Synthesis of Comb Copolymers with Pendant Chromophore Groups

Synthesis of Comb Copolymers with Pendant Chromophore Groups

(Parte 1 de 3)

Synthesis of Comb Copolymers with Pendant Chromophore Groups Based on RAFT Polymerization and Click Chemistry and Formation of Electron Donor-Acceptor Supramolecules

Xiwen Zhang,† Xueming Lian,† Li Liu,‡ Jian Zhang,† and Hanying Zhao*,†

Key Laboratory of Functional Polymer Materials, Ministry of Education, Department of Chemistry, Institute of Polymer Chemistry, Nankai UniVersity, Tianjin 300071, P. R. China

ReceiVed June 23, 2008; ReVised Manuscript ReceiVed September 8, 2008

ABSTRACT: Comb copolymers comprising hydrophilic poly(ethylene glycol) comb chains and hydrophobic fluorescent pyrenyl groups were synthesized by a combination of reversible addition-fragmentation chain transfer polymerizationand click chemistry.FTIR, 1H NMR, and gel permeationchromatographresultsindicatedsuccessful synthesis of the comb copolymers with well-defined structures. The self-assembly of comb copolymers in aqueous solution was investigated. The comb copolymers with different compositions were able to self-assemble into micellar structure or vesicle structure. The pendant pyrenyl groups on the comb copolymer chains had electron donor-acceptor (EDA) interaction with 4-bromo-N,N′-dimethylaniline (BDMA). Vesicle structure formed by BDMA and comb copolymer via EDA interaction was observed by transmission electron microscopy. The fluorescence properties of the supramolecular structure were studied in detail.

Introduction

To establish architecture-property relationships and to study self-assembly properties either at solid state or in solutions, polymers with different topological structures, for example, linear block, gradient graft, comb-shaped, star-shaped, hyperbranched, and dendritic copolymers, have been synthesized.1,2 In the past decade, controlled/living radical polymerization (C/ LRP) techniques have been used widely in the preparation of (co)polymers with different architectures, predetermined molecular weights, and low molecular weight polydispersities.3 Despite the versatilityof C/LRP techniques,it is still a challenge to find feasible means to introduce functional groups onto polymer chains. These functional polymers, for example, fluorescent groups labeled polymers, biofunctionalized polymers, and drug containing polymers, can find wide applications in chemistry, materials science, and biomedical science fields.4-7 However, because of the possible side reactions and low concentration of functional groups, highly efficient and controllable reactionsare required.Click chemistryis attractivebecause of the moderate reaction conditions conducted in multiple solvents, tolerance to numerous functional groups, high yields, and little or no side reactions.8-10 Therefore, click chemistry is particularly important in chemical synthesis in which high conversion of functional groups is desired. The combination of C/LRP and click chemistry is an efficient way to prepare functional polymeric materials. Some research groups have reportedthe synthesisof polymersbased on atom transferradical polymerization or nitroxide-mediated polymerization and subsequent azide-alkyne coupling reactions.1-15 Among the C/LRP techniques reported to date, reversible additionfragmentation chain transfer (RAFT) polymerization is one of the most versatiletechniquesdue to the facileexperimentalsetup and great potential for scale-up reactions.16,17 Taking advantage of the flexibility of RAFT polymerization and the efficiency and specificity of click chemistry, a variety of functional polymers were prepared.18-27

Because of the importance in various physical, chemical, and biological processes, electron donor-acceptor (EDA) interactions between organic molecular donor and acceptor have been extensively studied.28-3 The previous studies focused on EDA interactions between small molecules,28,29 in solid films,34-36 and in supramolecularstructures.37-40 However,the role of EDA interactions in the self-assembly structures of macromolecules still remains unknown.

It is difficultto conducthomopolymerizationof the monomers with chromophore groups by free radical polymerization due to the steric hindrance of the chromophore groups and the low solubilityof the polymersin ordinarilysolvents.41 It is necessary to find a new way to prepare functional polymers with chromophore groups. Herein we report the preparation of comb copolymers with hydrophilicpoly(ethyleneglycol) comb chains and pendant chromophore groups based on RAFT polymerization and click coupling reaction (Scheme 1). Because of wellknown photochemical properties and the electron or energy transfer abilities, pyrenyl groups were chosen to be introduced onto polymer chains. The grafting of the pyrenyl groups was carried out by copper-mediated cycloaddition [3 + 2] of azido pyrene onto main chain with pendent acetylene groups. Besides synthesis of the comb copolymers, we are also interested in the relationshipbetweenpolymerstructureand fluorescentproperties and the role of EDA interactions in the self-assembly of macromolecules.

Experimental Section

Materials. Poly(ethylene glycol) methyl ether methacrylate

(PEGMA, Aldrich, Mn ) 475) was purified by passing the THF solution of PEGMA through a basic aluminum oxide column and removingTHF under reducedpressure.CuBr (SinopharmChemical Reagent Co., 9.5%) was purified by washing with glacial acetic acid.42 4,4′-Azobis(4-cyanopentanoicacid)(ABCPA,Aldrich,97%) was recrystallized from methanol and dried under vacuum at room temperature. N,N,N′,N′′,N′′-Pentamethyldiethylenetriamine (PM-

DETA,9%),1-pyrenemethanol(98%),sodiumazide(NaN3, 9%), propargyl alcohol (PgOH, 9%), 2-bromoisobutyl bromide (98%),

N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide (EDC, 97%), 4-(dimethylamino)pyridine (DMAP, 9%), and 4-bromo-N,N′- dimethylaniline (BDMA, 97%) were purchased from Aldrich and used as received. Chain transfer agent (CTA) (4-cyanopentanoic acid) dithiobenzoate (CPADB) was prepared by using a method

* To whom correspondence should be addressed: e-mail hyzhao@ nankai.edu.cn, Tel 086-2-23498703.

† Department of Chemistry. ‡ Institute of Polymer Chemistry.

10.1021/ma801405j C: $40.75 2008 American Chemical Society Published on Web 10/14/2008

similar to previous literature.43-45 Propargyl methacrylate (PgMA) monomer was prepared by a reaction of PgOH with methacryloyl chloride in the presence of triethylamine. The CTA (propargyl 4-cyanopentanate) dithiobenzoate (PCPADB) was synthesized by esterfication of PgOH with CPADB (details can be found in the Supporting Information). All the polymerizations were performed in Schlenk flasks under nitrogen. All the solvents were distilled before use.

Synthesis of Pyrene-Br. 1-Pyrenemethanol (1.0 g, 4.3 mmol) was added to a solution of triethylamine (0.90 mL, 6.5 mmol) in 15 mL of anhydrous THF, and 2-bromoisobutylbromide (0.82 mL, 6.5 mmol) was added dropwise under stirring at 0 °C. The reaction was conducted at room temperature overnight. After the reaction, the precipitate was filtered and the solution was washed with HCl solution (1 mol/L), NaOH solution (1 mol/L), and water. The organic layer was dried over MgSO4 and filtered.The crude product was purified by column chromatography (hexane:ethyl acetate, 10:

5.92 (CH2O, 2H), 1.92 (CH3, 6H). 1H NMR spectrum of pyrenyl- Br is shown in Figure S1a. The resonance peak at 1.92 ppm was attributed to the protons on two methyl groups ((CH3)2CBr), which confirmed the successful synthesis of pyrenyl-Br.

Synthesis of Pyrenyl Azide (Pyrenyl-N3). Pyrenyl-Br (0.50 g,

1.3 mmol) and NaN3 (0.1 g, 1.6 mmol) were dissolved in 5 mL of DMF and stirred overnight at room temperature, and the product pyrenyl-N3 was recovered by filtration. The resonance peak at 1.92 ppm (peak Hc in Figure S1a) disappears completely, and a new peak at 1.46 ppm typical for the (CH3)2C-N3 protons can be observed (Hc′ in Figure S1b). The yield is about 95%. RAFT Polymerization of PEGMA. A typical polymerization was described as follows. PEGMA (2.0 mL, 4.6 mmol), ABCPA (5.8 mg, 0.020 mmol), and chain transfer agent CPADB (46.3 mg, 0.17 mmol) were dissolved in 2 mL of DMF in a 10 mL Schlenk flask. The solution was degassed by three freeze-pump-thaw cycles. The polymerization was conducted at 60 °C for 16 h. The polymerization was stopped by quenching the Schlenk flask in ice water. After being concentrated, the polymer was precipitated in cold diethyl ether, and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) with a characteristic pink color was obtained. The viscous polymer was dried under vacuum. The monomer conversion determined by gravimetry is 34%. The poly(poly(ethylene glycol) methyl ether methacrylate) prepared by using PCPADB as chain transfer agent was denominated as a-alkyne-PPEGMA7. The molecular weights and molecular weight distributions were determined by GPC (Table 1).

Synthesis of Poly(poly(ethylene glycol) methacrylate)-block- poly(propargyl methacrylate) (PPEGMAm-b-PPgMAn). PgMA (0.10 g, 0.81 mmol), macromolecular chain transfer agent (macro-

CTA) PPEGMA (0.30 g, 0.075 mmol), and ABCPA (4.2 mg, 0.015 mmol) were dissolved in 3 mL of DMF in a Schlenk flask. The solution was degassed by three freeze-pump-thaw cycles and was stirred at 60 °C for 8 h. The reaction was stopped by quenching the Schlenk flask in ice water. The crude polymer was analyzed by 1H NMR to determine the PgMA monomer conversion (Figure

S5). The comb copolymer prepared by using a-alkyne-PPEGMA7 as macromolecular chain transfer agent was denominated as

Synthesis of Pyrene-BearingComb Copolymers PPEGMAmb-PPyMAn throughHuisgen’s1,3-DipolarCycloadditions.Click reactions between akylyne groups on PPEGMAm-b-PPgMAn and pyrenyl-N3 were performed in DMF. A typical reaction was describedas follows.PEGMAm-b-PgMAn (0.15 g), PMDETA(35.3 µL, 0.014 mmol), and pyrenyl-N3 (0.029 g, 0.084 mmol) were dissolved in 3 mL of anhydrous DMF and were degassed by three freeze-pump-thaw cycles. Upon addition of CuBr (0.002 g, 0.014 mmol) the solutionturnedbrown.After stirringfor 24 h, the solution was passed through a neutral Al2O3 column to remove the copper complex, and then the concentrated crude product was precipitated in diethyl ether. The final product was dried under vacuum.

Characterization. 1H NMR measurements were performed on a Varian UNITY-plus 400 M nuclear magnetic resonance spec-

Scheme 1. Schematic Illustration of a General Approach to the Preparation of Comb Copolymers with Pendant Pyrenyl Groups Based on “Click Chemistry”

Table 1. Summary of Molecular Weights and Molecular Weight Distributions of Macromolecular Chain Transfer Agent Poly(poly(ethylene glycol) methacrylate) (PPEGMA),a,b Poly(poly(ethylene glycol) methacrylate)-block-poly(propargyl methacrylate)

PPEGMAm-b-PPgMAn Comb Copolymer,c and Pyrene-Bearing Block Copolymer PPEGMAm-b-PPyMAn Prepared by Click Reaction between Pyrenyl-N3 and PPEGMAm-b-PPgMAn d a The initiator used in all the reversible addition-fragmentation chain transfer (RAFT) polymerizations is 4,4′-azobis(4-cyanopentanoic acid) (ABCPA). b Conditions: RAFT polymerizations using (4-cyanopentanoic acid) dithiobenzoate (CPADB) as the chain transfer agent (CTA): [PEGMA]:[CPADB]: [ABCPA] ) 60:4:1; RAFT polymerizations using (propargyl 4-cyanopentanate) dithiobenzoate (PCPADB) as CTA: [PEGMA]:[PCPADB]:[ABCPA] )

48:4:1. c Conditions: RAFT polymerizations using PPEGMA13 as macro-CTA: [PgMA]:[PPEGMA13]:[ABCPA] ) 75:5:1. RAFT polymerizations using a-alkyne-PPEGMA7 as macro-CTA: [PgMA]:[ a-alkyne-PPEGMA7]:[ABCPA] ) 60:4:1. d Conditions: click coupling reactions in DMF: [alkyne]:[pyrene- N3]:[CuBr]:[PMDETA] ) 1:1.2:1:1. e Determined by gel permeation chromatograph based on polystyrene standards. f Determined by 1H NMR results.

7864 Zhang et al. Macromolecules, Vol. 41, No. 21, 2008 trometer (field strength, 9.4 T) using CDCl3 (Cambridge Isotope, D 9.8% + TMS 0.03%, CIL) as the solvent at room temperature.

Infraredspectrawere obtainedon a Bio-RadFTS 6000 systemusing diffuse reflectance sampling accessories. The apparent molecular weights and molecular weight distributions of the polymers were determined at 35 °C on a gel permeation chromatograph (GPC) equippedwitha Waters717 autosampler,Waters1525HPLCpump, threeWatersUltraStyragelcolumnswith 5K-600K,500-30K, and 100-10K molecular ranges, and a Waters 2414 refractive index detector. THF was used as eluent at a flow rate of 1.0 mL/min. Polymer solution (150 µL) was injected through Waters Styragel column.The number-averagemolecularweights(Mn) and molecular weight distributions of the polymers were calibrated on polystyrene standards. Ultraviolet-visible absorption spectra were recorded at 25 °C on a Cary 300 UV spectrophotometer using a quartz cell of 1 cm path length. The samples were scanned in the range of 800-200 nm. The scanning speed was set at 200 nm/min. Steadystate fluorescence spectra were recorded on a Varian Cary eclipse fluorescence spectrophotometer (Varian Instruments, Palo Alto, CA). The excitation slits and emission slits were set at 5 nm. Transmission electron microscopy (TEM) images were obtained on a Tecnai G2 20 S-TWIN electron microscope equipped with a Model 794 CCD camera (512 × 512) at an operating voltage of 200 kV. The TEM specimens were prepared by depositing aqueous solutions on Foemvar grids; water was evaporated in air. Before measurements the specimens were stained by RuO4.

Results and Discussion

As shown in Scheme 2, the preparation of PPEGMAm-b-

PPyMAn comb copolymers 9 is based on three-step synthetic strategy: (1) synthesis of pyrenyl-Br(2), pyrenyl azide (pyrenyl-

PPEGMAm-b-PPgMAn (8) by RAFT polymerization of PgMA; (3) click coupling reaction of precursors containing antagonist functionalities. In this paper the comb copolymers bearing pendant acetylene groups and pyrenyl groups were assigned as

PPEGMAm-b-PPgMAn and PPEGMAm-b-PPyMAn, where m, n indicate the repeating unit numbers of the respective blocks.

As shown in Scheme 2, pyrenyl-Br (2) was synthesized by a reaction of 1-pyrenemethanol and 2-bromoisobutyl bromide in anhydrous THF solution with triethylamine. Pyrenyl-Br (2) was reacted with 1.2 equiv of sodium azide in DMF at room temperature overnight. The 1H NMR result confirms that the conversion of the bromide to azide is quantitative (Supporting Information).

RAFT polymerization of PEGMA was conducted at 60 °C in DMF for 16 h. By employing macro-CTA PPEGMA (6),

PgMA was polymerized at 60 °C in DMF to yield PPEGMAm- b-PPgMAn (8) (Scheme 2). The copolymers were precipitated in ether and dried under vacuum. The macro-CTA PPEGMA and PPEGMAm-b-PPgMAn were analyzed by 1H NMR (spectra a and b in Figure 1). For PPEGMA a signal at 4.06 ppm couldbe detected;for PPEGMAm-b-PPgMAn not only the signal at 4.06 ppm but also a signal at 4.62 ppm due to the methylene protons on the ester groups of PgMA (Hb) could be observed. GPC analysis demonstrated high CTA efficiency and well- controlled polymerization (Figure 2). In the curve, the appearance of a small shoulder at high molecularregion might indicate some termination reactions which usually occur when two growing macroradicals combine together instead of undergoing the transfer to the RAFT agent46 or reaction between the alkyne groups of PgMA monomer and radicals during the polymerization.47 The molecular weights and molecular weight distributions of the polymers are summarizedin Table 1. The molecular weights were close to the theoreticalvalues calculatedaccording to the monomer conversions. For the PPEGMA macro-CTA prepared by using PCPADB as a CTA, there is an acetylene group at the end of the polymer chain, which could be used for further click coupling. In order to avoid the steric hindrance and guarantee high grafting efficiency of pyrenyl groups, the degrees of polymerization of the PgMA blocks were controlled at low levels. Pyrenyl groups were grafted onto polymer chains by click

PPgMAn (8) (Scheme 2). The coupling reactions catalyzed by the CuBr/PMDETA complex were conveniently performed in

DMF solution at room temperature. After 24 h of reaction the targetedPPEGMAm-b-PPyMAn combcopolymerswereobtained

(Scheme 2). A slight excess pyrenyl-N3 was used (1.2 equiv) in order to drive the coupling reactions to completion. The excess pyrenyl-N3 was removed by precipitation of the polymer

Scheme 2. Synthesis of Comb Copolymers with Hydrophilic Poly(ethylene glycol) Comb Chains and Pendant Pyrenyl

Groups Based on Reversible Addition-Fragmentation Chain Transfer Polymerization and Click Chemistrya a THF and DMF represent tetrahydrofuran and N,N-dimethylformamide, respectively.

Macromolecules, Vol. 41, No. 21, 2008 Synthesis of Comb Copolymers 7865

in diethyl ether, and the pure polymer was obtained. In this paper three comb copolymersa-pyrenyl-PPEGMA7-b-PPyMA3,

PPEGMA13-b-PPyMA6, and PPEGMA13-b-PPyMA24 were prepared. GPC traces showed clear shifts toward higher molecular weight region after click reaction (Figure 2). Comparing with the starting polymer PPEGMA13-b-PPgMA6, the molecular weight of PPEGMA13-b-PPyMA6 increased from 7.7K to 9.1K after click reaction (Table 1). The reaction was also monitored by 1H NMR spectroscopy (spectrum c in Figure 1). The disappearance of the signal of methylene protons adjacent to the acetylene group (CHCCH2-) at 4.61 ppm and the appearance of the new signal of methylene protons adjacent to the triazole ring at 5.13 ppm (R-CH2-triazole-) were observed (Figure 1). The 1,3-dipolar cycloaddition coupling reaction was also supported by FTIR spectra. Figure 3 shows FTIR spectra

PPyMA6. The absorption peak at 3248 cm-1 on spectrum b is attributed to the vibration of carbon-carbon triple bond.

(Parte 1 de 3)

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