Preparation of Tadpole-Shaped Amphiphilic Cyclic PS-b-linear PEO

Preparation of Tadpole-Shaped Amphiphilic Cyclic PS-b-linear PEO

(Parte 1 de 3)

Preparation of Tadpole-Shaped Amphiphilic Cyclic PS-b-linear PEO via ATRP and Click Chemistry

Yong-Quan Dong, Yin-Yin Tong, Bo-Tao Dong, Fu-Sheng Du, and Zi-Chen Li*

Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Polymer Chemistry & Physics of Ministry of Education, Department of Polymer Science and Engineering, College of Chemistry and Molecular Engineering, Peking UniVersity, Beijing 100871, China

ReceiVed October 21, 2008; ReVised Manuscript ReceiVed February 2, 2009

ABSTRACT: Amphiphilic tadpole-shaped copolymers consisting of a polystyrene (PS) ring and a poly(ethylene oxide) (PEO) tail were synthesized via atom transfer radical polymerization (ATRP) and click chemistry. First, PEO with a propargyl group and an ATRP initiating group was prepared via click chemistry and esterification. Then, a diblock copolymer, PEO-b-PS, which contained a propargyl group at the junction point and an azide group at the PS chain end, was prepared via ATRP of styrene, followed by transformation of the PS bromo end to an azide group. Finally, cyclization of the PS segment via click chemistry in dilute solution led to the formation of cyclic PS-b-linear PEO (c-PS-b-PEO). Because both the chain length of PEO and the ring size of cyclic PS can be easily tuned, a series of c-PS-b-PEOs was prepared. All of the polymers were characterized with gel permeation chromatography, NMR spectroscopy, FTIR, and matrix-assisted laser desorption time-of-flight mass spectrometry(MALDI-TOFMS). c-PS-b-PEOs showed smallerhydrodynamicvolumescomparedwith their linear precursors.Self-assemblyof one c-PS-b-PEO sampleand its linearprecursorin water was preliminarilyinvestigated by transmission electron microscopy. We found that vesicles were the main morphologies for both polymers, but they were different in size; those from c-PS-b-PEO were much larger.


During the past few years, growing interest has been directed to the synthesis and properties of nonlinear copolymers, includingmiktoarmstar, linear-dendritic,and macrocyclic-based copolymers.1-3 Compared with the corresponding linear analogs, the cyclic polymers exhibit distinct properties, such as different glass-transition temperatures, lower hydrodynamic volume, and reduced viscosity.2 Therefore, the macrocyclicbased homopolymers and copolymers, including cyclic block copolymers and sun-shaped, tadpole-shaped, eight-shaped, and θ-shaped polymers, have continued to attract more attention in the past decade.4-16 However,the propertiesof the macrocyclicbased copolymers, except for those of the cyclic block copolymers,17 have not been well studied experimentally because of the limited availability of such polymers. Therefore, synthesis of well-defined new cyclic polymers is still very important.

The formation of a macrocycleis the key step in the synthesis of macrocyclic-based polymers. Monomer insertion6,12,14,18,19 and cyclization of linear precursors are two well-known approaches20-23 to preparing well-defined cyclic polymers with narrow molecular weight distributions. The first approach is mainly applied to synthesize cyclic polyester and cyclic polyethylene. If a well-defined linear precursor with both R and ω ends is easily accessed, then the second approach can be used for many types of macrocycles with high efficiency. Anionic polymerization coupled to other reactions, such as nucleophilic substitution, metathesis reaction, and amidification, is among the most widely used strategy for preparing these polymers. Limited monomer types and rigorousconditionsfor the preparation of polymer precursors are the main disadvantages of this synthetic method. Recent development in the controlled radical polymerization (CRP), such as atom transfer radical polymerization (ATRP)24 and the reversible addition-fragmentation chain transfer polymerization,25 has made it possible to prepare many kinds of well-defined linear precursors with R,ω ends.

Combined with the click chemistry, a copper-catalyzed 1,3- dipolar cycloadditon reaction,26 CRP has been used to prepare many new macrocyclic polymers.13,16,27,28

The simplestexampleof tadpole-shapedpolymeris composed of one macrocycle connected to one linear polymer chain. If the chemical composition of the macrocycle is different from that of the linear chain, then the tadpole-shaped polymer is considered to be a block copolymer. Although much effort has been devoted to the synthesis of sun-shaped and tadpole-shaped amphiphilic copolymers with more than one tail,1,15 the availability of the simplest amphiphilic tadpole-shaped block copolymers is still very limited. Beinat et al. synthesized cyclic poly(chloroethyl vinyl ether)-b-linear polystyrene (PS) by cyclization of PCEVE segment via intramolecular coupling of the block copolymer precursor.4 Very recently, Shi et al. synthesized cyclic PS-b-linear poly(N-isopropylacrylamide) by combination of click chemistry and RAFT polymerization.13

Poly(ethylene oxide)-b-PS (PEO-b-PS) is a block copolymer with known amphiphilic property and immiscibility of the two blocks.The phasemorphology,29 crystalline,30 and self-assembly of PEO-b-PS in solution or air/water interfaces31-3 have been well studied. Therefore, it is of interest to synthesize cyclic PS- b-linear PEO (c-PS-b-PEO) and compare its properties with those of the linear counterparts.

In this work, we report the synthesis of a new tadpole-shaped amphiphilic block copolymer consisting of one PS ring and one PEO tail. The synthetic strategy is based on two click reactions and one ATRP, as shown in Scheme 1. Both the chain length of the PS ring and the PEO tail of the tadpole block copolymer can be tuned. The preliminary self-assembly of the c-PS-b-PEO in water is presented.

Experimental Section

Materials. Poly(ethylene glycol) monomethyl ether (Mn ) 2000 and 5000, Fluka), propargyl alcohol (98.0%, Shenyang Chemical

Works), R-bromoisobutyrate bromide (98%, Aldrich), CuBr methyl diethylenetriamine (PMDETA, 9%, Aldrich), and NaN3 (98.0%, Zhejiang Dongyangkaiming Chemicals Company) were

* Corresponding author. E-mail: Tel: +86-10-6275- 7155. Fax: +86-10-6275-1708.

10.1021/ma802361h C: $40.75 2009 American Chemical Society Published on Web 03/19/2009

used as received. 2-Aminoethanol (98%, Beijing Yili Chemicals Company) was distilled under vacuum. Triethylamine (9%, Shantou Xilong Chemical Factory) was dried with KOH and distilled just before use. Styrene (98%, Beijing Chemicals Com-

pany) was washed with 2 M NaOH, dried with CaCl2, and distilled over CaH2 under vacuum. Cyclohexanone (9.5%, Beijing Chemicals Company) was distilled over CaH2. N,N-Dimethylformamide

(DMF,9.5%,BeijingChemicalsCompany)was driedwithMgSO4 and distilled under vacuum. Dichloromethane (9.5%, Beijing

TongguangChemicalsCompany),chloroform(9%, Beijing Tongguang Chemicals Company), and tetrahydrofuran (THF, 9.9%, Beijing Chemicals Company) were refluxed individually in the presence of CaH2, followed by distillation. R-Methoxy-ω-azide- poly(ethyleneglycol)(PEO2000-N3 and PEO5000-N3) and acryloyl chloride were synthesized according to literature methods.34,35

Propargyl acrylate was synthesized from propargyl alcohol and acryloyl chloride according to literature method.36

Characterization. Gel permeation chromatography (GPC) was carried out in THF (flow rate: 1 mL/min) at 35 °C with a Waters 1525 binary HPLC pump equipped with a Waters 2414 refractive index detector and three Waters Styragel HR columns (1 × 104,1 × 103, and 500 Å pore sizes). Monodisperse PS standards were used for calibration. 1H NMR (400 or 300 MHz) and 13C NMR (75 MHz) spectra were recorded on a Bruker-400 spectrometer and

Varian-300 spectrometer in CDCl3 with tetramethylsilane as the internal reference for chemical shifts. Matrix-assisted laser desorp- tion ionizationtime-of-flightmass spectrometry(MALDI-TOFMS) was performed on a Bruker Biflex I spectrometer equipped with a 337 nm nitrogenlaser.R-Cyano-4-hydroxycinnamicacid was used as the matrix. Mass spectra were acquired in linear mode at an acceleration voltage of +19 kV. FT-IR spectra were recorded as KBr pellets using a Bruker VECTOR 2 FT-IR spectrometer. PreparativeGPC was performedwith a LC-9201 recyclingpreparative HPLC (Japan Analytical Industry) equipped with a JAIGEL- 2.5H column (600 × 200 mm2). Chloroform was the eluent at a flow rate of 3.5 mL/min.

Synthesis of N,N-Bis(2-propargyloxycarbonyl ethyl)-2-hydroxylethyl amine (BPHA). Propargyl acrylate (27 g, 0.25 mol) was dissolved in a mixture of THF (34 mL) and tert-butanol (38 mL). 2-Aminoethanol(5 g, 0.08 mol) was then addedto the mixture. The mixture was stirred for 24 h at room temperature. Solvent was removed by a rotary evaporator. The product was purified by silica gel chromatography (ethyl acetate/petroleum ether v/v ) 1/6) to

(COCH2CH2), 48.98 (NCH2CH2OH), 32.42 (COCH2CH2). Synthesis of 1. Take the synthesis of 1a as an example.

PEO2000-N3 (3.4g, 1.7 mmol),BPHA(4.8g, 17 mmol),PMDETA (700 µL, 3.5 mmol), and dichloromethane (85 mL) were added to an ampule and subjected to three freeze-pump-thaw cycles. CuBr (0.50 g, 3.5 mmol) was added when the mixture was frozen. The ampule underwent another freeze-pump-thaw cycle and was sealed under vacuum. The reaction was carried out for4ha t room temperature. Then, copper catalyst was removed with a neutral

Al2O3 column. The product (3.5 g) was obtained in 90% yield by precipitation from ethyl ether/petroleum ether (v/v 1/1). Mn,GPC ) 3430, Mw/Mn ) 1.03.

Polymer 1b was synthesized in a similar way, except that

PEO5000-N3 was used as the starting material. Yield: 95%, Mn,GPC

) 60, Mw/Mn ) 1.05. Synthesis of 2. Take the synthesis of 2a as an example. Polymer

1a (3.5 g, 1.1 mmol) and triethylamine (0.20 g, 2.0 mmol) were dissolvedin dichloromethane(30 mL). 2-Bromoisobutyratebromide (2.0 mL, 16 mmol) in dichloromethane (10 mL) was added dropwise to the mixture at 0 °C. The mixture was stirred overnight at room temperature. The precipitated salt was filtered, and the solvent was removed by evaporation. The crude product was dissolved in THF, and the solution was passed through a neutral

Al2O3 column. The polymer (3.3 g) was obtained in 8% yield by precipitation from ethyl ether/petroleum ether (v/v 1/1). Mn,GPC ) 3450, Mw/Mn ) 1.03.

Polymer 2b was synthesized in a similar way with 1b as the starting material. Yield: 79% Mn,GPC ) 6580, Mw/Mn ) 1.04. Synthesis of 3. Take the synthesis of 3a-2 as an example. First,

ATRP of St with 2a as the initiator was conducted. Following the procedure for the synthesis of 1a, polymer 2a (0.30 g, 0.13 mmol),

CuBr2 (1.3 mg, 5.8 µmol), styrene (1.30 g, 0.0130 mol), PMDETA (13.5 µL, 0.0680 mmol), cyclohexanone (0.74 mL), and CuBr (9.0

Scheme 1. Synthesis of Cyclic Polystyrene-b-linear Poly(ethylene oxide) (c-PS-b-PEO)a a (a) tert-Butanol/THF, r.t.; (b) CuBr/PMDETA, dichloromethane, r.t.; (c) 2-bromoisobutyrate bromide, triethylamine, dichloromethane; (d)

Macromolecules, Vol. 42, No. 8, 2009 Tadpole-Shaped Amphiphilic Cyclic PS-b-linear PEO 2941 mg, 0.063 mmol) were sealed in an ampule. After being stirred for 10 min at room temperature to allow the formation of catalyst complex, the ampule was placed in an oil bath preheated to 80 °C; the polymerization was carried out for 9 h at this temperature.

Copper catalyst was removed with a neutral Al2O3 column. The polymer (0.80 g) was obtained in 50% yield after precipitationfrom petroleum ether. Then, the bromine end group of this polymer was transformed to an azide group by reaction with NaN3. The above

polymer was dissolved in 6.0 mL of DMF, and NaN3 (0.16 g, 2.5 mmol) was added. The solution was stirred for 12 h at room temperature. Inorganic salts were removed by passing the reaction solutionthrough an Al2O3 column. After the removal of DMF using a rotary evaporator, the polymer was recovered by precipitation

PMDETA (150 µL, 0.70 mmol), CuBr (0.10 g, 0.70 mmol), and DMF (50 mL) were used to form a catalyst complex solution. The catalystsolutionwas degassedand thermostatedat 80 °C. A solution of 3a-2 (0.40 g, 0.044 mmol) in DMF (40 mL) was degassed with three freeze-pump-thaw cycles, and it was then added to the catalyst solution via a syringe four times (10 mL solution portion) at a time interval of 6 h. After the last addition, the reaction was carried out for 8 h. DMF was removed by a rotary evaporator, and copper catalyst was removed by a neutral Al2O3 column. The polymer was precipitated from petroleum ether and dried under vacuum.The cyclizationproductwas purifiedwith preparativeGPC.

Yield: 72%. Mn,GPC ) 8280, Mw/Mn ) 1.05. Synthesis of other tadpole copolymers was similar to that of 4a-

2. PMDETA (450 µL, 2.1 mmol), CuBr (0.30 g, 2.1 mmol), and DMF (100 mL) were used to form a catalyst complex solution. 4a-1. Diblock copolymer 3a-1 (0.70 g, 0.12 mmol) in 70 mL of DMF, 80 °C, seven times (10 mL each), time interval: 4 h. The product was purified with preparative GPC. Yield: 75%, Mn,GPC )

of DMF, 80 °C, seven times (10 mL each), time interval: 4 h. The product was purified with preparative GPC. Yield: 61%, Mn,GPC )

of DMF, 100 °C, four times (10 mL each), time interval: 8 h. The product was purified with preparative GPC. Yield: 65%, Mn,GPC )

of DMF, 100 °C, six times (10 mL each), time interval: 8 h. The

Self-Assembly of the Tadpole-Shaped Copolymers in Water.

Copolymer (10 mg, 3a-2 or 4a-2) was dissolved in 10 mL of THF, and the solution was stirred at 35 °C for 5 h. Polymer solution (1.0 mg/mL, 2.0 mL) was taken out, and double-distilled water was added to the solution at a rate of 0.3 vol %/min under stirring. In total, 10 mL of water was added. Most of the THF was then evaporated out on an evaporator for 10 h until blue tint became prominent. Residual THF was evaporated under reduced pressure. The final concentration of the aggregate suspension was 0.2 mg/ mL. A droplet of the sample solution was placed on a 400 mesh copper grid covered with Formvar membrane. Most of the liquid was removedby blottingwith a filterpaperafter30 min. The sample was then negatively stained with 2 µL of uranyl acetate solution (2% aqueous solution) for 30 s. The grid was air dried before observation was conducted on a JEOL JEM-100CXII at an acceleration voltage of 100 kV.

Results and Discussion

There are three main strategies for preparing tadpole-shaped block polymers: one is by direct chemical coupling of a functionalized macrocycle and a linear polymer chain; the second is by polymerization with a ring polymer as initiator; and the third is by intramolecular cyclization of a linear diblock polymer precursor. In the third method, tadpole-shaped copolymers can be obtained along with their linear analogs so that the differences between the two can be easily compared. As shown in Scheme 1, our method for preparing c-PS-b-PEO is by cyclization of a linear diblock copolymer, PEO-b-PS, which contains a propargyl group at the junction point of the two blocks and an azide group at the PS chain end. First, PEO containing a propargyl group and a 2-bromoisobutyrate group at the same chain end was synthesized via click chemistry and esterification.Then, linear PEO-b-PS precursor was synthesized via ATRP of styrene,followedby azidationof the formedbromo ends in PS chain with sodium azide. Finally, c-PS-b-PEO was prepared by intramolecular click chemistry under dilute condi- tions. Changing DPn values of azide-terminated PEO and the ATRP conditions of styrene can easily tune the block lengths of the copolymers.

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