridium sporogenes species were chosen for their redox enzyme systems and evaluated for their ability to induce polymer formation. Parameters including cell and catalyst concentration, initiator species, and monomer type were investigated. Water‐soluble synthetic polymers were produced in the presence of the bacteria with full preservation of cell viability. This method provides a means by which bacterial redox systems can be exploited to generate “unnatural” polymers in the presence of “host” cells, thus setting up the possibility of making natural–synthetic hybrid structures and conjugates.     

4,9‐Dihydro‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene‐4,9‐dione functionalized copolymers for organic photovoltaic devices

The synthesis of conjugated polymers 1 – 5 functionalized with 4,9‐dihydro‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene‐4,9‐dione in the backbone is reported and their use in the construction of organic solar cells is demonstrated. Increasing the molar ratio of 2,7‐dibromo‐3,8‐dihexyl‐4,9‐dihydro‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene‐4,9‐dione, relative to 4,4′‐dihexyl‐5,5′‐dibromo‐2,2′‐bithiophene, in the copolymer synthesis significantly lowers the solubility of these polymers. The incorporation of highly conjugated 3,8‐dihexyl‐4,9‐dihydro‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene‐4,9‐dione unit into the polymer backbone has been confirmed by UV–vis absorption. The observation of decreasing quantum yield for the emission in the order of 1 , 2 , 3 is consistent with copolymers with different comonomer content. The power conversion efficiencies of solar cells using blends of these polymers with PCBM ([6,6]‐phenyl C₆₁‐butyric acid methyl ester) were determined to be 0.11% for polymer 1 , 0.33% for 2 , and 0.26% for 3 , respectively. Under identical white light illumination, the power conversion efficiency of the device based on polymer 2 /PCBM as the active layer was three times higher compared to that of device based on polymer 1 /PCBM. Owing to the limited solubility and poor film‐forming ability of polymer 3 , the power conversion efficiency of solar cell based on 3 /PCBM blend is lower than that of 2 /PCBM blend, but is still larger than that of 1 /PCBM blend. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2680–2688, 2008     

Synthesis and characterization of indeno[1,2‐b]fluorene‐based white light‐emitting copolymer

An indenofluorene‐based copolymer containing blue‐, green‐, and red light‐emitting moieties was synthesized by Suzuki polymerization and examined for application in white organic light‐emitting diodes (WOLEDs). Tetraoctylindenofluorene (IF), 2,1,3‐benzothiadiazole (BT), and 4,7‐bis(2‐thienyl)‐2,1,3‐benzothiadiazole (DBT) derivatives were used as the blue‐, green‐, and red‐light emitting structures, respectively. The number‐average molecular weight of the polymer was determined to be 25,900 g/mol with a polydispersity index of 2.02. The polymer was thermally stable (T_d = ～398 °C) and quite soluble in common organic solvents, forming an optical‐quality film by spin casting. The EL characteristics were fine‐tuned from the single copolymer through incomplete fluorescence energy transfer by adjusting the composition of the red/green/blue units in the copolymer. The EL device using the indenofluorene‐based copolymer containing 0.01 mol % BT and 0.02 mol % DBT units ( PIF‐BT01‐DBT02 ) showed a maximum brightness of 4088 cd/m² at 8 V and a maximum current efficiency of 0.36 cd/A with Commission Internationale de L'Eclairage (CIE) coordinates of (0.34, 0.32). The EL emission of PIF‐BT01‐DBT02 was stable with respect to changes in voltage. The color emitted was dependent on the thickness of the active polymer layer; layer (～60 nm) too thin was unsuitable for realizing WOLED via energy transfer. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3467–3479, 2009     

Electrospun poly(aniline‐co‐ethyl 3‐aminobenzoate)/poly(lactic acid) nanofibers and their potential in biomedical applications

Poly(aniline‐co‐ethyl 3‐aminobenzoate) (3EABPANI) copolymer was blended with poly(lactic acid) (PLA) and co‐electrospun into nanofibers to investigate its potential in biomedical applications. The relationship between electrospinning parameters and fiber diameter has been investigated. The mechanical and electrical properties of electrospun 3EABPANI‐PLA nanofibers were also evaluated. To assess cell morphology and biocompatibility, nanofibrous mats of pure PLA and 3EABPANI‐PLA were deposited on glass substrates and the proliferation of COS‐1 fibroblast cells on the nanofibrous polymer surfaces determined. The nanofibrous 3EABPANI‐PLA blends were easily fabricated by electrospinning and gave enhanced mammalian cell growth, antioxidant and antimicrobial capabilities, and electrical conductivity. These results suggest that 3EABPANI‐PLA nanofibrous blends might provide a novel bioactive conductive material for biomedical applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.     

Synthesis of polycarbosilanes having sugar‐derived structures as novel materials for cell cultivation

Polycarbosilanes with or without sugar‐derived structures in the polymer side chains were synthesized and their application to materials for cell cultivation was investigated. Polysilacyclobutanes having glucose‐derived moieties or N‐acetylglucosamine‐derived moieties (polyBMSB‐glucose and polyBMSB‐AGA) were synthesized by ene‐thiol reaction between precursor poly(1‐(3‐butenyl)?1‐methylsilacyclubane) (polyBMSB) and tetraacetylglucose or tetraacetylglucosamine having a thiol group at the anomeric position and the successive deprotection of the acetyl groups gave polycarbosilanes with sugar‐derived structures in the side chains. Poly(1‐(3‐hydroxybutyl)‐1‐methylsilacyclobutane) was synthesized by hydroboration/oxidation of the precursor polyBMSB. The cell cultivation efficiency using the polymers with or without sugar moieties was evaluated by cultivation of WRL cells on the polystyrene dishes coated with the polymers. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2267–2272     

Synthesis and surfactochromicity of 1,4‐diketopyrrolo[3,4‐c]pyrrole(DPP)‐based anionic conjugated polyelectrolytes

Two novel anionic conjugated copolyelectrolytes PSDPPPV and PSDPPPE were synthesized via Heck/Sonogashira coupling reactions and characterized by FT‐IR, ¹H NMR, UV‐vis, and PL spectroscopy. The two polymers are respectively constituted of 2,5‐diethoxy‐1,4‐phenyleneethynylene (DPV) and 2,5‐diethoxy‐1,4‐phenyleneethynylene (DPE) with 1,4‐diketo‐2,5‐bis(4‐sulfonylbutyl)‐3,6‐diphenylpyrrolo[3,4‐c]pyrrole (SDPP) which is a novel water soluble diketopyrrolopyrrole derivative. PSDPPPV and PSDPPPE show broad absorption band in visible region and they exhibit strong fluorescence quenching in aqueous solution. The fluorescence of their aqueous solutions can be enhanced in the presence of cationic surfactant or polymer nonionic surfactant. Fluorescence enhancement by introduction of polyvinylpyrrolidone (PVP) shows linear response. This result provides a controllable method to increase fluorescence intensity of dipyrrolopyrrole‐based conjugate polyelectrolytes in aqueous phase. The optical properties suggested that PSDPPPV and PSDPPPE which are negatively charged conjugated polymers can assemble with positively charged photovoltaic materials to form ionic photoactive layer. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 739–751     

Visualizing Cholesterol Uptake by Self‐Assembling Rhodamine B‐Labeled Polymer Inside Living Cells via FLIM‐FRET Microscopy

Atherosclerosis is a widespread and hazardous disease characterized by the formation of arterial plaques mostly composed of fat, cholesterol, and calcium ions. The direct solubilization of cholesterol represents a promising, atheroprotective strategy to subside lipid blood levels and reverse atherosclerosis. This study deals with the in‐depth analysis of polymer‐mediated cholesterol dissolution inside living human cells. To this end, a recently described multifunctional block‐polymer is labeled with Rhodamine B (RhoB) to investigate its interaction with cells via fluorescence microscopy. This gives insight into the cellular internalization process of the polymer, which appears to be clathrin‐ and caveolae/raft‐dependent endocytosis. In cell single particle tracking reveals an active transport of RhoB polymer including structures. Förster resonance energy transfer (FRET) measurements of cells treated with a fluorophore‐tagged cholesterol derivative and the RhoB polymer indicates the uptake of cholesterol by the polymeric particles. Hence, these results present a first step toward possible applications of cholesterol‐absorbing polymers for treating atherosclerosis.     

Biologically active polymers. V. Synthesis and antimicrobial activity of modified poly(glycidyl methacrylate‐co‐2‐hydroxyethyl methacrylate) derivatives with quaternary ammonium and phosphonium salts

Antimicrobial copolymers bearing quaternary ammonium and phosphonium salts based on a copolymer of glycidyl methacrylate and 2‐hydroxyethyl methacrylate were synthesized. Poly(glycidyl methacrylate‐co‐2‐hydroxyethyl methacrylate) was modified for the introduction of chloromethyl groups by its reaction with chloroacetyl chloride. The chloroacetylated copolymer was modified for the production of quaternary ammonium or phosphonium salts. The antimicrobial activity of the obtained copolymers was studied against gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Shigella sp., and Salmonella typhae), gram‐positive bacteria (Bacillus subtilus and B. cereus), and the fungus Trichophyton rubrum by the cut‐plug method. The results showed that the three copolymers had high antimicrobial activity. A control experiment was carried out on the main polymer without ammonium or phosphonium groups. The copolymer bearing quaternary salt made from tributyl phosphine was the most effective copolymer against both gram‐negative and gram‐positive bacteria and the fungus T. rubrum. The diameters of the inhibition zones ranged between 20 and 60 mm after 24 h. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2384–2393, 2002     

Cation‐Dependent Stabilization of Electrogenerated Naphthalene Diimide Dianions in Porous Polymer Thin Films and Their Application to Electrical Energy Storage

Porous polymer networks (PPNs) are attractive materials for capacitive energy storage because they offer high surface areas for increased double‐layer capacitance, open structures for rapid ion transport, and redox‐active moieties that enable faradaic (pseudocapacitive) energy storage. Here we demonstrate a new attractive feature of PPNs—the ability of their reduced forms (radical anions and dianions) to interact with small radii cations through synergistic interactions arising from densely packed redox‐active groups, only when prepared as thin films. When naphthalene diimides (NDIs) are incorporated into PPN films, the carbonyl groups of adjacent, electrochemically generated, NDI radical anions and dianions bind strongly to K⁺, Li⁺, and Mg²⁺, shifting the formal potentials of NDI’s second reduction by 120 and 460 mV for K⁺ and Li⁺‐based electrolytes, respectively. In the case of Mg²⁺, NDI’s two redox waves coalesce into a single two‐electron process with shifts of 240 and 710 mV, for the first and second reductions, respectively, increasing the energy density by over 20 % without changing the polymer backbone. In contrast, the formal reduction potentials of NDI derivatives in solution are identical for each electrolyte, and this effect has not been reported for NDI previously. This study illustrates the profound influence of the solid‐state structure of a polymer on its electrochemical response, which does not simply reflect the solution‐phase redox behavior of its monomers.