Thermoresponsive Behavior of Cationic Polyrotaxane Composed of

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J. Phys. Chem. B 2009, 113, 682–690

Thermoresponsive Behavior of Cationic Polyrotaxane Composed of Multiple Pentaethylenehexamine-grafted r-Cyclodextrins Threaded on Poly(propylene oxide)-Poly(ethylene oxide)-Poly(propylene oxide) Triblock Copolymer Chuan Yang† and Jun Li*,†,‡ DiVision of Bioengineering, Faculty of Engineering, National UniVersity of Singapore, 7 Engineering DriVe 1, Singapore 117574; and Institute of Materials Research and Engineering, ASTAR (Agency for Science, Technology and Research), 3 Research Link, Singapore 117602 ReceiVed: October 17, 2008; ReVised Manuscript ReceiVed: NoVember 6, 2008

This paper reports the synthesis and the studies of the thermoresponsive behavior of a new cationic polyrotaxane consisting of multiple pentaethylenehexamine-grafted R-cyclodextrin (PEHA-grafted-R-CD) rings threaded on a poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEO-PPO) triblock copolymer. The PEHA-grafted R-CD rings were threaded and embedded in the PEO block of the block copolymer, forming a hydrophilic polyrotaxane domain, while the two PPO blocks flank the cationic polyrotaxane domain. The cationic polyrotaxane was found to form thermosensitive micelles in aqueous solution. The thermosensitive micellization phenomena were studied using 1H and fluorescence spectra. The critical micellization temperatures of the cationic polyrotaxane micelles at various concentrations were determined using a fluorescence probe technique. On the basis of the closed association model, the standard free energy (∆G°), enthalpy (∆H°) and entropy (∆S°) of micellization were calculated, and then the entropy change was confirmed to be the driving force for the micellization. Introduction Over the last few decades, supramolecular architectures have greatly intrigued researchers because of their unique structures and interesting properties.1-3 Polyrotaxanes, formed by multiple macrocycles threaded over a polymeric chain, is such an example.4 Cyclodextrins (CDs) are a series of cyclic oligosaccharides composed of 6, 7, or 8 D(+)-glucose units linked by R-1,4-linkages, and named R-, β-, or γ-CD, respectively.5,6 Since the first CD-based polyrotaxanes were synthesized with multiple R-CDs threaded and trapped over a polymer chain,7,8 growing interest has been focused on studies of such supramolecular structures.9-38 Stimuli-responsive materials exhibit reversible property changes in response to changes in environmental factors such as pH or temperature.39,40 Recently, a polyrotaxane composed of multiple methylated R-CD rings threaded on a high molecular weight poly(ethylene oxide) (PEO) chain and end-capped by bulky adamantyl groups was reported to have thermoresponsive property.41 The aqueous solutions of the polyrotaxane of methylated R-CD (MePR) showed a lower critical solution temperature (LCST) and form an elastic hydrogel with increasing temperature, which was induced by the hydrophobic association of methylated R-CD. Herein, we synthesized a cationic polyrotaxane composed of multiple pentaethylenehexamine (PEHA)-grafted R-CDs threaded on a poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEO-PPO) triblock copolymer chain. The PEHAgrafted R-CD rings were threaded and embedded in the PEO block of the block copolymer, forming a hydrophilic polyrotaxane domain, while the two PPO blocks flank the cationic * To whom correspondence should be addressed. Phone: +65-6516-7273; fax: +65-6872-3069; e-mail: [email protected]. † National University of Singapore. ‡ Institute of Materials Research and Engineering.

polyrotaxane domain. Due to the presence of the hydrophilic polyrotaxane domain and the thermosensitive PPO blocks, the cationic polyrotaxane was found to form thermosensitive micelles in aqueous solution. The thermosensitive micellization behaviors of the cationic polyrotaxane were studied using 1H and fluorescence spectra. On the basis of the closed association model, the standard free energy (∆G°), enthalpy (∆H°), and entropy (∆S°) of micellization were calculated, and the entropy contribution was confirmed to dominate the micellization process. Experimental Section Materials. The reverse Pluronic PPO-PEO-PPO triblock copolymer 1, with specified molecular weight and PEO content of Mn ) 3300, 10% PEO, was purchased from Aldrich. This copolymer had a chain composition of PO25EO12PO25. We analyzed the molecular characteristics of the triblock copolymer sample using GPC,1H NMR, and elemental analysis and found them to be within the specifications of the supplier. NHydroxysuccinimide (NHS), 1,3-dicyclohexylcarbodiimide (DCC), ethylenediamine, and N-carbobenzyloxy-L-phenylalanine (Z-LPhe-OH) were also bought from Aldrich. Pentaethylenehexamine (PEHA) was obtained from Fluka. 1,1′-Carbonyldiimidazole (CDI) and R-cyclodextrin were purchased from Tokyo Kasei incorporation. THF was dried with CaH2 and distilled under nitrogen atmosphere before use. Anhydrous dioxane and DMF were supplied by Aldrich. d6-DMSO and D2O used as solvents in the NMR measurements were obtained from Aldrich. Preparation of PO25EO12PO25-bis(Amine) (2). Reverse Pluronic PO25EO12PO25 triblock copolymer (1, 1.98 g, 0.60 mmol) was heated in a flask at 80 °C in vacuum overnight. When the flask cooled, 10 mL of anhydrous THF was injected under nitrogen. After all of 1 was dissolved, the THF solution of 1 was added dropwise over a period of 6 h under nitrogen to

10.1021/jp809207q CCC: $40.75  2009 American Chemical Society Published on Web 12/24/2008

Thermoresponsive Behavior of Cationic Polyrotaxane

J. Phys. Chem. B, Vol. 113, No. 3, 2009 683

SCHEME 1: Synthesis Procedures and Structures of Multiple OEI-grafted Cationic r-CD-PO25EO12PO25-Z-L-Phe Polyrotaxane

25 mL of anhydrous THF solution in which 1,1′-carbonyldiimidazole (CDI) (0.98 g, 6.0 mmol) was dissolved, and the mixture was stirred overnight under nitrogen at room temperature. The reaction mixture was concentrated to about 10 mL by evaporation. Then, the resulting solution was slowly added dropwise over a period of 3 h into 14.48 g (240 mmol) of ethylenediamine, which was dissolved in 10 mL of anhydrous THF with stirring at room temperature. The mixture was further stirred overnight. Excess ethylenediamine was removed by vacuum evaporation, and the resulting viscous liquid was purified by column chromatography on a Sephadex LH-20 column with methanol as eluent to give 2 as a viscous yellowish liquid. Yield, 1.53 g (73%). 1H (400 MHz, d6-DMSO, 22 °C): δ 5.70 (br, t, 2H, CONH), 3.42-3.63 (m, 48H and 150H, -CH2CH2O- of PEO block and -CH2CHO- of PPO block), 2.92 (m, 4H, CNCH2), 2.23 (m, 4H, CH2N), 1.18 (d, 150H, -CH3 of PPO block). Preparation of Polyrotaxane (4). PO25EO12PO25-bis(Amine) (2, 1.925 g) was added to 150 mL of R-CD aqueous solution (0.145 g/mL) in centrifuge tubes, followed by alterantely immersing the tubes in an ultrasonic waterbath and an ice waterbath. The solution gradually became turbid, producing the IC as precipitate. The reaction mixture was further stirred

overnight at 10 °C. The precipitated IC was isolated by centrifugation, and freeze-dried in vacuum. Yield, 3.311 g. N-Hydroxysuccinimide ester of Z-L-phenylalanine (Z-L-PheOsu) was prepared by condensation reaction of N-carbobenzyloxy-L-phenylalanine (Z-L-Phe-OH) with N-hydroxysuccinimide (NHS), and 1,3-dicyclohexylcarbodiimide (DCC) was used as condensing agent, as reported previously.42 The resulting Z-LPhe-Osu (3.973 g, 10 mmol) was dissolved in 10 mL of anhydrous DMF. This solution was slowly added dropwise under stirring to the resultant polypseudorotaxane. The reaction mixture was further stirred overnight. 300 mL of MeOH was poured into the resulting solution to precipitate the crude product. The precipitate was centrifuged and washed three times with MeOH. The resulting wet solid was dissolved in 50 mL of DMSO, and 1000 mL of DI water was poured into the solution to precipitate the product. The precipitate was centrifuged and washed thee times with DI water. Finally, the resulting wet solid was freeze-dried in vacuo to obtain polyrotaxane 4. Yield, 2.316 g (50.6%). 1H (400 MHz, d6-DMSO, 22 °C): δ 7.20-7.50 (m, 20H, H of phenyl), 5.68 (s, 36H, O(2)H of CD), 5.48 (d, 36H, O(3)H of CD), 4.79 (s, 36H, H(1)H of CD), 4.47 (s, 36H, O(6)H of CD), 3.20-3.92 (m, 216H, H(3), H(6), H(5),

684 J. Phys. Chem. B, Vol. 113, No. 3, 2009

Figure 1. Size exclusion chromatograms of R-CD (a), and 5 (b), detected with refractive index (RI) and optical rotation (OR), respectively.

H(2) and H(4) of CD; 48H, -CH2CH2O- of PEO block; 150H, -CH2CHO- of PPO block), 1.06 (s, 150H, -CH3 of PPO block). Preparation of Cationic Polyrotaxane (5). The resulting polyrotaxane 4 (0.275 g, 0.028 mmol) was dried in a flask at 40 °C in vacuum overnight. When the flask cooled, 40 mL of anhydrous DMSO was injected under nitrogen. After all of 4 was dissolved, the DMSO solution of 4 was added dropwise over a period of 6 h under nitrogen to 40 mL of anhydrous DMSO solution in which CDI (2.44 g, 15 mmol) was dissolved, and the mixture was stirred overnight under nitrogen at room temperature. A mixture of THF (300 mL) and Et2O (600 mL) was poured into the resulting solution to precipitate the product. The precipitate was centrifuged and washed for 3 times with THF. Then, the resulting wet solid was dissolved in 40 mL of anhydrous DMSO, and this solution was slowly added dropwise over a period of 3 h into 5.30 mL (18 mmol) of pentaethylenehexamine that was dissolved in 40 mL of anhydrous DMSO while stirring at room temperature. The mixture was further stirred overnight. THF (900 mL) was poured into the reaction mixture to precipitate the product. The precipitate was centrifuged and washed three times with THF, and the resulting crude product was purified by size exclusion chromatography (SEC) on a Sephadex G-50 column using deionized water as eluent. Finally, 0.238 g of white solid 5 was obtained (yield, 46.9%). 1 H (400 MHz, D2O, 22 °C): δ 7.05-7.40 (m, 20H, H of phenyl), 4.95 (s, broad, 36H, H(1)H of CD), 2.94-4.58 (m, broad, 216H, H(3), H(6), H(5), H(2), and H(4) of CD; 48H, -CH2CH2Oof PEO block; 150H, -CH2CHO- of PPO block; 63H, methylene of -CONHCH2-), 2.67 (m, 568H, methylene of pentaethylenehexamine), 1.08 (s, 150H, -CH3 of PPO block). Measurements. Gel permeation chromatography (GPC) analysis for the reverse Pluronic PO25EO12PO25 triblock copolymer 1 was carried out with a Shimadzu SCL-10AVP and LC-10ATVP system equipped with two Phenogel 5 µm and 50 and 1000 Å columns (size: 300 × 4.6 mm) in series and a Shimadzu RID-10A refractive index detector. THF was used

Yang and Li as eluent at a flow rate of 0.30 mL/min at 40 °C. Monodispersed poly(ethylene glycol) standards were used to obtain a calibration curve. Size exclusion chromatography (SEC) analysis for 5 was carried out with a Shimadzu SCL-10AVP and LC-10ATVP system equipped with a Sephadex G-75 column (size: 2.5 × 32 cm) and a Shimadzu RID-10A refractive index detector. PBS buffer solution (1×) was used as the eluent. Fractions were collected per 1 mL, and their optical rotation (OR) were measured using a HORIBA SEPA-300 high-speed accurate polarimeter at wavelength 589 nm with a cell length of 5 cm and response time of 2 s. The 1H spectra were recorded on a Bruker AV-400 NMR spectrometer at 400 MHz. The 1H measurements were carried out with an acquisition time of 3.2 s, a pulse repetition time of 2.0 s, a 30° pulse width, a 5208 Hz spectral width, and 32 K data points. Chemical shifts were referred to the solvent peaks (δ ) 4.70 ppm for D2O and 2.50 ppm for d6-DMSO). The 13C NMR spectra were recorded on a Bruker AV-400 NMR spectrometer at 100 MHz at room temperature. The 13C NMR measurements were carried out using composite pulse decoupling with an acquisition time of 0.82 s, a pulse repetition time of 5.0 s, a 30° pulse width, a 20 080 Hz spectral width, and 32 K data points. Steady-state fluorescence spectra were recorded on a Shimadzu RF-5301PC spectrofluorophotometer. Excitation spectra were monitored at 373 nm. The slit widths for both excitation and emission sides were maintained at 1.5 nm. Sample solutions were prepared by dissolving a predetermined amount of 5 in an aqueous pyrene solution of known concentration, and the solutions were allowed to stand for 1 day for equilibration. The concentration of pyrene was kept at 6.0 × 10-7 M. The morphological examination of the copolymer micelles was performed using a Philips CM300 high-resolution transmission electron microscope (TEM) operating at an acceleration voltage of 100 kV. A drop of 5 in an aqueous solution (10 g/L) containing 1 wt % phosphotungstic acid (PTA) was deposited onto a 200 mesh copper grid coated with carbon. Excessive solution was removed with a Kimwipes delicate wiper. The sample was dried at room temperature prior to measurement. Finally, the shape and size of the micelles were directly obtained from each transmission electron micrograph. A MultiMode-AFM atomic force microscopy (AFM) in a tapping mode was employed to image the nanoparticle samples. Briefly, silicon disks were soaked in 50% acetone for a minimum period of 2 h and then rinsed with distilled water. After the silicon disks were dried completely, 20 µL of 5 in an aqueous solution (10 g/L, let stand for 1 day for equilibration before use) was dropped on the silicon surface. The above solution was volatilized to dryness at room temperature prior to obtaining measurements. All AFM images were obtained with a scan rate of 0.5 or 1 Hz over a selected area of 3 × 3 µm. The imaging analysis was performed using Nanoscope software. Results and Discussion Synthesis of Cationic Polyrotaxane. Scheme 1 shows the synthesis procedures and the structures of 5. First, 2 was prepared from 1, which has a number-average molecular weight (MW) of 3300 and a 10 mol % content of ethylene oxide (EO) segments. For conversion of both of the terminal hydroxyl groups of the triblock copolymer 1 to amino groups, the hydroxyl groups were activated with CDI, followed by reaction with large excess of ethylenediamine to give 2. In this reaction, the polarity of the reaction solvent has a strong influence on



H spectra of R-CD (a), 2 (b), and 4 (c) in d6-DMSO.

Figure 2.

1

Figure 3.

13

C NMR spectra of R-CD (a), pentaethylenehexamine (b), and 5 (c) in D2O.

the conversion of 1. The reaction was complete in THF, but only part of 1 was converted into 2 in DMF, probably due to poor solubility of the two apolar PPO blocks in the polar organic solvent. Next, 2 was allowed to react with saturated solution of R-CD to obtain polypseudorotaxane 3, following similar pro-

cedures described in our previous report,23 in which it was found that R-CD will selectively recognize the middle PEO block of PPO-PEO-PPO triblock copolymer, forming an inclusion complex, where R-CD resides over the PEO block, while the flanking PPO blocks remain free of complexation. Then, 4 was


Yang and Li

H spectra of R-CD (a), 2 (b), pentaethylenehexamine (c), and 5 (d) in D2O.

Figure 4.

1

Figure 5.

1

H spectra of 0.5% 5 in D2O at different temperatures.

formed by dropping a large excess of Z-L-Phe-Osu to the dry powder of the above polypseudorotaxane 3 using an ester exchange method. Finally, pentaethylenehexamine chains were grafted to R-CD rings of 4 to give 5. Molecular Characterization of Cationic Polyrotaxane. Figure 1 shows the SEC profiles of 5 in comparison with pristine R-CD and 2. The elution curves were recorded against refractive index (RI) and optical rotation (OR). As shown in Figure 1, R-CD has relative small molecular size, which was eluted out at the low MW region of the column. In contrast, 5 was eluted out at a higher MW region of the column due to its larger molecular size. Meanwhile, the cationic polyrotaxane showed a single peak in the SEC profile, indicating that it is pure and that there was no intra- or intermolecular cross-linking. Figure 2 shows the 1H spectra of 4 in comparison with free R-CD and 2 in d6-DMSO. In Figure 1c, the peaks for R-CD, EO, and PO segments of the triblock copolymer and the phenyl

moieties of Z-L-Phe end groups are shown. The peaks are broader as compared to the corresponding free counterparts in Figure 2, panels a and b. This is due to the restricted molecular movement of the components in the polyrotaxane. Quantitative comparisons between the integral intensities of the peaks of R-CD and those of threading copolymer segments were used to derive the compositions of the polyrotaxane. It was found that 6 R-CD rings, on average, were threaded on and covered the PO25EO12PO25 triblock copolymer in each molecule of 4. Figure 3 shows the 13C NMR spectra of 5 in comparison with pristine R-CD and pentaethylenehexamine. In Figure 3c, all peaks attributed to R-CD, the grafting PEHA, and the threading block copolymer were observed clearly; the peaks were broadened because all components of the cationic polyrotaxane formed an integrated macromolecular system that restricted their molecular motion. The peak at δ 158.2 ppm corresponds to the carbon of carbonyl groups, which links the PEHA chains to



Figure 6. Steady-state fluorenscence excitation spectra monitored at 373 nm for the pyrene probe in an aqueous solution of cationic polyrotaxane 5 (2.5 g/L) at different temperatures. The temperature interval is 5 °C, and the concentration of pyrene is 6.0 × 10-7 M.

TABLE 1: Critical Micellization Temperature (CMT) for 5 concentration (g/L)

Figure 7. Plot of I337/I334 ratio of pyrene excitation spectra in water in the presence of 5 (2.5 g/L) as a function of temperature.

0.25 0.5 0.6 0.8 1.0 1.5 1.8 2.5 5.0 10.0 20.0

CMT (°C) – – 23.6 23.4 23.0 19.7 19.5 18.9 15.2 14.7 14.0

Figure 9. Plot of reciprocal TCMT vs [5], used for the determination of the micellization enthalpy in terms of the closed association model.

Figure 8. Temperature effects on the I337/I334 ratio of pyrene excitation spectra in aqueous solutions of 5 with various concentrations. The critical micellization temperatures (CMT) can be estimated from the first break in the curves.

R-CD rings. Similarly, the peak at 129.2 ppm was attributed to the phenyl moieties of Z-L-Phe end groups. Compared to pristine R-CD, the peak of C-6 of R-CD in 5 moved downfield and shifted from 60.8 to 64.5 ppm. This proved that the grafting of PEHA chains mainly happened at the 6-position hydroxyl

groups. In fact, of the three types of hydroxyl groups of R-CD, those at the 6-position (primary hydroxyl groups) are the most nucleophilic and are thought to be modified under the weak basic conditions.43 Figure 4 shows the 1H spectra of 5 in comparison with pristine R-CD, 2, and pentaethylenehexamine. In Figure 4d, the signals for R-CD, the grafting PEHA chains, the threading copolymer, and the phenyl moieties of Z-L-Phe ends were observed, and the peaks were much broader due to the restriction of the molecular motion by molecular interlocking and the grafting of PEHA units. From the 1H spectra, the average number of


Yang and Li

Figure 10. Micelles observed by TEM (a) and AFM (b) for 10 g/L of 5.

PEHA chains grafted to each R-CD (y) was estimated, and about 4.8 PEHA chains were found to conjugate to one R-CD ring in the cationic polyrotaxane 5. Micellization Behavior of 5 in an Aqueous Solution. Similar to the structure of amphiphilic copolymers, 5 contains two large hydrophobic flanking PPO blocks and one central hydrophilic IC domain. The IC domain contained 6 R-CD rings threaded and embedded in the PEO block of one PO25EO12PO25 triblock copolymer chain and each R-CD ring was grafted with 4.8 PEHA chains. For the PPO block, solubility strongly depends on temperature since the hydrogen bonding between water and PPO diminishes with increasing temperature.44-48 Hence, with increasing concentration or temperature, 5 may form multimolecular micelles. The temperature-dependent formation of micelles was confirmed by 1H and fluorescence spectra. Figure 5 shows 1H spectra of 5 in D2O at various temperatures. Distinct signals for the phenyl moieties of Z-L-Phe ends and methyl groups of the PPO block are apparent. It was clearly observed that, with an increase of temperature, the peaks attributed to the above phenyl and methyl moieties broadened rapidly. It may be attributed to the limited motions of these moieties. At low temperature, the phenyl moieties of Z-L-Phe ends and methyl groups of the PPO block were solvated and could move freely in the solution. Nevertheless, when the temperature increased beyond critical micellization temperature (CMT), micellization began to take place. The phenyl and methyl moieties were in a more confined environment, and their movements were limited and restricted, resulting in the broadening of the corresponding peaks. This result also indicates that the cores of the formed micelles consists mainly of the PPO blocks and Z-L-Phe ends and that the coronas are made up of the hydrated PEHA-grafted R-CD-PEO IC domains. Fluorescence probe technique is a powerful tool to study micellar properties of amphiphilic block copolymers.49-52 Often, pyrene is chosen as the fluorescence probe to monitor the change in the polarity of the microenvironment in the micelle. With the onset of micellization of block copolymers in an aqueous solution of pyrene, there is an increase in the quantum yield of the fluorescence, a change in the vibrational fine structure of the emission spectra, and a shift of the (0,0) absorption band from about 334 to 337 nm in the excitation spectra.49 According to the literatures,51,52 it is preferred to examine the (0,0) band change of pyrene in the excitation spectra and to compare the intensity ratio of I337 to I334. At low temperatures, this ratio takes the characteristic value of pyrene in water, whereas at high temperatures beyond CMT it takes the value of pyrene entirely in the hydrophobic environment. The change of the intensity

ratio corresponds to the transfer of pyrene molecules from the aqueous environment to the hydrophobic micellar cores, thus providing information on the location of the pyrene probe in the system. Figure 6 shows the excitation spectra for pyrene in water in the presence of 2.5 g/L of 5 ranging from 5 to 45 at 5 °C temperature intervals. It was clearly observed that a red shift of the (0,0) absorption band from 334 to 337 nm occurred with an increase of temperature. Figure 7 shows the intensity ratio between I337 and I334 of pyrene excitation spectra for the above sample as a function of temperature. The I337/I334 versus temperature plots present a sigmoidal curve. With an increase in temperature, the intensity ratio exhibited a substantial increase, indicating the incorporation of pyrene into the inner hydrophobic core of the micelles. A series of fluorescence spectra of 5 in aqueous solutions with concentrations from 0.25 to 20 g/L containing pyrene were taken in this way, and thus the CMT values for 5 at various concentrations were obtained from the first inflection of the intensity ratio of I337 to I334 versus temperature plot (Figure 8), and the results are listed in Table 1. Thermodynamics of Micelle Formation of 5. Similar to micellization of the pluronic PEO-PPO-PEO triblock copolymers, 5 could form micelles in water since water is a good solvent for PEHA-grafted R-CD-PEO IC domain and precipitant for the PPO block. Hence, the micellization of the cationic polyrotaxane was expected to obey the closed association model, which assumes that an equilibrium exists between unimers (A) and micelles (An). Resembling the thermodynamics for micellization of block copolymers, the standard free-energy change for the transfer of 1 mol of amphiphilic 5 from solution to the micellar phase (standard free energy of micellization, ∆G°) is given by eq 1,44-48

∆G◦ ) RTln(XCMC)

(1)

where R is the gas law constant, T is the absolute temperature, and XCMC is the critical micellization concentration (CMC) in mole fraction units. Similarly, the standard entropy and enthalpy of micellization, ∆S° and ∆H°, are obtained from eqs 2 and 3,44-48

∆S◦ ) (∆H◦ - ∆G◦)/T and

(2)


∆H◦ ) R[∂ ln(X)/∂(1/TCMT)]P


(3)

where X is the concentration expressed as mole fraction and TCMT is the critical micellization temperature. As shown in Figure 9, the inverse CMT values were plotted as a function of the logarithm of the cationic polyrotaxane concentration (mole-fraction units). Thus, the value of ∆H° is estimated to be 235.72 kJmol-1, which was calculated from the inverse slope of the linear fit to the 1/TCMT versus ln(mole fraction) data, in accordance with eq 3. On the basis of the assumption that ∆H is independent of temperature within the temperature measuring range, the value of ∆G° and ∆S° is estimated to be -34.03 kJ mol-1 and 0.911 kJ mol-1 K-1, respectively (calculated from eqs 1 and 2, respectively, at the CMT for 1 g/L of 5). The results indicate that the micellization process is dominantly driven by the entropy change, rather than enthalpy change. Although it is an enthalpically unfavorable and endothermic process, the enthalpy change only plays a minor role. Micellar Morphology of 5. The direct observation of the micellar structure of 5 was carried out using transmission electron microscopy (TEM) and atomic force microscopy (AFM). Figure 10 shows the TEM and AFM images of micelles of 5. As shown in Figure 10a, the micelles take an almost spherical shape, and most of the micelles have diameters in the range of 75-90 nm in the dried state. Also, a bright region is found to surround a dark region for each micelle. The peripheral bright region corresponds to the diffuse outer shell formed by the hydrated PEHA-grafted R-CD-PEO IC domains, whereas the central dark region is the dense inner core of the micelles formed by the hydrophobic PPO blocks. Similar micellar sizes and shapes were obtained from AFM images (Figure 10b). Conclusions In this study, a soluble cationic polyrotaxane composed of multiple PEHA-grafted R-CD rings threaded and embedded in a PPO-PEO-PPO triblock copolymer chain was synthesized based on the block-selected inclusion complexation between the block copolymer and R-CD. The results, calculated from 1H spectra, showed that there were 6 R-CD rings threaded onto one polymeric chain in the cationic polyrotaxane and that each R-CD ring was grafted with 4.8 PEHA chains. The cationic polyrotaxane synthesized is amphiphilic in nature since it has two large hydrophobic flanking PPO blocks and one central hydrophilic PEHA-grafted R-CD-PEO IC domain. With increasing concentration and temperature, the cationic polyrotaxane could form multimolecular micelles. The micellization phenomena were studied using 1H and fluorescence spectra. Similar to the thermodynamic analysis of the amphiphilic copolymers, a closed association model was introduced to describe and analyze the micellization process of the cationic polyrotaxane, thus the micellization parameters including standard free energy (∆G°), enthalpy (∆H°), and entropy (∆S°) were obtained. The positive ∆H° value indicates that the micellization of the cationic polyrotaxane is dominantly driven by the entropy change. The sizes and shapes of the micelles were also observed directly from TEM and AFM images. This new soluble, temperature-responsive cationic polyrotaxane may be used as a potential drug carrier in drug delivery. Acknowledgment. We acknowledge the financial support from the Academic Research Fund, Ministry of Education, Singapore (Grant code: R-397-000-031-112) and Institute of Materials Research and Engineering, Singapore.

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JP809207Q

Thermoresponsive Behavior of Cationic Polyrotaxane Composed of

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