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Gure 4Developing phosphonic acid bearing polyelectrolytes for their biocidal activity on surfaces, thermal properties, nanofiber and nano particle formation

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Abstract

Bacteria infection is a growing problem all over the world. Within this contribution, phosphonium-phosphonic acid or hexyl pyridinium-phosphonic acid bearing copolymer series derived via ring opening metathesis polymerization (ROMP) method are synthesized to investigate their biocidal activity on the glass surface. The presence of phosphonic acid moieties enhanced the coating capability on the iron oxide nanoparticles and the thermal properties of the copolymers. Biocidal activities of the polymers and iron oxide bearing polymers were tested against E.coli and S.aureus. Polymers possessing higher activity was then blended with commercial polyacrylonitrile for the nanofiber formation via electrospinning methods.

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... Apart from cancer treatment, IoNPs also showed antimicrobial and antibacterial properties [200] . Antibacterial action in food packaging of sulphar is stagnant due to hydrophobic nature. ...
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New approaches to treat bacterial infections are badly needed to address the increasing problem of antibiotic-resistance. This study explores phosphonium-functionalized block copolymer micelles as intrinsically antibacterial polymer assemblies. Phosphonium cations with varying alkyl lengths were conjugated to the terminus of a poly(ethylene oxide)-polycaprolactone block copolymer and the phosphonium-functionalized block copolymers were self-assembled to form micelles in aqueous solution. The size, morphology, and ζ-potential of the assemblies were studied and their abilities to kill Escherichia coli and Staphylococcus aureus were evaluated. It was found that the minimum bactericidal concentration depended on the phosphonium alkyl chain length and different trends were observed for Gram-negative and Gram-positive bacteria. The most active assemblies exhibited no hemolysis of red blood cells above the bactericidal concentrations, indicating that they can selectively disrupt the membranes of bacteria. Furthermore, it was possible to encapsulate and release the antibiotic tetracycline using the assemblies, providing a potential multi-mechanistic approach to bacterial killing.
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Electrospun nanofibers incorporated with antimicrobial agents have been produced with antimicrobial capability against a wide range of microorganisms. These nanofibers show promising applications in filtration, wound-dressing materials, protective textiles, tissue scaffolds, and biomedical devices. A comprehensive review is presented on current research and development activities of electrospun nanofibers incorporated with different antimicrobial agents. The effects of loading antimicrobial agents on the characteristics of precursor solutions with different polymer systems and properties of resultant electrospun nanofibers are summarized. The antimicrobial mechanism of selected antimicrobial agents and different methods on maximizing antimicrobial performance of electrospun nanofibers are also discussed. Keywords Electrospinning; Antimicrobial; Metallic nanoparticles; Carbon nanomaterials; Antibiotics; Biopolymers; ɛ-Poly-lysine Acknowledgment The authors would like to acknowledge the financial support from the Economic Development Assistantship Program of Louisiana State University, the USDA National Institute of Food and Agriculture McIntire Stennis project [1000017], and USDA-NIFA (Grant No. 2008-38814-04771).
Article
Poly(ethylene glycol)-poly(vinylphosphonic acid) block copolymers (PEG-b-PVPA) of low average molar mass were synthesized by RAFT/MADIX polymerization. Their intrinsic properties (i.e. anionic-neutral character which brings both ability to strongly interact with cations and steric stabilization) allow the one-step in situ synthesis of water dispersible iron oxide nanoparticles with controlled size and high colloidal stability. The effect of structural properties of the polymer (chain length of PEG and PVPA blocks) on the formation and/or stabilization of nanoparticles has been evaluated. Additionally, PVPA and PAA block complexing abilities were compared and the advantage of phosphonic acid groups over carboxylic acid groups was proven. Hemocompatibility tests carried out with the DHBCs alone and DHBC / iron oxide hybrid nanoparticles revealed that the hemolysis rates observed with phosphonated copolymers were much lower than for their carboxylated analogs.
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Magnetite nanoparticles due to the special specifications have been widely used in medical as well as industrial applications. In such applications, it is important to control morphology and size of the nanoparticles. In this work, magnetite nanoparticles were synthesized via the co-precipitation method. For investigating the effect of various precursors on mean size and morphology of synthesized nanoparticles, six groups of magnetite precursors were arranged. The magnetite product of each group was characterized by using XRD, SEM, TEM, VSM and the analytical methods. The results have shown the kind of precursors influence on the mean size of the synthesized nanoparticles. The reason for this behavior was explained by the double layer theory. However, kind of precursors did not have a sensible effect on the morphology of the synthesized nanoparticles.
Article
In this study, amphiphilic polyoxanorbornene with different alkyl and aromatic phosphonium side chains was synthesized. The biological activities of these polymers were determined by the minimal inhibitory concentration (MIC) against E. coli, S. aureus, M. tuberculosis and the yeast C. albicans, and cytotoxicity studies on red blood cells were performed. A series of polymers with different alkyl and aromatic substituents (methyl, ethyl, tripropyl, tert-butyl, phenyl, and tris 4-methoxyphenyl) and two types different molecular weight, 3000 g mol−1 and 10000 g mol−1, were prepared. It was observed that the biological activity of the polymers with aromatic group substituents had an MIC of 16, 8, 64 and 128 μg mL−1 against E. coli, S. aureus, M. tuberculosis and C. albicans, respectively, while those with non-aromatic carbons had a higher MIC compared to those with aromatic carbons. The aromaticity of the repeat unit had impressive effects on hemolytic activities as well. Zeta potential measurements of E. coli incubated with active and inactive polymer concentration revealed a relationship between the MIC and membrane surface charge density. Polymers bearing aromatic groups killed the bacteria with widespread damage after the polymers, holding the threshold concentration, were added to the bacteria.
Article
An antimicrobial peptide (AMP), Magainin II (Mag II) was covalently immobilized on poly(lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun fibrous membranes. The surface immobilization was characterized by X-ray Photoelectron Spectroscopy (XPS). Scanning Electron Microscopy (SEM) and Atomic Force Microscopy studies showed that the surface morphology of the fibers at micron scale was not affected by the immobilization process. The antibacterial activity of the bound Mag II was tested against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Bacterial adhesion tests, SEM and confocal analyses revealed that the attachment and survival of bacteria were inhibited on Mag II functionalized membranes. AMP immobilization strategy was introduced as a new perspective for the modulation of antibacterial properties on PLGA based materials prepared by electrospinning. Copyright © 2014 Elsevier B.V. All rights reserved.
Article
Surface modification which creates surfaces capable of killing adherent bacteria and simply repelling dead bacteria was performed on electrospun polyacrylonitrile (PAN) nanofibrous membranes. Briefly, nitrile groups on the PAN nanofiber surfaces were reduced into amino groups, extended tethers by coupling of hydrophilic flexible spacers, followed by reaction with polyhexamethylene guanidine hydrochloride (PHGH) to provide antibacterial properties. The surface morphology and chemical composition of the functionalized nanofibrous membrane were characterized by scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR/FT-IR) and energy-dispersive spectroscopy (EDS). Furthermore, the antibacterial activities of the PHGH-immobilized nanofibrous membranes were assayed with Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). It was found that these PHGH-immobilized nanofibrous membranes possessed highly effective antibacterial activities which were highly retained even after three cycles of antibacterial assays. The functionalized membranes also exhibited significantly enhanced easy-cleaning performance due to the incorporation of hydrophilic spacers. Water permeance results illustrated that the novel modified PAN nanofibrous membranes showed potential in the applications of water filtration.
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We report a new procedure, exploiting “green” chemistry, resulting in biocompatible magnetically-driven nanocomposites with high antibacterial and antifungal activities against ten tested bacterial strains and four Candida species. The nanocomposites consist of silver nanoparticles (NPs), biogenic magnetite NPs isolated from magnetotactic bacteria, and an environmentally friendly polymer – chitosan. These hybrids were prepared using an acidified chitosan suspension to cover biogenic magnetite NPs by a cross-linking method, followed by employing the NH2 groups of chitosan for the reduction of silver salt in an alkaline medium. Thus, in the procedure, chitosan acts as (i) a biocompatible matrix surrounding the magnetite NPs, (ii) a reducing agent for the silver ions, and (iii) a linker between magnetic and silver NPs. The size of the resulting silver NPs and the total amount of silver involved in the nanocomposites can be simply controlled by the initial concentration of the silver salt used in the reaction mixture. The as-prepared nanocomposites reveal increased bactericidal and antifungal activity when compared to previously reported magnetic silver NPs systems which were not prepared by green synthetic routes. The use of biogenic magnetite with an uniform shape and size, the absence of any other reducing agent during synthesis, the simple control of silver NPs size and loading, the biocompatible character of chitosan matrix, and a high antimicrobial effect predetermine the developed nanocomposites for targeted applications in biomedicine.
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The present study describes the preparation and characterization of poly(N-pyrrole phosphonic acid)–Fe3O4 (PPP/Fe3O4-NPs) nanocomposite. Structural characterizations and some physical properties such as magnetism, ac–dc conductivity performance and dielectric permittivity of the nanocomposite were performed by FT-IR, XRD, TGA, TEM and VSM (vibrating sample magnetometer). FT-IR measurements of the nanocomposite showed that the Fe3O4-NPs bound to the polymer chains via phosphonic acid moieties. From the XRD powder pattern, the crystallite size was estimated as 11±4nm which is consistent with the TEM micrographs and magnetic core size from VSM measurements. Analysis of conductivity and permittivity meausurements revealed the magnetic transition above 60 which gives rise to the maximum conductivity of 1.7×10−6Scm−1 at 100°C.
Article
We have developed a two-step synthetic sequence for our introductory organic laboratory that demonstrates key reactions that the students learn concurrently in the lecture portion of their organic chemistry course. It represents the Diels-Alder reaction and solvolysis of an anhydride accompanied by Fischer esterification. Both of these steps produce crystals in a dramatic manner that catches the students' attention. This sequence can stand on its own as part of an organic laboratory, or the product can be utilized as a monomer for ring-opening metathesis polymerization (ROMP) studies.
Article
Iron oxide nanoparticles (IONPs) are important tools for nanobiotechnology applications. However, aqueous instability and non-specific biodistribution problems limit the applications of IONPs. Considering this, alpha-phosphonic acid, omega-dithiopyridine functionalized polymers were synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization and used for stabilizing and biofunctionalizing IONPs. A new trithiocarbonate RAFT agent bearing dimethyl phosphonate group was utilized in the synthesis of well-defined telechelic polymers of styrene, oligoethylene glycol acrylate (OEG-A) and N-isopropylacrylamide (NIPAAm). IONPs were grafted with alpha-phosphonic acid, omega-dithiopyridine functionalized poly(OEG-A) through the alpha-chain end of the polymer, as evidenced by FTIR-ATR, XPS and zeta potential measurements. Using TGA results, the grafting density of the polymer chains was calculated between 0.12 and 0.23 chains/nm(2) particle depending on the molecular weight of the polymer. DLS measurements indicated that the particles grafted with poly(OEG-A) larger than 10 000 g/mol were stable in water for several days and the mean diameter of the particles was between 40 and 130nm depending on the molecular weight of the polymer. Moreover, particles stabilized with poly(OEG-A) with a M(n) = 62 000 g/mol were stable in phosphate buffer (pH 6.5, 0.1 M) containing varying concentrations of BSA. Polymer-stabilized IONPs were successfully functionalized with two different peptides, i. e. reduced glutathione as a model peptide and NGR motif as a tumor-targeting peptide through the omega-dithiopyridine functionality of the polymer, as measured by XPS and zeta potential analysis. Poly(OEG-A)-stabilized IONPs were also found to be resistant to protein adsorption.
Article
The first synthesis of adenine-containing polymers and block copolymers using the ring-opening metathesis polymerization of non-covalently protected monomers are shown. Studies of the copolymer 9 reveal an unexpected cylindrical morphology, which can be interpreted as arising from the hydrogen-bonding self-complementarity of the adenine units in the micellar core. Thus, further studies are currently conducted to fully characterize this morphogenesis mechanism as well as to study the effect of hydrogen-bonding guests on the polymer morphologies.
Article
Bacitracin-conjugated superparamagnetic iron oxide (Fe(3) O(4) ) nanoparticles were prepared by click chemistry and their antibacterial activity was investigated. After functionalization with hydrophilic and biocompatible poly(acrylic acid), water-soluble Fe(3) O(4) nanoparticles were obtained. Propargylated Fe(3) O(4) nanoparticles were then synthesized by carbodiimide reaction of propargylamine with the carboxyl groups on the surface of the iron oxide nanoparticles. By further reaction with N(3) -bacitracin in a Cu(I) -catalyzed azide-alkyne cycloaddition, the magnetic Fe(3) O(4) nanoparticles were modified with the peptide bacitracin. The functionalized magnetic nanoparticles were characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy, TEM, zeta-potential analysis, FTIR spectroscopy and vibrating-sample magnetometry. Cell cytotoxicity tests indicate that bacitracin-conjugated Fe(3) O(4) nanoparticles show very low cytotoxicity to human fibroblast cells, even at relatively high concentrations. In view of the antibacterial activity of bacitracin, the biofunctionalized Fe(3) O(4) nanoparticles exhibit an antibacterial effect against both Gram-positive and Gram-negative organisms, which is even higher than that of bacitracin itself. The enhanced antibacterial activity of the magnetic nanocomposites allows the dosage and the side effects of the antibiotic to be reduced. Due to the antibacterial effect and magnetism, the bacitracin-functionalized magnetic nanoparticles have potential application in magnetic-targeting biomedical applications.
Article
In this study, amphiphilic polyoxanorbornene with different quaternary alkyl pyridinium side chains were synthesized. The biological efficiencies of these polymers, with various alkyl substituents, were determined by bacterial growth inhibition assays and hemolytic activity (HC 50 ) against human red blood cells (RBCs) to provide selectivity of these polymers for bacterial over mammalian cells. A series of polymers with different alkyl substituents (ethyl, butyl, hexyl, octyl, decyl and phenylethyl) and two different molecular weights (3 and 10 kDa) were prepared. The impact of alkyl chain length divided the biological activity into two different cases: those with an alkyl substituent containing four or fewer carbons had a minimum inhibitory concentration (MIC) of 200 µg · mL ⁻¹ and a HC 50 greater than 1 650 µg · mL ⁻¹ , while those with six or more carbons had lower MICs ≤ 12.5 µg · mL ⁻¹ and HC 50 ≤ 250 µg · mL ⁻¹ . Using MSI‐78, the potent Magainin derivative which has an MIC = 12.0 µg · mL ⁻¹ and HC 50 = 120 µg · mL ⁻¹ , as a comparison, the polymers with alkyl substituents ≤C 4 (four carbons) were not very potent, but did show selectivity values greater than or equal to MSI‐78. In contrast, those with alkyl substituents ≥C 6 were as potent, or more potent, than MSI‐78 and in three specific cases demonstrated selectivity values similar to, or better than, MSI‐78. To understand if these polymers were membrane active, polymer induced lipid membrane disruption activities were evaluated by dye leakage experiments. Lipid composition and polymer hydrophobicity were found to be important factors for dye release. magnified image
Article
An approach to synthesize phosphoric acid type block copolymers derived from ring-opening metathesis polymerization (ROMP) using Grubbs third generation catalyst was presented. Block copolymers were synthesized by a nucleophile exchange reaction and Mitsunobu coupling, using easily accessible starting material exo-oxabicyclo-[2.2.1]hept-5-ene-2,3-dicarboximide. It is found that the completion of polymerization is indicated by the total disappearance of the characteristic monomer olefin protons at 6.5 ppm and the appearance of the backbone double bond singles at 5.8-6.1. The results also show that the ratio of the methylene peaks and the phosphonate ester peaks of the polymer is 0.50 and 0.40, resulting in the block ratio of 0.8. A strong vibration band at 1241 cm -1, due to vibrations of phosphonate esters, disappears after cleavage.
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The thermal degradation of poly(vinyl sulfonic acid) and its sodium salt, poly(4-styrenesulfonic acid) and its sodium salt, and poly(vinylphosphonic acid) was studied by a combination of techniques, including TGA/FTIR, to identify the volatile products which were evolved during the degradation as well as analysis of the residues which were obtained in order to propose a mechanism for the degradation. The motivation for the work was to attempt to identify new monomers which could be graft copolymerized onto a polymer in order to improve the thermal stability of that polymer.
Article
A nanostructured iron oxide (NanoFe3O4, particle size ca. 25 nm and roughness ca. 21 nm) film deposited onto a hydrolyzed indium-tin-oxide (ITO) coated glass plate has been used to immobilize cholesterol oxidase (ChOx) to fabricate an impedimetric cholesterol sensor. Electrochemical studies reveal that surface charged Fe3O4 nanoparticles provide better conformation for ChOx loading resulting in enhanced electron transfer between ChOx and the electrode. Impedimetric response studies of the ChOx/NanoFe3O4/ITO bioelectrode exhibit improved linearity (2.5 – 400 mg/dL), low detection limit (0.25 mg/dL), fast response time (25 s), high sensitivity (86 W/mg dL�1/cm�2) and a low value of the Michaelis-Menten constant (Km, 0.8 mg/dL) with a regression coefficient of 0.997.
Article
Two types of magnetic binary nanocomposites, Ag@Fe(3)O(4) and γ-Fe(2)O(3)@Ag, were synthesized and characterized and their antibacterial activities were tested. As a magnetic component, Fe(3)O(4) (magnetite) nanoparticles with an average size of about 70 nm and monodisperse γ-Fe(2)O(3) (maghemite) nanoparticles with an average size of 5 nm were used. Nanocomposites were prepared via in situ chemical reduction of silver ions by maltose in the presence of particular magnetic phase and molecules of polyacrylate serving as a spacer among iron oxide and silver nanoparticles. In the case of the Ag@Fe(3)O(4) nanocomposite, silver nanoparticles, caught at the surfaces of Fe(3)O(4) nanocrystals, were around 5 nm in a size. On the contrary, in the case of the γ-Fe(2)O(3)@Ag nanocomposite, ultrafine γ-Fe(2)O(3) nanoparticles surrounded silver nanoparticles ranging in a size between 20 and 40 nm. In addition, the molecules of polyacrylate in this nanocomposite type suppress considerably interparticle magnetic interactions as proved by magnetization measurements. Both synthesized nanocomposites exhibited very significant antibacterial and antifungal activities against ten tested bacterial strains (minimum inhibition concentrations (MIC) from 15.6 mg/L to 125 mg/L) and four candida species (MIC from 1.9 mg/L to 31.3 mg/L). Moreover, acute nanocomposite cytotoxicity against mice embryonal fibroblasts was observed at concentrations of higher than 430 mg/L (Ag@Fe(3)O(4)) and 292 mg/L (γ-Fe(2)O(3)@Ag). With respect to the non-cytotoxic nature of the polyacrylate linker, both kinds of silver nanocomposites are well applicable for a targeted magnetic delivery of silver nanoparticles in medicinal and disinfection applications.