Article pubs.acs.org/Macromolecules
Ternary Graft Copolymers and Their Use in Nanocapsule Preparation Feng Liu,†,‡ Jiwen Hu,*,†,‡ Guojun Liu,*,†,§ Chengmin Hou,† Shudong Lin,† Hailiang Zou,† Ganwei Zhang,† Jianping Sun,† Hongsheng Luo,† and Yuanyuan Tu† †
Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou, P. R. China 510650 University of Chinese Academy of Sciences, Beijing, P. R. China 100049 § Department of Chemistry, Queen’s University, 90 Bader Lane, Kingston, Ontario, Canada K7L 3N6 ‡
ABSTRACT: Grafting three types of polymer chains onto the backbone of a fourth polymer yielded a ternary graft copolymer. The copolymer dispersed oil droplets in water with one type of graft stretching into the oil phase, the second type forming a thin membrane separating the two phases, and the third type stretching into the water phase. Since the second type was also photo-cross-linkable, shining UV light on the system produced permanent nanocapsules. To produce the graft copolymer, the backbone polymer used was poly(3-azido-2-hydroxypropyl methacrylate), P(GMA-N3). The grafts used were all end-functionalized by alkyne groups, and the polymers were poly(ethylene glycol) methyl ether (MPEG), polystyrene (PS), and poly(2-cinnamoyloxyethyl methacrylate) (PCEMA), respectively. Evidently, MPEG was water-soluble, PS was soluble in the used oil decahydronaphthalene (DN), and PCEMA was photo-cross-linkable and soluble in neither water nor DN. The grafts denoted as MPEG−CCH, PS−CCH, and PCEMA−CCH were coupled to P(GMA-N3) via click chemistry between the azide and alkyne units. Under the used conditions, the one-pot grafting reactions were quantitative.
I. INTRODUCTION A linear polymer chain bearing three types of pendant polymer chains is a ternary graft copolymer.1−3 If the total density of the grafted chains is high so that they strongly repel one another due to steric hindrance and the backbone chain is long relative to the grafts, the copolymer is called a ternary cylindrical brush or heterografted ternary cylindrical brush. While there have been many reports on heterografted binary cylindrical brushes in the past two decades,4−13 ternary cylindrical brushes or graft copolymers have not caught the attention of the polymer community. This situation is not warranted as ternary graft copolymers or brushes are interesting and potentially useful. To illustrate this point, we have developed a facile one-pot method to synthesize a family of ternary graft copolymers. We show that these polymers are useful in the making of nanocapsules that may find applications in controlled release applications.14−17 Graft copolymers are normally synthesized from the “graftthrough”, “graft-from”, and “graft-onto” methods.1,18 In the graft-through method, macromonomers are prepared first. The polymerization of one type of macromonomer yields a cylindrical homopolymer brush.19,20 Heterograft binary cylindrical brushes are prepared from the random copolymerization of two types of macromonomers.21,22 The sequential polymerization of two or more types of macromomers yields blocky cylindrical brushes.22 Core−shell and core−shell−corona cylindrical brushes are prepared from the polymerization of diblock and triblock macromonomers, respectively.23,24 In the graft-from method, the grafts are prepared from polymerizing monomers using initiating sites on a polymer backbone. If two types of initiating sites are used to grow two types of polymer © XXXX American Chemical Society
chains, a heterograft binary brush or a binary graft copolymer is prepared.4 Binary graft copolymers are prepared in the graftonto method by attaching two different types of polymer chains onto a third polymer backbone.25,26 Compared to the other two methods, the graft-onto method may not achieve high grafting densities. An advantage is the easy characterization of the components before they are linked. Further, this method is suited for the one-pot synthesis of multicomponent graft copolymers. For applications where a high grafting density is not desired, this method yields versatile multicomponent copolymers. The graft-onto method was used in this study to produce the desired ternary graft copolymers. The backbone polymers used were two poly(3-azido-2-hydroxypropyl methacrylate), P(GMA-N3), samples. The grafts used were end-functionalized poly(ethylene glycol) methyl ether (MPEG), polystyrene (PS), and poly(2-cinnamoylethyl methacrylate) (PCEMA), respectively. The precursory grafts MPEG−CCH, PS−CCH, and PCEMA−CCH were coupled to P(GMA-N3) via Cucatalyzed alkyne−azide cycloaddition (CuAAC). At a [C CH] to [N3] molar ratio of ≤23/100 or when x + y + z of Scheme 1 was ≤23%, the one-pot grafting reactions were quantitative. The residual N3 groups were then deactivated by reaction with propargyl alcohol. To prepare nanocapsules, two of the synthesized copolymers were each used to disperse decahydronaphthalene (DN) in water by emulsification. Stretching into the emulsified DN Received: December 28, 2012 Revised: February 20, 2013
A
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recrystallization from toluene. TBAF, anhydrous aluminum chloride, EDC·HCl, N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA, Aldrich, 99%), DN, DCM, cinnamoyl chloride (Aldrich, 98%), and 2,2-dipyridyl (bpy, Aldrich, 99%) were all used as received. 2Methoxyethyl 2-bromoisobutyrate, propargyl 2-bromopropanoate, 4oxo-4-(prop-2-yn-1-yloxy)butanoic acid, and 3-(trimethylsilyl)-propargyl 2-bromoisobutyrate were synthesized according to literature procedures.25,42 All other reagents and solvents were used as received unless otherwise indicated. PGMA and P(GMA-N3). PGMA41 was prepared via atom transfer radical polymerization by using 2-methoxyethyl 2-bromoisobutyrate as the initiator and CuCl/PMDETA as the catalyst system. Diphenyl ether (20.0 mL), 2-methoxyethyl 2-bromoisobutyrate (0.675 g, 3.0 mmol), GMA (17.1 g, 0.120 mol), CuCl (0.315 g, 3.0 mmol), and a magnetic stirring bar were added into a 100 mL round-bottom flask. The flask was subjected to an “evacuate and argon backfill” process thrice before it was further deoxygenated by a “freeze, evacuate, thaw, and argon fill” process thrice. PMDETA (0.522 g, 3.0 mmol) was injected into the flask using a degassed syringe, and the flask was then immersed in a preheated oil bath at 30 °C for 30 min for GMA polymerization. This was followed by immersing the flask into liquid nitrogen and then exposing the contents to air. The resultant viscous reaction mixture was diluted with DCM (100 mL) and passed through an activated neutral alumina column. The filtrate was concentrated to ∼40 mL via rotary evaporation and subsequently added into 500 mL of hexane to precipitate the polymer. It was redissolved in ∼40 mL of DCM and precipitated into 500 mL of hexane again. The precipitate was dried under vacuum for 24 h to yield 16.9 g of PGMA in a 99% yield. PGMA102 was prepared analogously, except the use of a different GMA to initiator molar ratio. The yield of the final polymer was 96%. To attach azide groups, PGMA41 or PGMA102 (6.50 g, 0.046 mol of epoxide groups) was dissolved in DMF (150 mL). Sodium azide (6.5 g, 0.10 mol) and anhydrous aluminum chloride (0.10 g, 0.75 mmol) was then added to polymeric DMF solution, which was subsequently stirred at 50 °C for 25 h. After the reaction, insoluble impurities were removed by filtration. After most of the DMF had been evaporated, P(GMA-N3) was precipitated in water (500 mL). The polymer was redissolved in ∼20 mL of DMF and precipitated into 500 mL of water again. The product was filtrated, washed with water, and vacuum-dried to give 6.4 g of white solid at a 75% yield. PHEMA−CCH. Alkyne end-functionalized poly(2-hydroxyethyl methacrylate) (PHEMA−CCH) was prepared via ATRP using 3(trimethylsilyl)propargyl 2-bromoisobutyrate as the initiator. Methanol (8.0 mL), methyl ethyl ketone (12.0 mL), 3-(trimethylsilyl)propargyl 2-bromoisobutyrate (0.535 g, 1.93 mmol), HEMA (20.00 g, 0.154 mol), CuCl2 (25 mg, 0.19 mmol), and CuCl (0.191 g, 1.93 mmol), along with a magnetic stir bar, were placed inside a 100 mL round-bottom flask. The flask was subjected to an “evacuate and argon backfill” process thrice before it was further deoxygenated by a “freeze, evacuate, thaw, and argon fill” process thrice. Bpy (0.599 g, 4.0 mmol) dissolved in 0.5 mL of methanol was deoxygenated by a “freeze, evacuate, thaw, and argon fill” process thrice and then injected into the flask using a degassed syringe. The flask was immersed into an oil bath preheated to 50 °C, and the polymerization was allowed to go at this temperature for 2.5 h before the flask was removed and immersed into liquid nitrogen and opened to introduce air. The mixture was diluted with 100 mL of methanol and was subsequently passed through an activated neutral alumina column before it was concentrated via rotary evaporation to ∼30 mL. The concentrate was added into 500 mL of water to precipitate the polymer. The polymer was redissolved in ∼30 mL of methanol and precipitated into 500 mL of water again. The precipitate was dried under vacuum for 24 h, yielding 13.0 g of the product as a white powder in a 65% yield. To remove the trimethylsilyl protecting group in the initiating unit, the product obtained above (10.0 g), DMF (30 mL), and tetrabutylammonium fluoride (5.0 g, 0.019 mol) were stirred together at room temperature for 72 h. After most of the solvent was removed under reduced pressure, the polymer solution (∼10 mL) was precipitated in water (500 mL) to remove residual salts. The obtained
Scheme 1. Structure of PGMA-g-(PS-r-PCEMA-r-MPEG)
droplets were the DN-soluble PS chains. The water-soluble MPEG chains stretched away from the droplets into the aqueous phase. Since PCEMA is soluble in neither water nor DN, it formed a thin membrane separating the two phases. This membrane was photo-cross-linked by shining UV light on the system to yield “permanent” capsules. As far as the applications of cylindrical brushes are concerned, many reports have appeared on the applications of binary cylindrical brushes, core−shell and core−shell− corona cylindrical brushes, and blocky cylindrical brushes. For example, binary cylindrical brushes have been used to disperse oil in water to make miniemulsions.27 Binary cylindrical brushes have also been assembled in selective solvents into rodlike aggregates,28 spherical micelles,29,30 and vesicles.31 In the case of core−shell cylindrical brushes, their cores have been used to template metal and metal oxide nanoparticles32,33 or conducting polymer34 and for drug loading.35 Drug has also been loaded into capsules or tubes made from core−shell−corona cylindrical brushes.36 To make these hollow structures, the core block of the core−shell−corona brushes was degraded after the shell block was cross-linked.24,37,38 A remarkable application of the blocky cylindrical brushes has been in the making of photonic crystals.39,40
II. EXPERIMENTAL SECTION Materials. CuBr (98%), CuCl (98%), CuCl2 (99%), CuSO4·5H2O (99%), anhydrous aluminum chloride (99%), sodium ascorbate (SA, 99%), disodium ethylenediamine tetraacetate (EDTA, 99%), 2hydroxyethyl methacrylate (HEMA, 98%), styrene (St, 99%), glycidyl methacrylate (98%), tetrabutylammonium fluoride (TBAF, 98%), 1(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl, 98%), decahydronaphthalene (DN, 99%), dichloromethane (DCM, 99%), pyridine (99%), N,N-dimethylformamide (DMF, 99%), and diphenyl ether (99%) were purchased from Aladdin Reagent of China. CuBr and CuCl were purified by rinsing with glacial acetic acid, methanol, and diethyl ether before they were dried under vacuum, while CuSO4·5H2O, sodium ascorbate, and EDTA were used as received. CuCl2 was dried under vacuum before use. HEMA was purified according to a procedure described in the literature.41 The procedure involved washing an aqueous solution (25 vol % HEMA) of monomer with hexanes (4 × 200 mL), salting the monomer out of the aqueous phase by addition of NaCl, drying over MgSO4, and distilling under reduced pressure. Styrene was washed thrice with equal amounts of 10% NaOH aqueous solution and then washed with water until the water tested was neutral. It was dried over anhydrous sodium sulfate and then distilled under reduced pressure. Glycidyl methacrylate was purified via distillation under reduced pressure. Poly(ethylene glycol) methyl ether (MPEG, Mn = 5000 g/mol) was purchased from Aldrich and used as received. Pyridine was refluxed over CaH2 overnight and distilled prior to use. Diphenyl ether and methylbenzene (Aldrich, 99%) were refluxed over a sodium wire and distilled before use. N,N-Dimethylformamide (DMF) was dried over anhydrous magnesium sulfate for 3 days and distilled before use. Dimethylaminopyridine (DMAP, Aldrich, 99.9%) was purified via B
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Scheme 2. Synthetic Route toward PGMA-g-(PS-r-PCEMA-r-MPEG)
product was dried under vacuum for 24 h, thus generating 9.3 g of PHEMA−CCH as a white powder in a 93% yield. Synthesis of PCEMA−CCH. To cinnamate the hydroxyl groups of PHEMA−CCH, PHEMA−CCH (4.0 g) was mixed with cinnamoyl chloride (7.68 g) and dissolved in freshly distilled pyridine (160 mL). The mixture was stirred overnight before it was centrifuged to remove the pyridinium salt. After most of the solvent was removed under reduced pressure, the polymer solution was added to an excess of methanol to precipitate PCEMA−CCH. The polymer was redissolved in ∼15 mL of DMF and precipitated into 500 mL of methanol again. The polymer was then dried at room temperature under vacuum for 24 h, generating 7.63 g of product as white powder in a 93% yield. MPEG−CCH. MPEG−CCH was synthesized by esterification of MPEG with an excess of 4-oxo-4-(prop-2-yn-1-yloxy)butanoic acid using EDC·HCl and DMAP as catalysts. In particular, MPEG (20.0 g, 4.0 mmol, Mn = 5000 g/mol), 4-oxo-4-(prop-2-yn-1-yloxy)butanoic acid (1.87 g, 0.012 mol), DMAP (1.95 g, 0.016 mol), and EDC·HCl (2.29 g, 0.012 mol) were dissolved in 100 mL of DCM. The solution was then stirred at room temperature for 72 h before it was washed twice in sequence with each of the following liquids: 2 M HCl (5 mL), saturated NaHCO3 (10 mL), and distilled water (20 mL). The organic layer was collected and dried over anhydrous magnesium sulfate for 12 h and subsequently filtered. The filtrate was concentrated by rotary evaporation to ∼30 mL and then added into anhydrous diethyl ether (500 mL) to precipitate the polymer. The polymer was redissolved in ∼30 mL of DCM and precipitated into 500 mL of diethyl ether again.
The precipitate was dried under vacuum for 24 h, generating 16.0 g of MPEG−CCH as a white powder in an 80% yield. PS−CCH. PS−CCH was prepared by ATRP using propargyl 2-bromopropanoate as the initiator. Methylbenzene (15.0 mL), propargyl 2-bromopropanoate (0.210 g, 1.0 mmol), St (26.5 g, 0.255 mol), and CuBr (0.143 g, 1.0 mmol) and a magnetic stir bar were placed inside a 100 mL round-bottom flask. The flask was subjected to an “evacuate and argon backfill” process thrice before it was further deoxygenated by a “freeze, evacuate, thaw, and argon fill” process thrice. PMDETA (0.173 g, 1.0 mmol) was injected into the flask using a degassed syringe, and the flask was then immersed in a preheated oil bath at 90 °C. The mixture turned slightly green immediately and slightly yellow over time. The reaction was performed for 5.5 h before the flask was immersed into liquid nitrogen and the content was exposed to air. The mixture was diluted by adding 100 mL of tetrahydrofuran (THF). This solution was subsequently passed through an activated neutral alumina column before the filtrate was concentrated to ∼40 mL via rotary evaporation and added into 500 mL of methanol to precipitate the polymer. The polymer was redissolved in ∼30 mL of THF and precipitated into 500 mL of methanol again. The precipitate was dried under vacuum for 24 h, yielding 13.5 g of PS−CCH as a white powder in a 51% yield. Preparation of Ternary Graft Copolymers. In an example preparation, DMF (16.0 mL), P(GMA-N3)41 (0.11 g, 0.59 mmol of azide groups), PCEMA−CCH (0.22 g, 7.05 μmol of alkyne groups), PS−CCH (0.40 g, 0.030 mmol of alkyne groups), and an aqueous sodium ascorbate solution (90 mg, 4.54 mmol, dissolved into 0.20 mL of water) were mixed in a 50 mL round-bottomed flask and C
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Figure 1. 1H NMR spectra and peak assignments for PGMA41 and (PGMA-N3)41 (a), PHEMA−CCH and PCEMA−CCH (b), MPEG−C CH (c), and PS−CCH (d). NMR and Dynamic Light Scattering. 1H NMR spectra were obtained on a Bruker DMX-400 spectrometer. Deuterated chloroform (CDCl3), deuterated water (D2O), or deuterated dimethyl sulfoxide (DMSO-d6) was used as the solvent. The hydrodynamic diameters (Dh) of the capsules and their polydispersity indices (PDI) were determined by dynamic light scattering (DLS) on a Malven Zetasizer Nano System. The emulsions were passed through 1.0 μm filters before DLS measurements. The measurements were conducted in a 3.0 mL quartz cuvette, using an 800 nm diode laser at 25 °C, and the scattering angle used was 90°. Each set of Dh and PDI values was the average from five measurements. Transmission Electron Microscopy. To visualize the nanocapsules by transmission electron microscopy (TEM), dispersions of the capsules were aerosprayed43 onto nitrocellulose-coated 200 mesh copper grids before they were dried under high vacuum to remove any volatile residues. The samples were subsequently stained with RuO4 for 30 min before TEM observation on a JEM-100CX II microscope operated at 80 kV. Atomic Force Microscopy (AFM). Dispersions of the cross-linked nanocapsules were aero-sprayed onto freshly cleaved mica surfaces before they were dried under high vacuum to remove any volatile residues. The dried nanocapsules were observed using a MultiMode 8 SPM AFM system (Bruker) using a ScanAsyst mode.
deoxygenated via bubbling with argon for 50 min. Then, 0.20 mL of an aqueous solution of CuSO4·5H2O (50 mg, 0.20 mmol) was added. This was followed by stirring the reaction mixture at room temperature for 24 h. Subsequently, 6.0 mL of a degassed DMF solution of MPEG−CCH (0.40 g, 0.080 mmol of alkynyl groups) was introduced into the flask using a syringe. The reaction was allowed to go for another 48 h. Lastly, propargyl alcohol (0.80 g, 1.4 mmol) was injected into the flask, and the reaction mixture was stirred for 16 h to deactivate the residual azide groups. After all of the solvent was removed under reduced pressure, the product was dissolved with 100 mL of DCM and extracted with 10 mL of a saturated aqueous EDTA solution to remove the catalyst. The organic layer was then collected and dried with anhydrous sodium sulfate for 5 h. After most of the solvent was removed via rotary evaporation, the residue (∼2.0 mL) was added into diethyl ether to precipitate the polymer. The obtained product was dried under vacuum for 24 h, yielding 1.04 g of the product as a white powder in a 92% yield. Capsule Formation. Water (20 mL) and DN with volume between 0.10 and 0.20 mL were added into a 100 mL round-bottom flask immersed in a water bath. The mixture was stirred mechanically at 1600 rpm with a hemispherically shaped Teflon blade attached to the end of a stirring shaft. To it was added dropwise 0.50 mL DCM containing 20 mg of a graft copolymer. This was followed by stirring at room temperature for 30 min, at 32 °C for 2 h, and at 50 °C for 1 h to remove DCM. To cross-link the PCEMA layer, the emulsion was diluted with 1 volume of water and then irradiated in a quartz round-bottom flask under magnetic stirring at 25 °C for 1−2 h. The UV light was from a 100 W Hg lamp powered by a universal system. To determine the degree of PCEMA double-bond conversion, the sample was diluted with DMF and the absorbance decrease at 274 nm was monitored. The typical CEMA double conversion used was ∼60%. Size Exclusion Chromatography. The number-average molecular weight (Mn) and polydispersity index (Mw/Mn) of each polymer were determined at 35 °C using a Waters 1515 size exclusion chromatograph (SEC) equipped with a Waters 2414 refractive index (RI) detector. DMF containing tetrabutylammonium bromide (0.05 mg/L) or THF was used as the eluant and the columns used were the styragel HR3 and HR4 columns calibrated by narrow PS standards.
III. RESULTS AND DISCUSSION P(GMA-N3), MPEG−CCH, PS−CCH, and PCEMA− CCH were first synthesized, and then the latter three polymers were grafted onto the P(GMA-N3) backbone to yield PGMA-g-(PS-r-PCEMA-r-MPEG). Scheme 2 shows the reactions used to prepare the individual components and the final graft copolymers. P(GMA-N3). According to Scheme 2, PGMA was the precursor to P(GMA-N3). PGMA was synthesized by ATRP following a modified literature method:44 using diphenyl ether as the solvent, 2-methoxyethyl 2-bromoisobutyrate as the initiator, CuCl as the catalyst, and PMDETA as the ligand. 2Methoxyethyl 2-bromoisobutyrate was used as the initiator D
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Table 1. Preparation Conditions and Molecular Characteristics of the Precursory Polymers
a
sample
[M]0/[I]0
yielda (%)
NMR DP
NMR Mn, (kg/mol)
SEC Mn (kg/mol)
SEC Mw/Mn
PGMA41 P(GMA-N3)41 PGMA102 P(GMA-N3)102 MPEG−CCH PS−CCH PCEMA−CCH
40:1
99
100:1
96
255:1 80:1
51 65
41 41 102 102 114 130 121
5.8 7.5 14.4 18.8 5.0 13.5 31.5
5.4 7.9 13.8 19.5 8.7 15.6 16.4
1.21 1.26 1.22 1.25 1.02 1.11 1.16
Determined by gravimetric analysis.
Figure 2. IR spectra of PGMA41 (a), P(GMA-N3)41 (b), and ternary graft copolymers (GP 1) before (c) and after (d) reaction with excess propargyl alcohol.
by the disappearance of a characteristic infrared (IR) absorption peak at 909 cm−1 for the epoxide ring and the appearance of characteristic absorption peaks at 2104 cm−1 for the azide group and at 3500 cm−1 for hydroxyl group (Figure 2a,b). The P(GMA-N3) samples were also analyzed by SEC using THF as the eluant. Compared with their precursory PGMA, the “apparent” molecular weights of P(GMA-N3) increased, as expected. The polydispersity indices increased slightly as well and were 1.26 and 1.25 for P(GMA-N3)41 and P(GMA-N3)102, respectively. These peaks broadened probably because of the enhanced interaction between P(GMA-N3) and the SEC columns. For example, we previously observed very broad SEC peaks for P(GMA-N3) when DMF was used as the eluant, and the peaks narrowed after the P(GMA-N3) hydroxyl groups were reacted with acetic anhydride or were masked.25 PCEMA−CCH. According to Scheme 2, PCEMA−C CH was synthesized in three steps. First, reacting 3(trimethylsilyl)propargyl alcohol with 2-bromoisobutyric bromide following a literature procedure yielded 3-(trimethylsilyl)propargyl 2-bromoisobutyrate.25,42 The latter was then used to initiate HEMA polymerization to yield PHEMA−CCH. Reacting PHEMA−CCH with cinnamoyl chloride eventually produced PCEMA−CCH. The alkyne proton in 3-(trimethylsilyl)propargyl 2-bromoisobutyrate was replaced by a trimethylsilyl group because it was difficult to obtain well-defined PHEMA−CCH when propargyl 2-bromopropanoate was used as the initiator. This difficulty should be due to side reactions between the radicals and the terminal alkyne group during the polymerization.46 HEMA polymerization in methanol using 3-(trimethylsilyl)propargyl 2-bromoisobutyrate as the initiator has been reported.47 At the ratios of [HEMA]0/[initiatoir]0/[CuCl]0/ [bpy]0 of 80/1/1/2, we found that the polymerization in methanol was too fast to produce well-defined polymers. Thus, a modified literature method was used to synthesize PHEMA−
mainly to facilitate the degree of polymerization determination by NMR because the initiator’s −OCH3 group in the 1H NMR spectrum did not overlap with resonances of PGMA protons. Different halides were used in the initiator and the catalyst to slow down the rate of polymerization relative to initiation and thus to produce polymers with low polydispersity indices.44 Under these conditions, high monomer conversions were achieved within 30 min. Two PGMA homopolymers (PGMA41 and PGMA102 with GMA repeat units of 41 and 102) were synthesized using the monomer to initiator molar ratios [M]0/[I]0 of 40 and 100, respectively. The resultant polymers were analyzed by 1H NMR in CDCl3 solvent. Shown in Figure 1 is a 1H NMR spectrum for PGMA41. The repeat unit number of 41 was obtained from comparing the peak area of the initiator’s −OCH3 group at δ 3.35 ppm with that of the epoxide CH protons 3.21 ppm. The number 102 was determined analogously. These numbers compared well with the targeted repeat unit numbers and the high GMA conversions. The samples were also analyzed by size exclusion chromatography (SEC) using THF as the eluant. The polydispersity indices Mw/Mn were low at 1.21 and 1.22 for the two polymers based on PS calibration standards (Table 1). Coincidentally, the SEC number-average molecular weights Mn agreed with those calculated from the GMA repeat unit numbers determined by 1H NMR (Table 1). The azide groups were introduced by reacting the oxirane rings of GMA with sodium azide.25 Matyjaszewski and coworkers confirmed that the azide anion attacked exclusively the less substituted carbon atom of the epoxide rings.45 The completion of this reaction was confirmed by 1H NMR and FTIR results. The signals of the CH and CH2 protons of the epoxide ring at 2.62, 2.82, and 3.21 ppm disappeared in the P(GMA-N3)41 spectrum shown in Figure 1a after the reaction between PGMA and NaN3. This event was also accompanied E
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higher than that provided by the supplier because the SEC system was calibrated by PS rather than PEG standards. PS−CCH. The initiator used for ATRP of styrene was prepared by reacting propargyl alcohol with 2-bromopropionyl bromide. A literature method was followed for this synthesis as well as the synthesis of PS−CCH.25 The resultant PS−C CH was again carefully characterized by 1H NMR and SEC. Shown in Figure 1d is a 1H NMR spectrum of PS−CCH together with peak assignments. Comparing the integral of the a peak of the −CH3 protons occurring between 0.8 and 1.0 ppm and that of the e peaks of the benzene ring between 6.2 and 7.2 ppm yielded an average degree of polymerization (DP) of 130 for PS−CCH. This DP compares well with that calculated from the styrene to initiator molar feed ratio of 255 and the monomer conversion of 51% determined gravimetrically. This suggested that ATRP was well behaved. However, the number-average molecular weight of 1.36 × 104 calculated from this DP value was 14% lower than 1.56 × 104 determined from SEC. The difference could be due to the errors associated with SEC and 1H NMR measurements, and the more likely value should be between 1.36 × 104 and 1.56 × 104. The more interesting result from SEC was the low polydispersity index of 1.11 for the polymer. Ternary Graft Copolymers. PGMA-g-(PS-r-PCEMA-rMPEG) samples were synthesized by coupling P(GMA-N3) with MPEG−CCH, PS−CCH, and PCEMA−CCH. Since MPEG−CCH were known to readily graft to P(GMAN3),26,48 we started by reacting the more hindered PS−CCH and PCEMA−CCH chains with P(GMA-N3) for 24 h before MPEG−CCH addition. This was followed by another 48 h of reaction before an excess of propargyl alcohol was added to exhaust the residual azide groups. Three graft copolymers (GP) denoted as GP 1, 2, and 3 were prepared by grafting PS−CCH, PCEMA−CCH, and MPEG−CCH. While P(GMA-N3)41 was used as the backbone for GP 1 and 2, the backbone used for GP 3 was P(GMA-N3)102. The recipes used to prepare the copolymers are listed in Table 2.
CCH using 2-butanone and methanol (v/v = 3/2) as the solvent and CuCl/CuCl2 as the catalyst.48 The polymerization was stopped at a 65% HEMA conversion. The trimethylsilyl protecting group prevented the side reactions and was readily removed by stirring the resultant polymer in DMF with tetrabutylammonium fluoride. The resultant PHEMA−CCH was characterized by 1H NMR, and a spectrum for it is shown in Figure 1b together with peak assignments. The signal of the trimethylsilyl protecting group at 0.14 ppm was definitely absent in the spectrum, confirming the full removal of the protecting group. The PHEMA−CCH spectrum of Figure 1b also allowed the determination of the number of repeat units for PHEMA. Comparing the peak area of the initiator’s methylene protons (−CC−CH2−) at 4.60 ppm (Figure 1b) with those of the ethyl groups of the hydroxyethyl group of HEMA at 3.88 ppm yielded a repeat unit number of 120. This number was substantially larger than 52 calculated from [HEMA]0/ [Initiator]0 and HEMA conversion but should be correct because the initiation efficiency has been shown to be low in ATRP of HEMA in the past.41 Reacting PHEMA−CCH with cinnamoyl chloride yielded PCEMA−CCH. This cinnamation reaction was shown in the past to be quantitative.49 Its quantitative occurrence here can be concluded by comparing the 1H NMR spectra of PHEMA− CCH and PCEMA−CCH shown in Figure 1b. The c and d peaks of the PHEMA−CCH peaks at 3.56 and 3.88 ppm totally disappeared and were replaced by the c and d peaks of PCEMA−CCH at 4.06 and 4.25 ppm after the cinnamation reaction. The PCEMA−CCH spectrum of Figure 1b also allowed the comparison of integral of the methylene protons (HC CCH2−) of the terminal propargyl group at 4.6 ppm with that of the cinnamate aromatic protons between 7.26 and 7.57 ppm. This operation yielded a number-average degree of polymerization of 121 for PCEMA−CCH. This repeat unit number agreed with that determined at the PHEMA−CCH stage and rendered us confidence in our determined numbers. Aside from the low initiation efficiency, the polymerization seemed to be well behaved. The SEC polydispersity index (Mw/ Mn) of PCEMA was low at 1.16. MPEG−CCH. According to Scheme 2, MPEG−CCH was prepared in two steps. First, propargyl alcohol was reacted with succinic anhydride to produce 4-oxo-4-(prop-2-yn-1yloxy)butanoic acid.25 The latter was then reacted with the terminal hydroxyl group of a commercial MPEG polymer with a nominal molecular weight of 5000 to yield MPEG−C CH.42 Literature procedures were used to perform the reactions,25 and the resultant MPEG−CCH was carefully characterized by SEC and 1H NMR. Shown in Figure 1c is a 1H NMR spectrum of MPEG−CCH together with peak assignments. A comparison of the proton integrals corresponding to the MPEG terminal CH3−O− group (CH3−O−CH2− at 3.26 ppm), and that of the two methylene groups of 4-oxo-4-(prop2-yn-1-yloxy)butanoic acid (−OCCH2CH2COO− at 2.66 ppm) yielded a ratio of 3.00/4.03, which was the same, within experimental error, as 3/4. Thus, the esterification was quantitative. As expected for PEG prepared from anionic ring-opening polymerization, the polydispersity of this sample was low at 1.02. The SEC molar mass of this sample was apparent and was
Table 2. Preparation Conditions and Molecular Characteristics of Ternary Graft Copolymers sample
feed mass ratioa
feed molar ratio
GP 1 GP 2 GP 3
1.1:4.0:2.2:4.0 1.0:4.0:4.5:4.0 1.1:4.0:2.5:4.0
41:2.1:0.48:5.5 41:2.3:1.1:6.1 102:5.2:1.4:13.7
b
Mn,theorc (kg/mol)
Mn,SEC (×106 g/mol)
Mw/Mn
79 104 202
2.7 3.5 5.2
1.22 1.20 1.23
a
Mass ratio between P(GMA-N3), PS−CCH, PCEMA−CCH, MPEG−CCH. b [−N 3 ]:[PS−CCH]:[ PCEMA−CCH]:[ MPEG−CCH]. cMn,theor = Mn(P(GMA-N3)) + x × n × 13500 + y × n × 31500 + z × n × 5000.
The grafting reactions were followed, and the end products were analyzed by SEC, 1H NMR, and FTIR. Figure 3 compares SEC traces of the precursors except P(GMA-N3)102 and products made using the recipes shown in Table 2. Here DMF rather than THF was used as the eluant because the ternary graft copolymers were better solubilized in DMF. A side effect of using DMF was that the variation trend of the apparent molecular weights measured in THF and reported in Table 1 was missing by the data shown in Figure 3. For example, the P(GMA-N3)41 peak in Figure 3 had an abnormally short F
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The FTIR study yielded the FTIR spectra of Figure 2b−d for P(GMA-N3)41 and the GP 1 sample before and after its residual azide groups were reacted with excess propargyl alcohol. The azide peak at 2104 cm−1 relative to the carbonyl peak at 1680 cm−1 decreased significantly for two reasons. First, some azide peaks were consumed during the Cu-catalyzed alkyne−azide cycloaddition between polymeric backbone and polymeric side chains. Second, PCEMA bearing two pendant carbonyl groups per unit was grafted increasing the intensity of the peak at 1680 cm−1. More interestingly, the peak 2104 cm−1 totally disappeared after reaction of the graft copolymer with excess propargyl alcohol, in agreement with the capping of the residual azide groups by propargyl alcohol. A NMR study yielded Figure 4, showing two 1H NMR spectra of purified GP 1 measured in CDCl3 and DMSO-d6 and the assignments for the observed peaks. All the protons of the grafted MPEG, PS, and PCEMA chains were observed in the spectrum measured in CDCl3. A quantitative comparison of the integrals at 3.66, 7.08, and 7.66 ppm yielded a molar ratio of 45:12.7:1.0 for the EG, St, and CEMA repeat units, respectively. These values compared well with the expected values of 46:13.1:1.0 if the numbers of grafted MPEG, PS, and PCEMA chains per P(GMA-N3)41 chain were 5.5:2.1:0.48, which were calculated from the polymer feed ratios used for graft copolymer synthesis. Another interesting observation was the presence of the signals at 7.9 and 5.2 ppm for the t and s protons of the triazole linkage in the spectrum measured in DMSO-d6. These peaks provided direct evidence for the desired click chemistry. However, these signals were not seen in CDCl3 probably because of the lower mobility of the triazole linkage in this solvent. This mobility difference was possible because the P(GMA-N3) backbone is solvated in DMSO-d6 but not CDCl3. This reduced solubility of the P(GMA-N3) backbone in CDCl3 could have affected the mobility of the triazole linkage. Graft Copolymers vs Cylindrical Brushes. Graft copolymers become cylindrical brushes if the grafted side chains are sufficiently dense so that they repel one another and also the backbone chain is much longer than the grafts. At a grafting density of 20%, the average spacing between two grafts was 5 monomer units or 10 C−C bonds, which had a fully stretched length of 1.26 nm. A revisit of Table 2 revealed that the majority of the grafts in a PGMA-g-(PS-r-PCEMA-rMPEG) chain consisted of MPEG. To a first approximation, we
Figure 3. SEC traces of polymer precursors and ternary graft copolymers.
retention time, probably due to the excessive swelling of the P(GMA-N3) chains in DMF.25,45 These should not be a concern as the SEC molecular weights were not absolute but apparent anyhow. An important result of Figure 3 was that no SEC peaks for the precursors were observed for the reacted mixtures prepared using the recipes shown in Table 2. This was due to the low molar ratios used for the polymer alkyne to azide groups used during the reactions. For the samples listed in Table 2, the highest molar ratio used between MPEG−CCH, PS−C CH, and PCEMA−CCH and the azide groups of P(GMAN3) was 23%. At these low feed ratios, all the polymers added were quantitatively grafted under our reaction conditions. We also used a feed ratio of 30% between alkyne and azide. The final reaction mixture in this case showed peaks for the precursor polymers, and the polymers were thus not fully grafted at this high alkyne to azide feed ratio. The molecular weights of the graft copolymers should increase from GP 1 to GP 2 and GP 3. This trend was followed by the SEC traces for these samples shown in Figure 3. However, the apparent SEC molecular weights in column 5 of Table 2 for these samples were much higher than the theoretical values again because the SEC values were apparent. Unlike linear polymers which are randomly coiled, the graft copolymers were most likely stretched. Molecular weight determination for these samples based on PS standards should be far off.
Figure 4. 1H NMR spectra and peak assignments for GP 1. G
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absorbance.51 Typically, a CEMA double-bond conversion of 60% was used to lock in the capsule structure. Our experiments suggested that the amount of DCM used was important for proper emulsification. When 20 mg of GP 1, 0.10 mL of DN, and 20 mL of water were used together with 0.50 mL of DCM, a proper emulsion both before and after DCM evaporation was obtained. However, the emulsion at stage B in Scheme 3 turned unstable when the DCM amount was increased to 1.0 mL under otherwise identical conditions. After stirring stopped, the DCM/DN phase separated from the aqueous phase and settled at the bottom of the vial as shown in Figure 5a.
considered a homograft copolymer PGMA-g-MPEG and calculated the radius of gyration RG of a MPEG chain in the unperturbed state. The root-mean-square end-to-end distance of a MPEG chain with a molar mass of 5000 g/mol and in the unperturbed state was calculated using a literature formula to be 6.0 nm.50 Assuming random coil conformation, RG was calculated to be 2.5 nm. It was evidently difficult to squeeze in a MPEG chain with a diameter of 5.0 nm into a spacing of 1.26 nm. Thus, the grafts in our copolymer were crowded. Despite this, we will continue to call our polymers graft copolymers because the polymer backbone was substantially shorter than the graft chains. Nanocapsule Preparation. A literature method using a linear triblock copolymer for making capsules was modified and used to make the graft copolymer capsules.51 This method involved first dissolving PGMA-g-(PS-r-PCEMA-r-MPEG) in dichloromethane (DCM), which solubilized all three types of grafts. This solution was then slowly added into a stirred mixture of water and DN (A, Scheme 3), where DN solubilized Scheme 3. Schematic Illustration of the Preparation Process for the Capsules
Figure 5. Photographs of emulsions prepared using 20 mg of GP 1 but different amounts of DCM or DN at stage B (a) and stage C (b), respectively.
There are several possible reasons for the instability of the emulsion at the higher DCM amount of 1.0 mL. First, the used GP 1 amount was probably insufficient to stabilize so much of the discrete phase consisting of DCM/DN. Second, the density and the size of the droplets probably increased as the DCM amount increased. While DN has a density of 0.90 g/cm3 at 25 °C, DCM’s density is 1.33 g/cm3, which is substantially higher than 1.00 g/cm3 for water. Both a high density and large size for the oil droplets favored droplet settlement. Third, an increase in DCM volume fraction in the droplets would increase the solubility of MPEG chains in them, and the solubilization of MPEG chains in the oil phase would decrease the hydrophilic to hydrophobic balance of GP 1 and its function as a surfactant. A proper DN amount was also important. At 20 mg of GP 1, 20 mL of water, and 0.50 mL of DCM, the use of 0.10 mL of DN yielded a stable homogeneous emulsion after DCM evaporation. The use of 0.20 mL of DN yielded a creamy phase consisting probably of large capsules floating on the top of a homogeneous emulsion as shown in Figure 5b. In this study, only capsules prepared using 20 mg of GP 1 or 2, 0.50 mL of CH2Cl2, 0.10 mL of DN, and 20 mL of water were characterized. Capsules prepared from the above protocol were irradiated by UV light to cross-link the PCEMA layer before they were aero-sprayed onto nitrocellulose-coated grids and stained by RuO4 for TEM observations. Figures 6a and 6b show TEM images of cross-linked capsules prepared from GP 1 and 2, respectively. The structures in Figure 6a,b could be divided into three types. The first type consisted of a gray circle enclosed by a dark ring. Another dark ring close to the center existed in the second type of structures. This central ring turned into an illdefined dark dot or crease in the third type of structure.
only the PS chains. After the DCM solution was fully added, the DCM to DN volume ratio in the droplets should reach between 5/1 and 5/2 depending on the recipe used, and the droplet phase should solubilize both PCEMA and PS as illustrated in B of Scheme 3. Results of a previous study suggested that the solubilized PCEMA chains would collapse from the DN phase after DCM was preferentially evaporated via gentle heating (B → C).51 We further imagined that the PCEMA chains would form a continuous membrane separating the water and DN phases if the PCEMA chains were long enough and present in sufficient numbers. A membrane would form mainly to minimize interfaces between PCEMA and the two liquids. Shining light on the system would photo-cross-link PCEMA, yielding DN-filled stable nanocapsules (C → D).52−54 GP 1, 2, and 3 were used individually to prepare nanocapsules. The reported procedure did not work well for the high-molecular-weight GP 3 because it did not dissolve well in DCM. The preparation proceeded smoothly when either GP 1 or 2 was used. At stage B, a strong scattering whitish emulsion was obtained. The emulsion turned less scattering or whitish at stage C, suggesting the shrinkage of the original larger oil droplets. No visual changes were noticed for the samples before and after photolysis. However, our UV−vis spectrophotometric analysis detected decreases at 274 nm for CEMA double-bond H
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Figure 6. TEM images of cross-linked capsules aero-sprayed from water immediately after their preparation using GP 1 (a) or 2 (b) as the dispersant. Shown in (c) and (d) are TEM images of the corresponding capsules after their dialysis against DMF.
Figure 7. AFM topography images of cross-linked capsules aero-sprayed from water immediately after their preparation using GP 1 (a) or 2 (b) as the dispersant. Shown in (c) and (d) are AFM images of the corresponding capsules after their dialysis against DMF.
Further, the type 1 structure dominated in Figure 6b and was only a minor product in Figure 6a. The type 1 structure corresponded to round capsules because of the following considerations. First, the emulsification procedure should produce capsules. Second, a gray circle with
an outer dark ring is the projection expected of a capsule. Since RuO4 stained the PCEMA and PS chains, the dark rings must have been projections of the standing PCEMA walls bearing the dried PS chains. These walls appeared dark because of the large path lengths of the electron beam in them. Third, the average I
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diameters of the structures in Figures 6a and 6b were 60 ± 10 and 57 ± 12 nm, respectively. These structures were too large to be solid because a fully stretched PS chain of 130 repeat units would be only 33 nm long and the PS chains would be unlikely to be fully stretched in the core. A central ring was seen in the type 2 structure due to formation of a crater and thus a PCEMA cliff or wall bearing PS chains around the crater. When the craters were not so well developed or when only local dimples or folds were formed, dark dots or creases were seen close to the center of these particles or type 3 particles. We believe that the craters, folds, and creases were formed in the type 2 and 3 particles due to the collapsing of the capsules during DN evaporation before TEM analysis. This belief agrees with the observation that more type 1 structures were seen in Figure 6b than in Figure 6a because the capsules made from GP 2 containing more PCEMA chains were more robust and collapsed less than those made from GP 1. However, we cannot rule out the possible existence of the type 2 and 3 particles in the emulsion already because the sample has not been analyzed by an in situ technique such as cryo-TEM. Despite this, we can conclude with confidence that all types of structures observed were hollow consisting of either round or deformed capsules. We further note that the outer rings of the gray objects in Figure 6a were not uniformly dark or were not as well developed as in Figure 6b. This difference might again be due to the higher number of PCEMA and PS chains in GP 2 than in GP 1. From Figure 6b, we determined an average ring thickness of 6 ± 1 nm. Since this layer contained a contribution from the dried PS chains as well, the PCEMA wall should be thinner than 6 nm. Solutions of the cross-linked capsules were also aero-sprayed onto freshly cleaved mica surfaces and dried under high vacuum to remove DN before AFM observations. Figures 7a and 7b show the AFM topography images of the sprayed capsules prepared from GP 1 and 2, respectively. Round and bowlshaped particles coexisted in these two images. The average diameters of the particles in Figures 7a and 7b were 84 ± 10 and 80 ± 6 nm, respectively. Also, more bowl-shaped particles existed in Figure 7a than in Figure 7b. The AFM observations supported the TEM results. The AFM diameters were larger than the TEM diameters because of two reasons. First, AFM probed the size of the whole particles including the MPEG layer not seen by TEM. Second, the AFM size contained a contribution from the finite size of the AFM tip. Capsule Formation Mechanism. The emulsion droplets stabilized by GP 1 at different stages of capsule formation were studied by DLS. Figure 8 shows the droplet size distributions thus determined by DLS at stages B, C, and D of Scheme 3. From these distributions we also obtained the average hydrodynamic diameters Dh of 315, 198, and 196 nm, respectively. The Dh decrease from 315 to 198 nm from stage B to C corresponded to a 75% decrease in the hydrodynamic volume of the emulsion droplets after DCM evaporation. At a feed volume ratio of 5/1 for DCM/DN, DCM should account for 83% of the droplet volume before DN evaporation. These two values, 75% and 83%, agreed well given that the PEG corona thickness contributed to the detected Dh value, and this thickness might not change much before and after droplet shrinkage. Thus, the data suggested that DCM evaporation did not change the number of the emulsion droplets but decreased the size of the nanocapsules. This reasonable size change from B to C and the insignificant
Figure 8. DLS size emulsion droplets at different stages nanocapsule preparation using GP 1 as the dispersant.
Dh change from stage C to D supported the capsule formation mechanism proposed in Scheme 3. The DLS diameters were substantially larger than the AFM and TEM diameters for the capsules for several reasons. First, DLS probed the solvated particles and the other techniques probed the dried particles. Since the PCEMA layer was very thin, these particles should shrink substantially when solvent evaporated. Second, the MPEG chains should assume a more stretched conformation in the solvated than in the dried state. Third, the DLS diameter was a z-average, and the other diameters were the number-average values. The z-average value emphasized contributions from the larger capsules. Permanent Capsules. The capsular structure got locked in only if the PCEMA grafts of the different copolymer chains overlapped and photo-cross-linked properly. The 1,4-cycloaddition reaction of two double bonds of different CEMA units has been used extensively by the Liu group to lock in block copolymer micellar structures49 and solid structures52 and should work equally well here if the PCEMA grafts of different copolymer chains overlapped. To ensure the latter, the PCEMA chains were designed to be longer than the PGMA backbone. Also, the number of PCEMA chains per graft copolymer was increased from 0.48 to 1.1 from GP 1 to GP 2. The cross-linked capsules of GP 1 were dialyzed against DMF changed several times over 2 days, and DLS was then used to analyze the capsule sample. The sample had a Dh value of 198 nm, which was essentially the same as 196 nm, Dh for the sample before dialysis against DMF. Thus, the structural integrity was retained even for capsules prepared from GP 1. TEM and AFM images were also obtained of the cross-linked capsules after their dialysis against DMF and aero-spraying. The integrity of the particles was clearly retained in Figures 6c,d and 7c,d despite the possible extraction of some of the PGMA-g(PS-r-MPEG) chains particularly from the GP 1 capsules. Thus, the capsules were permanent structures.
IV. CONCLUSIONS ATRP has been used to prepare PGMA, PS−CCH, and PHEMA−CCH that was cinnamated to PCEMA−CCH. Reacting PGMA with sodium azide yielded P(GMA-N3). Further, MPEG has been end-functionalized to MPEG−C CH. Grafting PS−CCH, MPEG−CCH, and PCEMA− CCH to P(GMA-N3) via click chemistry yielded ternary J
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(15) Mora-Huertas, C. E.; Fessi, H.; Elaissari, A. Int. J. Pharm. 2010, 385, 113. (16) De Koker, S.; Hoogenboom, R.; De Geest, B. G. Chem. Soc. Rev. 2012, 41, 2867. (17) Esser-Kahn, A. P.; Odom, S. A.; Sottos, N. R.; White, S. R.; Moore, J. S. Macromolecules 2011, 44, 5539. (18) Zhang, M. F.; Muller, A. H. E. J. Polym. Sci., Polym. Chem. 2005, 43, 3461. (19) Vazaios, A.; Hadjichristidis, N. J. Polym. Sci., Polym. Chem. 2005, 43, 1038. (20) Heroguez, V.; Breunig, S.; Gnanou, Y.; Fontanille, M. Macromolecules 1996, 29, 4459. (21) Ishizu, K.; Shen, X. X. Polymer 1999, 40, 3251. (22) Xia, Y.; Olsen, B. D.; Kornfield, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2009, 131, 18525. (23) Cheng, C.; Qi, K.; Germack, D. S.; Khoshdel, E.; Wooley, K. L. Adv. Mater. 2007, 19, 2830. (24) Cheng, C.; Qi, K.; Khoshdel, E.; Wooley, K. L. J. Am. Chem. Soc. 2006, 128, 6808. (25) Sun, J. P.; Hu, J. W.; Liu, G. J.; Xiao, D. S.; He, G. P.; Lu, R. F. J. Polym. Sci., Polym. Chem. 2011, 49, 1282. (26) Zhao, P.; Yan, Y. C.; Feng, X. Q.; Liu, L. X.; Wang, C.; Chen, Y. M. Polymer 2012, 53, 1992. (27) Li, Y. K.; Zou, J.; Das, B. P.; Tsianou, M.; Cheng, C. Macromolecules 2012, 45, 4623. (28) Ishizu, K.; Sawada, N.; Satoh, J.; Sogabe, A. J. Mater. Sci. Lett. 2003, 22, 1219. (29) Yin, J.; Ge, Z. S.; Liu, H.; Liu, S. Y. J. Polym. Sci., Polym. Chem. 2009, 47, 2608. (30) Han, D. H.; Tong, X.; Zhao, Y. Macromolecules 2011, 44, 5531. (31) Lian, X. M.; Wu, D. X.; Song, X. H.; Zhao, H. Y. Macromolecules 2010, 43, 7434. (32) Djalali, R.; Li, S. Y.; Schmidt, M. Macromolecules 2002, 35, 4282. (33) Mullner, M.; Lunkenbein, T.; Breu, J.; Caruso, F.; Muller, A. H. E. Chem. Mater. 2012, 24, 1802. (34) Kang, E. H.; Lee, I. H.; Choi, T. L. ACS Macro Lett. 2012, 1, 1098. (35) Zhao, P.; Liu, L. X.; Feng, X. Q.; Wang, C.; Shuai, X. T.; Chen, Y. M. Macromol. Rapid Commun. 2012, 33, 1351. (36) Huang, K.; Jacobs, A.; Rzayev, J. Biomacromolecules 2011, 12, 2327. (37) Huang, K.; Canterbury, D. P.; Rzayev, J. Chem. Commun. 2010, 46, 6326. (38) Huang, K.; Rzayev, J. J. Am. Chem. Soc. 2011, 133, 16726. (39) Miyake, G. M.; Weitekamp, R. A.; Piunova, V. A.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 14249. (40) Sveinbjornsson, B. R.; Weitekamp, R. A.; Miyake, G. M.; Xia, Y.; Atwater, H. A.; Grubbs, R. H. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 14332. (41) Beers, K. L.; Boo, S.; Gaynor, S. G.; Matyjaszewski, K. Macromolecules 1999, 32, 5772. (42) Opsteen, J. A.; van Hest, J. C. M. Chem. Commun. 2005, 57. (43) Ding, J. F.; Liu, G. J. Macromolecules 1999, 32, 8413. (44) Canamero, P. F.; de la Fuente, J. L.; Madruga, E. L.; FernandezGarcia, M. Macromol. Chem. Phys. 2004, 205, 2221. (45) Tsarevsky, N. V.; Bencherif, S. A.; Matyjaszewski, K. Macromolecules 2007, 40, 4439. (46) Mansfeld, U.; Pietsch, C.; Hoogenboom, R.; Becer, C. R.; Schubert, U. S. Polym. Chem. 2010, 1, 1560. (47) Fan, X. S.; Wang, G. W.; Huang, J. L. J. Polym. Sci., Polym. Chem. 2011, 49, 1361. (48) Gao, H. F.; Matyjaszewski, K. J. Am. Chem. Soc. 2007, 129, 6633. (49) Henselwood, F.; Liu, G. J. Macromolecules 1997, 30, 488. (50) Ozdemir, C.; Guner, A. J. Appl. Polym. Sci. 2006, 101, 203. (51) Zheng, R. H.; Liu, G. J. Macromolecules 2007, 40, 5116. (52) Zhou, R. L.; Zhou, N.; Yan, X. H.; Liu, G. J. Chem. J. Chin. Univ. 2002, 23, 158. (53) Hoppenbrouwers, E.; Li, Z.; Liu, G. J. Macromolecules 2003, 36, 876.
graft copolymers PGMA-g-(PS-r-PCEMA-r-MPEG). The grafting reactions were facile and achieved in a one pot. At molar ratios ≤23% for the polymer terminal alkyne groups to azide groups, these polymer chains with repeat unit numbers between 110 and 130 units were grafted quantitatively. While this modular or graft-onto approach has been used to prepare one type of ternary graft copolymers, it should also be useful in the preparation of other types of ternary graft copolymers or graft copolymers with even more types of grafts. Copolymers prepared with a polymer grafting densities of ∼23% and P(GMA-N3)41 readily solubilized in CH2Cl2. Such a solution was added into a stirred water/DN mixture, and the polymer was concentrated at the DN/water interface to stabilize the DN/CH2Cl2 emulsion droplets. Evaporation of CH2Cl2 from the droplets yielded DN droplets that most likely contained PS chains stretching from the copolymer at the DN/ water interface. These droplets were stabilized by the MPEG chains solubilized in the aqueous phase. The PCEMA chains probably formed a membrane or wall separating the DN and water phases. Photolysis of this system yielded permanent capsules. This general method should be useful for preparing capsules from other graft copolymers or capsules with loads other than DN in the core phase, and the resultant capsules may find applications in controlled release applications.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] (J.H.);
[email protected] (G.L.). Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (No. 20474068, 51173204, 51203191), the Outstanding Overseas Chinese Scholars Funds of the Chinese Academy of Sciences, Guangdong Natural Science Foundation (S2012010009063), and the Leading Talents Program of Guangdong Province for providing financial support.
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dx.doi.org/10.1021/ma302663u | Macromolecules XXXX, XXX, XXX−XXX
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dx.doi.org/10.1021/ma302663u | Macromolecules XXXX, XXX, XXX−XXX
