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Polymer 55 (2014) 3925e3935

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Polymer

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Poly(ε-caprolactone)-block-poly(N-vinyl pyrrolidone) diblockcopolymers grafted from macrocyclic oligomeric silsesquioxane

Yulin Yi, Lei Li, Sixun Zheng*

Department of Polymer Science and Engineering and the State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University,Shanghai 200240, China

a r t i c l e i n f o

Article history:Received 15 April 2014Received in revised form17 June 2014Accepted 27 June 2014Available online 4 July 2014

Keywords:Diblock copolymerSilsesquioxaneMolecular brushes

* Corresponding author. Tel.: þ86 21 54743278; faxE-mail addresses: Zheng.Sixun@gmail.com, szheng

http://dx.doi.org/10.1016/j.polymer.2014.06.0830032-3861/© 2014 Elsevier Ltd. All rights reserved.

a b s t r a c t

Poly(ε-caprolactone)-block-poly(N-vinyl pyrrolidone) diblock copolymers grafted from macrocyclicoligomeric silsesquioxane (MOSS) (denoted MOSS[PCL-b-PVPy]12) were synthesized via the sequentialpolymerizations involving ring-opening polymerization (ROP) of ε-caprolactone (CL) and RAFT/MADIXpolymerization of N-vinyl pyrrolidone (NVP). The organic-inorganic brush-like diblock copolymers werecharacterized by means of nuclear magnetic resonance spectroscopy (NMR) and gel permeation chro-matography (GPC). Small angle X-ray scattering (SAXS) showed that all the MOSS[PCL-b-PVPy]12 wasmicrophase-separated in the amorphous state. The microphase-separated morphologies were quitedependent on the length of PVPy blocks and the crystallization behavior of PCL subchains was signifi-cantly affected by the lengths of PVPy subchains. In aqueous solutions, the MOSS[PCL-b-PVPy]12 can beself-assembled into the polymeric micelles as evidenced by dynamic light scattering (DLS) and trans-mission election microscopy (TEM). The critical micelle concentrations of the brush-like diblock co-polymers increased with increasing the lengths of PVPy blocks. It is proposed that the stability of themicellar cores was increased with the macrocyclic molecular brush structure of the diblock copolymersand the formation of the MOSS aggregates via MOSSeMOSS interactions.

© 2014 Elsevier Ltd. All rights reserved.

1. Introduction

Amphiphilic block polymers can self-assemble into polymericmicelles in aqueous solutions with the aggregates of hydrophobicblocks as the core and the hydrophilic blocks as the coronas.Ringsdorf et al. [1e3] first reported the utilization of polymericmicelles to encapsulate therapeutic agents. It was proposed thatthe hydrophobic cores can accommodate hydrophobic drugs andallow delivery in a controlled manner and the hydrophilic coronascan provide good stability and compatibility for the micelles in abloodstream. The design of polymeric micelles must meet severalstringent criteria for success [4e7]. Of them, the elimination withease from organism via degradation or dissolution is required forthe materials of the polymeric micelles. As the carrier of drugs, thepolymeric micelles must possess good stability so that no drugcargo release takes place before the drug reaches the target cells[7]. The preparation of biocompatible and biodegradable polymericmicelles with hydrophobic core and hydrophilic coronas is highly

: þ86 21 54741297.@sjtu.edu.cn (S. Zheng).

desired. Poly(N-vinyl pyrrolidone) (PVPy) is one of importantwater-soluble polymers; it has found wide applications in phar-maceutical and biomedical fields owing to its biocompatibility, lowtoxicity and antibiofouling properties [8]. Poly(ε-caprolactone)(PCL) has been widely used owing to its biodegradability, biocom-patibility and affinity with hydrophobic drugs [9]. Therefore,amphiphilic block copolymer micelles based on PVPy and PCL areattractive. In the past years, there have been a few of reports on thesynthesis and micellar characterization of the binary block co-polymers composed of PVPy and PCL. Lele et al. [10] first reportedthe synthesis and micellar characterization of PVPy-b-PCL-b-PVPytriblock copolymers via conventional radical polymerization of NVPin the presence of a, u-dithiol-terminated PCL. Chung et al. [11] andBartolozzi et al. [12] respectively reported the synthesis of PCL-b-PVPy diblock copolymers via the combination of conventionalradical polymerization of NVP with the different chain transferagents and the ring-opening polymerization (ROP) of ε-capro-lactone (CL). Levia et al. [13] investigated the self-assemblybehavior of a tri-armed star copolymer containing a PCL midblockand three PVPy arms. In the star-like block copolymer, the PVPyblocks were obtained via conventional radical polymerization.More recently, it was reported that the block copolymers were

Y. Yi et al. / Polymer 55 (2014) 3925e39353926

synthesized via the combination of living radical polymerizations(e.g., ATRP and RAFT) of NVP and ROP of CL. For instance, Jeon et al.[14] synthesized well-defined PVPy-b-PCL diblock copolymers viathe combination of cobalt-mediated controlled radical polymeri-zation of NVP and ROP of CL. Mishra and Ray et al. [15] reported thecontrolled synthesis of well-defined PVPy-b-PCL diblock copolymerby combining RAFT/MADIX polymerization of NVP and ROP of CL.More recently, Kang et al. [16] reported a one-pot synthesis ofPVPy-b-PCL block copolymers using a dual initiator for RAFTpolymerization of NVP and ROP of CL.

Macrocyclic molecular brushes are a class of interesting as-semblies in which multiple side chains are connected onto a cyclicbackbone. In 1985, Lehn et al. [17] first reported the synthesis of N-substituted crown ether with long dodecy chains. This cyclic mo-lecular brush was capable of displaying a liquid crystal phase inwhich the macrocyclic units were stacked, forming a tubular mes-ophase. In the past years, a variety of cyclic molecular brushes havebeen synthesized and their structure and properties were exten-sively investigated [18e22]. For instance, Fernadez-Lopez et al. [23]reported the synthesis of a medium-sized cyclic polypeptide graf-ted by long chains; the cyclic molecular brushes showed the po-tential applications in ion transport across membrane since theycan self-assemble into the structure of nanotubes via the stacking ofcyclic polypeptides. Recently, there has been ample literature toreport the preparation of macrocyclic molecular brushes withpolymers side chains to afford versatile properties [24e29].Macrocyclic oligomeric silsesquioxanes (MOSS) are a class ofinteresting organometallic molecules with stereoregular and rigidmacrocyclic nanostructures. Owing to the elemental and structuralfeatures, MOSS will be employed as a category of importantbuilding blocks for inorganic-organic hybrids [30e33]. In a previ-ous work [30], we reported the synthesis and characterization of a24-membered MOSS and the macrocyclic molecular brushes withMOSS backbone and with poly(ε-caprolactone) side chains. It is ofinterest to synthesize the macrocyclic molecular brushes withMOSS backbone and PCL-b-PVPy diblock copolymer side chains.

In this work, we firstly explored to synthesize the macrocyclicmolecular brush with MOSS backbone and with PCL-b-PVPydiblock copolymer side chains via the combination of ROP andRAFT/MADIX process. The MOSS macromer used in this work is a24-membered macrocyclic silsesquioxane containing twelve SiO3=2structural units in the backbone. The PCL-b-PVPy diblock copol-ymer chains grafted onto this MOSS (denoted MOSS[PCL-b-PVPy]12) would exhibit the self-assembly behavior in aqueous so-lutions which was quite different from their linear counterparts.Compared to linear PCL-b-PVPy diblock copolymers, the stability ofthe hydrophobic cores of MOSS[PCL-b-PVPy]12 micelles in aqueoussolutions would be increased owing to: i) the formation of thecovalent bonds between PCL ends and MOSS backbone and ii) theincrease in the hydrophobicity of the micellar cores via the intro-duction of the organosilicon component (viz. MOSS). The macro-cyclic molecular brushes were characterized by means of smallangle X-ray scattering (SAXS) and differential scanning calorimetry(DSC). Thereafter, the micellar behavior of the organic-inorganicmolecular brushes was investigated in terms of the measurementof critical micelle concentration (CMC), transmission electron mi-croscopy (TEM) and dynamic laser scattering (DLS).

2. Experimental

2.1. Materials

Organic silanes such as vinyltrimethoxylsilane and trimethyl-chlorosilane were purchased from Shanghai Reagent Co, China andused as received. Anhydrous copper (II) chloride was obtained from

Ruanshi Chemical Co., Jiangsu, China. Sodium hydroxide (NaOH),pyridine, b-mercaptoethanol were purchased from Shanghai Re-agent Co., China. Dodeca[trimethylsiloxyl(2-hydroxyethyl thio-ethyldimethylsiloxy)] cyclododecasiloxane (MOSS[CH2CH2SCH2CH2OH]12) was synthesized as reported previously [30]. It was re-ported that twelve ligands bonded onto the macrocyclic silses-quioxane backbone displayed a tris-cis-tris-trans configuration,constituting a saddle conformation [34,35]. All the organic solventssuch as anhydrous ethanol, butyl alcohol and toluene were ob-tained from commercial sources. Before use, toluene and pyridinewere distilled over calcium hydride (CaH2) and then stored in asealed vessel with the molecular sieve of 4Å. ε-Caprolactone (CL)was purchased from Fluka Co. Germany and it was distilled overCaH2 under decreased pressure prior to use. Stannous (II) octanoate[Sn(Oct)2] was of analytically pure grade, purchased from ShanghaiReagent Co., China.

2.2. Synthesis of organic-inorganic molecular brush with PCL sidechains

WithMOSS[CH2CH2SCH2CH2OH]12 as themacroinitiator, the ring-opening polymerization (ROP) of ε-caprolactone (CL) was performedto affordMOSS[PCL-OH]12 brushes. Typically, to aflask equippedwitha magnetic stirrer, MOSS[CH2CH2SCH2CH2OH]12 (0.10 g, 0.42 mmolwith respect of hydroxyl groups) and anhydrous toluene (15.0 mL)were charged; the system was dried via azotropic distillation toremove the trace ofmoisture. Cooled to room temperature, CL (3.20 g,28.1 mmol) and Sn(Oct)2 dissolved in anhydrous toluene (0.1 wt%with respect of CL) were added. The reactive mixture was degassedvia three pumpethawefreeze cycles and then immersed in a ther-mostated oil bath at 120 �C for 24 h. The crude product was dissolvedwith tetrahydrofuran and then precipitated with a great amount ofpetroleum ether. This procedure was repeated three times to purifythe sample. The precipitates were filtered and dried in vacuo at 30 �Cfor 24 h to give the polymer (3.08 g) with the yield of 93.1%. 1H NMR:4.07 ~ 4.04 [121H, OCO(CH2)4CH2], 3.65 (2H, CH2OH), 2.32 ~ 2.28[121H, OCOCH2(CH2)4], 1.68 ~ 1.60 (243H, OCOCH2CH2CH2CH2CH2),1.41 ~ 1.34 (121H, OCOCH2CH2CH2CH2CH2), 0.15 [9H, Si(CH3)3]. GPC:Mn ¼ 81,100,Mw/Mn ¼ 1.40.

2.3. Synthesis of MOSS[PCLeOOCCHCH3eSSCOC2H5]12

First, to a flask equippedwith amagnetic stirrer, MOSS[PCL-OH]12(0.25 g, 0.035 mmol with respect of hydroxyl groups), dichloro-methane (16 mL) and triethylamine (1.5 mL) and 2-bromopropionylbromide (0.076 g, 0.35 mmol) were charged with vigorous stirring;the reaction was performed at 0 �C for 1 h and at room temperaturefor 24 h. After removing the solids via filtration, the solution wasconcentrated via rotary evaporation anddropped into a great amountof cold methanol to afford the precipitates. The precipitates were re-dissolved in dichloromethane and the solution was dropped into200 mL of methanol to afford the precipitates. This procedure wasrepeated three times to purify the sample. After drying in a vacuumoven at 30 �C for 24 h, the product (denoted MOSS[PCL-OOCCHCH3Br]12) (0.23 g) was obtainedwith the yield of 89%.1HNMR(400 MHz, CDCl3): 4.10 ~ 4.00 (121H, OCOCH2), 2.38 ~ 2.25 [121H,OCOCH2(CH2)4], 1.72 ~ 1.52 (243H, OCOCH2CH2CH2CH2CH2),1.46 ~ 1.30 [121H, OCOCH2CH2CH2CH2CH2], 0.16 [9H, Si(CH3)3], 4.36[1H, OCOCHBrCH3] and 1.81 (3H, OCOCHBrCH3).

Second, to a flask equipped with a magnetic stirrer, the aboveMOSS[PCL-OOCCHCH3Br]12 (0.230 g, 0.032 mmol with respect of2-bromopropiomyl group), anhydrous pyridine (18 mL) anddichloromethane (25 mL) were charged with vigorous stirring.Thereafter, potassium ethyl xanthate (0.300 g, 1.88 mmol) wasadded to the flask with vigorous stirring and this reaction was

Y. Yi et al. / Polymer 55 (2014) 3925e3935 3927

performed at room temperature for 36 h. After the insolublesolids were removed via filtration, the solution was concentratedvia rotary evaporation and then dropped into 200 mL of coldmethanol to afford the precipitates. The precipitates were re-dissolved in dichloromethane and precipitated into cold meth-anol again. This procedure was repeated three times to purify thesamples. After drying in vacuo at room temperature, the product(viz. MOSS[PCLeOOCCHCH3eSSCOC2H5]12) (0.21 g) was obtainedwith the yield of 91.3%. 1H NMR (400 MHz, CDCl3): 4.10 ~ 4.00(121.4H, OCOCH2) 2.38 ~ 2.25 [121H, OCOCH2(CH2)4], 1.72 ~ 1.52(243H, OCOCH2CH2CH2CH2CH2), 1.46 ~ 1.30 [121H,OCOCH2CH2CH2CH2CH2], 0.16 [9H, Si(CH3)3], 4.36 (1H,OCOCHBrCH3), 1.56 (3H, OCOCHBrCH3) and 4.63 (2H,-SSOCH2CH3).

2.4. Synthesis of MOSS[PCL-b-PVPy]12

Typically, to a flask equipped with a magnetic stirrer, MOSS[PCLeOOCCHCH3eSSCOC2H5]12 (0.180 g, 0.0021 mmol), NVP(0.3530 g, 3.1 mmol), 1,4-dioxane (1.5 mL) and AIBN (1.8 mg,0.011 mmol) were charged with vigorous stirring. The flask wasconnected onto a Schlenk line to degas via three freeze-epumpethaw cycles. The polymerization was performed at 70 �Cfor 16 h to attain the desired conversion of the monomer. The crudeproduct was dissolved with tetrahydrofuran (10 mL) and the so-lution was dropped into 200 mL of cold petroleum ether to affordthe precipitates. After drying in a vacuum oven at 30 �C for 12 h, thepolymer (i.e., MOSS[PCL-b-PVP]12) (0.36 g) was obtained with theconversion of the monomer to be c.a. 51%. GPC: Mn ¼ 162,000 withMw/Mn ¼ 1.32.

2.5. Measurement and characterization

2.5.1. Nuclear magnetic resonance (NMR) spectroscopyThe NMR measurements were carried out on a Varian Mercury

Plus 400 MHz NMR spectrometer at 25 �C. The samples were dis-solved in deuterium chloroform and the NMR spectra wereobtained.

Scheme 1. Synthesis of MOSS[PCL-

2.5.2. Gel permeation chromatography (GPC)The molecular weights and molecular weight distribution of the

polymers were measured on a Waters 1515 Isocratic HPLC system(100 mL injection column, 10 mm PL gel 300 mm � 7.5 mm mixed Bcolumns) equipped with Waters 2414 Refractive Index Detector.N,N-Dimethylformamide (DMF) containing 0.01 mol/L lithiumbromide (LiBr) was used as the eluent at a flow rate of 1.0 mL/min.The column system was calibrated by standard polystyrene.

2.5.3. Differential scanning calorimetry (DSC)Thermal analysis was performed on a Perkin Elmer Pyris-1 dif-

ferential scanning calorimeter in a dry nitrogen atmosphere. Theinstrument was calibrated with a standard Indium. The samples(about 10.0 mg inweight) were first heated up to 180 �C and held atthis temperature for 3 min to remove thermal history, followed byquenching to �60 �C. In all the cases, the heating rate of 20 �C/minwas used to record the heating thermograms and the cooling rate of10 �C/min to record the cooling thermograms. Glass transitiontemperature (Tg) was taken as the midpoint of heat capacitychange, melting temperature (Tm) and crystallization temperature(Tc) were taken as the temperatures at the maxima of exothermictransitions and the endothermic minima of transitions,respectively.

2.5.4. Small angle X-ray scattering (SAXS)The SAXS measurements were taken on a small angle X-ray

scattering station (BL16B1) with a long-slit collimation system inthe Shanghai Synchrotron Radiation Facility (SSRF), Shanghai,China, in which the third generation of synchrotron radiation lightsource was employed. Two dimensional diffraction patterns wererecorded using an image intensified CCD detector. The experimentswere carried out with X-ray radiation at a wavelength of l ¼ 1.24Åat room temperature (25 �C). For the measurement at 100 �C, aLinkam hot stage (THMS600) with the precision of ±0.1 �C wasmounted, which allowed the samples transmitted with the light.The intensity profiles were output as the plot of scattering intensity(I) versus scattering vector, q ¼ (4p/l)sin(q/2) (q ¼ scattering angle).

b-PVPy]12 molecular brushes.

Y. Yi et al. / Polymer 55 (2014) 3925e39353928

2.5.5. Determination of critical micelle concentration (CMC)Ultraviolet-visible spectroscopy was carried out on an Agilent

Technologies Cary 60 UV-vis spectrometer. The aqueous solu-tions of MOSS[PCL-b-PVP]12 with the concentration range from0.001 to 1 mg/mL were prepared by diluting the stock solutionof MOSS[PCL-b-PVP]12 with deionized water. The solution ofpyrene dissolved in acetone (1.2 mg/L) was transferred to theabove vials with vigorous stirring and the acetone was elimi-nated by rotary evaporation at 60 �C for 5 h. In each vial, theconcentration of pyrene was controlled to be 0.1212 mg � L�1.All the suspensions of MOSS[PCL-b-PVP]12 were maintained atroom temperature for 12 h with vigorous stirring before UVspectroscopy was performed. The intensities of the absorptionpeaks at l ¼ 264 nm were used to analyze the critical micelleconcentration (CMC).

2.5.6. Dynamic light scattering (DLS)The above suspensions of MOSS[PCL-b-PVPy]12 at the concen-

tration of 0.01 g/L were subjected to dynamic laser scattering (DLS).The laser light scattering experiments were conducted on a Mal-vern Nano ZS90 equipped with a HeeNe laser operated at thewavelength of l ¼ 633 nm and the data were collected at a fixedscattering angle of 90�.

Fig. 1. 1H NMR spectra of MOSS[CH2CH2S

2.5.7. Transmission electron microscopy (TEM)The morphological observations were conducted on a JEOL JEM

2100F electron microscope at a voltage of 200 kV. To investigate theself-assembly behavior of the samples in aqueous solutions, thespecimens were prepared by dropping the suspensions of thepolymer in water (about 10 ml at 0.2 g � L�1) onto carbon-coatedcopper grids; the water was eliminated via freeze-dryingapproach. The specimens were directly observed. To investigatethe morphology of the samples in bulks, the THF solutions of thepolymers at the concentration of 1 wt % were cast on carbon-coatedcopper grids and the solvent was slowly evaporated at room tem-perature and then in vacuo at 30 �C for 2 h. The specimens weredirectly observed without a staining step.

3. Results and discussion

3.1. Synthesis of MOSS[PCL-b-PVPy]12

The route of synthesis for the macrocyclic molecular brusheswith MOSS backbone and with PCL-b-PVPy diblock copolymer sidechains is shown in Scheme 1. First, MOSS[PCL-OH]12 was synthe-sized via the ROP of ε-caprolactone (CL) with MOSS(CH2CH2SCH2-CH2OH)12 as the initiator as reported previously [30]. Thereafter,

CH2CH2OH]12 and MOSS[PCL-OH]12.

Fig. 2. 1H NMR spectra of MOSS[PCL-OH]12, MOSS[PCL- OOCC(CH3)2Br]12, MOSS[PCLeOOCCHCH3eSSCOC2H5]12 and MOSS[PCL-b-PVPy9K]12.

Fig. 3. GPC curves of MOSS[PCL-OH]12 and MOSS[PCL-b-PVPy]12 molecular brushes.

Y. Yi et al. / Polymer 55 (2014) 3925e3935 3929

the MOSS[PCL-OH]12 was reacted with 2-bromopropiomyl bromideto afford MOSS[PCL-OOCCHCH3Br]12. The latter was thenreacted with potassium ethyl xanthate to obtain MOSS[PCLeOOCCHCH3eSSCOC2H5]12, a xanthate-functionalized molec-ular brush. The MOSS[PCLeOOCCHCH3eSSCOC2H5]12 was used asthe macromolecular chain transfer agent to mediate the radicalpolymerization of N-vinyl pyrrolidone (NVP) to synthesize MOSS[PCL-b-PVPy]12 via the reversible addition-fragmentation chaintransfer/macromolecular design via the interchange of xanthate(RAFT/MADIX) process. The 1H NMR spectra of MOSS[PCL-OH]12,

Table 1Results of polymerization for the synthesis of MOSS[PCL-b-PVPy]12 brushes.

Samples LPCL (Da) LPVPy(Da) Mn,GPC (Da) Mw/Mn

MOSS[PCL-b-PVPy2K]12 6920 1430 103,000 1.38MOSS[PCL-b-PVPy6K]12 6920 6340 162,000 1.32MOSS[PCL-b-PVPy9K]12 6920 8760 191,000 1.31MOSS[PCL-b-PVPy12K]12 6920 12,000 231,000 1.29MOSS[PCL-b-PVPy16K]12 6920 15,900 277,000 1.26

Fig. 4. Plots of number-average molecular weights and polydispersity indices asfunctions of the molar ratio of NVP to the CTA, i.e., MOSS[PCLeOOCCHCH3e

SSCOC2H5]12. Fig. 6. SAXS profiles of MOSS[PCL-b-PVPy]12 molecular brushes at 100 �C.

Y. Yi et al. / Polymer 55 (2014) 3925e39353930

MOSS[PCL-OOCCHCH3Br]12, MOSS[PCLeOOCCHCH3eSSCOC2H5]12and MOSS[PCL-b-PVPy9K]12 are shown in Figs. 1 and 2. For MOSS[PCL-OH]12, the signals of resonance at 4.0, 3.6, 2.3, 1.6 and 1.4 ppmare assignable to the protons of methylene in the main chain of PCL.The signal of resonance at 3.60 ppm is assignable to the protons ofthe terminal hydroxymethyl groups, which can be used to estimatethe length of PCL chains with end group analysis. According to theratios of integral intensity of methylene proton resonance at3.6 ppm to the methylene protons in the middle of PCL chains, the

Fig. 5. SAXS profiles of MOSS[PCL-b-PVPy]12 molecular brushes at 25 �C.

length of each PCL side chain was estimated to c.a. Mn,NMR ¼ 6920.Notably, this value was slightly higher than the value of PCL lengthin terms of GPC measurement (Mn,GPC ¼ 6500) owing to decreasedhydrodynamic volume of the brush-like polymer in the GPC mea-surement. With the reaction of MOSS[PCL-OH]12 with 2-bromopropiomyl bromide, the signal of resonance at 3.6 ppmassignable to the protons of terminal hydroxymethyl groups

Fig. 7. DSC curves of MOSS[PCL-OH]12 and MOSS[PCL-b-PVPy]12 molecular brushes:Up: the heating scans at 20 �C/min; Down: the cooling cans at 10 �C/min.

10-3 10-2 10-1

Inte

nsity

(a.u.)

Log C (C: mg/ml)

MOSS[PCL-b-PVPy2K]12

MOSS[PCL-b-PVPy6K]12

MOSS[PCL-b-PVPy9K]12

MOSS[PCL-b-PVPy12K]12

MOSS[PCL-b-PVPy16K]12

Fig. 8. Plots of the absorbance intensity of pyrene at l ¼ 264 nm as functions of MOSS[PCL-b-PVPy]12 molecular brushes in aqueous solutions.

Y. Yi et al. / Polymer 55 (2014) 3925e3935 3931

completely disappeared. Concurrently, there appeased a sharpspectral line at 1.92 ppm, assignable to the resonance of methylprotons in 2-bromoisobutyl groups at the chain ends of PCL. Ac-cording to the ratios of the integral intensity of the methyl protonresonance to those of the methylene proton in the middle of PCLchains, it is judged that all the terminal hydroxymethyl groups ofPCL chains were fully cappedwith 2-bromoisobutyl group. It is seenthat with the reaction of MOSS[PCL-OOCCHCH3Br]12 with potas-sium ethyl xanthate, the sharp peak at 1.92 ppm completely shiftedto 1.56 ppm. In the meantime, there appeared a new peak of

Fig. 9. Hydrodynamic radius (Rh) of MOSS[PCL-b-PVPy]12 molecular brushes inaqueous solutions at room temperature.

resonance at 4.62 ppm assignable to the protons of methylenegroups in xanthate moiety. The results of 1H NMR spectroscopyindicates that MOSS[PCLeOOCCHCH3eSSCOC2H5]12 was success-fully obtained.

The above MOSS[PCLeOOCCHCH3eSSCOC2H5]12 was used asthe macromolecular chain transfer agent to mediate the radicalpolymerization of NVP to obtain MOSS[PCL-b-PVPy]12. By control-ling the molar ratios of MOSS[PCLeOOCCHCH3eSSCOC2H5]12 toNVP, the molecular brushes with constant length of PCL and vari-able lengths of PVPy were obtained. Representatively shown inFig. 2 is the 1H NMR spectrum of MOSS[PCL-b-PVPy9K]12. It is seenthat except for the peaks of resonance assignable to PCL subchainsthe signals of resonance at 1.71 ~ 2.22 and 3.01 ~ 3.92 ppm areassignable to PVPy subchains. The signals of resonance at 3.72 ppmare assignable to the protons of the methine groups in the mainchain of PVPy. The methylene protons of the pyrrolidone ringconnecting nitrogen atom were detected at 3.3 ppm and otherpyrrolidone ring methylene protons of the PVPy block overlappedbetween 1.71 and 2.22 ppm. The result of 1H NMR spectroscopyindicates that the product combined the structural features fromPCL and PVPy blocks. All the polymerized products were subjectedto gel permeation chromatography (GPC) to measure the molecularweights. The GPC curves were presented in Fig. 3 and the results ofpolymerization were summarized in Table 1. It is seen that all theMOSS[PCL-b-PVPy]12 samples displayed unimodal distribution ofmolecular weights. Shown in Fig. 4 are the plots of number-averaged molecular weights and values of polydispersity index(PDI) as functions of the molar ratio of [NVP] to MOSS[PCLeOOCCHCH3eSSCOC2H5]12. Notably, the molecular weights ofthe MOSS[PCL-b-PVPy]12 linearly increased with increasing themolar ratio of NVP to MOSS[PCLeOOCCHCH3eSSCOC2H5]12, sug-gesting that the molecular weights of MOSS[PCL-b-PVPy]12 can bewell controlled. The PDI values were measured to be in the range of1.26 ~ 1.38, i.e., the distribution of molecular weights was quitenarrow. The above result indicates that the radical polymerizationof NVP mediated with MOSS[PCLeOOCCHCH3eSSCOC2H5]12 was ina controlled manner.

3.2. Small angle X-ray scattering (SAXS)

All the MOSS[PCL-b-PVPy]12 molecular brushes were subjectedto small angle X-ray scattering (SAXS). Shown in Figs. 5 and 6 arethe SAXS profiles of the samples at room temperature (i.e., 25 �C)and at 100 �C, respectively. In all the cases, the intense scatteringpeaks were exhibited. At room temperature, two scattering peakswere detected at q¼ 0.1 and 0.3 nm�1 respectively for each sample.The positions of the peaks at q ¼ 0.1 nm�1 changed with thecompositions of the molecular brushes whereas those atq ¼ 0.3 nm�1 almost remained invariant. The SAXS profiles couldreflect the combined scattering of the microdomains of the brush-like block copolymers and the crystals of PCL blocks. To confirm thisspeculation, all the samples were heated to the temperature abovethe melting point of PCL (e.g., 100 �C). Upon heating to 100 �C, thescattering peaks at q ¼ 0.3 nm�1 disappeared whereas the scat-tering peaks at q ¼ 0.1 nm�1 remained unchanged. The formerare attributed to the crystals of PCL whereas the latter to themicrodomains of the brush-like block copolymers. This observationindicates that in amorphous state the MOSS[PCL-b-PVPy]12 mo-lecular brushes were microphase-separated and the microphase-separated morphologies were not affected by PCL crystallization.In other words, the crystallization of PCL blocks occurredwithin themicrodomains of PCL blocks. According to the positions of theprimary scattering, the values of the d spacing were calculated to beL ¼ 67.5, 47.4, 56.1, 68.6 and 66.5 nm for MOSS[PCL-b-PVPy2K]12,MOSS[PCL-b-PVPy6K]12, MOSS[PCL-b-PVPy9K]12, MOSS[PCL-b-

Y. Yi et al. / Polymer 55 (2014) 3925e39353932

PVPy12K]12 and MOSS[PCL-b-PVPy16K]12, respectively. It is notedthat both MOSS[PCL-b-PVPy6K]12 and MOSS[PCL-b-PVPy9K]12 hadrelatively smaller values of d spacing than other samples. Thisobservation could be interpreted with the formation of the co-continuous microdomains (e.g., lamellar nanophases) while themass fractions of both PCL and PVPy were quite close. Themicrophase-separated morphologies could exert a profound effecton the crystallization behavior of PCL subchains in theMOSS[PCL-b-PVPy]12 molecular brushes, which was readily investigated bymeans of differential scanning calorimetry (DSC).

3.3. Differential scanning calorimetry (DSC)

All the MOSS[PCL-b-PVPy]12 brushes were subjected to differ-ential scanning calorimetry (DSC) to investigate the crystallization

Fig. 10. TEM micrographs of MOSS[PCL-b-PVPy]12 specimens prepared via freeze-dryingPVPy6K]12, C) MOSS[PCL-b-PVPy9K]12, D) MOSS[PCL-b-PVPy12K]12 and E) MOSS[PCL-b-PVP

and melting behavior of PCL blocks in the brushes. Shown in Fig. 7are the DSC curves of the heating scans of the samples quenchedfrom 180 �C. In all the cases, the endothermic peaks at about 60 �Cwere exhibited. The endothermic peaks are attributed to themelting transition of PCL microdomains in the organic-inorganicmolecular brushes. It is seen that the melting temperatures (Tm's)decreased with increasing the length of PVPy blocks. For MOSS[PCL-OH]12, the melting temperature was measured to Tm ¼ 56 �C.While the length of PVPy blocks was 16,000 Da (viz. for MOSS[PCL-b-PVPy16K]12), the melting temperature was decreased toTm ¼ 41 �C. The decreased Tm's were attributable for the increasingimperfection of the PCL crystals. For MOSS[PCL-b-PVPy2K], MOSS[PCL-b-PVPy6K] and MOSS[PCL-b-PVPy9K], no cold crystallizationpeak was exhibited in the heating DSC curves; the singleexothermic peaks appeared, which quite resembled the case of

approach from the aqueous solutions: A) MOSS[PCL-b-PVPy2K]12, B) MOSS[PCL-b-y16K]12. The scale bar equals 500 nm.

Fig. 11. TEM micrograph of MOSS[PCL-b-PVPy9K]12. The film specimen was preparedvia solution casting with THF and the specimen was not stained before morphologicalobservation.

Y. Yi et al. / Polymer 55 (2014) 3925e3935 3933

MOSS[PCL-OH]12 brushes. This observation suggests that the crys-tallization of PCL blocks in these samples was very fast so that thecrystallization was carried out to completion during the quenchingprocess. In contrast, both MOSS[PCL-b-PVPy12K] and MOSS[PCL-b-PVPy16K] displayed the cold crystallization peaks at c.a. 15 �C in theheating scans. This observation suggests that the crystallization ofthe PCL blocks in both of the samples was significantly slow and didnot undergo to completion during the quenching process. Theabove DSC results can be interpreted on the basis of themicrophase-separated morphologies of the macrocyclic molecularbrushes. For MOSS[PCL-b-PVPy2K], MOSS[PCL-b-PVPy6K] andMOSS[PCL-b-PVPy9K], the mass fractions of PVPy blocks weresmaller than or close to those of PCL blocks. Therefore, the PCLmicrodomains could be continuous or co-continuous in the brush-like diblock copolymers. Owing to the continuity of the PCLmicrodomains, the crystallization of PCL blocks behaved as that ofMOSS[PCL]12. In contrast, the PCL microdomains were dispersed inthe continuous PVPy microdomains in MOSS[PCL-b-PVPy12K] andMOSS[PCL-b-PVPy16K]. In this case, the crystallization of PCL waslocalized with the isolated microdomains and thus was in aconfined manner. The confined crystallization behavior was readilyconfirmed with the cooling scans of DSC. Also shown in Fig. 7 arethe DSC curves of the cooling scans for MOSS[PCL-OH]12 and MOSS[PCL-b-PVPy]12 molecular brushes. For MOSS[PCL-OH]12, the crys-tallization of PCL side chains occurred at Tc ¼ 27.4 �C. Notably, allthe Tc's of the MOSS[PCL-b-PVPy]12 were significantly lower thanthat of MOSS[PCL-OH]12. The Tc values were measured to be 24.2,16.8, 15.4 and 8.9 �C for MOSS[PCL-b-PVPy2K]12, MOSS[PCL-b-PVPy6K]12, MOSS[PCL-b-PVPy9K]12, and MOSS[PCL-b-PVPy12K]12,respectively. For MOSS[PCL-b-PVPy16K]12, no crystallization peakwas detected in the cooling DSC scan, suggesting that the crystal-lization of PCL blocks was too slow to be detected in the coolingscan. All the Tc values of the molecular brushes were significantlylower than MOSS[PCL-OH]12, indicating that the crystallization ofPCL blocks in these molecular brushes were more difficult than inMOSS[PCL-OH]12. This result can be accounted for the formation ofmicrophase-separated morphologies in the molecular brushes. It isknown that the confined crystallization of polymers in the nano-meter scale can be affected by several factors such as size of crys-talline microdomains, inter-domain connectivity through grainboundary, edge and screw dislocations and rigidity of continuousmatrix around the crystalline microdomains [36e39]. If the crys-talline microdomains are isolated, homogeneous nucleation willdominate the crystallization process and thus no crystal growthprocess was needed to complete the crystallization [40,41]. In thepresent case, the inorganic MOSS backbone could act as the het-erogeneous nucleating agent to accelerate the crystallization of PCLblocks. Nonetheless, the confined crystallization behavior was stilldisplayed owing to the microphase-separated morphologies of themolecular brushes.

3.4. Self-assembly behavior in aqueous solutions

Both MOSS backbone and PCL subchains were hydrophobicwhereas PVPy subchains were hydrophilic. It is of interest toinvestigate the self-assembly behavior of the organic-inorganicamphililes in aqueous solutions. It is proposed that the PCL-b-PVPy diblock copolymers grafted onto MOSS backbone can self-assemble into the polymeric micelles in aqueous solutions withthe aggregates of PCL blocks as well as MOSS cores and PVPy blocksas the coronas. The critical micelle concentrations (CMC) of theMOSS[PCL-b-PVPy]12 brushes with variable lengths of PVPy sub-chains were measured with dye solubilization method [42e44].Shown in Fig. 8 are the plots of absorbance intensity of pyrene atl¼ 264 nm as functions of logarithmic concentration of MOSS[PCL-

b-PVPy]12 in aqueous solutions at room temperature. For eachsample, the absorbance intensity of pryrene remained nearlyinvariant below a certain concentration and then increased sub-stantially, implying that the dye was incorporated into the hydro-phobic regions of the self-assembled micelles. The CMCs weredetermined from the crossover points of two lines of absorbanceintensity of pyrene versus logarithmic concentration of MOSS[PCL-b-PVPy]12. The values were measured to be 2.55 � 10�3,3.68 � 10�3, 4.08 � 10�3, 4.76 � 10�3 and 5.25 � 10�3 mg/mL forMOSS[PCL-b-PVPy2K]12, MOSS[PCL-b-PVPy6K]12, MOSS[PCL-b-PVPy9K]12, MOSS[PCL-b-PVP12K]12 andMOSS[PCL-b-PVPy16K]12 inaqueous solutions. Notably, the CMCs increased with increasing thelengths of PVPy blocks.

Above the CMCs, all the organic-inorganic molecular brushescan be self-assembled into the micelles with various morphologiesand variable sizes, depending on themass fraction of PVPy blocks inthe molecular brushes. The hydrodynamic radii of the polymericmicelles in the aqueous solutions were measured by means ofdynamic light scattering (DLS). Shown in Fig. 9 are the plots ofhydrodynamic radius distribution as functions of hydrodynamicradius (Rh) for the aqueous suspensions of MOSS[PCL-b-PVPy]12 at25 �C. Apart from MOSS[PCL-b-PVPy2K]12, the intensity-averagedhydrodynamic radius (Rh) displayed unimodal distribution.Depending on the lengths of PVPy subchains, the values ofintensity-averaged hydrodynamic radius (Rh) were measured to be120, 129, 157, 158 and 213 nm for MOSS[PCL-b-PVPy16K]12, MOSS[PCL-b-PVPy12K]12, MOSS[PCL-b-PVP9K]12, MOSS[PCL-b-PVPy6K]12 and MOSS[PCL-b-PVP2K]12, respectively. The Rh valuesdecreased with increasing the length of PVPy blocks. The mor-phologies of the micelles were further investigated by transmissionelectron microscopy (TEM) and the TEM micrographs are shown inFig. 10. The specimens for the morphological observations wereprepared via freeze-drying approach with the aqueous solutions atthe concentration of 0.1 g/L at 25 �C. While the length of PVPysubchains were 9000 Da or longer, the spherical micelles wereexhibited wit the sizes of 20 ~ 100 nm in diameter. It is seen that thesizes of micelles decreased with increasing the lengths of PVPysbchains. While the lengths of PVPy was shorter than 9000 Da,

MOSS[PCL-b-PVPy]12

Self-assembly

In Water

Scheme 2. Self-assembly of MOSS[PCL-b-PVPy]12 in aqueous solutions.

Y. Yi et al. / Polymer 55 (2014) 3925e39353934

some cylindrical nanoobjects were formed. It is should be pointedout that the sizes of the micelles measured with TEM are notnecessarily identical with the Rh values by means of DLS. Theformer were obtained in the dry state and were much lower thanthe latter obtained in aqueous solution, which contains the domi-nant contribution of the solvated coronas (viz. PVPy).

Compared to linear (or organic) PCL-b-PVPy diblock copolymers[10e16], the stability of the hydrophobic cores of MOSS[PCL-b-PVPy]12 micelles in aqueous solutions could be increased owing to:i) the formation of the covalent bonds between PCL ends andMOSSbackbone and ii) the increase in the hydrophobicity of the micellarcores via the introduction of the organosilicon component (viz.MOSS). In the macrocyclic molecular brushes, every twelve PCLchainswere bonded onto a 24-membered silsesquioxane backbone.The chemical linkage of MOSS with PCL chains were much strongerthan the physical interactions via van der Waals forces in the PCLcores of the micelles from linear PCL-b-PVPy diblock copolymers. Inaddition, the MOSS aggregates could be formed via MOSSeMOSSinteractions owing to the immiscibility of MOSS with PCL chains.This speculation was readily confirmed by means of TEM. Repre-sentatively shown in Fig. 11 are the TEM micrograph of MOSS[PCL-b-PVPy9K]12 in bulks. It is seen that the spherical microdomains atthe size of 5 ~ 20 nm in diameter were dispersed in a continuousmatrix. It should be pointed out that themorphological observationwas carried out bymeans of TEMwithout a staining step. Therefore,the spherical microdomains are assignable to the MOSS aggregateswhereas the continuous matrix to PCL-b-PVPy according to thedifference in electron density between MOSS and PCL-b-PVPychains. The increase in the stability of the micelles is important forthe application of the polymeric micelles as drug delivery vehiclessince the micelles must be intact to prevent drug cargo releasebefore reaching the target cells. According to the above results, thestructures of the micelles could be depicted as in Scheme 2. Thehydrophobic cores of the polymeric micelles were composed of PCLchains as well as the MOSS aggregates via MOSSeMOSS in-teractions; the PVPy subchains constituted the coronas of themicelles.

4. Conclusions

The organic-inorganic macrocyclic molecular brushescomposed of MOSS backbone and PCL-b-PVPy diblock copolymerside chains were successfully synthesized via the combination ofring-opening polymerization of ε-caprolactone (CL) and RAFT/

MADIX polymerization of N-vinyl pyrrolidone. The molecularbrushes were characterized by means of nuclear magnetic reso-nance spectroscopy (NMR) and gel permeation chromatography(GPC). Small angle X-ray scattering (SAXS) showed that all theMOSS[PCL-b-PVPy]12 brushes displayed microphase-separatedmorphologies. The microphase-separated morphologies werequite dependent on the length of PVPy blocks, which significantlyaffect the crystallization behavior of PCL subchains as evidenced bydifferential scanning calorimetry (DSC). In aqueous solutions, theMOSS[PCL-b-PVPy]12 brushes can be self-assembled into the mi-celles as evidenced by dynamic light scattering (DLS) and trans-mission election microscopy (TEM).

Acknowledgment

The financial supports fromNatural Science Foundation of China(No. 51133003 and 21274091) were gratefully acknowledged. Theauthors thank the Shanghai Synchrotron Radiation Facility for thesupport under the projects of Nos. 10sr0260 & 10sr0126.

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