Synthesis of double hydrophilic graft copolymer containing poly(ethylene glycol) and poly(methacrylic acid) side chains via successive ATRP

Synthesis of Double Hydrophilic Graft CopolymerContaining Poly(ethylene glycol) and Poly(methacrylicacid) Side Chains via Successive ATRP

LINA GU, ZHONG SHEN, CHUN FENG, YAOGONG LI, GUOLIN LU, XIAOYU HUANG

Laboratory of Polymer Materials and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of OrganicChemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, People’s Republic of China

Received 17 February 2008; accepted 19 March 2008DOI: 10.1002/pola.22748Published online in Wiley InterScience (www.interscience.wiley.com).

ABSTRACT: A well-defined double hydrophilic graft copolymer, with polyacrylate asbackbone, hydrophilic poly(ethylene glycol) and poly(methacrylic acid) as side chains,was synthesized via successive atom transfer radical polymerization followed by theselective hydrolysis of poly(methoxymethyl methacrylate) side chains. The grafting-through strategy was first used to prepare poly[poly(ethylene glycol) methyl ether ac-rylate] comb copolymer. The obtained comb copolymer was transformed into macroini-tiator by reacting with lithium diisopropylamine and 2-bromopropionyl chloride.Afterwards, grafting-from route was employed for the synthesis of poly[poly(ethyleneglycol) methyl ether acrylate]-g-poly(methoxymethyl methacrylate) amphiphilic graftcopolymer. The molecular weight distribution of this amphiphilic graft copolymer wasnarrow. Poly(methoxymethyl methacrylate) side chains were connected to polyacry-late backbone through stable C��C bonds instead of ester connections. The final prod-uct, poly[poly(ethylene glycol) methyl ether acrylate]-g-poly(methacrylate acid), wasobtained by selective hydrolysis of poly(methoxymethyl methacrylate) side chainsunder mild conditions without affecting the polyacrylate backbone. This doublehydrophilic graft copolymer was found be stimuli-responsive to pH and ionicstrength. VVC 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4056–4069, 2008

Keywords: atom transfer radical polymerization (ATRP); double hydrophilic; graftcopolymers; synthesis

INTRODUCTION

The self-assembly behavior of amphiphilic co-polymers in selective solvents has been exten-sively studied, because of the potential variousapplications of these copolymers in pharmaceu-tics, coating, rheology modifier, colloidal stabili-zation, and template for the preparation ofnanomaterial.1–3 Recently, the aqueous copoly-

mer micellar systems have attracted muchattention due to their environmental friendli-ness and biocompatibility compared with themicelles formed in organic media.4–6 The aque-ous micelles can be formed from amphiphilic co-polymer or double hydrophilic copolymer (DHC)containing different hydrophilic segments. DHCrepresents a new class of amphiphilic copolymer.As the micelles were formed by DHC in aqueousmedia, one hydrophilic segment undergoes phys-ical or chemical transformations and becomeshydrophobic, while another hydrophilic segmentremains soluble in water.7–22 The micellizationof DHC is an almost fully reversible process

Correspondence to: X. Huang (E-mail: [email protected])

Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 46, 4056–4069 (2008)VVC 2008 Wiley Periodicals, Inc.

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which is very sensitive to pH,7–16 tempera-ture,7–9,13,15–18 and/or salinity.8,9 It is clear thatthe smart stimuli-responsibility is the most inter-esting advantage of DHC. The typical hydrophilicsegments used in DHC include poly(acrylicacid),7,8 poly(methacrylic acid) (PMAA),9,10 poly(ethylene glycol),8,9,11–14 poly(N-isopropylacryl-amide),13,16–18 poly(styrene sulfonic acid),19 poly(N-alkylaminoethyl methacrylate),7,14–16 poly(vi-nyl pyridine),9,13 poly(vinyl ethers),20 polyoxazo-line,21 polypeptides, and RNA.11,12,22

Recently, the studies on self-association ofamphiphilic or DHC mainly focused on linearblock copolymers.1–3 The critical micellizationconcentration (cmc), the aggregation number(Nagg), the shape, and the size of the micellesare mainly determined by the external solutionconditions, the composition, and the molecularweights of copolymers.3,23 However, it is discov-ered that the architecture of the copolymer alsoplays an important role for the properties of themicelles. Some researches showed that nonlin-ear block copolymers exhibited fundamentallydifferent micellization properties compared withthe linear copolymers.24–26 Graft copolymerwhich possesses confined and complicated struc-ture can bring additional complexity in the stud-ies on their solution association properties.27,28

More information about controlling the micellarmorphology and the design of new nanomaterialcan be obtained through the studies of the self-assembly behavior.

Generally, three strategies, including graft-ing-through, grafting-onto, and grafting-from,were employed to synthesize the graft copoly-mers.29 The development of atom transfer radi-cal polymerization (ATRP)30–33 and modifiedATRP34–37 has enabled the preparation of versa-tile comb copolymers with well-defined molecu-lar architectures from grafting-through38–40 andgrafting-from strategies.41 Especially, those sidechains can be formed in a well-defined way viaATRP initiated by the pendant initiating groupson the backbone through grafting-from strategy;the living characteristic of ATRP enabled it tocontrol both the molecular weights and molecu-lar weight distributions of side chains.

With the development of living radical poly-merization, researchers can design and conven-iently prepare the new structural graft polymer.Densely graft copolymer is a kind of copolymerwith intriguing structure.42,43 More complexdensely graft copolymers with two hydrophobicdouble-grafted brushes have been reported.44–46

In our previous study,47 we first reported thesynthesis of amphiphilic double-grafted copoly-mer bearing two different kinds of side chainsby successive ATRP using the grafting-throughand grafting-from strategies. But, none hasstudied the double hydrophilic densely graftedcopolymer with two different hydrophilic double-grafted brushes. In many cases, poly(ethyleneglycol) (PEG) was chosen as one hydrophilic seg-ment due to its biocompatibility. PEG segmentcan also complex with monovalence metallic cat-ion.48,49 PMAA was selected as the other hydro-philic segment among the typical hydrophilicpolymers because it is a weak polyelectrolyteand its ionization degree is governed by the pHand the ionic strength of the aqueous solu-tion.9,10

In this work, we report the synthesis of awell-defined densely grafted DHC via ‘‘grafting-from’’ strategy (Scheme 1). Poly[poly(ethyleneglycol) methyl ether acrylate]-g-poly(methoxy-methyl methacrylate) amphiphilic densely graftedcopolymer was synthesized via successive ATRP.Next, poly(methoxymethyl methacrylate) sidechains were selectively hydrolyzed to give thedensely grafted DHC. The aqueous solutionbehaviors of two graft copolymers, before and afterhydrolysis, were characterized under different pHand ionic strength.

EXPERIMENTAL

Materials

Poly(ethylene glycol) methyl ether acrylate(PEGMEA, Mn ¼ 454, Aldrich, 99%) was passedthrough a column filled with basic alumina.Copper (I) bromide (CuBr, Aldrich, 98%) waspurified by stirring overnight with acetic acid atroom temperature, followed by washing the solidwith ethanol, diethyl ether, and acetone prior todrying at 40 8C under vacuum for 1 day. Tris(2-(dimethylamino)ethyl)amine (Me6TREN)50 andmethoxymethyl methacrylate (MOMMA)51 weresynthesized according to previous literatures.Diisopropylamine (Aldrich, 99.5%) was driedover KOH for several days and distilled fromCaH2 under N2 prior to use. N-Phenyl-1-naph-thylamine (PNA, Alfa Aesar, 97%) was purifiedby recrystallization in ethanol for three times.Tetrahydrofuran (THF) was dried over CaH2 for7 days and distilled from sodium and benzophe-none under N2 prior to use. Methyl 2-bromopro-

DOUBLE HYDROPHILIC GRAFT COPOLYMER 4057

Journal of Polymer Science: Part A: Polymer ChemistryDOI 10.1002/pola

pionate (2-MBP, Acros, 99%), 2-bromopropionylchloride (Acros, 99%), n-butyllithium (n-BuLi,Aldrich, 1.6 M in hexane), N,N,N0,N0,N00;-pentame-thyldiethylenetriamine (PMDETA, Aldrich, 99%)and hexamethyltriethylenetetramine (HMTETA,Aldrich, 99%)were used as received.

Measurements

FTIR spectra were recorded on a Nicolet AVA-TAR-360 FTIR spectrophotometer with 4 cm�1

resolution. All 1H NMR and 13C NMR analyseswere performed on a Varian Mercury 300 spec-

trometer (300 MHz) in CDCl3, DMSO-d6, andD2O; TMS (1H-NMR) and CDCl3 (13C-NMR)were used as internal standards. Elementalanalysis was carried out on a Carlo-Erba 1106system. Bromine content was determined by thetitration with Hg(NO3)2. Conversion of MOMMAwas determined by gas chromatography (GC)using a HP 6890 system with an SE-54 column.Relative molecular weights and molecularweight distributions were measured by conven-tional gel permeation chromatography (GPC)system equipped with a Waters 1515 IsocraticHPLC pump, a Waters 2414 refractive index

Scheme 1. Synthesis of double hydrophilic graft copolymer PPEGMEA-g-PMAA.

4058 GU ET AL.


detector, and a set of Waters Styragel columns(HR3, HR4, and HR5, 7.8 3 300 mm). GPCmeasurements were carried out at 35 8C usingTHF as the eluent, with a flow rate of 1.0 mL/min. The system was calibrated with polysty-rene standards. The absolute molecular weightwas determined by GPC equipped with a multi-angle light scattering detector (GPC/MALS).THF was used as the eluent with a flow rate of1.0 mL/min. The detectors used were WyattOptilab rEX refractive index detector and WyattDAWN HELEOS 18-angle light scattering detec-tor with a 50 mW solid-state laser operating at658 nm. Steady-state fluorescent spectra of PNAwere measured on a Hitachi FL-4500 spectro-fluorometer with the band width of 5 nm for ex-citation and emission, and the emission inten-sity at 418 nm was recorded to determine thecmc with a kex ¼ 340 nm. Transmission electronmicroscope (TEM) images were obtained using aPhilips CM120 instrument operated at 80 kV.The hydrodynamic diameter (Dh) was measuredby dynamic laser light scattering (DLS) using aMalvern Nano-ZS90 Zetasizer.

Preparation of PPEGMEA Comb Copolymer

ATRP of PEGMEA was carried out in H2O/THFunder N2. CuBr (0.1722 g, 1.2 mmol) was firstadded to a 25-mL Schlenk flask (flame-driedunder vacuum prior to use) sealed with a rubberseptum for degassing, and kept under N2. Next,PEGMEA (Mn ¼ 454, 10 mL, 24 mmol) andMe6TREN (0.162 mL, 1.2 mmol) were intro-duced via a gas-tight syringe, and the mixturewas then stirred for several minutes. After-wards, the mixed solvent, H2O/THF (vol:vol¼ 10:1, 10.3 mL) which was purged with N2 for10 min and mixed under N2, was added via agastight syringe. Finally, the initiator, 2-MBP(0.134 mL, 1.2 mmol), was charged via a gas-tight syringe. The solution was degassed bythree cycles of freeze–pump–thaw, followed byimmersing the flask into an oil bath set at 40 8Cto start the polymerization. The flask was cooledby liquid nitrogen to terminate the polymeriza-tion after 5 h. THF was added for dilution andthe copper catalyst was removed by filtering thesolution through a short Al2O3 column. Theresulting solution was concentrated and precipi-tated into n-hexane. After repeated purificationby dissolving in THF and precipitating in n-hex-ane for three times, 9.403 g of poly[poly(ethyleneglycol) methyl ether acrylate] was obtained with

a yield of 86.3%. GPC: Mn ¼ 5400, Mw/Mn

¼ 1.09.FTIR (film), m (cm�1): 2869, 1728 (C¼¼O),

1455, 1109 (C��O��C), 952. 1H NMR: d (ppm):0.86 (3H, CH3CH), 1.26, 1.65 (2H, CH2CH), 2.18(1H, COCH(CH3)CH2), 2.22–2.53 (1H, CH2CH),3.39 (3H, OCH3), 3.68 (4H, OCH2CH2O), 3.88(3H, COOCH3), 4.18 (2H, COOCH2CH2O), 4.33(1H, CHBr). 13C NMR: d (ppm): 26.0, 29.7(CH2CH), 35.2, 38.9 (CH2CH), 55.1 (CH2OCH3),59.4–72.6 (OCH2CH2O), 174.0 (COOCH2).

1H NMR was used to determine the conver-sion of PEGMEA according to previous litera-ture.52 The procedure was same as the afore-mentioned polymerization except that the mixedsolvent was changed to D2O/THF (vol:vol¼ 10:1). The result showed that the conversionof PPEGMEA macromonomer was 100% becausethe signal of the double bond of the macromono-mer was not found in 1H NMR spectrum.

Synthesis of Macroinitiator

Dried THF (40mL) and diisopropylamine (1.12 mL,8 mmol) were added to a 500-mL sealed three-neck flask under N2. The solution was cooled to�78 8C and n-BuLi (5 mL, 8 mmol) was addedslowly. After 1 h, the mixture was treated withPPEGMEA 1 (3.632 g, Mn ¼ 5400, Mw/Mn

¼ 1.09) in 160 mL of dried THF under �78 8C.The reaction lasted for 3 h. Next, 2-bromopro-pionyl chloride (0.8 mL, 8 mmol) in 10 mL ofdried THF was introduced. After another 3 h,the reaction was terminated by water. The solu-tion was concentrated and dialyzed in water for1 day. The aqueous solution was extracted byCHCl3 and dried against NaSO4 overnight. Afterfiltration, the solution was concentrated andprecipitated into hexane. The product was driedunder vacuum to give 3.8279 g of PPEGMEA-Brmacroinitiator. GPC: Mn ¼ 5000, Mw/Mn ¼ 1.03.

FTIR (film): m (cm�1): 2871, 1734, 1453, 1351,1105, 951, 855. 1H NMR: d (ppm): 0.86 (3H,CH3CH), 1.26, 1.71 (2H, CH2��CH), 1.90 (3H,CH(CH3)Br), 2.28 (1H, COCH(CH3)CH2), 3.38(3H, ��OCH3), 3.67 (4H, OCH2CH2O), 3.89 (3H,COOCH3), 4.19 (2H, COOCH2CH2O), 4.33(1H, CHBr). 13C NMR: d (ppm): 18.7–21.0(CH(CH3)Br), 26.2–34.0 (CH2 on PPEGMEAbackbone), 41.0, 42.3 (CH on PPEGMEA back-bone), 47.1 (CH(CH3)Br), 52.2 (tert-C on PPEG-MEA backbone), 54.7 (CH2OCH3), 58.6–72.4(OCH2CH2O), 169.7–174.0 (O��C¼¼O), 211.1(C¼¼O). ELEM. ANAL.: C%¼ 50.06%, Br%¼ 10.06%.



Graft Copolymerization of MOMMA

CuBr (0.0718 g, 0.50 mmol) and PPEGMEA-Brmacroinitiator (0.3727 g, Mn ¼ 5000, Mw/Mn

¼ 1.03) in 1 mL of dried THF were added to a25-mL Schlenk flask (flame-dried under vacuumprior to use) sealed with a rubber septum underN2. After three cycles of evacuating and purgingwith N2, MMOMA (22.7 mL, 0.20 mol) and di-phenyl ether (2.3 mL, internal standard of GCmeasurement for the conversion of MMOMA)were charged via a gas-tight syringe. Finally,Me6TREN (0.136 mL, 0.50 mmol) was intro-duced via a gas-tight syringe. The flask wasdegassed by three cycles of freezing–pumping–thawing, followed by immersing the flask intoan oil bath set at 60 8C. The polymerization wasterminated by putting the flask into liquid nitro-gen after 0.5 h. The reaction mixture wasdiluted with THF and passed through an alu-mina column to remove the copper catalyst. Thesolution was concentrated and precipitated intocold ether. The white viscous solid was driedunder vacuum overnight to obtain the finalproduct, 5.315 g of poly[poly(ethylene glycol)methyl ether acrylate]-g-poly(methoxymethylmethacrylate). GPC: Mn ¼ 36,500, Mw/Mn

¼ 1.45. GPC/MALS: Mn,MALS ¼ 43,400.FTIR (film): m (cm�1): 2960, 2833, 1737, 1487,

1394, 1152, 1075, 918. 1H NMR: d (ppm): 0.88,1.02 (3H, CCH3), 1.40–2.20 (2H, CH2 and 1H,CH), 3.41 (3H, OCH2OCH3), 3.50 (4H, OCH2-

CH2O), 5.17 (2H, OCH2O).

Determination of Critical Micelle Concentration

PNA was used as fluorescence probe to measurethe critical micelle concentration (cmc) of PPEG-MEA-g-PMOMMA amphiphilic graft copolymer.The acetone solution of PNA (1 mM) was addedto a large amount of water until the concentra-tion of PNA reached 2 3 10�6 mol/L. Differentamounts of THF solutions of PPEGMEA-g-PMOMMA (1, 0.1, or 0.001 mg/mL) were addedto water containing PNA ([PNA] ¼ 2 3 10�6 mol/L). All fluorescence spectra were recorded at20 8C.

TEM Measurement of PPEGMEA-g-PMOMMA

THF solution of PPEGMEA-g-PMOMMA (0.2 mg/mL) was first filtered through a membrane with anominal pore size of 0.2 mm. Next, 0.25 mL ofdeionized water was added to 1.00 g of THF solu-

tion by a microsyringe and the solution was dia-lyzed against water with slow stirring for 5 days.For TEM measurement, a drop of micellar solu-tion was deposited on an electron microscopycopper grid coated with carbon film.

Selective Hydrolysis of PPEGMEA-g-PMOMMA

PPEGMEA-g-PMOMMA was dissolved in THFand treated with excess 1 M HCl at room tem-perature for 5 h. The reaction mixture was con-centrated and precipitated into dichlorome-thane. After filtration, the white powder wasdried overnight at 40 8C under vacuum to obtainPPEGMEA-g-PMAA double hydrophilic graft co-polymer.

FTIR (film): m (cm�1): 3700–2700 (broad,��COOH), 1705, 1485, 1391, 1266, 1176. 1H NMR:d (ppm): 0.92, 1.02 (3H, CCH3), 1.42–2.1 (2H, CH2

and 1H, CH), 3.50 (4H, OCH2CH2O), 12.38 (1H,COOH).

TEM Measurement of PPEGMEA-g-PMAA

PPEGMEA-g-PMOMMA was dissolved into pH-adjusted or salinity-adjusted water to reach afinal concentration of 1.5 mg/mL. For TEM mea-surement, a drop of aqueous solution was depos-ited on an electron microscopy copper gridcoated with carbon film, and excess solution wasremoved by filter paper after an hour and thesample grid was allowed to dry in air overnight.

RESULTS AND DISCUSSION

Synthesis and Characterization of Macroinitiator

Poly[poly(ethylene glycol) methyl ether acrylate](PPEGMEA 1) comb copolymer was preparedvia ATRP using Me6TREN as ligand; detailedcharacterization can be found from our previousreport.47 The unimodal and symmetrical GPCcurve (Fig. 1) with narrow molecular weight dis-tribution (Mw/Mn ¼ 1.09) evidenced the success-ful ATRP of PPEGMEA macromonomer. Theo-retical molecular weight of PPEGMEA 1 can beestimated from the feed ratio of PEGMEA to 2-MBP (20:1) and the conversion of PEGMEA(100%). The real molecular weight of PPEGMEA1 was calculated to be 9100 from 1H NMR,which is in accordance with the theoreticalvalue. It can be concluded that every PPEGMEA1 polymer chain possesses �20 PEG side chains.

4060 GU ET AL.


In this case, ester groups of the polyacrylatebackbone are used to connect PEG side chains.An alternative method is employed to connectATRP initiation groups to the a-carbon of theester groups by lithium diisopropylamine (LDA)and 2-bromopropionyl chloride. CHBr groups ofATRP initiation groups, ester groups, and CHBrend groups of PPEGMEA 1 are not affected dur-ing the reaction, as witnessed from previousreports.53–55 Thus, all the ATRP initiationgroups were connected to the polyacrylate back-bone through stable C��C bonds instead of esterconnections.

PPEGMEA-Br 2 was characterized by 1HNMR and 13C NMR. A new peak appeared at1.90 ppm, which was attributed to three protonsof newly introduced ��CH(CH3)Br group. But itwas overlapped with the signals of polyacrylatebackbone. No signal of alkene was found in theregion between 4.5 and 7.0 ppm, which meantthe possible elimination reaction of CHBr endgroup did not occur during the reaction. More-over, a new peak at 211.1 ppm, which belongedto the keton carbon of ��COCH(CH3)Br, wasfound in 13C NMR spectrum. All these evidencesconfirmed the successful introduction of ATRPinitiation groups.

The product was further analyzed by elemen-tal analysis besides 1H NMR. The approximategrafted ATRP initiation group density, In%, iscalculated from the elemental analysis result ofcarbon (C%) or bromine (Br%) according to thefollowing equations:

C% ¼ 48:4% 3 In%þ 54:9% 3 ð1� In%Þ ð1Þ

Br% ¼ 80 3 In%=½590 3 In%þ 454 3 ð1� In%Þ�ð2Þ

In eq 1, 48.4% is the carbon content of therepeated units with ATRP initiation group and54.9% is the carbon content of the repeatedunits without ATRP initiation group. Accordingto eq 1, the initiation group density, In%, is cal-culated to be 74.5%. In eq 2, 590 is the molecu-lar weight of the repeated units with ATRP ini-tiation group and 454 is the molecular weight ofthe repeated units without ATRP initiationgroup. So In% is calculated to be 68.9% accord-ing to eq 2. These two results were quite closewith each other, but the first one calculatedfrom the carbon content is more reliable due to

Figure 1. GPC traces of PPEGMEA 1, PPEGMEA-Br 2, and PPEGMEA-g-PMOMMA 3 in THF.



the definition of the analysis method. Therefore,about 20 3 74.5% ¼ 15 ATRP initiation groupswere introduced to the polyacrylate backbone.

Only a unimodal and symmetric peak wasobserved from GPC curve of PPEGMEA-Br 2(Fig. 1); the narrow molecular weight distribu-tion (Mw/Mn ¼ 1.03) meant the architecture ofthe backbone was not altered during the reac-tion with LDA and 2-bromopropionyl chlo-ride.53–55 The Mn of PPEGMEA-Br 2 macroini-tiator (Mn ¼ 5000) was slightly smaller thanthat of PPEGMEA 1 (Mn ¼ 5400), which is simi-lar with our previous studies,53–55 and so we canattribute this to the newly branched ATRP ini-tiation groups.

Synthesis and Characterization ofPPEGMEA-g-PMOMMA

ATRP of MOMMA was performed in bulk toovercome the limitation of the slow reactionspeed which is caused by the high In% (74.5%)of the macroinitiator.56 Different ligands(PMDETA, HMTETA and Me6TREN) weretested at 60 8C to optimize the reaction condi-tion for ATRP of MMOMA. The polymerizationusing PMDETA as ligand was too slow and thepolymerization using HMTETA as ligand wasnot successful. The suitable polymerization con-dition is to use Me6TREN as ligand. The poly-merization result under this condition is listedin Table 1. The molecular weight of the obtainedgraft copolymer was much higher than that ofthe macroinitiator, which indicates the polymer-ization of MOMMA. GPC curve of PPEGMEA-g-PMOMMA 3 graft copolymer (Fig. 1) showed aunimodal and symmetrical GPC curves withnarrow molecular weight distribution (Mw/Mn

¼ 1.45), which is characteristic of ATRP30 andat the same time indicated that intermolecularcoupling reactions could be neglected.56 In thisstudy, high feed ratio of the monomer to the

macroinitiator and a low conversion of themonomer were necessary to suppress the inter-molecular coupling reactions for the synthesis oflinear graft copolymer, as reported in previousworks.29,56–59

The structure of PPEGMEA-g-PMOMMA 3densely grafted copolymer was characterized byFTIR and 1H NMR. Figure 2(A) shows the FTIRspectrum of PPEGMEA-g-PMOMMA3 graft co-polymer. A sharp peak appeared at 918 cm�1,which is attributed to ��OCH2O�� group ofPMOMMA segment. The typical signals of poly-acrylate and PEG segments were found toappear at 1737, 1152, and 1075 cm�1.

1H NMR spectrum of PPEGMEA-g-PMOMMA3 is shown in Figure 3(A). The typical signals ofPMOMMA segment were found to appear at3.41 and 5.17 ppm. The peaks at 3.50 and 3.60ppm are corresponding to the PEG side chains.

Table 1. Synthesis of PPEGMEA-g-PMOMMA Graft Copolymera

Time (h) Mnb (g/mol) Mw/Mn

b Mn,MALSc (g/mol) NMOMMA

d Conv.e (%) cmcf (g/mL)

3 0.5 36,500 1.45 43,400 17.59 27.50 1.63 3 10�6

a Initiated by PPEGMEA 2 (Mn ¼ 5000, Mw/Mn ¼ 1.03, grafted ATRP initiation group density: 0.75/1), [MOMMA]:[Br group]:[CuBr]:[Me6TREN] ¼ 400:1:1:1.

b Measured by GPC in THF.c Obtained by GPC/MALS in THF.d The number of MOMMA repeating unit per PMOMMA side chain determined by GPC/MALS.e Conversion of MOMMA measured by GC.f Critical micelle concentration determined by fluorescence spectroscopy using PNA as probe.

Figure 2. FTIR spectra of PPEGMEA-g-PMOMMA3 (A) and PPEGMEA-g-PMAA 4 (B).

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1H NMR spectrum is the most commonmethod to determine the composition of the co-polymer. But some previous studies showed that1H NMR spectrum of amphiphilic copolymerwas affected by the conditions of the measure-ment.56,60–62 In our recent work, we also foundthat the compositions of amphiphilic denselygrafted copolymers obtained from 1H NMR spec-tra were dependent on the conditions of the mea-surements due to the complex structure.47 Since itwas difficult to determine the ‘‘actual’’ compositionof PPEGMEA-g-PMMOMA 3 by 1H NMR, theabsolute molecular weight of PPEGMEA-g-PMMOMA 3 amphiphilic graft copolymer wasmeasured by GPC/MALS in THF instead.

From the molecular weight of PPEGMEA 1(Mn ¼ 9100) and the absolute molecular weightof PPEGMEA-g-PMMOMA 3 (Mn,MALS ¼ 43,400)

determined by GPC/MALS, the number ofMMOMA repeating units per PS side chain(NMOMMA) was calculated according to eq 3 aslisted in Table 1.

NMMOMA ¼ ðMn;MALS � 9100Þ=ð15 3 130Þ ð3Þ

The obtained graft copolymer, PPEGMEA-g-PMOMMA 3, is a little different with our previ-ous reported centipede-like copolymer since thegraft density of PMOMMA is just 75%, less than100%. Here, we call it as a densely grafted co-polymer with well-defined structure (Scheme 1):a polyacrylate backbone (20 repeating units)with two different side chains, one is short PEG(8.4 repeating units per chain) at each graftingsite and the other is PMOMMA (17.59 repeatingunits per chain) at most grafting sites.

Figure 3. 1H NMR spectra of PPEGMEA-g-PMOMMA 3 (A) and PPEGMEA-g-PMAA 4 (B) in DMSO-d6.



Critical Micelle Concentrationof PPEGMEA-g-PMOMMA

Fluorescence spectroscopy is used to determinethe cmc of PPEGMEA-g-PMOMMA 3 in aqueoussolution with PNA as probe (Fig. 4). Here, PNAis a more suitable fluorescent probe than pyrenein terms of reproducibility since it displayshigher fluorescence activity in nonpolar environ-ments and the fluorescence can be very easilyquenched by polar solvents such as water.63

The cmc of PPEGMEA-g-PMOMMA 3 inNaCl solutions with different concentrationswere also measured. The cmc values are listedin Table 2.

The cmc of PPEGMEA-g-PMOMMA 3 wasalmost constant as the concentration of NaClranged between 0 and 15 mM. It can beexplained1,2 that the interface energy shifting

between PEG and PMOMMA side chains bal-anced with the interface energy shiftingbetween the two kinds of side chains and water,and therefore the cmc kept invariable. When thesalt concentration further increased, the cmcstarted to increase because the interface energyshifting between PEG and PMOMMA sidechains exceeded the interface energy shiftingbetween the two kinds of side chains and water.The cmc increased with ionic strength to com-pensate the loss of interface energy.

Properties of Micelles Formedby PPEGMEA-g-PMOMMA

The micelle structure formed by PPEGMEA-g-PMOMMA 3 was also studied using TEM. Figure5 shows the typical TEM image of micelles ofPPEGMEA-g-PMOMMA 3 amphiphilic graftcopolymer. The aggregates formed by PPEGMEA-g-PMOMMA 3 are large compoundmicelles.

Figure 6(A–D) shows the TEM images of themicelles of PPEGMEA-g-PMOMMA 3 formed inthe solutions with different THF contents. Theamphiphilic graft copolymer formed large com-pound micelles, including coexisted individualsphere or vesicle morphologies [Fig. 6(A)] with a

Figure 4. Dependence of fluorescence intensity ratioof PNA emission band at 418 nm on the concentrationof PPEGMEA-g-PMMOMA 3.

Table 2. Critical Micelle Concentrationsof PPEGMEA-g-PMOMMA 3 with DifferentIonic Strengths

CNaCl (mM) cmca (g/mL)

0 1.6310 1.5215 1.6320 4.5925 5.0730 7.40

a Determined by fluorescence spectroscopy using PNA asprobe at 20 8C.

Figure 5. TEM image of micelles formed by PPEG-MEA-g-PMOMMA 3.

4064 GU ET AL.


high THF content (80%). When THF contentdecreased, large compound micelles includingcoexisted combined spheres or vesicles morphol-ogies were observed in Figure 6(B,C). Finally, itwas found that pearl-necklace micelles appearedwith a lower THF content of 20% as shown inFigure 6(D).

Figure 6(E–H) shows the TEM images of themicelles of PPEGMEA-g-PMOMMA 3 formed inthe solutions with different salt concentrationswhen THF content is 80%. The aggregatesformed by PPEGMEA-g-PMOMMA 3 in thepresence of a low concentration of NaCl (10 mM)were similar with those in the absence of NaClas shown in Figure 6(E). When the concentra-tion of NaCl increased, large compound micellesturned into spheres [Fig. 6(F,G)] and dendriticcoral-like aggregates [Fig. 6(H)].

Hydrolysis of PMOMMA Side Chains

Hydrophobic PMOMMA side chains can be eas-ily hydrolyzed to hydrophilic PMAA side chainsby 1 M HCl with high efficiency. The resultedproduct, PPEGMEA-g-PMAA 4, is water soluble.The presence of the methacrylate acid groupswas confirmed from FTIR analysis [Fig. 2(B)]

because a broad absorbance appeared at 2800–3600 cm�1 after hydrolysis, which is characteris-tic of a carboxylic acid group; meanwhile, thepeak of ��OCH2O�� group at 918 cm�1 disap-peared and the peak of carbonyl shifted from1737 cm�1 to 1705 cm�1. 1H NMR spectrum ofthe graft copolymer after hydrolysis is shown inFigure 3(B). The characteristic strong peaks of��OCH2OCH3 group at 3.41 ppm and 5.17 ppm

Figure 6. TEM images of micelles of PPEGMEA-g-PMOMMA 3 formed with differ-ent THF contents or different NaCl concentrations. With different THF contents: (A)80%, (B) 60%, (C) 40%, and (D) 20%; with different NaCl concentrations of 80% THFcontent: (E) 10 mM, (F) 20 mM, (G) 25 mM, and (H) 30 mM.

Figure 7. Dependence of Dh of PPEGMEA-g-PMAA4 on pH.



completely disappeared, which demonstrates thesuccessful hydrolysis of PMOMMA side chains.The formation of PMAA segment was furtherconfirmed by the new signal at 12.33 ppm.

The hydrolyzed product, PPEGMEA-g-PMAA4, is typically a kind of DHC. With the presenceof carboxylic acid groups in PMAA side chains,the copolymer is predictable to be sensible to pHand ionic strength, and the self-assembly behav-ior of PPEGMEA-g-PMAA 4 is expected to bestimuli-responsive.

Effect of pH on the Self-Assembly Behaviorof PPEGMEA-g-PMAA 4

We used pH-adjusted water to check the solubil-ity of PPEGMEA 1 hydrophilic comb copolymerand PPEGMEA-g-PMAA 4 double hydrophilicgraft copolymer. PPEGMEA 1 was found to becompletely soluble in the whole pH range,whereas PPEGMEA-g-PMAA 4 is only soluble atpH > 4. PPEGMEA-g-PMAA 4 shows poor solu-bility when 4 < pH < 6 and good solubilitywhen pH > 6. This is reasonable because MAAis a kind of weak acid and better soluble underbasis conditions.

DLS and TEM technologies were employed toanalyze the aqueous solutions of PPEGMEA-g-PMAA 4 at different pH values. Figure 7 showsthe influence of pH on the hydrodynamic diame-ter (Dh) of PPEGMEA-g-PMAA 4. Large aggre-gates (Dh > 500 nm) were detected from the

aqueous solution of PPEGMEA-g-PMAA 4 when3 < pH < 7.

It can be explained9 that when pH < 3, thecharge repulsion of carboxylic acid groups madepolyelectrolyte to precipitate or form smallaggregates in aqueous solution; this is also evi-denced from the corresponding TEM imagewhen pH ¼ 2 [Fig. 8(A)], which shows thehybrids of precipitation and small aggregates.When 3 < pH < 7, large micelles with core-shellstructure formed; this can be observed from theTEM image when pH ¼ 5 [Fig. 8(B)]. Finally,the copolymer was easily dissolved in water

Figure 8. TEM images of aggregates formed by PPEGMEA-g-PMAA 4 at differentpHs: (A) pH ¼ 2 and (B) pH ¼ 5; samples were stained by phosphotungstic acid.

Figure 9. Dependence of Dh of PPEGMEA-g-PMAA4 on the concentration of NaCl.

4066 GU ET AL.


when pH > 7 and no precipitation or aggregatecan be observed in the TEM image (pH > 7).

All the above results assured us that PPEG-MEA-g-PMAA 4 double hydrophilic graft copoly-mer is sensitive to pH.

Effect of Ionic Strength on the Self-AssemblyBehavior of PPEGMEA-g-PMAA 4

NaCl was added to the aqueous solutions ofPPEGMEA-g-PMAA 4 when pH ¼ 5.85. Theaqueous solution behavior and morphology ofthe micelle under different ionic strengths werestudied by DLS and TEM. Figure 9 shows thedependence of Dh on the concentration of NaCl.When the concentration of salt was lower than0.5 M, Dh of the copolymer remained constant(185–190 nm). However, Dh of the copolymerdecreased sharply to 152–157 nm while the con-centration of salt was above the critical salt con-centration (0.5 M), which was caused by thedeaggregation process.1,8,9

TEM image [Fig. 10(A)] shows that largesheet-like micelles formed when the concentra-tion of NaCl is 0.3 M (below the critical salt con-centration, 0.5 M). With the increasing of ionicstrength, screening of the hydrogen bondsbetween PEG and water by NaCl has a signifi-cant effect on the water solubility of PEG,8,9

which will lead to the difficulty of forming largemicelles. In this study, small sphere micelles areobserved as shown in Figure 10(B) when theconcentration of NaCl was raised to 0.8 M,which is in accordance with previous report.1

From the results of TEM and DLS, it is clearthat PPEGMEA-g-PMAA 4 double hydrophilicgraft copolymer is sensitive to ionic strength.

CONCLUSIONS

In summary, we have presented the synthesis ofa kind of amphiphilic graft copolymer bearingtwo different side chains by the combination ofATRP and grafting-from strategy. Hydrophobicpoly(methoxymethyl methacrylate) side chainswere connected to the backbone through stableC��C bonds instead of ester connections. Thecritical micelle concentration of amphiphilicgraft copolymer in water was determined byfluorescence spectroscopy using PNA as probeand the morphologies of aggregates were foundto be large complex micelles explored by TEM.

A new double hydrophilic graft copolymerconsisting of two different hydrophilic sidechains can be obtained by selective hydrolysis ofpoly(methoxymethyl methacrylate) side chainsunder mild conditions with high efficiency. Thiskind of double hydrophilic graft copolymer isstimuli-responsive to pH and salinity, asexpected.

This new double hydrophilic graft copolymerhas the potential to be used as the template forpreparing metal/polymer nanocomposite, andfurther work is in progress.

The authors acknowledge the financial support fromthe National Natural Science Foundation of China(20404017), Shanghai Nano-Technology Program

Figure 10. TEM images of aggregates formed by PPEGMEA-g-PMAA 4 with differ-ent concentrations of NaCl: (A) CNaCl ¼ 0.3 M and (B) CNaCl ¼ 0.8 M.



(0652nm031), Shanghai Rising Star Program(07QA14066), and the Knowledge Innovation Programof the Chinese Academy of Sciences.

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Documents

Synthesis of double hydrophilic graft copolymer containing poly(ethylene glycol) and poly(methacrylic acid) side chains via successive ATRP