Poly(vinylidene fluoride) Membranes with Hyperbranched Antifouling

Article pubs.acs.org/IECR

Poly(vinylidene fluoride) Membranes with Hyperbranched Antifouling and Antibacterial Polymer Brushes Tao Cai,

†

Wen Jing Yang,

†

Koon-Gee Neoh,

†,‡

and En-Tang Kang*,

†,‡

†

NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Kent Ridge, Singapore 117576 Department of Chemical & Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 119260

‡

S Supporting Information *

ABSTRACT: Graft copolymers of poly(vinylidene fluoride) (PVDF) with poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMAEMA) side chains (PVDF-g-PDMAEMA copolymers) were synthesized via activators generated by electron transfer for atom transfer radical polymerization (AGET-ATRP) of 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA) directly from the secondary fluorine atoms on the PVDF backbone. Microporous membranes were fabricated from the PVDF-g-PDMAEMA amphiphilic copolymers by phase inversion in an aqueous medium. After quaternization by propargyl bromide, the resulting PVDF-g-PQDMAEMA membrane and pore surfaces bearing pendant propargyl moieties could be further functionalized via surface-initiated alkyne−azide click reaction of azido-terminated hyperbranched polyglycerols (HPG-N3) to form the PVDF-gP[QDMAEMA-click-HPG] membranes. The PVDF-g-P[QDMAEMA-click-HPG] membranes exhibit good resistance to protein adsorption and fouling. Alternatively, alkyne−azide click reaction of azido-terminated polyethylenimine (PEI-N3) on the PVDFg-PQDMAEMA membranes, followed by quaternization with 1-bromohexane, produce the PVDF-g-P[QDMAEMA-click-QPEI] membrane which is effective in reducing bacterial growth and proliferation under continuous-flow conditions.

1. INTRODUCTION As a practical membrane material, poly(vinylidene fluoride) (PVDF) has many unique properties including excellent chemical resistance, good mechanical strength, good thermal stability, and excellent solution processability.1,2 PVDF membranes have found applications in ultrafiltration, microfiltration, wastewater treatment, proton conduction, stimuliresponsive and controlled deliveries, and biotechnology.1−6 However, serious pore and surface fouling problems have limited their practical applications in many aqueous media. Thus, the ability to manipulate and control the surface properties of PVDF membranes is of crucial importance. Among the various modification techniques to overcome the surface limitations, graft copolymerization is expected to provide the desired physicochemical properties to the parent polymer with minimum alteration of its bulk properties. As a recently developed controlled/living radical polymerization method, atom transfer radical polymerization (ATRP) has attracted considerable attention. Ideally, the PVDF molecules could be functionalized, via the ATRP process, with polymer side chains of controlled length and density.7−11 The grafted side chains can, in turn, be used to control the surface composition and reactivity, morphology, and pore-size distribution of the PVDF membrane casted by phase inversion. In comparison to their linear counterparts, hyperbranched polymers have many unique features, such as high density, low viscosity, and multiple end functionalities. They have been investigated for applications in targeted drug delivery, as viscosity modifiers, as catalyst supports, and as scaffolds for biomaterials synthesis.12−19 In comparison to the method of direct graft polymerization of the corresponding monomers from the membrane surfaces, which usually requires high reaction temperature and may suffer from undesirable cross© 2012 American Chemical Society

linking reaction, postpolymerization coupling reactions allow the covalent attachment of hyperbranched polymers onto the membrane surfaces in a controlled manner and under mild conditions. In particular, alkyne−azide click reaction is a highly efficient and orthogonal organic reaction that offers high selectivity, excellent tolerance for functional groups, and no extraneous side products.20−27 In addition, the ease of synthesis of either alkyne or azide functionalities in hyperbranched polymer chains provides a direct route to the reconstruction of membrane surfaces via the simple one-step click reaction. In the present work, ATRP of 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA) using activators generated through direct electron transfer from the secondary fluorine atoms on the PVDF backbone has been carried out in the presence of a limited amount of air, using CuBr 2 as the catalyst, N,N,N′,N′,N″-pentamethyl diethylene triamine (PMDETA) as the ligand, and L-ascorbic acid as the reducing agent. The soobtained PVDF-g-PDMAEMA copolymers were compared to those obtained from thermally induced free-radical graft copolymerization of DMAEMA from ozone-preactivated PVDF backbones. The PVDF-g-PDMAEMA copolymers can be readily cast into microporous membranes by phase inversion in an aqueous medium. Through surface-initiated alkyne−azide click reaction, azido-terminated hyperbranched polymers (hyperbranched polyglycerols or polyethylenimine) can be covalently grafted onto the propargyl bromide quaternized PVDF-g-PDMAEMA membrane surfaces. The PVDF-g-P[QDMAEMA-click-HPG] membranes exhibit good antifouling Received: Revised: Accepted: Published: 15962

October 10, 2012 November 12, 2012 November 20, 2012 November 20, 2012 dx.doi.org/10.1021/ie302762w | Ind. Eng. Chem. Res. 2012, 51, 15962−15973

Industrial & Engineering Chemistry Research

Article

Scheme 1. a. Schematic Illustration of the Processes Involved for Graft Copolymerization of DMAEMA from PVDF Main Chains via AGET-ATRP, Preparation of PVDF-g-PDMAEMA Membrane by Phase Inversion, and Quaternization of PVDF-gPDMAEMA Membrane by Propargyl Bromide To Produce PVDF-g-PQDMAEMA Membrane with Pendant Alkyne Groupsa and b. Covalent Immobilization of Hyperbranched Polymer HPG-N3 or PEI-N3 onto the PVDF-g-PQDMAEMA Membrane Surface via Surface Alkyne-Azide Click Reaction

PVDF = poly(vinylidene fluoride); DMAEMA = 2-(N,N-dimethylamino)ethyl methacrylate; VC = L-ascorbic acid; PMDETA = N,N,N′,N′,N″pentamethyl diethylene triamine.

a

dimethylamino)ethyl methacrylate (DMAEMA, Sigma-Aldrich, 98%), was passed through an inhibitor removal column prior to being stored under an argon atmosphere at −10 °C. Copper(I) bromide (CuBr, Sigma-Aldrich, 99%) was purified by stirring in acetic acid for 4 h, followed by washing thoroughly with ethanol and diethyl ether before being stored under an argon atmosphere. Copper(II) bromide (CuBr2, ≥99%), γ-globulin (99%), propargyl bromide (80 wt % in toluene), L-ascorbic acid

property, while the PVDF-g-P[QDMAEMA-click-QPEI] membranes exhibit good antibacterial property, making the membranes potentially useful for wastewater treatment.

2. EXPERIMENTAL SECTION 2.1. Materials. Poly(vinylidene fluoride) (PVDF, Kynar K761 powders, Mw = 441 000 Da) were obtained from Elf Atochem of North America Inc. The monomer, 2-(N,N15963

dx.doi.org/10.1021/ie302762w | Ind. Eng. Chem. Res. 2012, 51, 15962−15973


Article

(VC, ≥99%), N,N,N′,N′,N″-pentamethyl diethylene triamine (PMDETA, 99%), 1-bromohexane (98%), N-methyl-2-pyrrolidone (NMP, reagent grade), and methoxypolyethylene glycol azide (PEG-N3, Mn = 5000 g/mol) were obtained from SigmaAldrich Chem. Co. and used as received without further purification. Toluene (reagent grade) and tetrahydrofuran (THF, reagent grade) were obtained from Merck Chem. Co. and used as received without further purification. The hydrophilic PVDF microporous membrane with a standard pore size of 0.22 μm was obtained from Millipore Corporation. Azido-terminated hyperbranched polyglycerols28,29 (HPG-N3, from gel permeation chromatography (GPC): Mn = 5300 g/ mol and polydispersity index (PDI) = 1.22) and azidoterminated polyethylenimine30,31 (PEI-N3, branched, Mw = 25,000 g/mol and Mn = 10,000 g/mol) were prepared according to procedures described in the literature. Details on the synthesis of PVDF-g-PDMAEMA via thermally induced free-radical graft copolymerization of DMAEMA from ozonepreactivated PVDF polymer, as well as on the synthesis of HPG-N3 and PEI-N3, are given in the Supporting Information (SI). The origin and purity of other reagents can also be found in the SI. 2.2. Synthesis of the PVDF-g-PDMAEMA Copolymer via Activators Generated by Electron Transfer for Atom Transfer Radical Polymerization (AGET-ATRP). A typical solution polymerization process with a molar ratio of [DMAEMA]:[-CH2CF2-]:[CuBr2]:[PMDETA]:[VC] molar ratio of 200:100:1:2:2 in NMP was carried out in the presence of a limited amount of air as follows. About 1 g of PVDF powder was first dissolved in 10 mL of NMP in a round-bottom flask. The temperature of the thermostatted bath was set to 50 °C to facilitate dissolution. After complete dissolution, the mixture was cooled to room temperature. About 5.26 mL (31.3 mmol) of DMAEMA monomer, 65.0 μL (0.313 mmol) of PMDETA, and 35.0 mg (0.156 mmol) of CuBr2 were added into the reaction mixture under vigorous stirring. Then, 55.0 mg (0.313 mmol) of VC was added, and the reaction flask was immediately sealed and placed in a thermostatted oil bath at 90 °C for a predetermined period of time. At the end of the reaction, the reaction mixture was cooled in an ice bath. Polymer precipitation was carried out in an excess volume of ethanol:H2O (3:1, v/v) mixture to remove the PDMAEMA homopolymer and catalyst complex. The precipitated copolymer was subsequently dried in a vacuum oven and purified twice by dissolving in DMF and reprecipitating in an excess volume of the ethanol:H2O (3:1, v/v) mixture. The resultant PVDF-g-PDMAEMA copolymers were dried in a vacuum oven at room temperature for 24 h. The process of AGET-ATRP of DMAEMA from PVDF is shown in Scheme 1a. 2.3. Fabrication of Microporous Membranes. The PVDF and PVDF-g-PDMAEMA microporous membranes were prepared by phase inversion from NMP solutions of the respective polymers in doubly distilled water. The polymer was dissolved in NMP to a concentration of 15 wt % at 50 °C. The solution was cooled to room temperature under continuous stirring. The casting solution was then sonicated for 30 min. The copolymer solution was then cast onto a glass plate, followed by spreading with a blade to cover the glass plate. The glass plate was subsequently immersed into an aqueous coagulation bath for 30 min at room temperature. The detached membrane was extracted in the aqueous medium, followed by rinsing twice with doubly distilled water for 24 h. The purified membranes were obtained by freeze-drying for

subsequent characterization and modification. The thickness of the membranes was about 120 ± 10 μm. 2.4. Quaternization of the PVDF-g-PDMAEMA Membranes by Propargyl Bromide (PVDF-g-PQDMAEMA Membranes). Six pieces of the 2 cm × 2 cm PVDF-gPDMAEMA membranes, propargyl bromide (1 mL, 80 wt % in toluene, 8.1 mmol), and toluene (10 mL) were introduced into a 25 mL single-necked round-bottom flask. The reaction was allowed to proceed at 70 °C for 24 h with stirring. After the reaction, the membranes were removed from the reaction mixture and subsequently washed with copious amounts of acetone and doubly distilled water to remove the unreacted propargyl bromide, followed by freeze-drying overnight. 2.5. Alkyne−Azide Click Reaction of HPG-N3 or PEI-N3 Polymers on the PVDF-g-PQDMAEMA Membrane and Pore Surfaces (PVDF-g-P[QDMAEMA-click-HPG] Membrane or PVDF-g-P[QDMAEMA-click-PEI] Membrane). The functional alkyne groups on the as-synthesized PVDF-gPQDMAEMA membrane and pore surfaces provide a direct route for the decoration of membrane surfaces, via the simple surface-initiated alkyne−azide click reaction, with a variety of hyperbranched polymers.20−22 Briefly, three pieces of the 2 cm × 2 cm PVDF-g-PQDMAEMA membranes, azido-terminated hyperbranched polyglycerols (HPG-N3) (or polyethylenimine (PEI-N3)) (200 mg), PMDETA (14 mg, 0.08 mmol), and THF (15 mL) were introduced into a 25 mL single-necked roundbottom flask. The reaction mixture was degassed with pure argon for about 30 min. CuBr (12 mg, 0.08 mmol) was then added to the reaction mixture, and the reaction flask was sealed under an argon atmosphere. The reaction was allowed to proceed at 50 °C for 24 h with continuous stirring. After the reaction, the membranes were removed from solution and subsequently rinsed thoroughly with copious amounts of ethanol and doubly distilled water, followed by freeze-drying overnight. The process of surface alkyne−azide click coupling of HPG-N3 or PEI-N3 hyperbranched polymers onto the PVDF-g-PQDMAEMA membrane and pore surfaces is shown in Scheme 1b. 2.6. Materials Characterization. Fourier transform infrared (FTIR) spectroscopy analysis of the graft copolymers were carried out on a Bio-Rad FTS 135 Fourier transform infrared spectrophotometer, and the diffuse reflectance spectra were scanned over the range of 400−4000 cm−1. 1H NMR spectra of the PVDF and PVDF-g-PDMAEMA polymers were measured on a Bruker ARX 300 instrument at room temperature with DMSO-d6 as the solvent. The thermal stability of the copolymers was studied by thermogravimetric analysis (TGA). The samples were heated from room temperature to about 700 °C at a heating rate of 10 °C/min under a dry nitrogen atmosphere in a Du Pont Thermal Analyst 2100 system, equipped with a TGA 2050 thermogravimetric thermal analyzer. The molecular weight and molecular weight distribution of PVDF-g-PDMAEMA copolymers prepared from AGET-ATRP were characterized by gel permeation chromatography (GPC) on a Waters GPC system, equipped with a Waters 1515 isocratic HPLC pump, a Waters 717 plus autosampler injector, a Waters 2414 refractive index detector, and a series of three linear Jordi columns (PLGel DVB 1000 Å, 300 × 7.5 mm, Cat. No. 79911GP-MXC, packed with 5 μm poly(divinylbenzene) particles), using N,N-dimethylformamide (DMF) as the eluent at a flow rate of 1.0 mL/min. The calibration curve was generated using polystyrene molecular weight standards. X-ray photoelectron spectroscopy (XPS) 15964



Article

ethanol and doubly distilled water to remove the unreacted 1bromohexane, followed by drying under reduced pressure. Both Gram-negative Escherichia coli (E. coli, ATCC DH5α) and Gram-positive Staphylococcus epidermidis (S. epidermidis, ATCC 35984) were cultured to determine the bactericidal efficiency of the PVDF-g-P[QDMAEMA-click-QPEI] membranes. All glassware and membranes were first sterilized by UV irradiation for 1 h prior to the experiment. The microbial adhesion, growth, and proliferation were evaluated in a flow chamber.32,33 To mimic bacteria-infected sites on the pristine and functionalized PVDF membranes (about 2 cm × 2 cm), the respective membranes were exposed initially to a microbial suspension in PBS (pH 7.4) at a bacteria concentration of 108 cell/mL for 4 h at 37 °C. The inoculated membranes were then fixed on a glass slide and positioned in a flow chamber. Sterilized culture medium was allowed to flow through the device for 18 h, followed by PBS for 0.5 h at room temperature, at a constant flow rate of 0.5 mL/min. After the incubation period, the membranes were fixed with 3% glutaraldehyde at 4 °C overnight. After step dehydration with serial ethanol for 10 min each and then coating of platinum, the surfaces of the substrates were imaged by SEM.

measurements were made on a Kratos AXIS Ultra DLD spectrometer with a monochomatized Al Kα X-ray source (1486.71 eV photons). The membranes were mounted on the standard sample studs by means of double-sided adhesive tapes. The core-level signals were obtained at the photoelectron takeoff angle (α, with respect to the sample surface) of 90°. All binding energies (BEs) were referenced to that of the neutral C 1s hydrocarbon peak at 284.6 eV or that of the CF2 peak of PVDF at 290.5 eV. In peak synthesis, the line width (full-width at half-maximum, or fwhm) for the Gaussian peaks was maintained constant for all components in a particular spectrum. Surface elemental stoichiometries were determined from peak-area ratios, after correcting with the experimentally determined sensitivity factors, and were reliable to ±5%. XPS has a probing depth of about 8 nm in an organic matrix. The surface morphology of the microporous membranes was studied by scanning electron microscopy (SEM), using a JEOL 6320 scanning electron microscope. The membranes were mounted on the sample studs by means of double-sided adhesive tapes. A thin layer of platinum was sputtered onto the membrane surface prior to the SEM measurement. The measurements were performed at an accelerating voltage of 15 kV. 2.7. Protein Adsorption Assays. To investigate the antifouling properties of the PVDF-g-P[QDMAEMA-clickHPG] membranes, protein adsorption experiments were carried out using γ-globulin as a model protein. The membranes were immersed and wetted in methanol for 30 min, followed by washing thrice with the phosphate buffer saline (0.01 M PBS, pH 7.4). The membranes were subsequently incubated in PBS containing 5 mg/mL of γglobulin for 24 h. After removal from the PBS of protein, the membranes were washed with PBS and doubly distilled water. The surface coverage of γ-globulin was quantified by XPS, using the nitrogen signal associated with γ-globulin as a marker. The relative [N]/[C] ratios before and after protein fouling were compared. The data reported were the average measurements from at least four similar membranes. Permeation experiments were performed using a microfiltration cell (Toyo Roshi UHP-25, Tokyo, Japan). The pristine or functionalized PVDF membrane was mounted on the microfiltration cell and exposed to doubly distilled water for 30 mL, followed by PBS containing 1 mg/mL of γ-globulin. The flow was induced by an imposed argon pressure of 5.9 kN/ m2. The effective membrane area was 3.14 cm2. The flux was calculated from the weight of the solution permeated per unit time and per unit area of the membrane. The data reported were the average measurements from at least four similar membranes and with a standard derivation of ±10%. The observed protein rejection ratio was calculated after a filtrate volume of 240 mL from the following equation: R = (Cf-Cp)/Cf × 100%, where Cf and Cp refer to protein concentrations in the feed and permeate solutions, respectively. 2.8. Antimicrobial Activity Assay in a Flow Chamber. Quaternization of the hyperbranched PEI polymer brushes grafted on the membranes was carried out prior to the antimicrobial activity assay. Two pieces of the 2 cm × 2 cm PVDF-g-P[QDMAEMA-click-PEI] membranes were immersed in a 10 mL solution of toluene containing 10 vol% 1bromohexane in a 25 mL single-necked round-bottom flask at 70 °C for 24 h to produce the PVDF-g-P[QDMAEMA-clickQPEI] membranes. After the quaternization reaction, the membranes were washed sequentially with copious amounts of

3. RESULTS AND DISCUSSION 3.1. Preparation of the Poly(vinylidene fluoride)graf t-Poly[2-(N,N-dimethylamino) ethyl methacrylate] Copolymers (PVDF-g-PDMAEMA Copolymers) via AGET-ATRP. Atom transfer radical polymerization (ATRP) has been employed to design and synthesize PVDF-based graft copolymers.7−11 Although the ATRP reaction suffers from low initiation efficiency and requires high reaction temperature, the one-step, direct initiation process from vinylidene fluoride (VDF) units in PVDF can be carried out.7,10,11 On the other hand, in the ATRP reaction which uses activators generated by the electron transfer (AGET-ATRP) process, a higher oxidation state catalyst derived from the Cu(II) complex, instead of the Cu(I) catalyst which is sensitive to air, is added to the reaction mixture, so that a stable dispersed medium is formed without initiation of polymerization.34−38 A reducing agent is added to reduce the air-stable Cu(II) complex, resulting in the generation of active catalyst in situ without any involvement of organic radicals or formation of reaction products that could initiate new chains. Thus, AGET-ATRP encompasses all the advantages of the standard ATRP, while providing the additional benefits of facile preparation, storage, and handling of the ATRP catalysts. In view of all the benefits described above, the PVDF-g-PDMAEMA copolymers were thus synthesized via AGET-ATRP of 2-(N,N-dimethylamino) ethyl methacrylate (DMAEMA), with direct initiation from the VDF units of PVDF in the present study. 3.2. Characterization of the PVDF-g-PDMAEMA Copolymers. The PVDF-g-PDMAEMA copolymer was first characterized by Fourier transform infrared (FTIR) spectroscopy. The FTIR spectrum of the PVDF-g-PDMAEMA copolymer is compared to those of the PVDF and PDMAEMA homopolymers in Figure 1a-c. The adsorption band at the wavenumbers of about 1730 cm−1 is associated with ester stretching of the PDMAEMA chains. On the other hand, the adsorption band in the region of 1120−1280 cm−1, characteristic of the -CF2- functional groups of PVDF, is also present in the copolymer sample.39 Thus, the FTIR spectroscopic results of the copolymer are consistent with the presence of grafted PDMAEMA chains on the PVDF backbone. 15965



Article

the methyl protons of PDMAEMA. The chemical shifts at δ = 3.9−4.1 ppm (d) are attributable to the methylene protons at the α-position of the ester groups, while the chemical shifts at δ = 2.2−2.3 ppm (f) are assigned to methyl protons of the -N(CH3)2 species of the PDMAEMA side chains.40,41 A molar ratio of about 1:4 for the methylene protons in the α-position of the ester groups (2H, d in Figure 2b) to the methylene protons (2H, a1, a2, and g in Figure 2b) in the PVDF main chain indicates that the bulk molar ratio of PDMAEMA units per repeat PVDF unit in the copolymer is about 0.25. Thus, the 1 H NMR results are consistent with the presence of DMAEMA graft chains in the graft copolymer structure. The structures for other PVDF-g-PDMAEMA copolymers have also been determined, and the results are presented in Table 1. For comparison purposes, PVDF-g-PDMAEMA copolymers have also been synthesized by thermally induced graft copolymerization of DMAEMA from ozone-preactivated PVDF backbones, as described in detail in the Supporting Information (SI). The 1 H NMR spectrum of PVDF-g-PDMAEMA synthesized from this method (Figure S1, SI) is similar to that of PVDF-gPDMAEMA synthesized from AGET-ATRP (Figure 2b). The results further confirm that AGET-ATRP can be effectively utilized for the direct graft copolymerization of DMAEMA from VDF units in PVDF. The thermal stability of the graft copolymers was studied by thermogravimetric analysis (TGA). Figure 3 shows the respective TGA curves of the PVDF homopolymer (Curve a), the three PVDF-g-PDMAEMA copolymers of different polymerization times (Curves b, c, and d from 8, 16, and 24 h of AGET-ATRP, respectively), and the PDMAEMA homopolymer (Curve e). In comparison to the PVDF and PDMAEMA homopolymers, a distinct two-step degradation process is observed for the PVDF-g-PDMAEMA copolymer samples. The first major weight loss occurring at about 250 °C is attributable to the thermal decomposition of PDMAEMA side chains, while the second major weight loss commencing at about 475 °C is attributable to the thermal decomposition of PVDF main chains. By comparing the weight remaining at 700 °C of these five polymer samples, the weight content of the PDMAEMA segments in the PVDF-g-PDMAEMA graft copolymers can be estimated (Table 1). The bulk graft concentrations of the PDMAEMA segments estimated from TGA results are in good agreement with those determined from 1H NMR results. With the increase in reaction time from 4 to 24 h, the numberaverage molecular weight (Mn) of the PVDF-g-PDMAEMA graft copolymers, as determined from gel permeation chromatography (GPC) measurements, increased from 3.7 × 105 to 6.6 × 105 g/mol, indicating an approximately linear increase in PDMAEMA content (Table 1). In addition, the polydispersity indices (PDI) of the copolymers are comparable to that of the starting PVDF polymer, consistent with the fact that AGET-ATRP of DMAEMA from PVDF was a controlled radical polymerization process. 3.3. Preparation of PVDF-g-PDMAEMA Copolymer Membranes by Phase Inversion and Quaternization of PVDF-g-PDMAEMA Membranes by Propargyl Bromide. The PVDF-g-PDMAEMA amphiphilic copolymers were cast into microporous membranes by phase inversion in doubly distilled water at room temperature from 15 wt % NMP solutions. The SEM micrographs in Figure 4a-d illustrate the difference in surface morphology of the microporous membranes cast from the PVDF homopolymer and the PVDF-g-PDMAEMA copolymers from 8, 16, and 24 h of

Figure 1. FTIR spectra of the (a) PVDF homopolymer, (b) PVDF-gPDMAEMA copolymer from 24 h of AGET-ATRP, and (c) PDMAEMA homopolymer.

The 1H NMR spectra of PVDF homopolymer and PVDF-gPDMAEMA copolymer from 24 h of AGET-ATRP are shown in Figures 2a and 2b, respectively. The chemical shifts in the

Figure 2. 1H NMR spectra of the (a) PVDF homopolymer and (b) PVDF-g-PDMAEMA copolymer from 24 h of AGET-ATRP in DMSO-d6.

range of δ = 2.7−3.0 ppm (a1) are attributable to the head-totail (ht) structure of the PVDF main chains, whereas the weaker chemical shifts in the range of δ = 2.2−2.4 ppm (a2) are assigned to the head-to-head (hh) or tail-to-tail (tt) stereoregularities.40,41 After graft copolymerization of DMAEMA from the PVDF backbones, the broad chemical shifts in the region of δ = 0.7−1.0 ppm (c in Figure 2b) are attributable to 15966



Article

Table 1. Characterization of the PVDF Homopolymer and PVDF-g-PDMAEMA Copolymers from AGET-ATRP and the Resulting Microporous Membranes polymer ATRP time (h) PVDF PVDF-gPDMAEMAa

0 4 8 16 24

Mn (g/mol)b × × × × ×

3.1 3.7 4.4 5.3 6.6

105 105 105 105 105

membrane

PDIb

([-DMAEMA-]/ [-CH2CF2-])bulkc

([-DMAEMA-]/ [-CH2CF2-])surfacee

Daf (μm)

SDf (μm)

RSDf (%)

1.28 1.35 1.29 1.27 1.33

0.06c (0.07)d 0.11 (0.12) 0.19 (0.19) 0.25 (0.27)

0.11 0.19 0.28 0.42

0.28 0.36 0.43 0.55

0.04 0.05 0.07 0.09

14.3 14.0 16.3 16.4

Reaction condition: 200:100:1:2:2 molar ratio of [DMAEMA]:[-CH2CF2-]:[CuBr2]:[VC]:[PMDETA] in NMP at 90 °C. DMAEMA = 2-(N,Ndimethylamino)ethyl methacrylate, VC = L-ascorbic acid, PMDETA = N,N,N′,N′,N″-pentamethyl diethylene triamine. bDetermined from GPC results (calibration using polystyrene molecular weight standards). Polydispersity index (PDI) = Mw/Mn. cDetermined from 1H NMR spectroscopy results. dDetermined from TGA results. Molecular weights of DMAEMA = 157 g/mol and -CH2CF2- (VDF) = 64 g/mol. eDerived from the curvefitted C 1s peak component area ratio of [-O-CO]/[-CF2-] of the respective sample (Figure 5b) since there is one [-CF2-] repeat unit in the PVDF backbone and one [-O-CO] repeat unit in the PDMAEMA side chains. fFrom SEM images, using the relationship average pore diameter Da = (∑ni=1Di)/n, absolute standard deviation of pore diameter SD = (∑ni=1(Di − Da)2/n)1/2 and relative standard deviation of pore diameters is RSD = SD/Da, based on 100 pores (n = 100) of diameter Di. a

chains, significantly larger SD and RSD in pore size distribution are observed (Table S1, SI). The lower values of SD and RSD for membranes cast from the AGET-ATRP copolymers indicate that the PVDF-g-PDMAEMA copolymers with more regular PDMAEMA graft chains can, in return, provide better control over the morphology and pore size distribution of the PVDF membranes during their casting by phase inversion. Figure 5a-c shows the respective wide scan, C 1s and N 1s core-level spectra of the PVDF-g-PDMAEMA membrane from 24 h of AGET-ATRP and cast by phase inversion in an aqueous medium. Carbon, nitrogen, oxygen, and fluorine signals are detected in the wide-scan spectrum (Figure 5a). The C 1s corelevel spectrum can be curved into five peak components with binding energies (BEs) at about 284.6, 285.7, 286.2, 288.5, and 290.5 eV, and with an area ratio of 5.9:5.3:1.0:1.0:2.4, attributable to the C-H, (-CH2-)PVDF/C-N, C-O, O-CO, and (-CF2-)PVDF species, respectively (Figure 5b).6,40 The peak component of the C-N species overlaps that of the (-CH2-)PVDF species. Taking into account the fact that the [-CH2-]:[-CF2-] peak component area ratio of PVDF is 1:1,7 associated with the chemical structure of PVDF main chains, the peak component area ratio for [C-N]:[C-O]:[O-CO] is about 2.9:1.0:1.0, which is in fairly good agreement with the theoretical ratio of 3:1:1 for the chemical structure of PDMAEMA.7,42 On the other hand, the graft concentration at the membrane surface, or the ([-DMAEMA-]/[-CH 2CF 2-]) surface ratio of 0.42, as determined from the ([O-CO]/[-CF2-]) peak component area ratio in the C 1s core-level spectrum of the copolymer membrane in Figure 5b, is higher than the corresponding bulk ratio of 0.25. Thus, surface enrichment of the more hydrophilic PDMAEMA component has occurred in the copolymer membranes during the phase inversion process in water. The amino moieties of PDMAEMA graft chains on the membrane and pore surfaces can be quaternized by propargyl bromide to produce PVDF-g-PQDMAEMA membrane with pendant propargyl moieties. The presence of quaternized PDMAEMA side chains on the membrane surfaces is ascertained by the XPS wide scan, C 1s, N 1s, and Br 3d core-level spectra of the PVDF-g-PQDMAEMA membrane (Figures 5d-f and inset 5f′). The marked increase in intensity of the C-N+ peak component in the C 1s core-level spectrum (Figure 5e) and the appearance of the Br 3d core-level (Figure 5f′) signal indicate that the PVDF-g-PDMAEMA membrane surface have been successfully quaternized by propargyl

Figure 3. Thermogravimetric analysis curves of the (a) PVDF homopolymer, three PVDF-g-PDMAEMA copolymers from (b) 8 h, (c) 16 h, and (d) 24 h of AGET-ATRP, and (e) PDMAEMA homopolymer.

AGET-ATRP. The SEM images reveal that the PVDF-gPDMAEMA membranes have a more well-defined pore size distribution and a higher degree of porosity, induced by the hydrophilic PDMAEMA graft chains during phase inversion, than those of the pristine PVDF membrane. The SEM images also reveal that the pore size of the PVDF-g-PDMAEMA membranes increases with the increase in ATRP time and thus the PDMAEMA graft chain length. The average pore diameters (Da), and the corresponding standard deviation (SD) and relative standard deviation (RSD), of the four PVDF-gPDMAEMA membranes, as determined from statistical analysis of the SEM images, are summarized in Table 1. With the increase in ATRP time, Da of the PVDF-g-PDMAEMA membranes increases from 0.28 to 0.55 μm, and the SD increases correspondingly from 0.04 to 0.09 μm, while the RSD remains at around 15%. The increase in Da and SD with the increase in DMAEMA graft concentration confirms that the membrane morphology is dependent on the DMAEMA graft density and graft chain length and is thus controllable. For PVDF-g-PDMAEMA membranes cast from PVDF-g-PDMAEMA copolymers with similar [-DMAEMA-]/[-CH2CF2-]bulk ratio, but synthesized by thermally induced free-radical graft copolymerization of DMAEMA from ozone-preacitvated PVDF 15967



Article

Figure 4. SEM micrographs of the microporous membranes cast from a 15 wt % NMP solution of the corresponding polymers by phase inversion: (a) the pristine PVDF membrane and the PVDF-g-PDMAEMA membranes from (b) 8 h, (c) 16 h, and (d) 24 h of AGET-ATRP. All images shown are the respective surfaces in contact with the glass substrate during membrane casting by phase inversion.

Figure 5. XPS wide-scan and C 1s and N 1s core-level spectra of the PVDF-g-PDMAEMA membrane from 24 h of AGET-ATRP (a,b,c) before and (d,e,f) after quaternization by propargyl bromide. The inset (f′) shows the Br 3d core-level spectrum of the quaternized membrane surface.

80% of the DMAEMA repeat units have been quaternized. The quaternized PVDF-g-PQDMAEMA membrane surface becomes more hydrophilic, and its static water contact angle decreases from about 45° to 20°. 3.4. Functionalization of the PVDF-g-PQDMAEMA Membranes via Click Grafting of Azido-Terminated Hyperbranched Polyglycerols (HPG-N3): The Antifouling PVDF-g-P[QDMAEMA-click-HPG] Membranes. Owing to its dendritic architecture with abundant end-group functionality, thermal stability, and biocompatible polyether scaffold,

bromide. The N 1s core-level spectrum can be curve-fitted into two peak components with BEs at 399.7 and 402.7 eV, attributable to the neutral amine and positively charged nitrogen (N+) species, respectively (Figure 5f).7,42,43 The surface concentration of positively charged (N+) species, or the extent of quaternization, can be expressed as the [N+]/[N] ratio (determined from the corresponding N+ peak component and total nitrogen spectral area ratio within the probing depth of the XPS technique). The [N+]/[N] ratio is about 0.8 after 24 h of the N-alkylation reaction (Figure 5f), indicating that about 15968



Article

Figure 6. XPS wide-scan and C 1s and N 1s core-level spectra of the (a,b,c) PVDF-g-P[QDMAEMA-click-HPG] membrane via surface click grafting of HPG-N3 on the PVDF-g-PQDMAEMA membranes from 24 h of AGET-ATRP and (d,e,f) PVDF-g-P[QDMAEMA-click-QPEI] membranes via surface click grafting of PEI-N3, followed by quaternization with 1-bromohexane, on the PVDF-g-PQDMAEMA membranes from 24 h of AGETATRP. The Br 3d core-level spectrum of the quaternized membrane surface is shown in the inset (f′).

from the changes in the C 1s core-level line shape of the PVDFg-P[QDMAEMA-click-HPG] membrane. The two carbon species associated with the PVDF main chains, viz., (-CH2)PVDF and (-CF2-)PVDF with respective BEs at 285.8 and 290.5 eV, have disappeared completely. The spectrum is dominated by the peak component at BE of about 286.2 eV, attributed to the C-O species of the HPG polymer chains. The N 1s corelevel spectrum can be curve-fitted with three peak components using the following approach. The peak component at about 399.5 eV is assigned to the amine nitrogen ((C)-N-) moieties of both the triazole rings and nonquaternized PDMAEMA polymer. The peak component at about 398.4 eV is assigned to the imine moiety (=N-) of the triazole rings. The peak component at about 402.7 eV is assigned to the positively charged nitrogen (N+) of quaternized PDMAEMA polymer (Figure 6c).7,42,43 The molar ratio of the three nitrogen species, viz., the imine moiety (=N-), the amine nitrogen ((C)-N-) moiety, and the positively charged nitrogen (N+), is about 1.4:0.95:1.0, as determined from the spectral area ratio of the three peak components. The [=N-]/[N+] ratio (1.4:1.0) suggests that about 70% of alkyne groups have undergone the alkyne−azide click reaction. Taking into account the fact that the extent of quaternization of the starting PVDF-gPQDMAEMA membrane is about 80%, the spectral area ratio of the imine moiety (=N-) to amine ((C)-N-) moiety has increased from 1.4:0.7 (or 2:1) for the triazole ring to 1.4:0.95, arising from the contribution of the amine nitrogen moiety in the nonquaternized PDMAEMA polymer. The intensity of the N 1s signal for the PVDF-g-P[QDMAEMA-click-HPG] membrane has been reduced considerably, in comparison to that of the N 1s signal for the starting PVDF-g-PQDMAEMA membrane. The XPS results have thus provided direct evidence to the successful click grafting of the HPG polymer on the PVDF-g-PQDMAEMA membrane surface. The presence of HPG polymer brushes on the membrane and pore surfaces imparts the surface with significant resistance

hyperbranched polyglycerol (HPG) has found various biomedical applications and has been explored as a substitute for linear poly(ethylene glycol) (PEG) in applications, such as antifouling coatings.12−16 Most of the polymers used in filtration membranes, such as polysulfone, polyethylene, PVDF, and nylon, display nonspecific protein adsorption. For good performance in filtration of solutions containing proteins and other biological molecules, membrane fouling should be minimized. The introduction of antifouling coatings on the membrane surface is a good approach to reduce nonspecific protein adsorption. The HPG polymer brushes covalently attached to the membrane and pore surfaces will shield the underlying membrane, preventing the direct contact of protein molecules with the PVDF matrix and reducing protein adsorption. In the case of neutral hydrophilic polymer brushes, the steric barrier due to high conformational entropy of the anchored chains is the main contributing factor toward protein repulsion. HPG-coated materials can effectively resist nonspecific protein adsorption and short-term bacterial adhesion but have limited success in preventing eventual biofilm formation.44 The surface-initiated alkyne−azide click reaction of azidoterminated hyperbranched polyglycerols (HPG-N3) on the PVDF-g-PQDMAEMA membrane leads to the formation of HPG polymers covalently attached onto the membrane and pore surfaces. Figure 6a-c shows the XPS wide-scan, C 1s and N 1s core-level spectra of the PVDF-g-P[QDMAEMA-clickHPG] membrane. In comparison to the starting PVDF-gPQDMAEMA membrane (see Figure 5d-f), marked changes in the XPS wide-scan and C 1s core-level spectra are observed for the PVDF-g-P[QDMAEMA-click-HPG] membrane. The F 1s signal has disappeared in the wide-scan spectrum, indicating that the PVDF-g-P[QDMAEMA-click-HPG] membrane surface has been fully covered by the HPG polymer layer, to a thickness beyond the probing depth of the XPS technique (∼8 nm for organic matrix45). The same result can also be deduced 15969



Article

viscosity on the permeate side of the membranes.46−48 In comparison to the commercial “low-protein binding” Millipore hydrophilic PVDF membrane of comparable mean pore size, slower decreases in permeation rate are observed for the PVDFg-P[QDMAEMA-click-PEG] and the PVDF-g-P[QDMAEMAclick-HPG] membranes under prolonged flux, with the latter exhibiting better antifouling property owing to the presence of hyperbranched HPG brushes. The protein rejection ratio for the PVDF-g-P[QDMAEMA-click-HPG] membrane, as calculated after a filtration volume of 240 mL, is about 95%, which is higher than that of 91% for the PVDF-g-P[QDMAEMA-clickPEG] membrane and that of 83% for the commercial Millipore hydrophilic PVDF membrane. These hydrophilic polymer brushes can form highly hydrated ultrathin coatings that provide an effective enthalpic and entropic barrier to nonspecific protein adsorption and impart the membrane surface with improved antifouling property. These results indicate that HPG polymer brushes on the membrane surface could be a good alternative to PEG polymer brushes in the development of nonfouling surfaces, in addition to providing the opportunity for further surface functionalization. 3.5. Functionalization of the PVDF-g-PQDMAEMA Membranes via Click Grafting of Azido-Terminated Polyethylenimine (PEI-N3): The Antibacterial PVDF-gP[QDMAEMA-click-QPEI] Membranes. The choice of polyethylenimine (PEI) is straightforward because of the high density of amine groups and their ease of conversion into quaternary ammonium cations.49−54 PEI is a strong base and will be positively charged in a neutral medium. Generally, positively charged polymers tend to bind negatively charged proteins, such as bovine serum album (BSA), via electrostatic interactions to result in accumulation of the proteins on the membrane and pore surfaces.55,56 As a result, the antifouling efficiency of HPG-N3 is higher than that of PEI-N3. On the other hand, the antibacterial efficiency of the quaternized PEI polymer is higher than that of HPG, nonquaternized PEI, and PEG. Quaternized PEI has a much higher density of quaternary ammonium which can kill bacteria on contact with or attached to the membrane surfaces, while the hydrophilic HPG only reduces bacteria contact and adhesion to the membrane surfaces.57−59 The lethal action of polycationic biocides arises from interaction of the polycations with the cytoplasmic membrane of microorganisms, resulting in ultimate membrane disruption.60−64 The process of covalent attachment of quaternized PEI polymers onto the PVDF-g-PQDMAEMA membranes involved (i) click grafting of azido-terminated polyethylenimine (PEI-N3) onto the PVDF-g-PQDMAEMA membrane to produce the PVDF-g-P[QDMAEMA-click-PEI] membrane via alkyne−azide click reaction and (ii) quaternization of the PVDF-g-P[QDMAEMA-click-PEI] membrane by 1bromohexane to produce the antibacterial PVDF-g-P[QDMAEMA-click-QPEI] membrane. Figure 6d-f,f′ shows the XPS wide-scan, C 1s, N 1s, and Br 3d core-level spectra of the PVDF-g-P[QDMAEMA-clickQPEI] membrane. The C 1s core-level spectrum can be curved into five peak components with BEs at about 284.6, 285.7, 286.2, 287.4, and 288.5 eV, attributable to the C-H, C-N, C-O/ C-N+, N-CO, and O-CO species, respectively (Figure 6e).42 The disappearances of the F 1s signal in the wide-scan spectrum (Figure 6d), as well as the (-CH2-)PVDF and (-CF2-)PVDF peak components with respective BEs at 285.8 and 290.5 eV in the C 1s core-level spectrum (Figure 6e) and associated with the underlying PVDF, indicate that the

to protein adsorption. The surface composition of the membranes after exposure to a 5 mg/mL γ-globulin solution for 24 h was analyzed by XPS. The relative amount of surfaceadsorbed protein can be expressed simply as the increase in surface [N]/[C] ratio over that arising from the initial alkyne− azide click reaction. The dependence of surface [N]/[C] ratio on the concentration of click-grafted HPG polymer of the PVDF-g-P[QDMAEMA-click-HPG] membranes upon exposure to the γ-globulin solution for 24 h is summarized in the inset of Figure 7. The level of γ-globulin adsorption on the

Figure 7. Permeation rate through the Millipore hydrophilic PVDF membrane with a standard pore size of d = 0.22 μm (open triangle, Δ, average pore size of d = 0.56 μm, as determined from mercury porosimetry), PVDF-g-P[QDMAEMA-click-PEG] membrane (solid circle, ●) and PVDF-g-P[QDMAEMA-click-HPG] membrane (solid square, ■) as a function of the filtration volume of doubly distilled water for 30 mL, followed by a 1 mg/mL γ-globulin solution under an imposed pressure of 5.9 kN/m2. Inset: Dependence of the extent of γglobulin adsorption (expressed as the increase in [N]/[C] ratio after γglobulin exposure) on the PVDF-g-P[QDMAEMA-click-HPG] membrane (solid square, ■) and the starting PVDF-g-PDMAEMA membrane (open circle, ○) at different AGET-ATRP times. Zero h ATRP time corresponds to the pristine PVDF membrane cast by phase inversion.

PVDF-g-P[QDMAEMA-click-HPG] membrane from 4 h of AGET-ATRP is less than 50% of that of the corresponding PVDF-g-PDMAEMA membrane and less than 25% of that of the pristine PVDF membrane. For membranes from 8 h or more of AGET-ATRP, the amount of protein adsorption is further reduced. For comparison purposes, linear azido-terminated poly(ethylene glycol) (PEG, Mn = 5000 g/mol) with comparable molecular weight has been clicked onto PVDF-g-PQDMAEMA to produce the PVDF-g-P[QDMAEMA-click-PEG] membrane using reaction conditions similar to those used for the preparation of PVDF-g-P[QDMAEMA-click-HPG] membrane. The effect of γ-globulin fouling on the permeability of commercial (Millipore) hydrophilic PVDF membranes, the PVDF-g-P[QDMAEMA-click-PEG] and the PVDF-g-P[QDMAEMA-click-HPG] membranes were investigated as a function of time under a fixed filtration pressure of 5.9 kN/m2 (Figure 7). The decline in permeation rate with the filtrate volume can be attributed to protein fouling on the membrane and pore surfaces, solute buildup at the membrane-solution interface, and deposition of proteins along with increased fluid 15970



Article

Figure 8. SEM images of (a,d) pristine PVDF membrane, (b,e) PVDF-g-PQDMAEMA membrane, and (c,f) PVDF-g-P[QDMAEMA-click-QPEI] membrane after exposure to PBS suspensions of E. coli (top) and S. epidermidis (below) at an initial cell concentration of 108 cells/mL for 4 h at 37 °C, followed by incubation in the culture medium in a flow chamber at a constant flow rate of 0.5 mL/min for 18 h at room temperature.

thickness of the PEI graft layer has exceeded the sampling depth of the XPS technique (∼8 nm for organic matrix45). The N 1s spectrum can be curve-fitted with three peak components using the following approach. The peak component at about 399.6 eV is assigned to the amine nitrogen ((C)-N-) of the triazole rings and nonquaternized PEI polymer. The peak component at the BE of 398.4 eV is assigned to the imine nitrogen (=N-) of the triazole rings. The peak component at about 402.7 eV is assigned to the positively charged nitrogen (N+) of quaternized PEI polymer (Figure 6f).7,42,43 The molar ratio of the three nitrogen species, viz., the imine nitrogen (=N), the amine nitrogen ((C)-N-), and the positively charged nitrogen (N+) is about 1:3:13, as determined from the spectral area ratio of the three peak components. Taking into account the fact that the [=N-]/[-N-] ratio is 2:1 in the triazole ring from the alkyne−azide click reaction, the [N+]/[N] ratio is about 0.84 (Figure 6f), indicating that about 84% of the nitrogen in the PEI polymer have been quaternized. The corresponding Br 3d core-level spectrum has a spin−orbit split doublet, Br 3d5/2 and Br 3d3/2 with BEs at 67.4 and 68.5 eV, respectively, attributable to the ionic bromide (Br−) species (Figure 6f′).42 The XPS-derived [Br−]/[N+] ratio is about 1.04, which is consistent with the quaternized ammonium structure. The XPS results thus confirmed that a quaternized PEI polymer layer has been immobilized onto the PVDF-g-PQDMAEMA membrane surfaces. A flow chamber is commonly used in simulating microbial adhesion, growth, and proliferation on surfaces under continuous-flow conditions.32,33 In this study, bacterial cells from an inoculums suspension were first allowed to adhere onto the membrane surface, mimicking bacteria-infected sites. After the adhesion phase, a flow of growth medium is maintained to allow bacterial growth and biofilm formation. In comparison to the E. coli inoculated surface, the SEM image shows that S. epidermidis form much thicker and more uniform

biofilm on the pristine PVDF membrane surface (Figures 8a and 8d, respectively). This result is consistent with the earlier reports that S. epidermidis (ATCC 35984) has a strong biofilm formation ability.56 On the other hand, a significant decrease in the number of viable bacterial cells was observed for the PVDFg-PQDMAEMA membrane (Figures 8b and 8e) and PVDF-gP[QDMAEMA-click-QPEI] membrane (Figures 8c and 8f), with the latter membrane exhibiting a distinctively higher bactericidal efficiency owing to the much higher density of quaternary ammonium cations. The bacteria cells which were killed upon contact with the quaternized PEI polymer layer were not firmly attached to the surface and were washed away, leaving behind a much cleaner membrane surface. The above results reveal that the PVDF-g-P[QDMAEMA-click-QPEI] membrane surfaces are highly effective in preventing bacterial adhesion, growth, and proliferation and thus biofilm formation.

4. CONCLUSIONS PVDF copolymers with grafted PDMAEMA side chains (PVDF-g-PDMAEMA copolymers) were synthesized in the single step AGET-ATRP of DMAEMA via the direct initiation from the secondary fluorine atoms on the PVDF backbone in the presence of a limited amount of air. Microporous membranes were prepared from the NMP solution of the PVDF-g-PDMAEMA copolymers of different graft concentrations by phase inversion in an aqueous medium. Reaction of propargyl bromide with the PVDF-g-PDMAEMA membrane produced the quaternized PVDF-g-PQDMAEMA membrane with additional alkyne groups on the membrane surface, which provided a versatile platform for further surface functionalization reactions. Azido-terminated hyperbranched polymers, such as HPG-N3 or PEI-N3, were grafted onto the membrane surface via the simple alkyne−azide click reaction. The present study has shown that the covalently immobilized hyperbranched polymers are a good alternative to their linear counterparts in 15971



Article

molecular weight hyperbranched polyglycerols. Macromolecules 2006, 39, 7708−7717. (15) Sisson, A. L.; Haag, R. Polyglycerol nanogels: highly functional scaffolds for biomedical applications. Soft Matter 2010, 6, 4968−4975. (16) Konkolewicz, D.; Monteiro, M. J.; Perrier, S. Dendritic and hyperbranched polymers from macromolecular units: elegant approaches to the synthesis of functional polymers. Macromolecules 2011, 44, 7067−7087. (17) Voit, B. I.; Lederer, A. Hyperbranched and highly branched polymer architectures-synthetic stractegies and major characterization aspects. Chem. Rev. 2009, 109, 5924−5973. (18) Wilms, D.; Wurm, F.; Nieberle, J.; Bohm, P.; Kemmer-Jonas, U.; Frey, H. Hyperbranched polyglycerols with elevated molecular weights: a facile two-step synthesis protocol based on polyglycerol macroinitiators. Macromolecules 2009, 42, 3230−3236. (19) Jayant, K.; Marcelo, C.; Nilesh, M. D.; Rainer, H. Multifunctional dendritic polymers in nanomedicine: opportunities and challenges. Chem. Soc. Rev. 2012, 41, 2824−2848. (20) Huisgen, R. Cycloadditions-definition, classification, and characterization. Angew. Chem., Int. Ed. 1968, 7, 321−328. (21) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click chemistry: diverse chemical function from a few good reactions. Angew. Chem., Int. Ed. 2001, 40, 2004−2021. (22) Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radic, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew. Chem., Int. Ed. 2002, 41, 1053−1057. (23) Golas, P. L.; Matyjaszewski, K. Marrying click chemistry with polymerization: expanding the scope of polymeric materials. Chem. Soc. Rev. 2010, 39, 1338−1354. (24) Iha, R. K.; Wooley, K. L.; Nystrom, A. M.; Daniel, J. B.; Kade, M. J.; Hawker, C. J. Applications of orthogonal “click” chemistries in the synthesis of functional soft materials. Chem. Rev. 2009, 109, 5620− 5686. (25) Ishizu, K.; Tsubaki, K.; Mori, A.; Uchida, S. Architecture of nanostructured polymers. Prog. Polym. Sci. 2003, 28, 27−54. (26) Hoogenboom, R. Thiol-yne chemistry: a powerful tool for creating highly functional materials. Angew. Chem., Int. Ed. 2010, 49, 3415−3417. (27) Chen, G. J.; Kumar, J.; Gregory, A.; Stenzel, M. H. Efficient synthesis of dendrimers via a thiol-yne and esterification process and their potential application in the delivery of platinum anti-cancer drugs. Chem. Commun. 2009, 41, 6291−6293. (28) Zhang, X. J.; Cheng, J.; Wang, Q. R.; Zhong, Z. L.; Zhuo, R. X. Miktoarm copolymers bearing one poly(ethylene glycol) chain and several poly(ε-caprolactone) chains on a hyperbranched polyglycerol core. Macromolecules 2010, 43, 6671−6677. (29) Roller, S.; Zhou, H.; Haag, R. High-loading polyglycerol supported reagents for Mitsunobu- and acylation-reactions and other useful polyglycerol derivatives. Mol. Diversity 2005, 9, 305−316. (30) Ignatova, M.; Voccia, S.; Gabriel, S.; Gilbert, B.; Cossement, D.; Jerome, R.; Jerome, C. Stainless steel grafting of hyperbranched polymer brushes with an antibacterial activity: synthesis, characterization, and properties. Langmuir 2009, 25, 891−902. (31) Shen, Z.; Chen, Y.; Frey, H.; Stiriba, S. E. Complex of hyperbranched polyethylenimine with cuprous halide as recoverable homogeneous catalyst for the atom transfer radical polymerization of methyl methacrylate. Macromolecules 2006, 39, 2092−2099. (32) Cringus-Fundeanu, I.; Luijten, J.; van der Mei, H. C.; Busscher, H. J.; Schouten, A. J. Synthesis and characterization of surface-grafted polyacrylamide brushes and their inhibition of micorbial adhesion. Langmuir 2007, 23, 5120−5126. (33) Bakker, D. P.; van der Mats, A.; Verkerke, G. J.; Busscher, H. J.; van der Mei, H. C. Comparison of velocity profiles for different flow chamber designs used in studies of microbial adhesion to surfaces. Appl. Environ. Microbiol. 2003, 69, 6280−6287. (34) Luo, R.; Sen, A. Electron-transfer-induced iron-based atom transfer radical polymerization of styrene derivatives and copoly-

enhancing the antifouling and antibacterial efficacy of membrane surfaces, as well as in providing additional sites for further surface functionalization.

■

ASSOCIATED CONTENT

S Supporting Information *

Experimental details on the synthesis of PVDF-g-PDMAEMA copolymers from thermally induced free radical polymerization, HPG-N3 and PEI-N3. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*Phone: +65-65162189. Fax: +65-67791936. E-mail: cheket@ nus.edu.sg. Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) Junginckel, B. J. In The Polymeric Materials Encyclopedia; Salamone, J. C., Ed.; CRC Press: Boca Raton, FL, 1996; Vol. 7, pp 7114−7123. (2) Seiler, D. A. In Modern Fluoropolymers; PVDF in the Chemical Process Industry; Scheirs, J., Ed.; Wiley: New York, 1997; Chapter 25, pp 487−506. (3) Souzy, R.; Ameduri, B.; Boutevin, B. Synthesis and (co)polymerization of monofluoro, difluoro, trifluorostyrene and ((triluorovinyl)oxy)benzene. Prog. Polym. Sci. 2004, 29, 75−106. (4) Chang, Y.; Chang, W. J.; Shih, Y. J.; Wei, T. C.; Hsiue, G. H. Zwitterionic, sulfobetaine poly(vinylidene fluoride) membranes with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization. ACS Appl. Mater. Interfaces 2011, 3, 1228− 1237. (5) Ameduri, B. From vinylidene fluoride (VDF) to the applications of VDF-containing polymers and copolymers: recent developments and future trends. Chem. Rev. 2009, 109, 6632−6686. (6) Kang, E. T.; Zhang, Y. Surface modification of fluoropolymers via molecular design. Adv. Mater. 2000, 12, 1481−1494. (7) Xue, J.; Chen, L.; Wang, H. L.; Zhang, Z. B.; Zhu, X. L.; Kang, E. T.; Neoh, K. G. Stimuli-responsive multifunctional membranes of controllable morphology from poly(vinylidene fluoride)-graft-poly[2(N,N-dimethylamino)ethyl methacrylate] prepared via atom transfer radical polymerization. Langmuir 2008, 24, 14151−14158. (8) Zhang, M. F.; Russell, T. P. Graft copolymers from poly(vinylidene fluoride-co-chlorotrifluoroethylene) via atom transfer radical polymerization. Macromolecules 2006, 39, 3531−3539. (9) Cai, T.; Kang, E. T.; Neoh, K. G.; Teo, S. L. M. Surfacefunctionalized and surface-functionalization poly(vinylidene fluoride) graft copolymer membranes via click chemistry and atom transfer radical polymerization. Langmuir 2011, 27, 2936−2945. (10) Hester, J. F.; Banerjee, P.; Won, Y. Y.; Akthakul, A.; Acar, M. H.; Mayes, A. M. ATRP of amphiphilic graft copolymers based on PVDF and their use as membrane additives. Macromolecules 2002, 35, 7652− 7661. (11) Akthakul, A.; Hochbaum, A. I.; Stellacci, F.; Mayes, A. M. Size fractionation of metal nanoparticles by membrane filtration. Adv. Mater. 2005, 17, 532−535. (12) Calderon, M.; Quadir, M. A.; Sharma, S. K.; Haag, R. Dendritic polyglycerols for biomedical applications. Adv. Mater. 2010, 22, 190− 218. (13) Yeh, P.-Y. J.; Kainthan, R. K.; Zou, Y. Q.; Chiao, M.; Kizhakkedathu, J. N. Self-assembled monothiol-terminated hyperbranched polyglycerols on a gold surface: a comparative study on the structure, morphology, and protein adsorption characteristics with linear poly(ethylene glycol)s. Langmuir 2008, 24, 4907−4916. (14) Kainthan, R. K.; Muliawan, E. B.; Hatzikiriakos, S. G.; Brooks, D. E. Synthesis, characterization, and viscoelastic properties of high 15972



Article

merization of styrene and methyl methacrylate. Macromolecules 2008, 41, 4514−4518. (35) Jakubowski, W.; Min, K.; Matyjaszewski, K. Activators regenerated by electron transfer for atom transfer radical polymerization of styrene. Macromolecules 2006, 39, 39−45. (36) Zhu, W. P.; Zhong, M. J.; Li, W. W.; Dong, H. C.; Matyjaszewski, K. Clickable stars by combination of AROP and aqueous AGET-ATRP. Macromolecules 2011, 44, 1920−1926. (37) Jakubowski, W.; Matyjaszewski, K. Activator generated by electron transfer for atom transfer radical polymerization. Macromolecules 2005, 38, 4139−4146. (38) Zhao, T.; Zhang, L. F.; Zhang, Z. B.; Zhou, N. C.; Cheng, Z. P.; Zhu, X. L. A novel approach to modify poly(vinylidene fluoride) via iron-mediated atom transfer radical polymerization using activators generated by electron transfer. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 2315−2324. (39) The Systematic Identification of Organic Compounds, 7th ed.; Shriner, R. L., Hermann, C. K. E., Morrill, T. C., Curtin, D. Y., Fuson, R. C. J., Ed.; Wiley & Sons: New York, 1998. (40) Pham, Q.-T.; Petiaud, R.; Llauro, M.-F.; Waton, H. Proton and Carbon NMR Spectra of Polymers; John Wiley & Sons: Chichester, UK, 1984; Vol. 3, p 455. (41) Samanta, S.; Chatterjee, D. P.; Manna, S.; Mandal, A.; Garai, A.; Nandi, A. K. Multifunctional hydrophilic poly(vinylidene fluoride) graft copolymer with supertoughness and supergluing properties. Macromolecules 2009, 42, 3112−3120. (42) The Handbook of X-ray Photoelectron Spectroscopy, 2nd ed.; Moulder, J. F., Stickle, W. F., Sobol, P. E., Bomben, K., Eds.; PerkinElmer Corporation (Physical Electronics): Wellesley, MA, 1992; pp 216−217. (43) Cai, T.; Kang, E. T.; Neoh, K. G. Poly(vinylidene fluoride) graft copolymer membranes with “clickable” surfaces and their functionalization. Macromolecules 2011, 44, 4258−4268. (44) Zhao, K. Y. H.; Zhu, X. Y.; Wee, K. H.; Bai, R. B. Achieving highly effective non-biofouling performance for polypropylene membranes modified by UV-induced surface graft polymerization of two oppositely charged monomers. J. Phys. Chem. B 2010, 114, 2422− 2429. (45) Tan, L.; Woon, L. L.; Wong, H. K.; Kang, E. T.; Neoh, K. G. Surface modification of plasma-pretreated poly(tetrafluoroethylene) films by graft copolymerization. Macromolecules 1993, 26, 2832−2836. (46) Wavhal, D. S.; Fisher, E. R. Membrane surface modification by plasma-induced polymerization of acrylamide for improved surface properties and reduced protein fouling. Langmuir 2003, 19, 79−85. (47) Karabelas, A. J.; Mourouzidis-Mourouzis, S. A. Whey protein fouling of large pore-size ceramic microfiltration membranes at small cross-flow velocity. J. Membr. Sci. 2008, 323, 17−27. (48) Wang, Y. N.; Tang, C. Y. Fouling of nanofiltration, reverse osmosis, and ultrafiltration membranes by protein mixtures: the role of inter-foulant-species interaction. Environ. Sci. Technol. 2011, 45, 6373− 6379. (49) Hu, X. F.; Ji, J. Covalent layer-by-layer assembly of hyperbranched polyether and polyethyleneimine: multilayer films providing possibilities for surface functionalization and local drug delivery. Biomacromolecules 2011, 12, 4264−4271. (50) Mansouri, J.; Harrisson, S.; Chen, V. Strategies for controlling biofouling in membrane filtration systems: chanllenges and opportunities. J. Mater. Chem. 2010, 20, 4567−4586. (51) Nurit, B.; Yael, H. H.; Liat, B. H.; Ira, Y. F.; Abraham, J. D.; Ervein, I. W. Surface antimicrobial activity and biocompatibility of incorporated polyethylenimine nanoparticles. Biomaterials 2008, 29, 4157−4163. (52) Hsu, B. B.; Klibanov, A. M. Light-activated covalent coating of cotton with bactericidal hydrophobic polycations. Biomacromolecules 2011, 12, 6−9. (53) Rahim, M. A.; Nam, B.; Choi, W. S.; Lee, H. J.; Jeon, C. Polyeletrolyte complex particle-based multifunctional freestanding films containing highly loaded bimetallic particles. J. Mater. Chem. 2011, 21, 11831−11837.

(54) Chen, B.; Liu, M.; Zhang, L. M.; Huang, J.; Yao, J. L.; Zhang, Z. J. Polyethylenimine-functionalized graphene oxide as an efficient gene delivery vector. J. Mater. Chem. 2011, 21, 7736−7741. (55) Xu, Y.; Takai, M.; Ishihara, K. Protein adsorption and cell adhesion on cationic, neutral, and anionic 2-methacryloyloxyethyl phosphorylcholine copolymer surfaces. Biomaterials 2009, 30, 4930− 4938. (56) Ba, C. Y.; Ladner, D. A.; Economy, J. Using polyelectrolyte coating to improve fouling resistance of a positively charged nanofilration membrane. J. Membr. Sci. 2010, 347, 250−259. (57) Lichter, J. A.; Vliet, K. J. V.; Rubner, M. F. Design of antibacterial surfaces and interfaces: polyelectrolyte multilayers as a multifunctional platform. Macromolecules 2009, 42, 8573−8586. (58) Kenawy, E.-R.; Worley, S. D.; Broughton, R. The chemistry and applications of antimicrobial polymers: a state-of-the-art review. Biomacromolecules 2007, 8, 1359−1384. (59) Ferreira, L.; Zumbuehl, A. Non-leaching surfaces capable of killing microorganisms on contact. J. Mater. Chem. 2009, 19, 7796− 7806. (60) Cai, T.; Wang, R.; Yang, W. J.; Lu, S. J.; Neoh, K. G.; Kang, E. T. Multi-functionalization of poly(vinylidene fluoride) membranes via combined “grafting from” and “grafting to” approaches. Soft Matter 2011, 7, 11133−11143. (61) Ozcam, A. E.; Roskov, K. E.; Spontak, R. J.; Genzer, J. Generation of functional PET microfibers through surface-initiated polymerization. J. Mater. Chem. 2012, 22, 5855−5864. (62) Vigliotta, G.; Mella, M.; Rega, D.; Izzo, L. Modulating antimicrobial activity by synthesis: dendritic copolymers bases on nonquaternized 2-(dimethylamino)ethyl methacrylate by Cu-mediated ATRP. Biomacromolecules 2007, 8, 1359−1384. (63) Spasova, M.; Mespouille, L.; Coulembier, O.; Paneva, D.; Manolova, N.; Rashkov, I.; Dubois, P. Amphiphilic poly(D- or Llactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) block copolymers: controlled synthesis, characterization, and stereocomplex formation. Biomacromolecules 2009, 10, 1217−1223. (64) Roy, D.; Knapp, J. S.; Guthrie, J. T.; Perrier, S. Antibacterial cellulose fiber via RAFT surface graft polymerization. Biomacromolecules 2008, 9, 91−99.

15973


Poly(vinylidene fluoride) Membranes with Hyperbranched Antifouling

Recommend Documents