Efficient Metal-Free “Grafting Onto” Method for Bottlebrush Polymers

Article pubs.acs.org/Macromolecules

Efficient Metal-Free “Grafting Onto” Method for Bottlebrush Polymers by Combining RAFT and Triazolinedione−Diene Click Reaction Lifen Xiao,† Yongming Chen,‡ and Ke Zhang*,† †

State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100190, P. R. China ‡ Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China S Supporting Information *

ABSTRACT: An efficient metal-free “grafting onto” method was developed for preparing bottlebrush polymers based on the combination of reversible addition−fragmentation chain transfer polymerization (RAFT) and triazolinedione (TAD)−diene Diels− Alder cycloaddition reaction. In this approach, RAFT and a following postfunctionalization process were used to prepare the polyacrylate backbone with conjugated diene side group in each repeat unit (PHEA−diene) and the various TAD-terminated polymer sides including poly(methyl methacrylate) (PMMA), poly(tert-butyl acrylate) (PtBA), and polystyrene (PS). The TAD−diene Diels− Alder cycloaddition reaction was then employed to efficiently couple the resultant polymer backbone and side chains, which produced the corresponding bottlebrush polymers of PHEA448-g-PMMA27, PHEA448-g-PtBA25, and PHEA448-g-PS25 with a high grafting density above 90% in only 1 min in the presence of slight molar excess (1.2 times) of TAD to diene groups. The quantitative grafting density could be further achieved in less than 10 min coupling reaction. Atomic force microscopy (AFM) characterization visualized the worm-like molecular morphology for all cases.

■

INTRODUCTION Bottlebrush polymers are a unique type of graft polymers with a linear polymer backbone densely grafted by polymer side chains. The presence of steric repulsion among bulky polymer side chains largely extended the polymer backbone, endowing the bottlebrush polymers with a persistent worm-like molecular morphology. It is the unique molecular structure that privileges the bottlebrush polymers to play a critical role in a variety of application fields such as photonics,1,2 lithography,3 supersoft elastomer,4,5 drug delivery,6−8 and as ideal molecular templates for the preparation of one-dimensional nanomaterials.9−12 The current preparation methods of bottlebrush polymers can be generalized into three categories: “grafting through”, “grafting from”, and “grafting onto” strategies.13−18 While “grafting through” methods produce bottlebrush polymers by directly polymerizing macromonomers, “grafting from” methods prepare bottlebrush polymers using the polymer backbone as a macroinitiator to polymerize polymer side chains in situ. In the “grafting onto” approach, the polymer backbone and side chains are prepared separately, and then the highly efficient coupling reactions are used to connect them together and form the bottlebrush polymers. Although the first two strategies have been widely used to prepare various types of bottlebrush polymers,13−18 the development of “grafting onto” methods should be paid more attention for the formation of bottlebrush polymers currently.19−24 This is caused by the explosion of modern click © XXXX American Chemical Society

chemistry and their successful application in polymer science, which has made the concept of modular construction become a popular approach for preparing topological polymers.25 To date, several highly efficient coupling reactions have been employed to prepare graft polymers including atom transfer nitroxide radical coupling chemistry,26,27 thiol−expoxy coupling chemstry,28 thiol−ene chemistry,29,30 thiol−yne chemistry,31 and Diels−Alder reaction between anthracene and maleimide.32 A few of them, however, have been successfully demonstrated to prepare the bottlebrush polymers with a high grafting density, in which almost every two carbon repeating unit of the backbone bears at least one polymer chain. Copper-catalyzed azide−alkyne cycloaddition (CuAAC) may be the most popular and successful coupling tool to prepare this kind of bottlebrush polymer.19−24 With an optimized reaction condition, for a polymethacrylate backbone with an azide group in each repeat unit, CuAAC could graft varied alkyne-terminated polymer side chains with a DP around 50−100 including poly(ethylene oxide), polystyrene, polyacrylates, and poly(N-alkyl acrylamide)s to achieve a high grafting density above 85%.23,24 Atomic force microscopy (AFM) was used to visualize the resultant bottlebrush polymers, in which the wormlike molecular morphology was obtained for Received: April 14, 2016 Revised: June 7, 2016

A

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Scheme 1. Metal-Free Preparation Methods for the Formation of Bottlebrush Polymers Based on “Grafting Onto” Strategya

a

Urazole-CTA 1, PMMA-Urazole, PMMA-TAD, and PHEA-Diene represent the urazole functional RAFT agent, urazole-terminated PMMA, triazolinedione-terminated PMMA side chains, and PHEA backbone containing diene side groups.

backbone and side chains and form the corresponding bottlebrush polymers with a high efficiency.

all cases. However, when alkyne-terminated polymethacrylates used as side chains, the similar condition only produce a grafting density around 50%, indicating the grafting density was affected by the chemical structures of the linear polymer side chains in CuAAC coupling reaction.24 In addition, another distinct disadvantage for CuAAC is the requirement of Cu metal catalyst, which may affect the applications of resultant bottlebrush polymers in some fields requiring clean materials such as biology and photoelectronics. Metal-free click reactions have gained more and more interest recently in the fields of biology and organic and material chemistry.33−36 After a deep investigation in the past a few years, some of these reactions have gained fast reaction rate comparable to CuAAC (10 M−1 s−1) including SPAAC,37 tetrazine and strained alkenes/alkynes,38,39 light-induced Diels−Alder reactions,40,41 and triazolinedione (TAD)-based click chemistry.42,43 Imaginably, if these metal-free click reactions are used to prepare bottlebrush polymers by the “grafting onto” strategies to replace CuAAC, not only metal-free preparation methods could be developed but also the coupling efficiency between polymer backbone and side chains may be improved. Few of investigations, however, have been carried out in this field up to date. Recently, Du Prez and co-workers have demonstrated that TAD based Diels−Alder and Alder−ene reactions could meet the criteria of click chemistry, in which these reactions typically completed within a time scale of seconds at room temperature without the requirement of any catalyst.42,43 From this, TAD-based click reactions have already been employed to prepare block copolymers by polymer coupling,42 polymer networks,44−46 layer-by-layer thin film,47 and rewritable polymer brush micropatterns on surfaces.48 For the first time, we introduced the TAD-based click chemistry into the field of bottlebrush polymer preparation and developed a novel metal-free method for the formation of bottlebrush polymers following the “grafting onto” strategy. Scheme 1 illustrates the detailed preparation process, in which the formation of bottlebrush polymers with poly(methyl methacrylate) (PMMA) side chains was used as an example. In this approach, the polymer backbone with conjugated diene side groups and TAD-terminated polymer side chains were separately prepared by reversible addition−fragmentation chain transfer polymerization (RAFT). The TAD−diene Diels−Alder click reaction was then employed to couple the resultant polymer

■

EXPERIMENTAL SECTION

Preparation of RAFT Agent with Urazole Group (Urazole-CTA 1). Pentafluorophenyl-(4-phenylthiocarbonylthio-4-cyanovalerate) (2 g, 4.14 mmol) and 4-aminophenyl 1,2,4-triazolidine-3,5-dione (0.76 g, 3.93 mmol) were dissolved in 20 mL of DMF and stirred at 40 °C for 12 h. After removing the DMF under reduced pressure, the crude product was purified by column chromatography (SiO2, DCM/MeOH = 20/1) and then recrystallized in DCM to obtain red solid product (0.75 g) with a yield of 40%. 1H NMR (DMSO-d6) δ (ppm): 10.42 (s, 2H), 10.27 (s, 1H), 7.89 (d, 2H), 7.68 (t, 3H), 7.51 (t, 2H), 7.36 (d, 2H), 2.72 (t, 2H), 2.65−2.54 (m, 2H), 1.96 (s, 3H). 13C NMR (DMSO-d6) δ (ppm): 169.68, 154.02, 144.60, 138.84, 134.05, 129.46, 127.22, 127.13, 126.88, 119.71, 119.21, 46.79, 40.83, 40.55, 40.27, 39.99, 39.71, 39.16, 33.43, 32.13, 23.74.

Preparation of Hexa-2,4-dienyl Ester Succinic Anhydride. HDEO (5 g, 51 mmol), succinic anhydride (6.12 g, 61.2 mmol), and DMAP (1.2 g, 10.2 mmol) were dissolved in 100 mL of anhydrous DCM. The reaction mixture was stirred at room temperature for 12 h. After that, EDC (10.2 g, 53 mmol) was added, and the reaction was kept stirring for another 12 h. The reaction mixture were then washed with HCl aqueous solution (pH = 2) (2 × 100 mL) and water (3 × 100 mL). After collecting the organic phase and dried over anhydrous magnesium sulfate, a white solid product (7.3 g) was obtained from roving the organic solvent with a yield of 77%. 1H NMR (CDCl3) δ (ppm): 6.24 (m, 1H), 6.10−5.98 (m, 1H), 5.75 (m, 1H), 5.65−5.54 (m, 1H), 4.60 (d, 2H), 2.87−2.51 (m, 4H), 1.75 (d, 3H). 13C NMR (CDCl3) δ (ppm): 171.40, 167.88, 135.27, 134,99, 131.55, 131.36, 130.40, 130.35, 123.48, 123.75, 77.48, 77.06, 65.52, 65.26, 43.02, 30.24, 29.10, 28.94, 28.55, 18.14. B

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

0.0264 mmol of diene groups) in 1 mL of chloroform was then added into the above side chain solution to start the grafting reaction at room temperature. Samples were taken out at different reaction times and quenched by adding 2,3-dimethyl-2-butene for tracing the grafting reaction. After the grafting reaction, the excess of PMMA27 side chains were removed through preparative GPC to obtain the pure brush polymer of PHEA448-g-PMMA27. All of the other polymer brushes were prepared by the same procedure. The FT-IR spectra of PHEA448-gPMMA58, PHEA448-g-PtBA25, and PHEA448-g-PS25 are shown in Figure S1 as C, D, and E, respectively.

Preparation of PHEA−Diene Polymer Backbone. PHEA448 was prepared as follows. 2-Hydroethyl acrylate (HEA) (0.8 g, 6.9 mmol), Sethyl-S′-(α,α′-dimethyl-α″-acetic acid) trithiocarbonate (EDMAT) (1.5 mg, 0.0069 mmol), AIBN (0.4 mg, 0.00025 mmol), and DMF (0.8 g) were added into a Schlenk tube equipped with a stir bar. After degassing by three freeze−evacuate−thaw cycles, the polymerization was carried out in an oil bath at 65 °C for 2 h and then quenched by exposure to air. The crude product was precipitated in diethyl ether for three times and then preserved in DMF solution (ca. 50 mg/mL). The FT-IR spectrum of PHEA448 is shown in Figure S1A.

■

RESULTS AND DISCUSSION Preparation of Polymer Side Chains. As shown in Scheme 1, the TAD-terminated polymer side chains were synthesized in

PHEA448−diene was prepared by postmodifying PHEA448. PHEA448 (1 mL, 50 mg of polymer, 0.43 mmol of hydroxyl groups) was diluted into 3 mL of solution, in which hexa-2,4-dienyl ester succinic anhydride (325 mg, 0.86 mmol) and DMAP (10.5 mg, 0.086 mmol) were added and stirred for 12 h at room temperature. The reaction solution was then dialyzed in chloroform for 24 h to produce the pure PHEA448−diene product, which was stored in chloroform. The accurate concentration was quantified as 7.69 mg/mL by 1H NMR using small molecular (cis-5norbornene-exo-2,3-dicarboxylic anhydride) as internal standard. The FT-IR spectrum of PHEA448-diene is shown in Figure S1B. Preparation of Urazole-Terminated Polymer Side Chains. The preparation of urazole-terminated PMMA27 side chain was used as an example. MMA (2 g, 20 mmol), Urazole-CTA 1 (90.6 mg, 0.2 mmol), AIBN (8.2 mg, 0.05 mmol), and 1,4-dioxane (2 g) were added into a Schlenk tube equipped with stir bar. After degassing by three freeze− evacuate−thaw cycles, the polymerization was carried out in an oil bath at 60 °C for 7 h and was quenched by exposure to air. The crude product was precipitated in hexane for three times and dried under vacuum at room temperature. Preparation of Triazolinedione (TAD)-Terminated Polymer Side Chains by Oxidization. TAD-terminated polymer side chains were prepared by oxidizing the corresponding urazole-terminated polymer side chains. Urazole-terminated polymer side chains (1 mmol) and DABCO-Br (0.3 mmol) were dissolved in 10 mL of dichloromethane. The reaction solution was stirred for 3 h at room temperature to finish the oxidization reaction. After filtration, the filtrate containing TAD-terminated polymer side chains was used directly without further purification. Preparation of HDEO-Modified PMMA27. TAD-terminated PMMA27 (0.1 g, 0.0317 mmol) and HDEO (62.1 mg, 0.634 mmol) were mixed in 2 mL of DCM, which was stirred for 1 min at room temperature to finish the modification reaction. The crude product was precipitated in petroleum ether/ethyl acetate (v/v = 2/1) for three times and dried under vacuum at room temperature. Preparation of Brush Polymers via TAD-Based Click Chemistry. The preparation of PHEA448-g-PMMA27 brush polymer was used as an example. TAD-terminated PMMA27 (0.1 g, 0.0317 mmol) was dissolved in 2 mL of dichloromethane, in which 0.25 mL of toluene was added as internal standard for calculating the percentage of reacted side chains via GPC characterization. PHEA448−diene (7.66 mg,

Figure 1. RAFT kinetics of MMA polymerization in the presence of Urazole-CTA 1. (A) Dependence of ln([M]0/[M]) on reaction time, (B) evolution of GPC traces, and (C) molecular weights and molecular weight distribution during polymerization. Polymerization conditions: [MMA]0/[Urazole-CTA 1]0/[AIBN]0 = 100/1/0.2, 60 °C, dioxane as solvent (mMMA/mdioxane = 1/1).

two steps. Urazole functional RAFT agent (Urazole-CTA 1) was used to prepare urazole-terminated polymer side chain precursors by a standard RAFT procedure in the first step. The highly reactive TAD-terminated polymer side chains were then obtained by postfunctionalizing the resultant urazole-terminated polymers through a selective urazole oxidation reaction. Since C

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules Table 1. Synthesis and Characterization of UrazoleTerminated PMMA, PtBA, and PS Polymer Side Chain Precursors and the PHEA Polymer Backbone Precursors run

polymer

feed ratioa

time (h)

convb (%)

Mnc

Mw/Mnc

1 2 3 4 5

PMMA27 PMMA58 PtBA25 PS25 PHEA448

100:1:0.2 200:1:0.2 250:1:0.2 1000:1:0.1 1000:1:0.4

7 5 10 7.5 2

27.2 29.1 9.9 2.5 44.8

2640 5000 3940 3820 138500

1.11 1.12 1.10 1.06 1.27

a Initial molar ratio of monomer/Urazole-CTA 1/AIBN. bCalculated from the 1H NMR spectrum. cCalculated from GPC, in which THF or DMF (only for run 5) was used as the eluent and polystyrene standards were used for the calibration.

Urazole-CTA 1 (Scheme 1) was a fundamental new RAFT agent and reported for the first time, its RAFT polymerization behavior was systematically investigated to polymerize various vinyl monomers including methyl methacrylate (MMA), tert-butyl acrylate (tBA), and styrene (St) at the beginning of polymer side chain preparation. Figure 1 shows the corresponding kinetics of MMA RAFT polymerization, in which the polymerization was carried out in dioxane solution (mMMA/mdioxane = 1/1) at 60 °C, and the ratio of [MMA]0/[Urazole-CTA 1]0/[AIBN]0 was used as 100/1/0.2. Under this polymerization condition, the MMA conversion achieved 76% in 22.5 h. The semilogarithmic plot of ln([M]0/ [M]) versus reaction time was linear (Figure 1A), indicating MMA consumption by first-order kinetics and implying a constant concentration of active centers during the polymerization. GPC curves showed monomodal molecular weight distributions for all cases (Figure 1B). In addition, Mn,GPC increased linearly with MMA conversion up to 76% (Figure 1C), and the Mw/Mn remained lower than 1.1 throughout the polymerization (Figure 1C). These results strongly indicated the living nature of RAFT polymerization for MMA when UrazoleCTA 1 was used as RAFT agent. Similarly, the RAFT kinetics of tBA (Figure S2) and St (Figure S3) polymerization were further investigated to demonstrate the universality of Urazole-CTA 1. The tBA polymerization was performed in DMF solution (mtBA/mDMF = 80/20) at 60 °C with a ratio of 250/1/0.2 for [tBA]0/[Urazole-CTA 1]0/[AIBN]0. Under this polymerization condition, the tBA conversion achieved 33.7% in 19 h. As shown in Figure S2A, the semilogarithmic plot of ln([M]0/[M]) versus reaction time was linear, indicating tBA consumption by a first-order kinetics during the polymerization. From Figure S2B, the monomodal and symmetric peak shapes were obtained within 16 h polymerization, corresponding to a tBA conversion below ca. 30% (Figure S2C). A slight shoulder peak at high molecular weight direction, however, was observed after the tBA conversion went above ca. 30%. From Figure S2C, Mn,GPC increased linearly with tBA conversion, and the Mw/Mn remained below 1.1 throughout the polymerization. These results indicate that the RAFT polymerization of tBA shows the living behavior in the presence of the Urazole-CTA 1, in which the well-defined urazole-terminated poly(tert-butyl acrylate) (PtBA) could be obtained when controlling the tBA conversion below 30%. Figure S3 shows the RAFT kinetics of St polymerization, where the St polymerization was performed in DMF solution (mSt/mDMF = 85/15) at 60 °C, and the ratio of [St]0/[UrazoleCTA 1]0/[AIBN]0 was used as 500/1/0.1. A St conversion was

Figure 2. 1H NMR spectra of Urazole-CTA 1 (A), urazole-terminated PMMA27 (B), and HDEO-modified PMMA27 (C). DMSO-d6 was used as deuterated solvent.

achieved around 6.2% in 13 h under this polymerization condition. Although the presence of the linear semilogarithmic plot of ln([M]0/[M]) versus reaction time (Figure S3A), the linear increase of Mn,GPC with MMA conversion (Figure S3C), and the lower Mw/Mn than 1.1 throughout the polymerization (Figure S3C), a shoulder peak at high molecular weight direction was clearly observed from the corresponding GPC curves (Figure S3B) when St conversion was above ca. 4%. This indicated that the novel Urazole-CTA 1 may not be a good candidate for polymerizing St and only produce well-defined polystyrene (PS) with a monomodal and symmetrical GPC peak shape at very lower monomer conversion (100 times) of 2,3dimethyl-2-butene.

PMMA27. Compared to that (black curve) of urazole-terminated PMMA27, the monomodal and symmetric peak shape was preserved, but the peak position was shifted to the high molecular weight direction completely. The Mn and Mw/Mn was calculated as 3450 and 1.09, respectively. These results strongly indicated the successful preparation of well-defined TAD-terminated polymers from this procedure, in which the TAD end groups held a high reactivity with conjugated diene groups. Preparation of Polymer Backbone. The polymer backbone of poly(2-hydroethyl acrylate) (PHEA)-diene (Scheme 1) with conjugated diene side groups was synthesized by a two-step procedure, which was detailed in the Experimental Section. In the first step, RAFT polymerization was used to polymerize 2hydroethyl acrylate (HEA) monomer and prepare the welldefined PHEA having the hydroxyl side groups. Table 1 (run 5) shows the detailed polymerization condition, in which the polymerization was performed in DMF solution (mHEA/mDMF = 1/1) at 60 °C and the ratio of [HEA]0/[RAFT agent]0/[AIBN]0 was used as 1000/1/0.4. A HEA conversion of 44.8% was achieved after 2 h polymerization, producing the PHEA with a degree of polymerization (DP) of 448. Figure S5 (black) shows the corresponding GPC curve, in which a monomodal and symmetric GPC curve was obtained with Mn = 138 500 and Mw/ Mn = 1.27. In the second step, the resultant PHEA448 was then postmodified by hexa-2,4-dienyl ester succinic anhydride to produce the polymer backbone of PHEA448-diene. Figure S6B shows the corresponding 1H NMR characterization. Compared F

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

used as internal standard to evaluate the conversion of TADterminated PMMA27 side chains during the coupling reaction, which was preadded into the DCM solution of polymer side chains. The percentage of grafted PMMA27−TAD could be calculated by comparing the peak intensities of the TADterminated PMMA27 and toluene in the GPC curves. This finally produced the grafting density for the resultant PHEA448-gPMMA27 by multiplying the initial molar ratio of 1.2 between TAD and diene groups. As shown in Table 2 (runs 1−3), the grafting density from GPC could achieve as high as 90.2% after only 1 min reaction. It could increase to 95.5% after 5 min reaction and further to 96.8% after 10 min reaction. Compared to the GPC curve (Figure 3A, black) of PHEA448−diene backbone, the monomodal and symmetric peak shapes were preserved for all of the resultant PHEA448-g-PMMA27, but the peak positions were shifted completely to the high molecular weight direction (Figure 3A, blue, magenta, and olive curves). This strongly indicated the successful formation of bottlebrush polymers. After the formation of PHEA448-g-PMMA27 bottlebrush polymers, the preparative GPC technique was used to completely remove the unconnected PMMA27 side chains (Figure S7). Figure 4 shows the 1H NMR characterization of PHEA448−diene backbone (A) and the purified PHEA448-gPMMA27 bottlebrush polymers with 1 min (B), 5 min (C), and 10 min (D) coupling reaction. Compared to that (A) of the PHEA448−diene backbone, the intensities of characteristic proton signals of Hf‑i for diene side group significantly decreased from the 1H NMR spectra (B, C, and D) of the resultant PHEA448-g-PMMA27. In addition, a new proton signal (Hj) appeared at 5.66−6 ppm after the coupling reaction, which could be ascribed to the new formed double bond from TAD−diene Diels−Alder cycloaddition. The grafting density could be again calculated from the 1H NMR spectrum of the resultant PHEA448g-PMMA27 using the area ratio between Hg and Hf,h‑j with an equation of (Hf,h−j − 3Hg)/(Hf,h−j − Hg). By this method, the grafting densities of 90.5% and 96.5% were calculated for the PHEA448-g-PMMA27 after 1 and 5 min reaction (Table 2, runs 1 and 2), which well agreed with those obtained from above GPC calculation. After 10 min coupling reaction, the Hg signal almost disappeared from the 1H NMR spectrum (D) of the resultant PHEA448-g-PMMA27, and an area ratio of 1/2 was obtained between Hk and Hj, clearly indicating a quantitative coupling reaction efficiency for this case. To further demonstrate the high efficiency of TAD−diene Diels−Alder reaction for the formation of bottlebrush polymers, TAD-terminated PMMA58 with a bigger DP was used as side chains to prepare the bottlebrush polymer of PHEA448-gPMMA58. The coupling reaction condition was used same to that of PHEA448-g-PMMA27 preparation except that the initial molar concentration of PMMA58 was used as 0.008 M. Figure 3B shows the GPC characterization of the resultant PHEA448-gPMMA58 at different reaction time. Compared to that (Figure 3B, black curve) of PHEA448−diene backbone, the monomodal and symmetric peak shapes were preserved for all of the resultant PHEA448-g-PMMA58, but the peak positions were shifted completely to the high molecular weight direction (Figure 3B, blue, magenta, olive, and navy curves). The grafting densities calculated from the GPC curves are shown in Table 2 (runs 4− 7). A high grafting density of 84.2% was achieved after only 5 min coupling reaction, which could increase to 90.5% in 30 min. After 1 h reaction, a final grafting density of 93.8% was obtained at the measured range. After removing the unconnected PMMA58 side chains by preparative GPC (Figure S8), the 1H NMR

Figure 5. AFM height images of PHEA448-g-PMMA27 (A), PHEA448-gPtBA25 (B), and PHEA448-g-PS25 (C).

Figure 3A shows the GPC characterization of the resultant PHEA448-g-PMMA27 at different reaction times. Toluene was G

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

or highly oriented pyrolytic graphite (HOPG) (for PHEA448-gPS25). Figure 5 shows the AFM images of PHEA448-g-PMMA27 (A), PHEA448-g-PtBA25 (B), and PHEA448-g-PS25 (C), in which the worm-like molecular morphologies were obtained for all cases. By taking 100 molecules for statistics analysis, the average height, width, and contour length were obtained as 2.3 ± 0.2 nm (standard deviation), 18 ± 2 nm, and 102 ± 27 nm for PHEA448g-PMMA27, 2.4 ± 0.2 nm, 18 ± 2 nm, and 93 ± 17 nm for PHEA448-g-PtBA25, and 1.8 ± 0.2 nm, 25 ± 3 nm, and 108 ± 17 nm for PHEA448-g-PS25, respectively. By dividing the average contour length with DP (448) of PHEA448−diene backbone, the length per monomer unit (lm) was calculated as 0.23 ± 0.06, 0.21 ± 0.04, and 0.24 ± 0.04 nm for PHEA448-g-PMMA27, PHEA448-gPtBA25, and PHEA448-g-PS25. These lm values were very close to the lmax of 0.25 nm for a fully stretched all-trans −CH2−CH2− bond conformation, demonstrating the PHEA448−diene backbone was highly extended by the densely grafted PMMA27, PtBA25, and PS25 side chains.

characterization was performed for all cases (Figure S9). Compared to that (Figure 4A) of PHEA448−diene backbone, the Hf−i proton signal intensities of diene group significantly decreased from the 1H NMR spectra (Figure S9A−D) of the resultant PHEA448-g-PMMA58. In addition, the new proton signal of Hj was appeared at 5.66−6 ppm ascribed to the new formed double bond from TAD−diene Diels−Alder cycloaddition. The grafting densities calculated from the 1H NMR characterization are also shown in Table 2 (runs 4−7), which were similar to those from above GPC characterization for all cases. Inspired by the successful preparation of bottlebrush polymers with PMMA side chains, the TAD−diene Diels−Alder cycloaddition was further extended to prepare bottlebrush polymers with other kinds of polymer side chains such as PS and PtBA. For the formation of PHEA448-g-PS25 and PHEA448-g-PtBA25, the coupling reaction conditions were the same as that of PHEA448-gPMMA58 preparation, in which initial molar concentration of polymer side chains was used as 0.008 M and the initial molar ratio between TAD and diene group was kept as 1.2/1. Figures 3C and 3D show the GPC characterization of the resultant PHEA448-g-PtBA25 and PHEA448-g-PS25 with different coupling reaction time. Compared to those (black curves) of PHEA448−diene backbone, the monomodal and symmetric peak shapes were preserved for all of the resultant PHEA448-g-PtBA25 (Figure 3C, blue and magenta curves) and PHEA448-g-PS25 (Figure 3D, blue and magenta curves), but the peak positions were shifted completely to the high molecular weight direction. This strongly indicated the successful formation of brush polymers. The grafting densities calculated from the GPC curves are shown in Table 2 (runs 8 and 9 for PHEA448-g-PtBA25 and runs 10 and 11 for PHEA448-g-PS25). The grafting densities could achieve above 90% after only 1 min reaction for grafting both PtBA25 and PS25 side chains. They could further increased above 95% after 10 min reaction. Figures S10 and S11 show the 1H NMR characterization of the purified PHEA448-g-PtBA25 and PHEA448-g-PS25 by preparative GPC to completely remove the unconnected PtBA25 (Figure S12) and PS25 (Figure S13). Compared to the 1H NMR spectra of PHEA448−diene backbone (Figures S10A and S11A), a new proton signal (Hj) appeared at 5.66−6 ppm after the coupling reaction, which could be ascribed to the new formed double bond from TAD−diene Diels−Alder cycloaddition. In addition, the Hf−i proton signal intensities of diene group significantly decreased from the 1H NMR spectra of the resultant PHEA448g-PtBA25 (Figure S10B) and PHEA448-g-PS25 (Figure S11B) after 1 min coupling reaction. The grafting densities calculated from the 1H NMR characterization were above 90% for both cases (Table 2, runs 8 and 10), in which the values were similar to those calculated from GPC characterization. After 10 min coupling reaction, the Hg signal disappeared from the 1H NMR spectra of the resultant PHEA448-g-PtBA25 (Figure S10C) and PHEA448-gPS25 (Figure S11C), and an area ratio of 1/2 was obtained between Hk and Hj for both cases. This clearly indicated an almost quantitative reaction efficiency for coupling PHEA448− diene backbone and polymer side chains of PtBA25 and PS25 using this reaction condition. AFM Characterization of Brush Polymers. AFM was finally used to characterize the molecular morphology of the resultant bottlebrush polymers. The visualization samples were prepared by spin-coating the diluted bottlebrush polymer solution in CHCl3 (ca. 0.05 mg/mL) on the surface of freshly cleaved mica (for PHEA448-g-PMMA27 and PHEA448-g-PtBA25)

■

CONCLUSIONS A novel “grafting onto” method was developed for the formation of various bottlebrush polymers by combining RAFT and TAD− diene click reaction, which required no any metal catalyst during the whole preparation process. In this method, diene-containing polyacrylate backbone with one conjugated diene group in every repeated unit (PHEA-diene) and TAD-terminated polymer sides were prepared by RAFT accompanying with a postfunctionalization process. The bottlebrush polymers with varied polymer side chains were then efficiently prepared by coupling the resultant polymer backbone and side chains based on the TAD−diene click reaction. Exemplified by coupling PHEA448−diene backbone with a DP of 448 and TAD-terminated PMMA27, PtBA25, and PS25 side chains with a DP around 25 in the presence of a slight molar excess (1.2 times) of TAD to diene groups, the grafting density could achieve above 90% in only 1 min coupling reaction, which could become quantitative in less than 10 min. In addition, for a longer PMMA58 side chain with a DP of 58, a high grafting density above 90% could also be obtained in 30 min using the same coupling condition. AFM characterization visualized the worm-like morphology for all three kinds of bottlebrush polymers with different PMMA, PS, and PtBA side chains. Because of the high grafting efficiency and metal-free characteristics, it is expected that this novel “grafting onto” method should become one of the basic tools for producing clean bottlebrush polymers with varied polymer side chains.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b00782. Experimental section and Figures S1−S13 (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*Fax +86-010-62559373; e-mail [email protected] (K.Z.). Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS Generous support was primarily provided by Ministry of Science and Technology of China (2014CB932200) and National H

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

(19) Gao, H.; Matyjaszewski, K. Synthesis of Molecular Brushes by “Grafting Onto” Method: Combination of ATRP and Click Reactions. J. Am. Chem. Soc. 2007, 129, 6633−6639. (20) Engler, A. C.; Lee, H. I.; Hammond, P. T. Highly Efficient “Grafting onto” a Polypeptide Backbone Using Click Chemistry. Angew. Chem., Int. Ed. 2009, 48, 9334−9338. (21) Sun, J.; Hu, J.; Liu, G.; Xiao, D.; He, G.; Lu, R. Efficient Synthesis of Well-Defined Amphiphilic Cylindrical Brushes Polymer with High Grafting Density: Interfacial “Click” Chemistry Approach. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 1282−1288. (22) Tang, H.; Li, Y.; Lahasky, S. H.; Sheiko, S. S.; Zhang, D. CoreShell Molecular Bottlebrushes with Helical Polypeptide Backbone: Synthesis, Characterization, and Solution Conformations. Macromolecules 2011, 44, 1491−1499. (23) Zhao, P.; Yan, Y.; Feng, X.; Liu, L.; Wang, C.; Chen, Y. Highly Efficient Synthesis of Polymer Brushes with PEO and PCL as Side Chains via Click Chemistry. Polymer 2012, 53, 1992−2000. (24) Yan, Y.; Shi, Y.; Zhu, W.; Chen, Y. Highly Efficient Synthesis of Cylindrical Polymer Brushes with Various Side Chains via Click Grafting-Onto Approach. Polymer 2013, 54, 5634−5642. (25) Barner-Kowollik, C.; Du Prez, F. E.; Espeel, P.; Hawker, C. J.; Junkers, T.; Schlaad, H.; Van Camp, W. Clicking” Polymers or Just Efficient Linking: What Is the Difference? Angew. Chem., Int. Ed. 2011, 50, 60−62. (26) Fu, Q.; Lin, W.; Huang, J. A New Strategy for Preparation of Graft Copolymers via “Graft Onto” by Atom Transfer Nitroxide Radical Coupling Chemistry: Preparation of Poly(4-glycidyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl-co-ethylene oxide)-graft-polystyrene and Poly(tert-butyl acrylate). Macromolecules 2008, 41, 2381−2387. (27) Li, Y.; Zhang, Y.; Yang, D.; Li, Y.; Hu, J.; Feng, C.; Zhai, S.; Lu, G.; Huang, X. PAA-g-PPO Amphiphilic Graft Copolymer: Synthesis and Diverse Micellar Morphologies. Macromolecules 2010, 43, 262−270. (28) Gadwal, I.; Rao, J.; Baettig, J.; Khan, A. Functionalized Molecular Bottlebrushes. Macromolecules 2014, 47, 35−40. (29) Cesana, S.; Kurek, A.; Baur, M. A.; Auernheimer, J.; Nuyken, O. Polymer-Bound Thiol Groups on Poly(2-oxazoline)s. Macromol. Rapid Commun. 2007, 28, 608−615. (30) Le Fer, G.; Babinot, J.; Versace, D. L.; Langlois, V.; Renard, E. An Efficient Thiol-Ene Chemistry for the Preparation of Amphiphilic PHABased Graft Copolymers. Macromol. Rapid Commun. 2012, 33, 2041− 2045. (31) Sprafke, J. K.; Spruell, J. M.; Mattson, K. M.; Montarnal, D.; McGrath, A. J.; Pötzsch, R.; Miyajima, D.; Hu, J.; Latimer, A. A.; Voit, B. I.; Aida, T.; Hawker, C. J. Revisiting Thiol-Yne Chemistry: Selective and Efficient Monoaddition for Block and Graft Copolymer Formation. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 319−326. (32) Durmaz, H.; Dag, A.; Cerit, N.; Sirkecioglu, O.; Hizal, G.; Tunca, U. Graft Copolymers via ROMP and Diels-Alder Click Reaction Strategy. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 5982−5991. (33) Tasdelen, M. A.; Yagci, Y. Light-Induced Click Reactions. Angew. Chem., Int. Ed. 2013, 52, 5930−5938. (34) Tang, W.; Becker, M. L. ″Click” Reactions: A Versatile Toolbox for the Synthesis of Peptide-Conjugates. Chem. Soc. Rev. 2014, 43, 7013−7039. (35) Espeel, P.; Du Prez, F. E. Click”-Inspired Chemistry in Macromolecular Science: Matching Recent Progress and User Expectations. Macromolecules 2015, 48, 2−14. (36) Delaittre, G.; Guimard, N. K.; Barner-Kowollik, C. Cycloadditions in Modern Polymer Chemistry. Acc. Chem. Res. 2015, 48, 1296−1307. (37) Sletten, E. M.; Bertozzi, C. R. From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions. Acc. Chem. Res. 2011, 44, 666−676. (38) Taylor, M. T.; Blackman, M. L.; Dmitrenko, O.; Fox, J. M. Design and Synthesis of Highly Reactive Dienophiles for the Tetrazine−transCyclooctene Ligation. J. Am. Chem. Soc. 2011, 133, 9646−9649. (39) Hansell, C. F.; Espeel, P.; Stamenović, M. M.; Barker, I. A.; Dove, A. P.; Du Prez, F. E.; O’Reilly, R. K. Additive-Free Clicking for Polymer Functionalization and Coupling by Tetrazine−Norbornene Chemistry. J. Am. Chem. Soc. 2011, 133, 13828−13831.

Science Foundation of China (51533009). K.Z. thanks the Bairen project from The Chinese Academy of Sciences for support.

■

REFERENCES

(1) Runge, M. B.; Bowden, N. B. Synthesis of High Molecular Weight Comb Block Copolymers and Their Assembly into Ordered Morphologies in the Solid State. J. Am. Chem. Soc. 2007, 129, 10551− 10560. (2) Miyake, G. M.; Piunova, V. A.; Weitekamp, R. A.; Grubbs, R. H. Precisely Tunable Photonic Crystals From Rapidly Self-Assembling Brush Block Copolymer Blends. Angew. Chem., Int. Ed. 2012, 51, 11246−11248. (3) Sun, G.; Cho, S.; Clark, C.; Verkhoturov, S. V.; Eller, M. J.; Li, A.; Pavía-Jiménez, A.; Schweikert, E. A.; Thackeray, J. W.; Trefonas, P.; Wooley, K. L. Nanoscopic Cylindrical Dual Concentric and Lengthwise Block Brush Terpolymers as Covalent Preassembled High-Resolution and High-Sensitivity Negative-Tone Photoresist Materials. J. Am. Chem. Soc. 2013, 135, 4203−4206. (4) Mukumoto, K.; Averick, S. E.; Park, S.; Nese, A.; Mpoukouvalas, A.; Zeng, Y.; Koynov, K.; Leduc, P. R.; Matyjaszewski, K. Phototunable Supersoft Elastomers using Coumarin Functionalized Molecular Bottlebrushes for Cell-Surface Interactions Study. Macromolecules 2014, 47, 7852−7857. (5) Daniel, W. F. M.; Burdynska, J.; Vatankhah-Varnoosfaderani, M.; Matyjaszewski, K.; Paturej, J.; Rubinstein, M.; Dobrynin, A. V.; Sheiko, S. S. Solvent-Free, Supersoft and Superelastic Bottlebrush Melts and Networks. Nat. Mater. 2016, 15, 183−189. (6) Johnson, J. A.; Lu, Y. Y.; Burts, A. O.; Xia, Y.; Durrell, A. C.; Tirrell, D. A.; Grubbs, R. H. Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP. Macromolecules 2010, 43, 10326−10335. (7) Lu, X.; Tran, T. H.; Jia, F.; Tan, X.; Davis, S.; Krishnan, S.; Amiji, M. M.; Zhang, K. Providing Oligonucleotides with Steric Selectivity by Brush-Polymer-Assisted Compaction. J. Am. Chem. Soc. 2015, 137, 12466−12469. (8) Tan, X.; Li, B. B.; Lu, X.; Jia, F.; Santori, C.; Menon, P.; Li, H.; Zhang, B.; Zhao, J. J.; Zhang, K. Light-Triggered, Self-Immolative Nucleic Acid-Drug Nanostructures. J. Am. Chem. Soc. 2015, 137, 6112− 6115. (9) Yuan, J.; Xu, Y.; Walther, A.; Bolisetty, S.; Schumacher, M.; Schmalz, H.; Ballauff, M.; Müller, A. H. E. Water-Soluble Organo-Silica Hybrid Nanowires. Nat. Mater. 2008, 7, 718−722. (10) Huang, K.; Rzayev, J. Well-Defined Organic Nanotubes from Multicomponent Bottlebrush Copolymers. J. Am. Chem. Soc. 2009, 131, 6880−6885. (11) Huang, K.; Rzayev, J. Charge and Size Selective Molecular Transport by Amphiphilic Organic Nanotubes. J. Am. Chem. Soc. 2011, 133, 16726−16729. (12) Huang, K.; Johnson, M.; Rzayev, J. Synthesis of Degradable Organic Nanotubes by Bottlebrush Molecular Templating. ACS Macro Lett. 2012, 1, 892−895. (13) Zhang, M.; Müller, A. H. E. Cylindrical Polymer Brushes. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 3461−3481. (14) Sheiko, S. S.; Sumerlin, B. S.; Matyjaszewski, K. Cylindrical Molecular Brushes: Synthesis, Characterization, and Properties. Prog. Polym. Sci. 2008, 33, 759−785. (15) Feng, C.; Li, Y.; Yang, D.; Hu, J.; Zhang, X.; Huang, X. WellDefined Graft Copolymers: From Controlled Synthesis to Multipurpose Applications. Chem. Soc. Rev. 2011, 40, 1282−1295. (16) Lee, H. I.; Pietrasik, J.; Sheiko, S. S.; Matyjaszewski, K. StimuliResponsive Molecular Brushes. Prog. Polym. Sci. 2010, 35, 24−44. (17) Rzayev, J. Molecular Bottlebrushes: New Opportunities in Nanomaterials Fabrication. ACS Macro Lett. 2012, 1, 1146−1149. (18) Verduzco, R.; Li, X.; Pesek, S. L.; Stein, G. E. Structure, Function, Self-Assembly, and Applications of Bottlebrush Copolymers. Chem. Soc. Rev. 2015, 44, 2405−2420. I

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules (40) Oehlenschlaeger, K. K.; Mueller, J. O.; Heine, N. B.; Glassner, M.; Guimard, N. K.; Delaittre, G.; Schmidt, F. G.; Barner-Kowollik, C. LightInduced Modular Ligation of Conventional RAFT Polymers. Angew. Chem., Int. Ed. 2013, 52, 762−766. (41) Hiltebrandt, K.; Pauloehrl, T.; Blinco, J. P.; Linkert, K.; Börner, H. G.; Barner-Kowollik, C. λ-Orthogonal Pericyclic Macromolecular Photoligation. Angew. Chem., Int. Ed. 2015, 54, 2838−2843. (42) Billiet, S.; De Bruycker, K.; Driessen, F.; Goossens, H.; Van Speybroeck, V.; Winne, J. M.; Du Prez, F. E. Triazolinediones Enable Ultrafast and Reversible Click Chemistry for the Design of Dynamic Polymer Systems. Nat. Chem. 2014, 6, 815−821. (43) De Bruycker, K.; Billiet, S.; Houck, H. A.; Chattopadhyay, S.; Winne, J. M.; Du Prez, F. E. Triazolinediones as Highly Enabling Synthetic Tools. Chem. Rev. 2016, 116, 3919−3974. (44) Wang, Z.; Yuan, L.; Trenor, N. M.; Vlaminck, L.; Billiet, S.; Sarkar, A.; Du Prez, F. E.; Stefik, M.; Tang, C. Sustainable Thermoplastic Elastomers Derived from Plant Oil and Their “Click-Coupling” via TAD Chemistry. Green Chem. 2015, 17, 3806−3818. (45) Zhao, Y.; Chen, J.; Zhu, W.; Zhang, K. Unique PostFunctionalization Method for ROMP Polymers Based on Triazolinedione Alder-Ene Chemistry. Polymer 2015, 74, 16−20. (46) Türünç, O.; Billiet, S.; De Bruycker, K.; Ouardad, S.; Winne, J.; Du Prez, F. E. From Plant Oils to Plant Foils: Straightforward Functionalization and Crosslinking of Natural Plant Oils with Triazolinediones. Eur. Polym. J. 2015, 65, 286−297. (47) Vonhören, B.; Roling, O.; De Bruycker, K.; Calvo, R.; Du Prez, F. E.; Ravoo, B. J. Ultrafast Layer-by-Layer Assembly of Thin Organic Films Based on Triazolinedione Click Chemistry. ACS Macro Lett. 2015, 4, 331−334. (48) Roling, O.; De Bruycker, K.; Vonhören, B.; Stricker, L.; Körsgen, M.; Arlinghaus, H. F.; Ravoo, B. J.; Du Prez, F. E. Rewritable Polymer Brush Micropatterns Grafted by Triazolinedione Click Chemistry. Angew. Chem., Int. Ed. 2015, 54, 13126−13129.

J

DOI: 10.1021/acs.macromol.6b00782 Macromolecules XXXX, XXX, XXX−XXX