Synthesis of Macrocyclic Molecular Brushes with Amphiphilic Block Copolymers as Side Chains

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1 Synthesis of Macrocyclic Molecular Brushes with Amphiphilic Block Copolymers as Side Chains XIAOSHAN FAN, GUOWEI WANG, JUNLIAN HUANG The Key Laboratory of Molecular Engineering of Polymer, State Education Ministry of China, Department of Macromolecular Science, Fudan University, Shanghai , China Received 9 December 2010; accepted 21 December 2010 DOI: /pola Published online 2 February 2011 in Wiley Online Library (wileyonlinelibrary.com). ABSTRACT: Macrocyclic molecular brushes c-phema-g-(ps-b- PEO) consisting of macrocyclic poly(2-hydroxylethyl methacrylate) (c-phema) as backbone and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) amphiphilic block copolymers as side chains were synthesized by the combination of atom transfer radical polymerization (ATRP), click chemistry, and single-electron transfer nitroxide radical coupling (SET-NRC). First, a linear a- alkyne-x-azido heterodifunctional PHEMA (l-hcbc-phema-n 3 ) was prepared by ATRP of HEMA using 3-(trimethylsilyl)propargyl 2-bromoisobutyrate as initiator, and then chlorine end groups were transformed to AN 3 group by nucleophilic substitution reaction in DMF in the presence of an excess of NaN 3. The 3-trimethylsilyl groups could be removed in the presence of tetrabutylammonium fluoride, and the product was cyclized by click chemistry in high dilution conditions. The hydroxyl groups on c-phema were transferred into bromine groups by esterification with 2-bromoisobutyryl bromide and then initiate the ATRP of styrene. The formed macrocyclic molecular brushes c-phema-g-ps were coupled with the TEMPO-PEO to afford the target macrocyclic molecular brushes c-phema-g- (PS-b-PEO) by SET-NRC, and the efficiency is as high as 8085%. All of the intermediates and final product were characterized with 1 H NMR, Fourier transform infrared (FTIR), and gel permeation chromatography in details VC 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: , 2011 KEYWORDS: amphiphiles; atom transfer radical polymerization; click chemistry; macrocycles; molecular brush; single electron transfer nitroxide radical coupling INTRODUCTION Because of their unique endless topology, cyclic polymers exhibit significant different physical properties in both solution and bulk compared with the linear counterparts, such as higher glass-transition temperature, lower hydrodynamic volume, reduced intrinsic viscosity, higher refractive index. 1 As the first recognition, design, and synthesis of cyclic polymers, it has always attracted polymer chemists interests. Over the past few decades, diverse topologically appealing cyclic polymers have been synthesized, including cyclic homopolymers, cyclic block copolymers, and sun-shaped, tadpole-shaped, eight-shaped, h-shaped polymers The synthesis of these novel cyclic polymers not only riched the macromolecular architectures but also provided the model compounds for further understanding and exploring the impact of polymer structure on their properties. Therefore, the synthesis of cyclic polymers is a very interesting subject for polymer chemists. Macrocyclic graft polymers (also-called sun-shaped polymers) are a kind of cyclic polymers with complicated architecture, in which multiside chains are connected to a macrocyclic backbone. In 1985, Lehn and coworkers initiatively synthesized N-substituted crown ether with long dodecyl chains and investigated its properties. The results revealed that the cyclic grafted molecule displayed a liquid crystal phase, in which the cyclic units were stacked, forming a tubular mesophase Afterward, medium-size cyclic molecules (commonly containing units) bearing long chains were synthesized and their properties were studied in detail. For example, Ghadiri et al. synthesized a mediumsized cyclic polypeptide grafted by long chains, and the nanotubes with specified internal diameters was constructed because of the stacking of cyclic polypeptides through the hydrogen-bonding interactions between them, which shows the potential applications in ion transport across membranes. 24 However, macrocyclic polymers or macrocyclic graft copolymers with long side chains may show the different properties from the small- or medium-sized cycles mentioned before because of their flexible chain and large size. 25,26 Thus, polymeric chemists try to introduce some side chains with different structure onto macrocyclic polymers and anticipate to obtain cyclic polymers with some fascinating properties. Up to now, a varieties of sun-shaped polymers with the lower grafting density have been reported in literature, such as c-peo-g-ps, c-peo-g-pcl, and c-pcl-g- PEO However, the sun-shaped polymers with densely Correspondence to: J. Huang ( jlhuang@fudan.edu.cn) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 49, (2011) VC 2011 Wiley Periodicals, Inc. SYNTHESIS OF MACROCYCLIC MOLECULAR BRUSHES, FAN, WANG, AND HUANG 1361

2 JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI /POLA SCHEME 1 Synthesis of macrocyclic molecular brushes c-phemag-(ps-b-peo). side chains (or macrocyclic molecular brushes), especially those with amphiphilic block copolymer side chains, are rarely reported due to the synthesis difficulties. 27,28 In this presentation, the synthesis of macrocyclic molecular brushes c-hema-g-(ps-b-peo) with macrocyclic poly(2- hydroxyethyl methacrylate) (c-hema) as the backbone and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) amphiphilic block copolymers as side chains was described by the combination of atom transfer radical polymerization (ATRP), click reaction, and single-electron transfer nitroxide radical coupling reaction (SET-NRC ; Scheme 1). RESULTS AND DISCUSSION Synthesis of l-cbc-phema-n 3 Precursor The l TMS-CBC-PHEMA-Cl was synthesized by ATRP of HEMA at 50 C using 3-(trimethylsilyl)propargyl 2-bromoisobutyrate as initiator and CuCl/bpy as catalyst. The alkyne group of the initiator was protected with a trimethylsilyl group first to prevent side reactions. The polymerization was stopped at relatively low monomer conversions (ca., 35%) to ensure high contents of chlorine end group. 32,33 The chlorine-end group in the PHEMA was easily transformed to azide group through nucleophilic substitution reaction in DMF in the presence of an excess of NaN 3. The trimethylsilyl protective group was then removed in the presence of tetrabutylammonium fluoride (TBAF), and the polymer l-cbc- PHEMA-N 3 was obtained. As shown in Figure 1(a), the gel permeation chromatography (GPC) trace of l-tms-cbc-phema-cl was a monomodal peak with narrow distribution (M w /M n ¼ 1.24). The 1 H NMR spectrum of l-tms-cbc-phema-cl was given in Figure 2(A). The number-average degree of polymerization (DP) could be derived from the integration ratio of the peak (c) at 3.90 ppm for the methylene protons (ACOOACH 2 A)ofthe HEMA repeating units and the peak (h) at 0.14 ppm for the methyl protons (ASi(CH 3 ) 3,) of the TMS-protecting group, the value is 112. Figure 2(B) showed the 1 H NMR spectrum 1362 WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

3 ARTICLE FIGURE 1 GPC traces for l-tms-cbc-phema-cl (a), l-hcbc- PHEMA-N 3 (b), and c-phema (c) with DMF as the elute. of l-cbc-phema-n 3. Compared with the spectrum of l-tms- C ¼C-PHEMA-Cl, the protons signal at 0.14 ppm disappeared completely, indicating TMS-protecting group was removed quantitatively. Synthesis of c-phema The click cyclization of l-hcbc-phema-n 3 was carried out using CuBr/PMETA as catalyst in DMF at 90 C under high dilute conditions ( g/ml). Determined by GPC in DMF, the M n and M w /M n of the obtained c-phema were 1.12 and 1.26 kg/mol, respectively [Fig. 1(c)], the GPC trace of c-phema clearly shifted to the longer retention time comparing with the precursor l-cbc-phema-n 3, and no intermolecular reaction products with multitimes molecular weight were detected. The shift to the longer retention time for c-phema may attribute to the reduction of the hydrodynamic radius because of the formation of a more compact conformation by the cyclization The hgi value, the ratio of the apparent peak molar masses of c-phema to that of l- CBC-PHEMA-N 3, was about 0.79, which is coincident with the reported results of other cyclic polymers ( ) Figure 2(C) showed the 1 H NMR spectrum of c-phema, it showed that the appearance of a new resonance peak (h) at 7.70 ppm, which was assigned to the proton of triazole ring after click reaction of alkyne and azide groups. 9 Figure 3 was the Fourier transform infrared (FTIR) spectra of l-cbc- PHEMA-N 3 before (a) and after cyclization (b). It clearly indicated that the characteristic azide absorbance peak at 2110 cm 1 for l-cbc-phema-n 3 [Fig. 3(a)] disappeared completely after cyclization as Figure 3(b) showed. Based on these results, it can be reliably concluded that the cyclization reaction was completed successfully. Esterification of the Hydroxyl Groups of c-phema with 2-Bromoisobutyryl Bromide (c-phema-br) The esterification of the pendant hydroxyl groups on c- PHEMA with 2-bromoisobutyryl bromide was carried out easily in the anhydrous pyridine and produced an ATRP macroinitiator c-phema-br bearing multibromine moieties on the macrocyclic backbone. As Figure 4(b) showed that the GPC trace of c-phema-br was a monomodal and symmetric peak, no side reaction was found in the bromimation. The 1 H NMR spectrum of c-phema-br was shown in Figure 5(A). Compared with c-phema [Fig. 2(C)], the peak (e) (AOH) at 4.79 ppm disappeared completely, and the peaks (c) (ACH 2 AOCO) and (d) (ACH 2 AOH) at 3.90 and 3.58 ppm shifted to 4.13 and 4.33 ppm in Figure 5(A), it means that the esterification reaction was performed completely. Synthesis of c-phema-g-ps The macrocyclic molecular brushes c-phema-g-ps with PS homopolymers as side chains were prepared by ATRP of styrene using the c-phema-br as macroinitiator, and the length of the PS side chains can be controlled by varying the polymerization time. Two samples of c-phema-g-ps copolymers with different length of the PS side chains were synthesized, FIGURE 2 1 H NMR spectra for l-tms-cbc-phema-cl (A), l- HCBC-PHEMA-N 3 (B), and c-phema (C) in DMSO-d 6. FIGURE 3 FTIR spectra l-phema-n 3 (a) and c-phema (b). SYNTHESIS OF MACROCYCLIC MOLECULAR BRUSHES, FAN, WANG, AND HUANG 1363

4 JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI /POLA where M n,ps was the M n of PS chains after cleavage from c- PHEMA-g-PS, which could be determined by GPC; N Br was the number of ABr groups on c-pehma-br; M n,c-phema-br was calculated from the DP (112) of c-phema-br. The data were listed in Table 1. FIGURE 4 GPC traces for c-phema (a), c-phema-br (b), c- PHEMA 112 -g-ps 44 (c), and c-phema 112 -g-(ps 44 -b-peo 55 ) (d) with DMF as the elute. which was listed in Table 1. The polymerization was stopped at a relatively lower monomer conversion (<30%) to keep a high degree of bromo-end functionality for the following SET-NRC reaction. 25,26 The 1 H NMR spectrum of c- PHEMA 112 -g-ps 44 was shown in Figure 5(B), the new peaks (f) at ppm and (e) at ppm corresponding to the phenyl-ring protons of St units and the methine proton (ACH 2 CH(Ph)ABr) neighboring to terminal bromine appeared, respectively. Figure 4(c) was the GPC trace of c- PHEMA 112 -g-ps 44, which displayed a monomodal peak in the lower retention time compared with the precursor c-phema- Br, it means the bromide groups on the c-phema-br successfully initiated the polymerization of St. The M n of c- PHEMA 114 -g-ps 44 determined by GPC analysis was 8.37 kg/ mol (M w /M n ¼ 1.20), which was much smaller than the value predicted theoretically due to the sharp difference of the hydrodynamic volume between the graft polymers and the linear polystyrene standard. 42,43 To obtain the reliable molecular weights of macrocyclic molecular brushes, the PS side chains were cleaved from c-phema-g-ps, and the M n of c-phema-g-ps could be calculated on the following formula: M n;c-phema-g-ps ¼ M n;ps N Br þ M n;c-phema-br (1) Synthesis of c-phema-g-(ps-b-peo) The macrocyclic molecular brushes c-phema-g-(ps-b-peo) with the PS-b-PEO amphiphilic block side chains were prepared by the SET-NRC coupling reaction of TEMPO-PEO to c-phema-g-ps, and the reaction was completed using Cu(0)/ N,N,N 0,N 00,N 00 -pentamethyldiethylenetriamine (PMDETA) as catalyst in tetrahydrofuran (THF) at room temperature. In Figure 4(d), the GPC trace of c-phema 114 -g-(ps 44 -b-peo 55 ) was a monomodal peak and clearly shifted to the lower retention time compared with the precursor c-phema 114 -g- PS 44, the M n and M w /M n of c-phema 114 -g-(ps 44 -b-peo 55 ) were 8.37 kg/mol and 1.20, respectively. The M n of c-phema 114 -g-(ps 44 -b-peo 55 ) determined by GPC was also unreliable, which was smaller than the real value. Figure 5(D) showed the 1 H NMR spectrum of c-phema 114 -g-(ps 44 - b-peo 55 ), the peak (f) at ppm was attributed to the phenyl-ring protons of St units, and the new peak (h) at ppm was attributed to the methylene protons of PEO blocks. When compared with Figure 5(B), the peak (e) at ppm attributed to the methine proton (ACH 2 CH(Ph)ABr) disappeared completely after SET-NRC reaction due to the change of carbon bromine bond to carbon oxygen bond after coupling, which further confirmed the successful synthesis of the macrocyclic molecular brushes c-phema-g-(ps-b-peo). The efficiency of SET-NRC coupling can be calculated by 1 H NMR spectrum according to the following formula: E SET-NRC ¼ A h A f M nðpsþ M nðpeoþ % (2) FIGURE 5 1 HNMRspectraforc-PHEMA- Br in DMSO-d 6 (A), c-phema 112 -g-ps 44 (B) in CDCl 3, TEMPO-PEO (C) in CD 3 OD, in the presence of Pd/C and HCOONH 4 and c-phema 112 -g-(ps 44 -b-peo 55 ) (D) in CDCl WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

5 ARTICLE TABLE 1 Characterization of Macrocyclic Molecular Brushes c-phema-g-(ps-b-peo) c-phema-g-ps c-phema-g-(ps-b-peo) Samples M n,ps a ( 10 3 M n b ( 10 5 M c ( 10 3 M w /M n c M n d ( 10 5 M c n ( 10 3 M w /M c E.F. e c-phema 112 -g-(ps 18 -b-peo 55 ) % c-phema 112 -g-(ps 33 -b-peo 55 ) % a The molecular weight of PS side chains measured by GPC using PS as standard performed in THF. b The molecular weight of c-phema-g-ps measured using eq 1. c The molecular weight and polydispersity of c-phema-g-ps and c- PHEMA-g-(PS-b-PEO) measured by GPC using PEO as standard performed in DMF. d The molecular weight of c-phema-g-(ps-b-peo) measured by 1 H-NMR using eq 3. e The efficiency of SET-NRC measured by 1 H NMR using eq 2. in which A h and A f represent the integral areas of the phenyl-ring protons at ppm of PS blocks and the methylene protons at ppm of PEO blocks. M n(ps) and M n(peo) are the M n of PS and PEO obtained by GPC; 104 and 44 are the molecular weight of the monomer styrene and ethylene oxide, respectively. The Table 1 showed the calculated results, a satisfactory efficiency about 8085% was obtained, in another words, on PHEMA macroring, PS-b-PEO copolymers were grafted. Based on the efficiency of SET-NRC, the M n of c-phema-g-(ps-b-peo) can be obtained using the following formula: M n ¼ M nðc-phema-g-psþ þ M nðpeoþ N ðpsþ E SET-NRC (3) where M n(peo) was the M n of TEMPO-PEO obtained by GPC; N (PS) is the number of PS side chains on c-phema-g-ps. Thus, the macrocylic molecular brushes with dense side chains of PS-b-PEO were provided. EXPERIMENTAL Materials 2-Hydroxyethyl methacrylate (HEMA, 98%, J&K) was purified according to the literature. 44 Styrene [St, >99.5%, Sinopharm Chemical Reagent (SCR)] was washed with 10% NaOH aqueous solution and water three times successively, then dried over CaH 2 and distilled under reduced pressure. Ethylene oxide (EO, 99%, SCR) was dried over CaH 2 for one week and then distilled, stored at 20 C. CuBr (95%, SCR) was stirred overnight in acetic acid, filtered, washed with ethanol and diethyl ether successively, and dried in vacuo. CuCl (97%, SCR) was purified using the same procedure of CuBr. Copper powder (99%, Aldrich) was sealed in toluene and used without further purification. PMDETA (99%, Aldrich), pyridine (99%, Aldrich), 2-bromoisobutyryl bromide (EBiB, 98%, Aldrich), TBAF (97%, Aldrich), and sodium azide (NaN 3, 98%, SCR) were used as received without further purification. Diphenylmethyl potassium (DPMK) solution with concentration of 0.64 mol/l was prepared according to the literature. 45 1,4-Hydroxyl-TEMPO (HTEMPO) prepared according to a previous work was purified by recrystallization with hexane. THF (99%, SCR) was refluxed and distilled from potassium naphthalenide solution. 3-(Trimethylsilyl)- propargyl 2-bromoisobutyrate was synthesized according to the literature. 46 All other reagents and solvents were used as received except declaration. Characterization The number average molecular weight and polydispersity index M w /M n were estimated by GPC. For the measurement of PEO, GPC was performed in 0.1 M NaNO 3 aqueous solution at 40 C with an elution rate of 0.5 ml/min on an Agilent 1100 equipped with a G1310A pump, a G1362A refractive index detector, and a G1315A diode-array detector, and PEO standard samples were used for calibration. For PS side chains cleaved from the c-phema-g-ps copolymers, GPC was performed in THF at 35 C with an elution rate of 1.0 ml/min on an Agilent 1100 equipped with a G1310A pump, a G1362A refractive index detector, and a G1314A variable wavelength detector, and polystyrene standard samples were used for calibration. GPC traces of the rest polymers were performed in DMF with 0.5 M LiBr at 40 C with an elution rate of 1.0 ml/min on a Water Breeze 1525GPC equipped with two PL mix-d columns and PEO standard samples were used for calibration. 1 H NMR spectra were recorded on a Bruker (500 MHz) NMR instrument using CDCl 3, DMSO-d 6, and CD 3 OD as the solvent. All FTIR spectra were recorded as KBr pellets on a Magna 550 FTIR instrument. The ultrafiltration membrane separator was purchased from Shanghai Institute of Applied Physics, Chinese Academy of Science; the cutoff molecular weight of used poly(ether sulfone) film was M w,cutoff ¼ 6,000 g/mol (calibrated by globin). Synthesis of l TMS-CBC-PHEMA-Cl by ATRP (2) (See Scheme 1) The mixture of HEMA (10 ml, 82.0 mmol), 3-(trimethylsilyl)- propargyl 2-bromoisobutyrate (25.0 ll, mmol), bpy (52.0 mg, mmol), and methanol (10mL) was added to an 100-mL ampoule and degassed by three freeze-pumpthaw cycles, and the CuCl (16.3 mg, mmol) was then added to the ampoule under nitrogen as fast as possible, followed by another three freeze-pump-thaw cycles. After sealed under nitrogen, the ampoule was immersed into an oil bath at 50 C for 4 h, then taken out from the oil bath and dipped in liquid nitrogen to stop the polymerization. SYNTHESIS OF MACROCYCLIC MOLECULAR BRUSHES, FAN, WANG, AND HUANG 1365

6 JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI /POLA The crude product was diluted with methanol, and the solution was passed through a column filled with neutral alumina to remove the copper complex. The solution was concentrated under vacuum and precipitated twice in cold diethyl ether. The solid product was collected and dried under vacuum at 40 C to a constant weight. (M n,nmr ¼ 14,500 g/mol; M n,gpc ¼ 14,100 g/mol; M w /M n ¼ 1.24). Synthesis of l-hcbc-phema-n 3 (3) (See Scheme 1) To a 100-mL round-bottomed flask, l-tms-cbc-phema-cl (2.64 g, mmol), DMF (35 ml), and NaN 3 (61.5 mg, mmol) were added, and the reaction mixture was allowed to stir at 50 C for 48 h. After the removal of salts by centrifugation, the remaining DMF solution was collected, in which 5-mL THF solution of TBAF (30 equiv) was added. The reaction mixture was allowed to stir overnight at room temperature. After most of the solvent was removed at reduced pressure, the remaining portion was precipitated/ dissolved in water/dmf twice to remove residual salts. The obtained product was dried under vacuum at the presence of P 2 O 5 for 12 h. (M n,gpc ¼ 14,300 g/mol; M w /M n ¼ 1.24). Synthesis of c-phema (4) (See Scheme 1) A 100-mL round-bottomed flask containing 0.28g l-hcbc- PHEMA-N 3 in 80 ml of DMF was degassed by three freezepump-thaw cycles. Another 500-mL round-bottomed flask charged with DMF (300 ml), PMDETA (0.95 ml, 4.20 mmol), and CuBr (0.60 g, 4.20 mmol) was thoroughly deoxygenated by bubbling with 99.99% nitrogen for 2 h, then it was placed into a preheated 90 C oil bath. Under vigorous magnetic stirring and the protection of nitrogen flow, the l-hcbc-phema-n 3 solution was added dropwise into the CuBr/PMDETA solution via a peristaltic pump at a rate of 1 drop/30 s. After the addition of the polymer solution was finished, the reaction mixture was allowed to stir for additional 7 h. After DMF was removed under reduced pressure, the crude product was dissolved with methanol and purified by an ultrafiltration membrane separator to remove the copper complex. The separated CH 3 OH solution was concentrated to a constant weight and dried overnight under vacuum at 40 C. (M n,gpc ¼ 11,200 g/mol; M w /M n ¼ 1.26). Esterification of c-phema with 2-Bromoisobutyryl Bromide (c-phema-br) (5) (See Scheme 1) In a 10-mL round-bottomed flask, c-phema (0.20g, 1.54 mmol AOH) was added and dissolved in 5-mL anhydrous pyridine. After cooling to 0 C in an ice-water bath, 2-bromoisobutyryl bromide (1.0 ml, 7.70 mmol) was added dropwise to the rapidly stirring solution over 30 mins. The solution was stirred for 1 h at 0 C, and then at room temperature for 24 h. The reaction mixture was precipitated directly in about 100-mL water, and the separated precipitate was dissolved with a small amount THF and reprecipitated in water. The obtained product was dried under vacuum at the presence of P 2 O 5 for 24 h. (M n,nmr ¼ 31,200 g/mol; M n,gpc ¼ 14,600g/mol; M w /M n ¼ 1.26). Synthesis of c-phema-g-ps (6) (See Scheme 1) In a typical procedure to synthesize c-phema 112 -g-ps 44 (112 and 44 represent the DP of HEMA and St monomers), c- PHEMA-Br (50.0 mg, mmol ABr), CuBr (25.7 mg, mmol), bpy (28.0 mg, mmol), and St (3 ml) were introduced into an ampoule and degassed by three freeze-pump-thaw cycles. The ampoule was immersed into oil bath at 90 C under rapidly stirring. The polymerization was processed for 6 h and stopped by putting the ampoule in liquid nitrogen. The reaction mixture was diluted with THF and passed through a column filled with neutral alumina to remove the copper complex. The polymer was precipitated twice in cold methanol and dried under vacuum to a constant weight. (M n,gpc ¼ 54,100 g/mol; M w /M n ¼ 1.21). Cleavage of PS Side Chains from c-phema-g-ps In a typical procedure, g c-phema 112 -g-ps 44 was dissolved in 10 ml of THF, to which 20-mL KOH solution (1 M in ethanol) was added, and the mixture was refluxed for 72 h. After evaporating to dryness, the polymer was dissolved in CH 2 Cl 2 and purified by dissolution/precipitation with methylene chloride/ethanol, the PS homopolymer was dried at 50 Cfor24h.(M n,gpc ¼ 4600 g/mol; M w /M n ¼ 1.23). Synthesis of TEMPO-Poly(ethylene oxide) (TEMPO-PEO) Tempo-PEO was prepared by ring-opening polymerization of EO in THF using DPMK and HTEMPO as coinitiator. HTEMPO (1.78 g, 10.4 mmol) dried by azeotropic distillation with toluene was dissolved in 100-mL THF. The mixture was introduced into a 250-mL ampoule, then DPMK (8.2 ml, 5.20 mmol) and EO (35.0 ml, mol) were injected into the ampoule under nitrogen successively. The reaction was carried out at 50 C for 72 h, then 2-mL methanol was added to terminate the polymerization. After removing the solvent, the mixture was diluted with CH 2 Cl 2 and precipitated into an excessive amount of diethyl ether for three times. The precipitate was dried under vacuum at 40 C, and the pink powder was obtained. (M n,nmr ¼ 2,500 g/mol; M n,gpc ¼ 2,400 g/mol; M w /M n ¼ 1.12.) Synthesis of c-phema-g-(ps-b-peo) by SET-NRC (7) (See Scheme 1) In a typical procedure to synthesize c-phema 112 -g-(ps 44 -b- PEO 55 ) (subscripts 112, 44, and 55 represent the DP of HEMA, St, and EO monomers, respectively), TEMPO-PEO (0.220 g, mmol), Cu (0) (4.96 mg, mmol), PMDETA (18.4 ll, mmol), and THF (4 ml) were introduced into an ampoule. The mixture was degassed by three freeze-pump-thaw cycles, and then the degassed 4-mL THF solution of c-hema 112 -g-ps 44 (0.101 g, mmol ABr) was introduced into the reaction system under stirring. The reaction lasted for 24 h at room temperature, and then it was stopped via exposure to air and dilution with THF. The insoluble Cu (0) was removed by filtration, and the filtrate was diluted with methanol and separated through an ultrafiltration membrane separator to remove the copper complex and excessive TEMPO-PEO. After all the solvents were evaporated, c-phema 112 -g-(ps 33 -b-peo 55 )was obtained. (M n,gpc ¼ 83,700g/mol; M w /M n ¼ 1.20) WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

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