Article pubs.acs.org/Macromolecules
Self-Assembly of Polymer Nanostructures through Halogen Bonding Interactions of an Iodoperfluoroarene-Functionalized Polystyrene Derivative Alan Vanderkooy, Philipp Pfefferkorn, and Mark S. Taylor* Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6, Canada S Supporting Information *
ABSTRACT: A structurally novel iodoperfluoroarene-substituted polystyrene has been synthesized, and its noncovalent halogen bonding interactions with polymeric Lewis bases have been studied. RAFT polymerization was used to generate halogen bond donating polystyrene derivatives with low dispersities. Coassembly of the halogen bond donor polymer with an aminefunctionalized methacrylate block copolymer was achieved using a solvent switching protocol and studied by electron microscopy and dynamic light scattering analysis. The structures obtained include spheres, wormlike structures, and vesicles as well as “inverted” morphologies such as hexagonally packed hoops and bicontinuous structures, which have been challenging to access by conventional assembly methods. The ability to access such inverted structures suggests that complexes generated by noncovalent interactions between complementary macromolecules can display high effective packing parameters, giving rise to behavior that has generally required unconventional macromolecular architectures (e.g., dendrimers, branched, or triblock copolymers). The effects of polymer composition, assembly conditions, and the presence of halogen bond donating small molecules on the outcome of the assembly are discussed, along with NMR and X-ray photoelectron spectroscopy studies of the interpolymer halogen bonding interactions in this system.
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INTRODUCTION Assembly of block copolymers is a general approach for preparing well-defined structures having dimensions on the order of tens to hundreds of nanometers.1,2 Such structures are useful in drug delivery, catalysis, surface patterning, and other applications. Noncovalent interactions such as hydrogen bonding, ion pairing, and metal chelation can serve as driving forces for polymer self-assembly, with the reversible nature of the interactions potentially endowing stimulus-responsive properties to the obtained structures.3−7 The present study is aimed at using halogen bonding interactions to direct polymer micelle formation. Halogen bonding occurs when an electrondeficient, covalently bonded halogen is attracted to a nucleophilic site in a noncovalent interaction.8 Such interactions can show appreciable strength in solution along with a pronounced directionality: the most favorable orientation places the Lewis basic site (the halogen bond acceptor) at an angle of 180° relative to the X−R bond axis of the donor. Other potentially exploitable features of halogen bonding include its responsiveness to structural modifications of the donor (e.g., donor ability I > Br > Cl > F) and distinct solvent effects from hydrogen bonding as well as the hydrophobic nature of the © XXXX American Chemical Society
commonly employed donor groups and their affinities for soft Lewis bases.9−13 Applications of halogen bonding have appeared at a rapid pace in recent years,14−18 including several examples in the materials science field.19−30 However, only a handful of studies of macromolecules functionalized with halogen bond donor groups have been conducted. Notable examples include studies of molecularly imprinted polymers,31 layer-by-layer assembly,32 topochemical polymerization,33,34 and self-healing polymers.35 In 2015, we used reversible addition−fragmentation chain transfer (RAFT) polymerization to achieve the controlled synthesis of halogen bond donor-functionalized poly(methacrylates) (2, Figure 1) and showed that they underwent coassembly with amine-functionalized block copolymers to generate spherical, vesicle-like, and worm-like architectures in the solution phase.36 These observations established that halogen bonding between complementary macromolecules could be used to generate polymer-based assemblies. However, Received: February 7, 2017 Revised: April 24, 2017
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DOI: 10.1021/acs.macromol.7b00281 Macromolecules XXXX, XXX, XXX−XXX
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Figure 1. Halogen bond donating polystyrene 1 and poly(methacrylate) 2 and halogen bond accepting poly(2-(dimethylamino)ethyl methacrylate) 3. The donor and acceptor groups are highlighted in red and blue, respectively. Figure 2. Representation of a block copolymer illustrating the quantities (length l, volume v, and area a) that determine the packing parameter p (eq 1); predicted equilibrium morphologies for various packing parameters. Dark blue and light green denote hydrophobic and hydrophilic blocks, respectively.
it appeared that the assemblies were formed under kinetic control: varying the core volume fraction relative to the corona had little influence on morphology. Our goals in building on this initial demonstration were to diversify the types of morphologies that could be generated by assembly of complementary halogen bonding macromolecules and to identify unique features of this approach relative to established methods for the assembly of block copolymers. Here, we describe the realization of these aims, through the synthesis of a structurally new, polystyrene-based macromolecular donor (1, Figure 1) and the study of its coassembly with amine-functionalized, polymeric partners. The observed structures follow expected trends based on consideration of the packing parameter p (eq 1), where v is the volume of the coreforming block, a is the area on the surface of the micelle occupied by a corona block, and l is the length of the hydrophobic block (Figure 2).1,2,37 v p= (1) a×l
double-comb diblocks, dendrimers) that have been used by other researchers to access inverted structures.41−51 The importance of halogen bonding in the behavior of the present system is probed in detail, using several distinct approaches. Control experiments using a polymer having the electrophilic iodo substituent replaced by a fluoro group show that halogen bonding plays a key role in the polymer assembly process. This conclusion is further supported by the ability of a competitive, small-molecule halogen bond donor to disrupt the formation of polymer assemblies. Evidence for interpolymer halogen bonding has been obtained using X-ray photoelectron spectroscopy (XPS) in the solid state and 19F nuclear magnetic resonance (NMR) spectroscopy in solution. The latter technique has been used to elucidate trends in affinity and halogen bond donor site occupancy as a function of the degree of polymerization of the acceptor.
The site of covalent linkage between core- and coronaforming blocks also plays a role in determining the morphology. Using macromolecular partners having a high fraction of coreforming blocks, two inverted morphologies (p > 1) were obtained: one with circular, internal cavities in a hexagonal arrangement (HII: Figure 2) and the other a porous morphology that appears to be bicontinuous. The evolution of these structures over time has been studied, and intermediate stages have been identified. Porous structures of the type obtained here are high in surface area and are of particular interest for applications such as size-selective separations, controlled pharmaceutical release, catalysis, and template materials. 38−40 Accessing such inverted structures is a challenge: the high proportion of core-forming block in the requisite dissymmetric macromolecules promotes kinetic trapping of intermediate morphologies. We propose that in the current system the noncovalent interaction between polymers results in an increase in the volume of the coreforming segment and thus favors the formation of inverted morphologies. This is significant because it suggests that noncovalent macromolecular complexes may be alternatives to the unconventional covalent architectures (e.g., triblocks,
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EXPERIMENTAL SECTION
General. Reactions were carried out without effort to exclude air or moisture, unless otherwise indicated. Stainless steel syringes were used to transfer air- and moisture-sensitive liquids. Flash chromatography was carried out using neutral silica gel from Silicycle. Gravity column chromatography (purification of 4a) was carried out using neutral alumina from Sigma-Aldrich. Materials. 2-(Dimethylamino)ethyl methacrylate was filtered through basic alumina prior to use in polymerizations. Azobis(isobutyronitrile) (AIBN) was recrystallized from methanol. Copper(I) bromide was purified prior to use by stirring 2 g in 20 mL of acetic acid overnight and isolated by vacuum filtration. The obtained CuBr was washed sequentially with ethanol and ether, dried in vacuo, and transferred to a glovebox for storage. Tetrahydrofuran, toluene, and dichloromethane were purified by passing through two columns of activated alumina under nitrogen (Innovative Technology, Inc.). Deuterated benzene, chloroform, and water were purchased from Cambridge Isotope Laboratories. Bis(thiobenzoyl) disulfide was prepared according to a previous report.52 Pd(dppf)2Cl2·CH2Cl2 was purchased from STREM Chemicals Inc. Sodium hydroxide was purchased from Fisher Scientific. All other starting materials were purchased from Sigma-Aldrich. B
DOI: 10.1021/acs.macromol.7b00281 Macromolecules XXXX, XXX, XXX−XXX
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Macromolecules Characterization. Nuclear magnetic resonance (NMR) spectra were recorded using the following spectrometers: Agilent DD2 600, Agilent DD2 500, Bruker Avance III 400, Varian NMR System 400, and Varian Mercury 400. The spectra were processed using MestReNova. 1H NMR are reported in parts per million (ppm) relative to tetramethylsilane and referenced to residual protium in the solvent. Spectral features are tabulated in the following order: chemical shift (δ, ppm); multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quin = quintet, m = complex multiplet, app = apparent, br = broad); number of protons; coupling constants (J, Hz). 19F NMR spectra were calibrated to an external standard in a capillary: either 2,2,2-trifluoroethanol (δ −78.22 ppm, C6D6) or hexafluorobenzene (δ −164.9 ppm, C6D6). High-resolution mass spectra (HRMS) were obtained on time-of-flight mass spectrometers, equipped with either a direct analysis in real time (DART) or electron ionization (EI) ion source. Infrared (IR) spectra were obtained on a PerkinElmer Spectrum 100 instrument equipped with a single-bounce diamond/ ZnSe ATR accessory, either in the solid state or as neat liquids, as indicated. Spectral features are tabulated as follows: wavenumber (cm−1); intensity (s = strong, m = medium, w = weak, br = broad). Gel permeation chromatography (GPC) was conducted at 85 °C using a 1.0 g/L solution of lithium chloride in N-methylpyrrolidone (NMP) as eluent, at a flow rate of 1.0 mL/min through two Agilent PLgel 5 μm MIXED-C columns and an Agilent PLgel 5 μm MIXED-C guard column. The GPC instrument was equipped with a refractive index detector. Poly(methyl methacrylate) (PMMA) standards were used for calibration. Dynamic light scattering (DLS) was carried out without dilution. Data were collected with a Malvern Nanoseries Zetasizer. Measurements were made at 25 °C with a HeNe laser (633 nm) and at a scattering angle of 173°. Particle sizes were determined by two methods: distribution analysis using a non-negatively constrained least-squares algorithm and cumulants analysis. X-ray photoelectron spectroscopy (XPS) was carried out using a ThermoFisher Scientific instrument equipped with a monochromated Al Kα X-ray source. Polymer blends (2 with 3g and 1b with 3g) were prepared for XPS by allowing an acetone solution containing an equal concentration of amino and iodo functionalities (∼30 mM) to evaporate slowly in an uncapped vial. Subsequently, the blends were further evaporated under high vacuum for at least 2 h. Monomer and Polymer Synthesis. Representative synthetic protocols are presented here. Polymers 3a−3g were synthesized by ATRP in a similar manner to a previous report (see the Supporting Information).36 Full experimental details, including the syntheses of 1b, 1c, 4b, 5a, and 6, are described in the Supporting Information. 2,3,5,6-Tetrafluoro-4-iodo-4′-vinyl-1,1′-biphenyl (4a). An ovendried Schlenk flask was evacuated and refilled with argon three times. Tetrafluoro-1,4-diiodobenzene (500 mg, 1.24 mmol, 1 equiv), 4vinylphenylboronic acid (184 mg, 1.24 mmol, 1 equiv), and Pd(dppf)Cl2·CH2Cl2 (15 mg, 0.018 mmol, 1.5 mol %) were added to the flask, which was then evacuated and refilled with argon four times. 20 mL of dry THF was added to the solid starting materials to give a orange/red solution where all the starting materials except for the Pd catalyst were dissolved completely. To this was added 1.24 mL of a 3 M aqueous solution of sodium hydroxide (3.7 mmol, 3 equiv), which had been previously degassed by sparging with argon. After adding the aqueous base, the solution slowly turned black. The mixture was heated and stirred in an oil bath at 60 °C for 48 h. The reaction mixture was evaporated, and purification of the crude mixture was carried out by gravity column chromatography (diameter 3.0 cm, height 20.0 cm) on neutral alumina using hexanes as eluent (Rf ≈ 0.4). 4a was isolated as a white solid in 46% yield (215 mg, 0.58 mmol); mp 117−120 °C. 1H NMR (CDCl3, 400 MHz) δ = 7.55−7.52 (m, 2 H), 7.44−7.42 (m, 2 H), 6.77 (dd, J = 17.6, 10.9 Hz, 1 H,), 5.85 (dd, J = 17.6, 0.8 Hz, 1H), 5.36 (dd, J = 10.9, 0.8 Hz, 1H). 19F NMR (CDCl3, 376 MHz) δ = −121.9 to −122.0 (m, 2F), −142.6 to −142.7 (m, 2F). 13 C NMR (CDCl3, 100 MHz) δ = 147.6 (d, 1J(C, F) = 245 Hz), 143.6 (d, 1J(C, F) = 250 Hz), 138.8, 136.2, 130.4, 126.6 (two signals: see the 1 H coupled spectrum in the Supporting Information), 121.3, 115.6, 70.9. FTIR (solid state, cm−1): 3088 (w), 3064 (w), 3002 (w), 1826 (w), 1736 (w), 1630 (m), 1559 (w), 1515 (m), 1457 (s), 1420 (m),
1400 (m), 1391 (m), 1319 (w), 1288 (m), 1279 (m), 1208 (w), 1153 (w), 1116 (w), 1049 (w) 1030 (w), 1016 (m), 984 (s), 962 (s), 944 (s), 908 (s), 837 (s), 793 (m), 755 (m), 716 (m), 651 (w). HRMS (DART) calculated m/z for C14H7F4I: 378.9607; found: 378.9600. Polymer 1a. An anisole solution of AIBN and chain transfer agent 5a was degassed in a Schlenk flask by four freeze−pump−thaw cycles and subsequently backfilled with argon. 600 μL of this solution containing AIBN (0.5 mg, 3 μmol, 0.2 equiv) and 5a (5.8 mg, 15 μmol) was transferred using a degassed syringe to another Schlenk flask containing 4a (505 mg, 1.34 mmol, 89 equiv) which had been previously evacuated and refilled with an atmosphere of argon ten times. The reaction mixture was then submerged and stirred in an oil bath at 90 °C. The reaction was stopped after 6 h by submersion in liquid nitrogen. Analysis of an aliquot by 19F NMR indicated approximately 50% conversion of the monomer. The polymer was precipitated twice from DCM into hexane and cooled to −20 °C before being isolated by filtering/decanting. The product was transferred to a vial as a solution in chloroform, then concentrated, and dried in vacuo. The polymer was obtained as a pink solid (251 mg). 1H NMR spectroscopy indicated a degree of polymerization of roughly 50 (Mn = 1.9 × 104 Da) based on integration of the signals corresponding to the aromatic protons of the monomer and the terminal methoxy signal at 3.33 ppm. GPC (1.0 g/L LiCl in NMP, 85 °C, calibrated to PMMA standards) indicated a Đ of 1.12 and Mn of 16 000 Da, relative to PMMA. 1H NMR (CDCl3, 600 MHz) δ = 6.50−7.17 (br m, ∼191H), 3.41−3.71 (br m, 12H), 3.33 (br, 3H), 0.87−2.17 (br m, ∼162H). 19F NMR (CDCl3, 565 MHz) δ = −122.4 to −121.9 (br m, 2F), −143.3 to −143.2 (br m, 2F). FTIR (solid state, cm−1): 2924 (w), 1610 (w), 1565 (w), 1518 (w), 1470 (s), 1411 (s), 1290 (m), 1191 (w), 1152 (m), 1045 (w), 1020 (w), 965 (s), 899 (w), 832 (s), 788 (s), 759 (m), 735 (m), 714 (m). Protocol for Coassembly of Complementary Halogen Bonding Polymers. In a typical experiment, the halogen bond acceptor and donor polymers were dissolved separately in acetone at a concentration of iodo and amine functional groups of 4.8 mM. The acceptor polymer solution was added to the donor polymer solution at a 1:1 volume ratio by one quick injection while stirring at 60 rpm (diluting each polymer to 2.4 mM concentration of repeat units). These mixed solutions were made at a scale of approximately 3.6 mL and allowed to stir for 15−17 h. Subsequently, 2.0 mL of the acetone solution was removed and stirred at 60 rpm while acetonitrile was added by syringe pump at a constant rate over 24 h so that the final composition was 4:1 (acetonitrile:acetone v/v). 2 mL of these solutions was set aside for analysis, and the remainder was dialyzed against 1.0 L of water for 4−5 h using regenerated cellulose dialysis membrane (Fisherbrand) with molecular weight cutoff 6000−8000 Da. The external solution was replaced halfway through dialysis. The polymer assemblies were analyzed by TEM by preparing a grid minutes after mixing. They were also analyzed after stirring in acetone overnight, post acetonitrile addition, and in their final aqueous condition. Additional microscopy images are provided as Supporting Information. Electron Microscopy. Samples for transmission electron microscopy (TEM) analysis were prepared on carbon/Formvar grids purchased from Ted Pella, Inc. (product number 01822-F). Grids were prepared by placing 2 μL of the solution to be analyzed on the grid and wicking away the excess fluid using a Kimwipe within seconds of the application. TEM micrographs were collected using a Hitachi H7000 using an acceleration voltage of 75 or 100 kV. Scanning electron microscopy (SEM) micrographs were taken on the same grids as TEM using an FEI Quanta FEG 250. 19 F NMR Titrations. 19F NMR spectra were acquired using an Agilent DD2 600 MHz spectrometer. The toluene solvent for these experiments was purified through two columns of activated alumina under nitrogen to exclude water. The NMR tubes were equipped with a sealed capillary containing benzene-d6 to provide a quasi-internal lock signal. 2,2,2-Trifluoroethanol was dissolved in the benzene capillary to provide a quasi-internal 19F NMR reference signal (10 mM, δ = −78.22 ppm). C
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Macromolecules Scheme 1. Synthesis of Halogen Bond Donor- and Acceptor-Functionalized Polymers
A previously reported titration protocol was adapted.53 A parent solution of the halogen bond donor (1.1 mM of iodo functionality) in toluene was prepared. This parent solution was then used to prepare a solution of halogen bond acceptor. For a set of interpolymer titrations, the same parent solution of 1a was used to prepare each of the acceptor solutions of 3a−3c. The samples for titration were then prepared by mixing the two solutions in varying proportions using a syringe. The chemical shifts of the signals near −122 ppm were tracked. Changes in chemical shift (|Δδ|) and acceptor concentration were fitted to a 1:1 binding isotherm (based on the concentrations of iodo and dimethylamino groups) to determine the association constants and maximum chemical shift changes. The association constants for the polymers should be regarded as apparent association constants (Ka,app). Titration curves are provided as Supporting Information.
found to be relatively low, consistent with controlled radical polymerizations (Đ = 1.12, 1.13, and 1.23, respectively, for 1a, 1b, and 1c). In a similar fashion, perfluoroarene-bearing control polymer 6 was generated with a degree of polymerization of 70 and a dispersity of 1.13. For the complementary, halogen bond accepting macromolecules, we employed poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) derivatives of the type used in our previous study. Sterically unhindered amine groups are known to be good acceptors of halogen bonds, giving rise to appreciable association constants with iodoperfluoro-organics in nonpolar or moderately polar organic solvents (e.g., acetone, acetonitrile).11,57 Atom transfer radical polymerization (ATRP)58,59 was used to generate PDMAEMA homopolymers 3a−3c and 3g, having degrees of polymerization ranging from 40 to 240, as well as PEO-b-PDMAEMA block copolymers 3d−3f. Solution-Phase Assembly of Complementary Halogen Bonding Polymers. The protocol developed in our previous report for coassembly of polymers 2 and 3namely, slow addition of water to a solution of the complementary polymers in DMSO, followed by dialysis against water36led to nanoporous networks up to several micrometers in diameter for mixtures of homopolymer 1b with block copolymers 3d−3f. This same protocol yielded smaller networks and branched worms for combinations of two block copolymers 1c with 3d− 3f (see the Supporting Information). A clear dependence of aggregate structure on the chain lengths of the acceptor and core volume fractions was not evident, suggesting that these were kinetically trapped morphologies. Accordingly, a more gradual, multistage process was investigated, with the goal of accessing a more diverse set of structures under conditions that would favor thermodynamic control. A solution of the two polymers in acetone having equal concentrations of donor and acceptor functional groups (2.4 mM) was stirred overnight at room temperature. Acetonitrile was added by syringe pump
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RESULTS AND DISCUSSION Monomer and Polymer Synthesis. Halogen bond donorfunctionalized styrene derivative 4a was generated by a Suzuki− Miyaura cross-coupling of tetrafluoro-1,4-diiodobenzene and 4vinylphenylboronic acid (Scheme 1).54 Using a similar protocol, pentafluorophenyl-substituted 4b was prepared as a control lacking the ability to act as a halogen bond donor. Subjecting 4a to the radical initiator azobis(isobutyronitrile) (AIBN) and a chain transfer agent, bearing either a triethylene glycol (5a) or poly(ethylene oxide) (PEO) substituent (5b), resulted in efficient RAFT polymerization.36,55,56 In this way, three halogen bond donor-functionalized macromolecules were generated: poly(iodotetrafluoro-4′-vinyl-1,1′-biphenyl) (PIVP) derivatives 1a and 1b, having degrees of polymerization of roughly 50 and 70, respectively, as well as PEO-b-PIVP-based copolymer 1c. The degrees of polymerization were determined by end-group analysis, based on integration of the proton nuclear magnetic resonance (1H NMR) spectra. Dispersities (Đ) were determined by gel permeation chromatography (GPC) against poly(methyl methacrylate) standards and were D
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acceptor blocks (due to the presence of the electron-dense iodine substituents) and the low-contrast regions correspond to solvated PEO coronas. To probe the mechanism of formation of the hexagonally packed hoop structures, we conducted TEM imaging of samples taken at various stages of the assembly process (Figure 4). Within minutes of combining the acetone solutions of the
over 24 h. The resulting mixture (4:1 acetonitrile:acetone by volume) was subjected to dialysis against water, using a regenerated cellulose membrane with a molecular weight cutoff of 6000−8000 Da. Imaging was carried out by transmission electron microscopy (TEM) after wicking the excess fluid from droplets loaded onto the Formvar side of carbon/Formvar grids. Using this multistage protocol, the combination of halogen bond donating polystyrene 1b (degree of polymerization ∼70) and amine-functionalized block copolymer acceptor 3f (acceptor block degree of polymerization ∼120) resulted in assemblies having structured interiors (Figure 3). Analysis by dynamic
Figure 3. Transmission electron micrograph of hexagonally packed hollow hoop structures formed from polymers 1b and 3f by stirring in acetone overnight, followed by slow addition of acetonitrile by syringe pump and dialysis against water. TEM was conducted by loading 2 μL of the dialyzed solution onto a carbon/Formvar grid and wicking away the excess fluid.
light scattering (DLS) showed the presence of particles with apparent hydrodynamic diameter of 340 nm (PdI 0.306) as judged by cumulants analysis, a result that is roughly consistent with the dimensions of the objects observed by TEM. A close evaluation of the TEM images indicated that the structures are hexagonally packed hollow hoops, an inverted morphology (Figure 2).60−62 Although the initial examples of block copolymer-based structures having this type of internal inverse hexagonal (HII) phase were reported nearly 20 years ago by Eisenberg and co-workers, these architectures remain relatively uncommon in solution-phase block copolymer self-assembly.47,48,50,51,63 Eisenberg’s group obtained hexagonally packed hollow hoops from polystyrene(410)-b-poly(acrylic acid)(13) (numbers in parentheses indicate the degrees of polymerization of the two blocks) by slow addition of water to a DMF solution of the polymer, followed by introduction of NaCl to the resulting mixture.60 It was proposed that the hoops were arranged in a polystyrene matrix, with hydrated poly(acrylic acid) groups lining their inner surfaces. The group showed how the hexagonal packing and anisotropy of these structures could give rise to different contrast patterns depending on their orientation in the TEM experiment. This feature is evident in the TEM images shown in Figure 3, where the high-contrast regions correspond to the interacting halogen bond donor−
Figure 4. Transmission electron micrographs showing evolution of hexagonally packed hollow hoop morphology by assembly of 1b and 3f. (A) Structures formed upon stirring a solution of the two polymers in acetone at room temperature for a few minutes. (B) Structures formed upon stirring the acetone solution overnight. (C) Structures formed after addition of acetonitrile by syringe pump. TEM was conducted by loading 2 μL of the solution onto a carbon/Formvar grid and wicking away the excess fluid.
donor and acceptor polymers, a mixture of unilamellar vesicles and raspberry-like compound vesicles was observed. Stirring this mixture overnight caused the distribution to shift such that the unilamellar vesicles were no longer evident, with compound vesicles being the dominant structures. Upon slow addition of acetonitrile, the hexagonally packed hollow hoop structures were formed and remained qualitatively unchanged after dialysis against water. These observations suggest that the particles with HII internal structure are formed from vesicles via aggregation and rearrangement, a pathway that was initially proposed by Eisenberg’s group.60 Changing the degree of polymerization of the halogen bond acceptor block while maintaining the same donor polymer resulted in a distinct type of inverted morphology. Thus, conducting the same multistage assembly protocol using donor E
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Macromolecules 1b and copolymer 3e (having a degree of polymerization of 70, rather than 120 as described above) resulted in porous, internally structured particles with similar appearance to previously reported bicontinuous structures (Figure 5).41,64
Figure 6. Transmission electron micrograph of structures formed from polymers 1b and 3e by stirring in acetone for a few minutes, followed by addition of acetonitrile by syringe pump over 15 h and dialysis against water. TEM was conducted by loading 2 μL of the dialyzed solution onto a carbon/Formvar grid and wicking away the excess fluid.
acetonitrile carried out over an hour, HII structures were still obtained (Supporting Information). Reducing the acceptor block size still further to 30 units (copolymer 3d) generated another distinct morphology: large vesicles, including a significant fraction with nonspherical shapes, were formed when 1b and 3d were subjected to the acetone → acetonitrile → water protocol (Figure 7). The
Figure 5. Scanning electron micrograph (A) and transmission electron micrographs (B) of structures formed from polymers 1b and 3e by stirring in acetone overnight, followed by slow addition of acetonitrile by syringe pump and dialysis against water. Microscopy was conducted by loading 2 μL of the dialyzed solution onto a carbon/Formvar grid and wicking away the excess fluid.
TEM imaging over the course of the assembly process showed that stirring in acetone initially produced vesicles, with some fused structures becoming evident after the overnight treatment. Presumably the vesicles underwent more fusion and rearrangement upon addition of acetonitrile to generate the bicontinuous-like structures (Supporting Information). Again, further structural evolution was not evident upon dialysis against water. Recent work has shown how periodic, porous structures can be obtained via solution-phase assembly of block copolymers, with vesicles implicated as intermediate morphologies.38,39,49,50 The formation of inverted structures required sufficient time for equilibration and assembly evolution via aggregation of particles and rearrangement of the polymer chains. In keeping with the morphological evolution experiments described in the preceding paragraph, vesicles were obtained by reducing the acetone incubation of 1b and 3e to just a few minutes, followed by addition of acetonitrile over 15 h and dialysis against water (Figure 6). Furthermore, experiments with the longer acceptor 3f suggested that allowing time for evolution in acetone is more critical than the rate of acetonitrile addition. When the acetone incubation was shortened to minutes, a mixture of vesicles and internally structured particles was formed, but when the acetone solution was incubated overnight and the addition of
Figure 7. Transmission electron micrographs of structures formed from polymers 1b and 3d by stirring in acetone, followed by slow addition of acetonitrile by syringe pump and dialysis against water. TEM was conducted by loading 2 μL of the dialyzed solution onto a carbon/Formvar grid and wicking away the excess fluid.
vesicle walls appeared to be brittle, as they cracked upon drying during sample preparation for TEM imaging. For this combination of macromolecules, smaller vesicles and lamellae with branches were evident at the acetone stage of the protocol. The large, multi-micrometer-sized vesicles only appeared upon addition of acetonitrile (see the Supporting Information). Kim and co-workers observed a similar progression from inverted structures to large vesicles and lamellae upon decreasing the volume of the core-forming block.49 Presumably, the large size is favored due to minimization of curvature, while the closed shape avoids the energy costs associated with rim-capping.1 This end-capping energy penalty has also been invoked to explain the formation of closed rings rather than straight rods in the HII phase.60 F
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extent than the overall length, resulting in a high packing parameter for the macromolecular complexes. Because the two components of an interpolymer complex can be varied separately, and the strengths of noncovalent interactions can be modulated to a significant effect by structural variation, this may represent a versatile and useful alternative approach to accessing inverted structures by macromolecular assembly. Role of Halogen Bonding in Polymer Assembly: Control Experiments. To assess the importance of the halogen bonding interaction in the behavior discussed above, we subjected perfluorophenyl-substituted polymer 6 (Scheme 1) to the coassembly protocol with copolymer 3f. Because of the iodine-to-fluorine substitution, polymer 6 lacks the ability to act as a halogen bond donor. This control experiment did not result in ordered assemblies of the type shown in Figure 3, indicating that halogen bonding between complementary polymers is important for the formation of these structures. As an additional control experiment, we assessed the ability of 1-iodoperfluorohexane (C6F13I), a competitive halogen bond donor, to disrupt the assembly process. Consistent with our previous report,36 C6F13I was able to prevent formation of assemblies from 1b and 3f when a DMSO → water assembly process was employed (see the Supporting Information). Under the multistep protocol (acetone → acetonitrile → water), a different effect was observed. Addition of C6F13I (50 mM, ∼20 equiv relative to the interacting functional groups) diverted the assembly of 1b and 3f to a mixture of vesicles and spherical particles, rather than the hexagonally packed hoops that were otherwise formed from this combination of polymers (Figure S30). Iodoperfluorohexane is a competitive halogen bond donor, but its fluorous nature could conceivably influence the polymer assembly in other ways. Accordingly, we conducted further control experiments evaluating the effects of perfluorohexane (C6F14) on the assembly of 1b and 3f. As anticipated, this fluorous additive did not disrupt the assembly in the manner observed using the competitive donor C6F13I. Instead, it served to accelerate the evolution of the assembled morphologies (Figures S29 and S31): for example, the incubation time in acetone needed to generate the HII structures could be reduced from several hours to 10 min in the presence of C6F14. We propose that C6F14 facilitates the rearrangement of polymer chains through a plasticizing effect, consistent with NMR spectroscopic studies of assemblies of 2 and 3 in the presence of C6F14.36 In contrast, shortening the time for treatment with the competitive donor (C6F13I) did not appear to affect its ability to interfere with the assembly process (Figure S32). The distinct behaviors of C6F13I and C6F14 as additives suggest that the disruption observed using the former is a result of competitive halogen bonding rather than a fluorous effect. Halogen Bonding in Interpolymer Complexes: X-ray Photoelectron Spectroscopy. To obtain further evidence for halogen bonding between the complementary polymers, we employed X-ray photoelectron spectroscopy (XPS). This technique has been used to study condensed-phase halogen bonding in supramolecular liquid crystals,65−67 layer-by-layer polymer assemblies,32 and iodoperfluoroalkane−PEO star polymer supramolecular adducts,28 with a decrease in the binding energies of the iodine 3d electrons generally being observed upon interaction with a Lewis base. The X-ray photoelectron spectrum of polymer 1b displayed signals at binding energies of 633 and 622 eV, corresponding to the iodine 3d doublet (Figure 9). A blend of polymers 1b and 3g
Halogen bond donor copolymer 1c, which bears a stabilizing PEO block, displayed distinct behavior from homopolymer 1b. The PEO-b-PIVP-derived copolymer 1c is capable of assembly on its own, in analogy to the well-documented behavior of PSb-PEO:1 a mixture of spheres and wormlike structures was obtained from 1c under the acetone → acetonitrile → water assembly process (Figure 8A). The longer acceptor copolymer
Figure 8. Transmission electron micrographs of structures formed from polymer 1c alone (A) and in combination with polymer 3d (B) by stirring in acetone, followed by slow addition of acetonitrile by syringe pump and dialysis against water. TEM was conducted by loading 2 μL of the dialyzed solution onto a carbon/Formvar grid and wicking away the excess fluid.
3f combined with 1c also resulted in a mixture of spheres and worms (see the Supporting Information). However, the presence of the shorter halogen bond acceptor copolymers was able to alter the course of the assembly of 1c. For example, the spheres could be favored (no worm-like structures evident after dialysis against water) by coassembly of 1c with 3d or 3e under the standard conditions (Figure 8B). For the most part, the behavior of this system (spheres from 1c and 3d versus spheres and worms from 1c and 3f; vesicles from 1b and 3d versus inverted structures from 1b and 3e or 3f) appears to be consistent with the expected evolution of morphologies upon increasing the fraction of the less soluble blocks relative to the more soluble one (here, the interacting halogen bond donor and acceptor segments and the PEO block, respectively).1 Polymer architecture also has an effect, as illustrated by the behavior of a homopolymer/block copolymer combination (1b and 3d) and that of two block copolymers (1c and 3f). The PEO content of these two systems is similar, and yet distinct morphologies were obtained (vesicles in the former case versus spheres and worms in the latter case). Whether this is a thermodynamic effect related to variation of the packing parameter37 or a kinetic effect arising from solubility differences between the donor copolymer and homopolymer remains to be established. Kim and colleagues have demonstrated that the packing parameter (p) and assembly morphology can be modulated not only by varying the degrees of polymerization of the two blocks but also by changing the polymer chain architecture.50 For example, introducing branching to the core-forming block provides a way to increase its volume-to-length ratio (v/l) and thus leads to inverted morphologies, as would be expected for a higher packing parameter (eq 1). We propose that a similar effect is responsible for the formation of inverted morphologies in the present study. Halogen bonding between the coreforming blocks likely increases the overall volume to a greater G
DOI: 10.1021/acs.macromol.7b00281 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 9. X-ray photoelectron spectra (range of energies corresponding to iodine 3d electrons) of polymer 1b (- - -) and a blend of polymers 1b and 3g (). The spectra have been shifted vertically to align the baselines. Figure 10. Changes in 19F NMR chemical shift of halogen bond donor (resonance corresponding to the fluoro groups ortho to the iodine substituent) upon addition of acceptor in toluene. Titration data are shown for the interactions of polymer 1a with polymer 3a (■), polymer 3b (◆), polymer 3c (▲), and methacrylate monomer 7 (●) and of the iodotetrafluoroaryl-substituted styrene monomer 4a with monomer 7 (×). The curve of best fit to a 1:1 binding model is shown for each data set. The concentration of dimethylamino functional groups is recorded on the x-axis.
was prepared by allowing an acetone solution containing an equal concentration of halogen bond donor and acceptor repeat units to evaporate slowly in an uncapped vial, followed by further drying under high vacuum. XPS of the blend showed four signals in the iodine 3d region: along with the original doublet, a new doublet was apparent at lower binding energies (629 and 618 eV). The direction and magnitude of the shift in binding energies are consistent with other reported XPS data for halogen bonding of iodoperfluoro-organics.28 The observation of signals corresponding to both “free” and halogenbonded iodoperfluoroaryl groups suggests that the halogen bond donor sites are not fully occupied in the polymer− polymer complex. Deconvolution of the signals for the blend of 1b and 3g indicated that the halogen bond donor site occupancy is roughly 50−60%. Full occupancy of binding sites would not be expected due to the effects of entropy, functional group screening, steric hindrance, and other factors: incomplete occupancy is well established for blends of hydrogen bonding polymers.68 Halogen Bonding Interactions in Solution. The halogen bonding interactions between complementary macromolecules were further studied in the solution phase, using 19F NMR spectroscopy. Titrations of halogen bond donor 1a with polymeric acceptors 3a−3c were conducted in toluene solvent. Addition of increasing concentrations of the halogen bondaccepting polymer resulted in an upfield change in the chemical shift of the signals corresponding to the fluorine substituents ortho to the halogen bond-donating iodo group (Figure 10).11,69 This characteristic change in the 19F NMR spectrum provides further evidence that the polymers interact through halogen bonding. The dependence of the chemical shift on the concentration of dimethylamino groups was fitted to a 1:1 binding model, enabling the determination of an apparent association constant Ka,app for each combination (Table 1). Each entry in the table is the average result from multiple titration experiments. It is important to note that these are apparent rather than true Ka values: not only is the analysis based on functional group concentrations, but also the 1:1 binding model is an approximation when multivalent donors and acceptors are employed.70 A value of 190 M−1 was obtained for Ka,app between donor polymer 1a and acceptor polymer 3b, having degrees of polymerization of 50 and 120, respectively. The corresponding interactions of the 2-(dimethylamino)ethyl methacrylate monomer 7 with halogen bond donor monomer 4a, and with polymer 1a, had association constants less than 1 M−1, reflecting a significant multivalency effect for the polymer− polymer complexation. These observations are consistent with
Table 1. Apparent Association Constants for Polymer− Polymer Halogen Bonding and Nonpolymeric Controls
entry
donor
acceptor
Ka/M−1 a
1 2 3 4 5 6
4a 1a 1a 1a 1a 2a
7 7 3a 3b 3c 3g
