两亲性

Amphiphilic ethyl cellulose brush polymers with mono and dual side chains:Facile synthesis,self-assembly,and tunable temperature-pH responsivities

Weizhong Yuan a ,b ,*,Jinchun Zhang a ,Hui Zou a ,Tianxiang Shen a ,Jie Ren a ,b ,*

a Institute of Nano and Bio-polymeric Materials,School of Materials Science and Engineering,Tongji University,Shanghai 201804,People ’s Republic of China b

Key Laboratory of Advanced Civil Materials,Ministry of Education,Shanghai 201804,People ’s Republic of China

a r t i c l e i n f o

Article history:

Received 19October 2011Received in revised form 10December 2011

Accepted 5January 2012

Available online 11January 2012Keywords:

Ethyl cellulose Brush polymers

Tunable temperature-pH responsivities

a b s t r a c t

Novel amphiphilic ethyl cellulose (EC)brush polymers with mono and dual side chains of poly(2-(2-methoxyethoxy)ethyl methacrylate)-co -oligo(ethylene glycol)methacrylate)(P(MEO 2MA-co -OEGMA))and poly(2-(N,N -dimethylamino)ethyl methacrylate)(PDMAEMA)were synthesized by the combination of atom transfer radical polymerization (ATRP)and click chemistry.The molar ratio of P(MEO 2MA-co -OEGMA)and PDMAEMA was varied through changing the feed ratio of these polymers and the coupling ef ?ciency of click chemistry is relatively high.The brush polymers can self-assemble into spherical micelles/aggregates.The micelles/aggregates show the tunable temperature-pH responsive properties.The cloud points and the pH-triggered phase transition were in ?uenced by EC chains and the ratio of P(MEO 2MA-co -OEGMA)and PDMAEMA side chains.The brush polymers have the great potential applications as biomedical or intelligent materials.

ó2012Elsevier Ltd.All rights reserved.

1.Introduction

Considerable attention has been paid to the amphiphilic poly-mers due to the versatile structures of self-assembly and the potential applications in nanotechnology and biomedical ?elds [1e 10].Furthermore,amphiphilic polymers with stimuli-responsive properties have attracted the increasing interest because these intelligent macromolecules can present the capa-bility of responding the external stimuli such as temperature,pH value,light,and ionic strength [11e 16].Among the stimuli-responsive properties,temperature and pH value are considered as the two most important stimuli means because they can be operated easily and have wide applications in drug or gene delivery,smart bioactive surface,and molecular recognition agents [17e 24].

Cellulose is the most abundant and renewable bio-polymeric material in nature and has been widely used in membranes and pharmaceuticals due to the nontoxicity,biocompatibility,and mechanical strength [25e 28].With the increasing demands in various areas such as smart micelles or vesicles,biological gel,and antibacterial surface,it is essential to modify the structure and

enhance the function of cellulose or its derivatives by grafting polymerization [29e 32].The synthesis and self-assembly behavior of amphiphilic cellulose-based brush polymers have attracted much interesting.Yuan et al.prepared the cellulose-graft -poly(2-(N,N -dimethylamino)ethyl methacrylate)(cellulose-g -PDMAEMA)by atom transfer radical polymerization (ATRP)and self-assemble into nano-aggregates with temperature/pH-responsive properties [33].Liu and Huang et al.investigated the synthesis and self-assembly of amphiphilic hydrox-ypropylcellulose (HPC)brush copolymers,including HPC-g -PDMAEMA and HPC-graft -poly(4-vinylpyridine)(HPC-g -P4VP)[32,33].Moreover,the cellulose brush copolymer with block copolymer side chains was also investigated.Malmstr ?m et al.reported the preparation of unimolecular nanocontainers from HPC-graft -poly(ε-caprolactone)-block -poly((acrylic acid))(HPC-g -PCL-b -PAA)by the combination of ring-opening polymerization (ROP)and ATRP [34].In general,the cellulose-based graft polymers are synthesized by “graft from ”method,but the strategy is complicated,especially to prepare the graft copolymers with complex side chains.Therefore,cellulose polymers with mono side chains and simple structure usually synthesized by “graft from ”approach.Huang and Liu et al.reported the synthesis of pH-responsive ethyl cellulose-graft -PDMAEMA (EC-g -PDMAEMA)[35],EC-g -PAA [36],EC-graft -polystyrene (EC-g -PS)[37],and EC-graft -poly(2-hydroxyethyl methacrylate)(EC-g -PHEMA)[38],and EC-graft -poly(ethylene glycol)methyl ether methacrylate (EC-g -

*Corresponding authors.Key Laboratory of Advanced Civil Materials,Ministry of Education,Shanghai 201804,People ’s Republic of China.Tel./fax:t862169580234.

E-mail addresses:yuanwz@https://www.360docs.net/doc/292345093.html, (W.Yuan),renjie@https://www.360docs.net/doc/292345093.html, (J.

Ren).

Contents lists available at SciVerse ScienceDirect

Polymer

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0032-3861/$e see front matter ó2012Elsevier Ltd.All rights reserved.doi:10.1016/j.polymer.2012.01.003

Polymer 53(2012)956e 966

P(PEGMA))[39]by ATRP.Tang et al.reported the synthesis of ethyl cellulose with azobenzene-containing polymethacrylates via ATRP. These EC copolymers contained mono side chains and presented non-adjustable functions[40].The“graft to”method is to link the pre-synthesized macromolecules with clear structure into the polymer main chain easily by coupling reaction.However,new approaches should be introduced to overcome the relatively low graft ef?ciency of the common“graft to”ways.

Click chemistry,termed by Sharpless and coworkers,has been introduced into the synthesis of novel polymeric materials with well-de?ned structures and unique properties due to its high speci?city,quantitative yields,and near-perfect?delity in the presence of most functional groups[41e50].Therefore,it is promising to use click chemistry to facilely synthesize the graft polymers with complex architectures.In our previous work, chitosan graft polymers with complex side chains were synthe-sized easily by click chemistry[51].Matyjaszewski and Gao reported the synthesis of poly(2-hydroxyethyl methacrylate)-graft-poly(ethylene oxide)(PHEMA-g-PEO)molecular brush by the“graft to”method via click chemistry[52].Emrick et al.re-ported the preparation of PEG or peptide-graft aliphatic poly-esters by click chemistry[53].Wang et al.prepared amphiphilic centipede-like brush copolymers with poly(ε-caprolactone)(PCL) and poly(ethyl ethylene phosphate)side segments via click chemistry by one-pot syntheses strategy[54].Obviously,due to the unique properties of click chemistry,the pre-synthesized functional side chains can be grafted to EC main chains and to easily prepare the multifunctional or adjustable functional EC brush copolymers.

The work presented here demonstrates the synthesis of a series of ethyl cellulose(EC)brush polymers with mono and dual side chains,in which poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-oligo(ethylene glycol)methacrylate)(P(MEO2MA-co-OEGMA))and poly(2-(N,N-dimethylamino)ethyl methacrylate)(PDMAEMA)are the homo-and hetero-grafts linked into a EC backbone by click chemistry(Scheme1).

The poly(ethylene glycol)-based copolymers,P(MEO2MA-co-OEGMA),exhibit a critical phase transition temperature in water, which can be?nely tuned between26 C and90 C depending on the ratio of MEO2MA and OEGMA[55e60].Moreover,P(MEO2MA-co-OEGMA)copolymers present good properties,such as water solubility,nontoxicity,biocompatibility,and antimunogenicity [61,62].PDMAEMA,an important hydrophilic polyelectrolyte with antibacterial,hemostatic,and anticancer activity,shows dually responsive properties,namely thermo-and pH-responsivity [63e70].The brush polymers are expected to self-assemble in aqueous solutions to present temperature,temperature-pH,and tunable temperature-pH triggered phase transition behaviors respectively according to the alteration of ratio of P(MEO2MA-co-OEGMA)and PDMAEMA side chains.Such brush polymers have great potential applications as nano-carriers for therapeutic agents or gene and nano-materials for intelligent sensors[71]and nano-reactor[72].

2.Experimental

2.1.Materials

EC(M n?19,000g/mol;the degree of ethyl substitution is2.3) was obtained from Luzhou North Chemical Industry Co.,Ltd.and was dried at120 C for20h under vacuum before use. 2-Bromoisobutyryl bromide(Aldrich,USA),sodium azide(NaN3, Alfa Aesar),and propargyl alcohol(Alfa Aesar)were used as received.N,N,N’,N",N"-pentamethyldiethylenetriamine(PMDETA) (Acros Organic,USA)was stirred overnight with CaH2and distilled under reduced pressure.DMAEMA(Acros Organic,USA)was dried over CaH2and distilled under reduced pressure.MEO2MA and OEGMA(M n?475g/mol)were purchased from Aldrich and passed through a column of activated basic alumina to remove inhibitors. CuCl,CuBr,and2,20-bipyridine(bpy)were recrystallized and dried under vacuum.Propargyl2-bromoisobutyrate(PBIB)was prepared from2-bromoisobutyryl bromide and propargyl alcohol according to the literature[73].

2.2.Characterization

2.2.1.Attenuated Total Internal Re?ectance Fourier Transform Infrared(ATR FT-IR)

ATR FT-IR spectra of samples were recorded on a Hyperion2000 spectrometer(Bruker,Germany).

2.2.2.Nuclear Magnetic Resonance Spectroscopy(NMR)

1H NMR spectra were obtained from a Bruker DMX500NMR spectrometer with CDCl3or DMSO-d6as the solvent.The chemical shifts were relative to tetramethylsilane at d?0ppm for protons.

2.2.

3.Gel Permeation Chromatography(GPC)

The molecular weight and molecular weight distribution were measured on a Viscotek TDA302gel permeation chromatography equipped with two columns(GMHHR-H,M Mixed Bed).THF was used as eluent at a?ow rate of1mL/min at30 C.

2.2.4.Turbidity Measurement

The optical transmittance of the brush polymers micellar solu-tions was monitored as a function of temperature at a?xed wave number of500nm by means of a Lambda35UV e vis spectropho-tometer(Peking-Elmer,USA)equipped with a circulating water bath.The aqueous polymer solution concentration of2mg/mL was used.The cloud point was de?ned as the temperature to10% decrease of optical transmittance.

2.2.5.Dynamic Light Scattering(DLS)

Morphology of the micelles/aggregates of brush polymers in water was investigated using DLS techniques.The experiments were performed on a Malvern Autosizer4700DLS spectrometer. DLS was performed at a scattering angle90 .The R h was obtained by a cumulant analysis.

2.2.6.Transmission Electron Microscopy(TEM)

The morphology of brush polymers micelles/aggregates was observed with a JEOL JEM-2010TEM at an accelerating voltage of 120kV.The samples for TEM observation were prepared by placing 10m L of the brush polymers micelles/aggregates solution on copper grids coated with thin?lms and carbon.

2.3.Synthesis of2-bromoisobutyryl ethyl cellulose(EC-Br)and azide-ethyl cellulose(EC-N3)

The synthetic procedure of EC-Br was as follows.EC(6.08g, 0.32mmol)was dissolved in anhydrous chloroform(80mL)under stirring.To this solution was added triethylamine(3.8g, 37.6mmol)under argon at room temperature.The mixture was stirred and cooled to0 C with ice bath.Then2-bromoisobutyryl bromide(8.65g,37.6mmol)in anhydrous chloroform(20mL) was added dropwise to the mixture within40min the reaction mixture was stirred for30h at room temperature before it was washed with saturated NaHCO3aqueous solution and deionized water.EC-Br was obtained by?ltration and dried in vacuum.Then, EC-Br(4.76g,0.2mmol),NaN3(13g,0.4mmol),and DMF(80mL) were added into a150-mL round-bottom?ask equipped with

W.Yuan et al./Polymer53(2012)956e966957

a magnetic stirrer,and the reaction was carried out at 45 C for 24h.Then the solution was poured into excess deionized water for three times and EC-N 3was obtained after ?ltration and dried in vacuum.

EC-Br:ATR FT-IR (cm à1):2974(n C-H ),2830e 2940(n C-H ),1742(n C ?O ).1H NMR (CDCl 3,d ,ppm): 2.96-4.38(CH and CH 2in EC backbone),1.94(C(CH 3)2Br),1.15(CH 3in EC backbone).

EC-N 3:ATR FT-IR (cm à1):2974(n C-H ),2830e 2940(n C-H ),2110(n azide group ),1748(n C ?O ).1H NMR (CDCl 3,d ,ppm):2.96-4.38(CH and CH 2in EC backbone),1.48(C(CH 3)2N 3),1.15(CH 3in EC backbone).2.4.Synthesis of alkynyl-PDMAEMA

Alkynyl -PDMAEMA was obtained by ATRP of DMAEMA mono-mer using PBIB as initiator.In a typical procedure,PBIB (0.34g,1.66mmol),DMAEMA (10.44g,66.4mmol),PMDETA (288mg,1.66mmol),CuBr (238mg,1.66mmol),and DMF (10mL)were added into a dried reaction ?ask.The reaction system was degassed with three freeze-evacuate-thaw cycles and back ?lled with argon.Then the reaction was performed at 50 C for 6h the crude product was dissolved in THF and passed through a neutral aluminum oxide column to remove the copper catalysts.The polymer was obtained by precipitation into cold hexane and dried in vacuo .

M n,NMR ?5600,M n,GPC ?5400,M w /M n ?1.26.1H NMR (CDCl 3,d ,ppm):4.65(CH ^CCH 2O),4.07(CH 2CH 2N),2.58(CH 2CH 2N),2.48(CH ^CCH 2O), 2.30(N(CH 3)2), 1.76-2.02(CH 2C(CH 3)),0.78-1.11(CH 2C(CH 3)).

2.5.Synthesis of alkynyl-P(MEO 2MA-co-OEGMA)

Alkynyl -P(MEO 2MA-co -OEGMA)was obtained by ATRP of MEO 2MA and OEGMA monomers using PBIB as initiator.In a typical procedure,a dried reaction ?ask with a magnetic stirrer was charged with PBIB (0.328g,1.6mmol),MEO 2MA (9.96g,53mmol),OEGMA (2.19g,4.6mmol),bpy (500mg,3.2mmol),CuCl (158mg,1.6mmol),and DMF (15mL).The ?ask was degassed with three freeze-evacuate-thaw cycles and back ?lled with argon.Then,the polymerization was performed at 60 C for 9h.After being cooled to room temperature,the reaction ?ask was open to air,and the crude product was diluted with ethanol and passed through a neutral alumina oxide column to remove the copper catalysts.Then the ?ltered solution was puri ?ed by dialysis (molecular weight cut-off:3000Da)against water to remove unreacted MEO 2MA and OEGMA.Water was removed by azeotropic distilla-tion with methanol and the puri ?ed alkynyl -P(MEO 2MA-co -OEGMA)was obtained.

M n,NMR ?6800,M n,GPC ?6500,M w /M n ?1.19.1H NMR (CDCl 3,d ,ppm): 4.65(CH ^CCH 2O), 4.09(COOCH 2CH 2O), 3.63(COOCH 2-CH 2O), 3.39(OCH 2CH 2OCH 3), 2.49(CH ^CCH 2O), 1.71-2.01(CH 2C(CH 3)),0.74-1.08(CH 2C(CH 3)).

2.6.Synthesis of EC-(g-P(MEO 2MA-co-OEGMA))-g-PDMAEMA EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA brush polymers were prepared via click chemistry.A typical procedure was

as

Scheme 1.Synthesis of EC brush polymers with mono and dual side chains of P(MEO 2MA-co -OEGMA)and PDMAEMA by the combination of ATRP and click chemistry.

W.Yuan et al./Polymer 53(2012)956e 966

958

follows.EC-N3(0.21g,containing0.2mmol of azide groups), alkynyl-PDMAEMA(0.56g,0.1mmol),and alkynyl-P(MEO2MA-co-OEGMA)(0.68g,0.1mmol)were dissolved in DMF.Then CuBr (29mg,0.2mmol)and PMDETA(35mg,0.2mmol)were added into the above solution.After degassed via three freeze-evacuate-thaw cycles and back?lled with argon,the reaction was carried out at 70 C for48h the result polymers was obtained by dialysis against water to remove unreacted alkynyl-PDMAEMA and alkynyl-P(MEO2MA-co-OEGMA).Water was removed by azeotropic distillation with methanol and the puri?ed EC-(g-P(MEO2MA-co-OEGMA))-g-PDMAEMA was obtained.

ATR FT-IR(cmà1):2762e3002(n C-H),1730(n C?O).1H NMR (CDCl3,d,ppm): 4.10(COOCH2CH2O), 4.08(CH2CH2N), 3.68 (COOCH2CH2O), 3.42(OCH2CH2OCH3), 2.59(CH2CH2N), 2.30 (N(CH3)2), 1.55e2.00(CH2C(CH3)), 1.18(CH3in EC backbone), 0.81e1.11(CH2C(CH3)).

2.7.Preparation of self-assembled micelles/aggregates of brush polymers

Samples for transmittance,TEM and DLS were prepared as follows.Brush polymer(50mg)was dissolved in DMF(10mL)and

subsequently dialyzed against distilled water for72h(molecular weight cut-off:14,000Da).During the dialysis process,the brush polymers self-assembled into micelles/aggregates with EC core and PDMAEMA and(or)P(MEO2MA-co-OEGMA)corona.For different measurements,the micelles/aggregates solutions can be diluted to different concentrations by distilled water and equilibrated at20 C for48h.The micelles/aggregates solutions had a concentration of 2mg/mL for transmittance measurement and1mg/mL for TEM and DLS.

3.Results and discussion

3.1.Preparation of amphiphilic ethyl cellulose brush polymers with mono and dual side chains

Amphiphilic ethyl cellulose brush polymers with mono and dual side chains of PDMAEMA and P(MEO2MA-co-OEGMA)were prepared via the combination of ATRP and click chemistry.In order to adjust the pH/temperature responsivity,the feed ratio of PDMAEMA/P(MEO2MA-co-OEGMA)was varied(mol%/mol%:0/100, 25/75,50/50,75/25,100/0).

EC-Br was obtained by the reaction of the remaining hydroxyl groups of EC with2-bromoisobutyryl bromide under moderate conditions.Fig.1a and b show the ATR FT-IR spectra of EC and EC-Br.

Compared to the spectrum of EC,the intensity of the peak absorption band at3370e3560cmà1corresponding to hydroxyl groups decreased obviously and a new peak at1742cmà1corre-sponding to carbonyl absorption of2-bromoisobutyryl group appeared in Fig.1b.1H NMR spectrum of EC-Br was shown in Fig.2a.The signal at1.94ppm assigned to the methyl protons(c)of 2-bromoisobutyryl group can be observed besides the signals assigned to protons of EC main chains.According to the integral ratio between peaks c and a,it can be calculated that54.8%of hydroxyl groups of EC has been transferred into2-bromoisobutyryl groups.EC-N3was obtained by the reaction of EC-Br with excess NaN3.Fig.1c shows the ATR FT-IR spectrum of EC-N3and the characteristic absorption peak of the azide group at about 2110cmà1can be observed.As shown in Fig.2b,the peak of the methyl protons of2-bromoisobutyryl group shifted to1.48ppm. But according to the integral ratio between peaks c and a(in Fig.2b),it can be calculated that67.4%of Br atoms has been replaced by azide https://www.360docs.net/doc/292345093.html,ly,the number of azide groups in the EC-N3is about26per100glucose units.

Alkynyl-P(MEO2MA-co-OEGMA)was prepared by ATRP of MEO2MA and OEGMA monomers using PBIB as the initiator.The feed molar ratio of MEO2MA and OEGMA is92%/8%.1H NMR spectrum of alkynyl-P(MEO2MA-co-OEGMA)was shown in Fig.3a. All the resonance signals can be attributed to the protons of the alkynyl-terminated polymer.The virtual molar ratio of PMEO2MA and OEGMA calculated from1H NMR analysis by comparing inte-gration areas of peaks f and g(in Fig.3a)is92.2%/7.8%(mol%/mol%). The actual degree of polymerization(DP)was calculated to be from 1H NMR analysis by comparing integration areas of peaks e and b(in Fig.3a).

Alkynyl-PDMAEMA was prepared by ATRP of DMAEMA mono-mer using PBIB as the initiator.1H NMR spectrum of alkynyl-PDMAEMA was shown in Fig.3b.All the resonance signals can be ascribed to the protons of the alkynyl-terminated polymer.The actual DP was calculated to be from1H NMR analysis by comparing integration areas of peaks e and b(in Fig.3b).

The synthesis of amphiphilic EC brush polymers with mono and dual side chains was accomplished via the click reaction of EC-N3, alkynyl-P(MEO2MA-co-OEGMA)and(or)alkynyl-PDMAEMA.

The Fig.1.ATR FT-IR spectra of(a)EC,(b)EC-Br,(c)EC-N3,and(d)EC-(g-P(MEO2MA-co-OEGMA))-g-PDMAEMA(sample

3).

Fig.2.1H NMR spectra of(a)EC-Br and(b)EC-N3.

W.Yuan et al./Polymer53(2012)956e966959

typical ATR FT-IR spectrum of EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA was shown in Fig.1d.After click reaction,the absor-bance peak of azide group disappeared.In addition,an intensive peak at 1730cm à1corresponding to carbonyl absorption of P(MEO 2MA-co -OEGMA)and PDMAEMA segments was observed.From 1H NMR of the EC-based amphiphilic copolymer (Fig.3c),all characteristic signals of P(MEO 2MA-co -OEGMA)and PDMAEMA side chains can be discerned.The virtual ratio of P(MEO 2MA-co -OEGMA)and PDMAEMA can be calculated by comparing the integration areas of peaks f and i (Fig.3c).Moreover,the number-average molecular weight (M n )of the polymer brushes

determined by 1H NMR spectrum and the grafting ef ?ciency through click reaction can be calculated by the integral ratio of peak a (methyl protons in EC backbone)to peaks d and g (d tg)(methylene protons in P(MEO 2MA-co -OEGMA)and PDMAEMA side chains,respectively).As shown in Table 1,the grafting ratios of P(MEO 2MA-co -OEGMA)to PDMAEMA measured by 1H NMR spectra were 0/100,29/71,55/45,76/24,100/0(mol%/mol%)respectively.The coupling ef ?ciency of brush polymers is above 80%,indicating the relatively high ef ?ciency of click chemistry.The GPC traces of alkynyl -P(MEO 2MA-co -OEGMA),alkynyl -PDMAEMA and brush polymer (sample 3)are shown in Fig.4

.

Fig.3.1H NMR spectra of (a)alkynyl -P(MEO 2MA-co -OEGMA),(b)alkynyl -PDMAEMA,and (c)EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA (sample 3).

Table 1

Characterization of polymers.Sample

[alkynyl -PDMAEMA]/[alkynyl -P

(MEO 2MA -co -OEGMA)](mol%/mol%)M n,NMR a M n,GPC b M w /M n b

Coupling

ef ?ciency (%)a

Feed ratio

Actual ratio a

alkynyl -PDMAEMA

e 56005400 1.26e alkynyl -P(MEO 2MA-co -OEGMA)e 68006500 1.19e 10/1000/100149,000138,000 1.4585.1225/7529/71138,000129,000 1.5181.9350/5055/45134,000123,000 1.5382.8475/2576/24126,000118,000 1.5680.65

100/0

100/0

125,000

115,000

1.48

83.6

a The actual ratio,M n,NMR,and coupling ef ?ciency of click chemistry were determined by 1H NMR spectroscopy.b

M n,GPC and M w /M n were determined by GPC analysis with polystyrene standards.THF was used as eluent.

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3.2.Self-assembly behavior and temperature-pH responsivities of brush polymers

As amphiphilic brush polymers,EC-g -P(MEO 2MA-co -OEGMA),EC-g -PDMAEMA,and EC-(g -P(MEO 2MA-co -OEGMA))-g

-PDMAEMA

Fig. 4.GPC curves of alkynyl -P(MEO 2MA-co -OEGMA),alkynyl -PDMAEMA,and EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA (sample

3).

Fig.5.The schematic self-assembly processes of the brush polymers (EC-g -P(MEO 2MA-co -OEGMA),EC-g -PDMAEMA,and EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA)and the photographs of the micelles/aggregates solutions at different temperatures and pH

values.

Fig.6.Temperature dependence of transmittance for the micelles/aggregates solu-tions of sample 1e 5at pH 7.

W.Yuan et al./Polymer 53(2012)956e 966961

can self-assemble into micelles/aggregates.The hydrophilic P(MEO2MA-co-OEGMA)and(or)PDMAEMA side chains are mainly in the corona of the micelles/aggregates,whereas the hydrophobic backbone of EC is mainly in the core of the micelles/aggregates. Fig.5shows the schematic reversible transformation process of micelles/aggregates and the micelles/aggregates solutions photo-graphs at different temperatures and pH values.P(MEO2MA-co-OEGMA)is temperature-responsive polymer and has a critical phase transition temperature in water.But PDMAEMA is dually responsive(temperature and pH)polymer and has a phase transi-tion temperature in water and a pH-triggered phase transition point.In this work,the cloud point of P(MEO2MA-co-OEGMA) was designed lower than that of PDMAEMA segments.Therefore,EC-(g-P(MEO2MA-co-OEGMA))-g-PDMAEMA micelles/aggregates was expected to present unique temperature-pH responsivities. The micelles/aggregates solution of EC-g-P(MEO2MA-co-OEGMA)is transparent at low temperature(such as25 C)but became turbid when the temperature is higher than the cloud point(such as 45 C).Under the cloud point,the P(MEO2MA-co-OEGMA)chains are hydrophilic and the micelles/aggregates are stable,but above the cloud point,the hydrogen bonds of ether oxygen between P(MEO2MA-co-OEGMA)chains and the water molecules are broken,P(MEO2MA-co-OEGMA)chains collapse and become hydrophobic.As for EC-g-PDMAEMA micelles/aggregates solution, at low temperature(such as25 C),the micelles/aggregates are very stable,therefore the solution is transparent.When the

micelles/ Fig.7.Temperature dependence of hydrodynamic radium(R h)for the micelles/aggregates of sample1e5at pH7.

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962

aggregates solution is heated to the temperature higher than the cloud point (such as 75 C)or changes from neutral to basic condition (such as pH 12),the hydrophilic PDMAEMA chains become hydrophobic.

The hydrogen-bonding interaction of water molecules and N,N -dimethylaminoethyl groups are destroyed at high temperature and the conformation of PDMAEMA chains changes from an expanding shape to a compact coil.Moreover,at acidic and neutral conditions,N,N -dimethylaminoethyl groups are protonated and the PDMAEMA chains are quasi-completely charged (pKa of PDMAEMA is about 7.5).When the pH value increases,PDMAEMA chains are depronoated and transform to hydrophobic.Therefore,the micelles/aggregates solution presents turbidity.For EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA,the brush polymer presents various self-assembly behaviors due to its unique struc-ture.At low temperature (such as 25 C),the micelles/aggregates with EC core and P(MEO 2MA-co -OEGMA)/PDMAEMA corona are stable,and the micelles/aggregates solution is transparent.When the temperature increases above the cloud point of P(MEO 2MA-co -OEGMA)(such as 45 C),the P(MEO 2MA-co -OEGMA)segments become hydrophobic and the micelles/aggregates are composed of EC/P(MEO 2MA-co -OEGMA)core and PDMAEMA corona.So the micelles/aggregates are still stable and the solution is transparent.After the temperature increases above the cloud point of PDMAEMA segments (such as 75 C),the PDMAEMA chains transform to hydrophobic and the micelles/aggregates tend to aggregate into aggregates.The solution becomes turbid.In addi-tion,when pH value increases (such as pH 12),PDMAEMA segments become hydrophobic.The micelles/aggregates are made up of EC/PDMAEMA core and P(MEO 2MA-co -OEGMA)corona and still remain stable.The transparent solution can be observed.Fig.6shows the transmittance curves of EC-g -P(MEO 2MA-co -OEGMA)(sample 1),EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA (sample 2e 4),and EC-g -PDMAEMA (sample 5)micelles/aggregates solutions.

It can be seen that the transmittance curves show sharp tran-sition during heating process.The cloud point of sample 1is about 37.4 C.Moreover,the cloud point values of samples 2e 5are 44.6 C,52.1 C,56.9 C,and 62.1 C respectively.Obviously,the presence of PDMAEMA side chains can enhance the temperatures of phase transition and the cloud point values increase with the increase of PDMAEMA content in the brush polymers.Fig.7shows the plots of the hydrodynamic radius (R h )of samples 1e 5in water as a function of temperature.

For EC-g -P(MEO 2MA-co -OEGMA)(sample 1),in the lower temperature ranges,the R h values are relatively small and change slightly.In contrast,the values increased drastically in the higher temperature ranges.At low temperatures,EC-g -P(MEO 2MA-co -OEGMA)segments exist in random coil conformation owing to the hydrogen-bonding interaction between P(MEO 2MA-co -OEGMA)and water molecules.When the temperature increases above the cloud point,polymer chains shrink into a globular structure due to the break of the hydrogen bonds.Therefore,the chains collapsed and became https://www.360docs.net/doc/292345093.html,ly,at elevated temperature,P(MEO 2MA-co -OEGMA)chains within the micelles/aggregates get insoluble,and this breaks the hydrophilic/hydrophobic balances of originally formed micelles/aggregates at lower temperatures.Therefore,the intermolecular hydrophobic attractions are ther-modynamically favored and the micelles/aggregates aggregate occurred,which results in the increase of the

micelles/aggregates

Fig.8.pH dependence of hydrodynamic radium (R h )for the micelles/aggregates of sample 2e 5at 25 C.

W.Yuan et al./Polymer 53(2012)956e 966963

Fig.9.TEM images of EC-g -P(MEO 2MA-co -OEGMA)(sample 1)micelles/aggregates at (a)25 C and (b)45 C;EC-(g -P(MEO 2MA-co -OEGMA))-g -PDMAEMA)(sample 3)micelles/aggregates at (c)25 C and (d)60 C;EC-g -PDMAEMA (sample 5)micelles/aggregates at (e)25 C and (f)70 C;sample 3micelles/aggregates at (f)pH 2and (g)pH 9;sample 5micelles/aggregates at (h)pH 2and (i)pH 9.

W.Yuan et al./Polymer 53(2012)956e 966

964

size.For sample2,the temperature at that the R h increased dras-tically is higher than that of sample1due to the presence of some PDMAEMA side chains in the polymer.As for sample3,owing to the close molar content of P(MEO2MA-co-OEGMA)and PDMAEMA, the R h of micelles/aggregates increased to some degree at the temperatures higher than40 C.In this temperature ranges,the P(MEO2MA-co-OEGMA)side chains changed into hydrophobic polymers,so the stability of the micelles/aggregates decreased and the micelles/aggregates tend to aggregate into larger aggregates. When the temperature continually increased to higher tempera-ture,the P(MEO2MA-co-OEGMA)and PDMAEMA side chains all became hydrophobic,the aggregates further aggregated into bigger particles.For sample4(the content of PDMAEMA is much higher than that of P(MEO2MA-co-OEGMA))and EC-g-PDMAEMA(sample 5),the change tendency of R h values of the micelles/aggregates is similar to that of sample1except the temperature at that the R h increased drastically is much higher than that of sample1.Because the cloud point of PDMAEMA is higher than that of P(MEO2MA-co-OEGMA),the micelles/aggregates shrunk and began to aggregate into aggregates with larger size at higher temperature than the micelles/aggregates of EC-g-P(MEO2MA-co-OEGMA).Obviously, due to the different cloud point values,the brush polymers micelles/aggregates show tunable change of size according to the change of the ratio of P(MEO2MA-co-OEGMA)and PDMAEMA side chains in the polymers.Fig.8shows the plots of the R h of samples 2e5in water as a function of pH value.For sample2,the micelles/ aggregates size did not have the obvious change at different pH conditions because the content of pH non-responsive P(MEO2MA-co-OEGMA)segments is much higher than that of pH-responsive PDMAEMA segments in the brush polymer.For samples3and4, the R h of micelles/aggregates obviously decreased from acidic to basic solutions.In these two brush polymers,the content of PDMAEMA segments is higher than that of P(MEO2MA-co-OEGMA) segments,so the conformational change of PDMAEMA chains has the comparatively obvious effect on the size of the micelles/ aggregates.At acidic solutions,PDMAEMA chains were protonated and presented expanding conformation.At basic solutions, PDMAEMA chains were deprotonated and presented compact conformation.Therefore,the micelles/aggregates shrunk to some extent.For example,the R h values of sample3decreased from about107nm at pH2to about76nm at pH10.The polymer brushes of sample5are PDMAEMA segments,so the change of the micelles/ aggregates size is the largest in all the four samples.Because at basic solutions,all the PDMAEMA side chains of brush polymer became hydrophobic after deprotonation.At pH2,the R h of micelles/aggregates is about127nm,but at pH10,the R h decreased to about56nm.As a comparison,EC-g-PDMAEMA-g-PCL amphi-philic brush copolymer prepared by the combination of ROP and ATRP present complicated synthesis process and the multi-responsive properties(such as tunable temperature-pH responses)could be obtained.In addition,it is dif?cult to control the molecular weight and molecular weight distribution of the side chains in the brush copolymer[74].Similarly,EC-g-P(PEGMA) prepared by ATRP could not present tunable thermosensitivity under the current structure[39].

TEM images of the micelles/aggregates at different temperature and pH values are shown in Fig.9.Fig.9a and b are the micelles/ aggregates images of EC-g-P(MEO2MA-co-OEGMA)(sample1)at 25 C and45 C,respectively.It can be seen that the spherical micelles/aggregates forming at low temperature deformed and aggregated at the temperatures higher than the cloud point of sample1.Fig.9c and d are the micelles/aggregates images of EC-(g-P(MEO2MA-co-OEGMA))-g-PDMAEMA(sample3)at25 C and60 https://www.360docs.net/doc/292345093.html,pared to the micelles/aggregates at25 C,the morphology of micelles/aggregates deformed and the serious aggregation occurred at the temperature higher than the cloud point.Fig.9e and f are the micelles/aggregates images of EC-(g-P(MEO2MA-co-OEGMA))-g-PDMAEMA(sample3)at pH2and pH9,respectively.The spherical micelles/aggregates can be observed at two images,but the micelles/aggregates size at basic condition was smaller than that at acidic solution.Fig.9g and h are the images of EC-g-PDMAEMA(sample5)at25 C and70 C.At high temperature,the micelles/aggregates were instable and aggregated into large aggregates.Fig.9i and j are the images of sample5at pH2and pH9.At basic solution,the micelles/aggre-gates shrank and the size decreased comparing to the micelles/ aggregates at acidic condition.In addition,the micelles/aggregates presented in the TEM images were found to aggregate and adhere to each other.During the process of preparing samples for TEM measurements,the water evaporation may also lead to the collapse, shrinkage,and aggregate of the micelles/aggregates.But the change of the micelles/aggregates sizes can be observed at different conditions.The TEM images were in accordance with the results of the transmittance and DLS.The tunable temperature-pH respon-sivities of the micelles/aggregates self-assembled from EC brush polymers can be accomplished through adjusting the ratio of temperature responsive P(MEO2MA-co-OEGMA)and temperature-pH dually responsive PDMAEMA side chains in the brush polymers.

4.Conclusions

Amphiphilic EC brush polymers with mono and dual side chains of P(MEO2MA-co-OEGMA)and PDMAEMA were easily prepared by the combination of ATRP and click chemistry.The graft ratio of these two side chains can be adjusted via the alteration of the feed ratio of alkynyl-P(MEO2MA-co-OEGMA)and alkynyl-PDMAEMA due to the unique properties of click reaction.These brush poly-mers can self-assemble into micelles/aggregates with various conformations.The self-assembly behavior and tunable temperature-pH responsive properties of EC brush polymers were investigated by transmittance,DLS,and TEM.Investigations show that the cloud points,pH-triggered phase transition and the adjustment of micelles/aggregates size of EC brush polymer micelles/aggregates solutions were in?uenced by the EC chains and the ratio of temperature responsive P(MEO2MA-co-OEGMA)and temperature-pH dual responsive PDMAEMA side chains.The EC brush polymers with tunable temperature-pH responsivities have the potential applications in the biomedical and smart materials. Acknowledgements

The authors gratefully acknowledge the?nancial support of the National Natural Science Foundation of China(no.20804029). References

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