Study of the Synthesis, Crystallization, and Morphology of Poly

Poly(ethylene glycol)−poly(ε-caprolactone) diblock copolymers PEG−PCL were .... Macromolecules 0 (proofing), ... Biomacromolecules 2006 7 (1), 25...
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Biomacromolecules 2004, 5, 2042-2047

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Study of the Synthesis, Crystallization, and Morphology of Poly(ethylene glycol)-Poly(E-caprolactone) Diblock Copolymers Chaoliang He, Jingru Sun, Chao Deng, Ting Zhao, Mingxiao Deng, Xuesi Chen,* and Xiabin Jing State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China Received May 10, 2004; Revised Manuscript Received July 6, 2004

Poly(ethylene glycol)-poly(-caprolactone) diblock copolymers PEG-PCL were synthesized by ring-opening polymerization of -caprolactone using monomethoxy poly(ethylene glycol) as the macroinitiator and calcium ammoniate as the catalyst. Obvious mutual influence between PEG and PCL crystallization was studied by altering the relative block length. Fixing the length of the PEG block (Mn ) 5000) and increasing the length of the PCL block, the crystallization temperature of the PCL block rose gradually from 1 to about 35 °C while that of the PEG block dropped from 36 to -6.6 °C. Meanwhile, the melting temperature of the PCL block went up from 30 to 60 °C, while that of the PEG block declined from 60 to 41 °C. If the PCL block was longer than the PEG block, the former would crystallize first when cooling from a molten state and led to obviously imperfect crystallization of PEG and vice versa. And they both crystallized at the same temperature, if their weight fractions were equal. We found that the PEG block could still crystallize at -6.6 °C even when its weight fraction is only 14%. A unique morphology of concentric spherulites was observed for PEG5000-PCL5000. According to their morphology and real-time growth rates, it is concluded that the central and outer sections in the concentric spherulites were PCL and PEG, respectively, and during the formation of the concentric spherulite, the PEG crystallized quickly from the free space of the PCL crystal at the earlier stage, followed by outgrowing from the PCL spherulites in the direction of right angles to the circle boundaries until the entire area was occupied. Introduction Biodegradable aliphatic polyesters have received great attention over the past two decades. Among them, poly(caprolactone) (PCL), poly(lactic acid), poly(glycolic acid), and their copolymers have been widely used in medical applications, for example, in bone fracture fixation, as sutures, as tissue engineering scaffolds, and as drug release carriers.1-5 Recently, poly(ethylene glycol) (PEG)-PCL block copolymers have been prepared by ring-opening polymerization of -caprolactone (-CL) using PEG as the macroinitiator.6-11 Especially, our group has developed a new and safe catalyst for the ring-opening polymerization of -CL and L-lactide under relatively low temperatures.11-14 Such block copolymers exhibit various properties, such as biocompatibility, amphiphilicity, self-assembly, permeability, and controllable biodegradability. However, studies of the morphology and the crystallization (melting) properties of such block copolymers are rather limited.11-23 It was reported that the crystallization properties of a PCL-PEG-PCL triblock copolymer depend on the length of each block.11-13 Gan et al.18 studied the isothermal crystallization and melting behavior of the PEG-PCL diblock copolymers with the PEG weight fraction of 0.20. It was concluded that only the PCL block is crystallizable when the PEG content is lower than 20%. Bogdanov et al.21,22 characterized the thermal properties of three different * To whom correspondence should be addressed. Tel.: + 86-4315262112. Fax: + 86-431-5685653. E-mail: [email protected].

structures of PEG-PCL block copolymers. It was established that the PCL block crystallized first and fixed the total structure of the spherulites, leading to significant imperfect crystallization of the PEG block. Shiomi et al.23 observed the morphology of spherulites of PCL-PEG-PCL triblock copolymers with different lengths of each block. As a result, the triblock copolymers with PCL contents of 60 and 66 wt % were observed to have a unique morphology of concentric spherulites, of which the central and outer sections were PCL and PEG, respectively. The copolymer with a PCL content of 83 wt % gave only PCL spherulites, whereas that with a PCL content of 34 wt % showed only PEG spherulites. Up to date, no comparative study on the crystallization (melting) behavior and spherulite morphology of a series of PEGPCL diblock copolymers with different lengths of PCL block has been reported. In this paper, seven PEG-PCL diblock copolymers with different block lengths were prepared using calcium ammoniate as the catalyst. The remarkable mutual influence between the two blocks was observed and explained. Experiment Materials. -CL (from Aldrich) was purified by vacuum distillation over CaH2. Monomethoxy poly(ethylene glycol) (mPEG) with molecular weights of 2000 and 5000 (from Aldrich) were dried by an azeotropic distillation with dry toluene. Metal calcium was used as received. Xylene was dried by refluxing over sodium metal under an argon atmosphere.

10.1021/bm049720e CCC: $27.50 © 2004 American Chemical Society Published on Web 08/18/2004

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PEG-PCL Synthesis, Crystallization, and Morphology Table 1: Molecular Weight and Composition of PEG-PCL Diblock Copolymers sample

Mn of PEGa

PCL in feed (wt %)

Mn of PCLb

Mn of the copolymerc

Mw/Mnc

PCL in copolymerb (wt %)

PEG5000-PCL2070 PEG5000-PCL3020 PEG5000-PCL5000 PEG5000-PCL7990 PEG5000-PCL15 200 PEG5000-PCL30 600 PEG2000-PCL33 000

5000 5000 5000 5000 5000 5000 2000

28.6 37.5 50.1 61.5 75.1 85.7 93.8

2070 3020 5000 7990 15 200 30 600 33 000

13 890 15 416 18 066 23 882 30 798 42 572 40 649

1.10 1.14 1.15 1.10 1.19 1.31 1.44

29 38 50 62 75 86 94

a

Nominal value. b Evaluated by 1H NMR. c Determined by GPC (calibrated with polystyrene standards).

Polymerization. The PEG-PCL diblock copolymers were synthesized by ring-opening polymerization of -CL using mPEG as the macroinitiator and calcium ammoniate as the catalyst, respectively. Gaseous NH3 was purified by passing it through a sodium sulfate column and a sodium hydroxide column in turn and was liquidized in a bath with a mixture of dry ice and ethanol. The liquidized NH3 was introduced into a flask containing metal Ca under -40 °C. Ten minutes later, the excess of NH3 was evaporated by warming the flask to room temperature. Then the reaction product was transferred into another flask, in which stoichiometric mPEG and -CL in xylene solution were added. The reaction was carried out at 60 °C for 24 h. The product was isolated by dissolving in CHCl3 and precipitating into isopropyl alcohol, followed by centrifugation and drying in a vacuum at room temperature for 24 h. Casting Films. The samples used for crytallization were prepared by casting three drops of a 1 wt % chloroform solution of the copolymers on a clean cover glass and then airing for 2 days at room temperature followed by drying under vacuum for 2 days. Measurements. The molecular weights and polydispersity of the polymers were determined by GPC (Waters 410 GPC apparatus equipped with a Styragel HT6E column) with tetrahydrofuran as the eluent at 35 °C and polystyrene standards for column calibration. 1H NMR spectra of the polymers in deuterated chloroform solutions were recorded by a Brucker 300 MHz spectrometer with tetramethylsilane as the internal standard. The molecular weight of the PCL component in the copolymer was calculated from 1H NMR spectra on the basis of PEG’s molecular weight. Differential scanning calorimetry (DSC) was carried out on a DSC-7 (Perkin-Elmer) at a heating rate of 10 °C/min under a nitrogen atmosphere. Wide-angle X-ray diffraction (WAXD) was carried out by a Rigaku X-ray diffractometer with a Nifiltered Cu KR radiation (λ ) 0.1546 nm) at room temperature. The scan rate was 4° 2θ/min. The selected voltage and current were 40 kV and 200 mA, respectively. The morphology of spherulites was observed under a polarized optical microscope (Linkam TM 600) equipped with crossed polarizers. Results and Discussion Synthesis and Characterization. Seven PEG-PCL diblock copolymers (shown in Table 1) with different molecular weights and compositions were easily synthesized by adjusting the feed molar ratio of mPEG/-CL in the presence of

Figure 1. DSC curves of PEG (Mn ) 5000): (a) first heating; (b) cooling; and (c) second heating. 10 °C/min.

Figure 2. DSC curves of PCL (Mn ) 8000): (a) first heating; (b) cooling; and (c) second heating. 10 °C/min.

calcium ammoniate. The reaction mechanism was presented in our previous work.11-14 The content of PCL, which varied from 29 to 94 wt % in the copolymers, was calculated by using relative intensities of the characteristic peak of 1H NMR at 2.31 ppm for PCL and that at 3.65 ppm for PEG. The sharp unimodal distribution of the GPC traces indicated that the copolymerization has been completed successfully and no homopolymerization occurred. DSC and WAXD Analyses. The melting and crystallization behaviors of the PEG-PCL diblock copolymers are investigated by DSC. Figures 1-4 show the DSC curves obtained. The DSC curves of homo-PEG and homo-PCL are also included for comparison. All samples are first heated

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Figure 3. DSC curves of the first cooling for PEG-PCL diblock copolymers, 10 °C/min.

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Figure 5. WAXD (at room temperature) of PCL, PEG homopolymers, and PEG-PCL diblock copolymers. Table 2: Melting and Crystallizing Temperatures (°C) of the Diblock Copolymers

Tc,PEG PEG5000 PEG5000-PCL2070 PEG5000-PCL3020 PEG5000-PCL5000 PEG5000-PCL7990 PEG5000-PCL15 200 PEG5000-PCL30 600 PEG2000-PCL33 000 PCL

Figure 4. DSC curves of the second heating for PEG-PCL diblock copolymers, 10 °C/min.

to 100 °C, then cooled to -50 °C at 10 °C/min, and finally heated to 100 °C at 10 °C/min. Figure 1 shows the DSC curves of PEG5000. It has a monomodal peak in the first heating curve a with a melting point at Tm ) 66.6 °C and in the cooling curve b with crystallization point at Tc ) 42.6 °C. There are bimodal peaks in the endotherm in the second heating curve c corresponding two melting points at 58.3 and 64.6 °C, owing to the melting of PEG lamellae with different fold numbers.20 The DSC curves of PCL homopolymer are shown in Figure 2. It shows single melting and crystallization peaks at Tm(second heating) ) 57.3 °C and Tc ) 31.6 °C, respectively. The difference between the second melting temperature and the crystallization temperature (∆T ) Tm - Tc) is about 23 °C for PEG homopolymer and 25 °C for PCL homopolymer, respectively. Both homopolymers have a close melting temperature (Tm,PEG ) 64.6 °C and Tm,PCL ) 57.3 °C, respectively). The cooling and melting behaviors by DSC for the diblock copolymers are presented in Figures 3 and 4, respectively. There are two exothermic peaks and two endothermic peaks in all diblock copolymers except PEG5000-PCL5000 and PEG2000-PCL33000. For these two, only a single exothermic peak and a single endothermic peak are observed. All

Tc,PCL

42.6 36.2 1.1 35.0 16.2 34.9 32.2 35.6 19.5 33.3 -6.6 35.3 34.3 31.6

Tm,PEG 64.6, 58.3 60.0 60.1 58.7 50.4 49.8 40.6

Tm,PCL 30.4 41.2 58.4 59.6 60.4 60.1 57.3

of the melting and crystallization points are summarized in Table 2. To assign these DSC peaks to corresponding blocks, the DSC data are analyzed with the help of WAXD results.21,22 As shown in Figure 5, both PCL and PEG blocks in PEG5000-PCL2070, PEG5000-PCL3020, PEG5000PCL5000, PEG5000-PCL7990, and PEG5000-PCL15200 can crystallize and form separate crystal phases because their WAXD curves are just a summation of the PEG and PCL crystal patterns. However, for PEG5000-PCL30 600 and PEG2000-PCL33 000, only the crystal patterns typical for the PCL crystal phase are observed. The WAXD results show the lower crystallizability of the PCL blocks in PEG5000-PCL2070 and PEG5000-PCL3020, lower crystallizability of the PEG blocks in PEG5000PCL7990, PEG5000-PCL15200, PEG5000-PCL30600, and PEG2000-PCL33000, and almost coequal crystallizability of PEG and PCL blocks in PEG5000-PCL5000. And the absence of PEG crystal patterns in PEG5000-PCL30 600 WAXD patterns may be due to the fact that PEG blocks are still in the molten state (Figure 3, Tc ) -6.6 °C) at room temperature. The result of WAXD also explain that microphase separation takes place in all of the diblock copolymers. The PCL and PEG components form two separate microdomains. Therefore, from the DSC curves and WAXD results, the crystallization and melting temperature of each block for all diblock copolymers can be assigned clearly and summarized in Table 2. For example, the strong exothermic peak (36.2

PEG-PCL Synthesis, Crystallization, and Morphology

°C) in Figure 3 and endothermic peak (60.0 °C) in Figure 4 for PEG5000-PCL2070 are due to PEG blocks, while the weak exothermic peak (1.1 °C) and endothermic peak (30.4 °C) are due to PCL blocks. On the other hand, the exothermic peak (35.6 °C) in Figure 3 and endothermic peak (58.4 °C) in Figure 4 for PEG5000-PCL7990 are attributed to PCL blocks, while the exothermic peak (32.2 °C) in Figure 3 and endothermic peaks (50.4 °C) in Figure 4 are attributed to PEG blocks. From the DSC curves and WAXD results of the diblock copolymers, it can be concluded that the crystallization and melting properties are significantly affected by the PCL/PEG ratio in the diblock copolymer. Fixing the length of PEG (Mn ) 5000), the crystallizations of both PEG and PCL are affected obviously by the length of PCL. For PEG5000PCL2070 and PEG5000-PCL3020, in which the PCL block is shorter, the PEG blocks crystallize earlier and bring about constraints to the crystallization of PCL blocks, but when the PCL block is longer than the PEG block (in PEG5000PCL8000 to PEG5000-PCL30 600, as well as PEG2000PCL33 000), the PCL blocks crystallize first instead and the PEG blocks have to crystallize under a confined condition. And when the contents of PEG and PCL are equal to each other (in PEG5000-PCL5000), they crystallize at the same temperature (34.9 °C). From the DSC and WAXD results, the crystallization of the restricted blocks in the copolymer requires a higher degree of undercooling. Noticeably, it is found from the DSC curves (Figure 3) that PEG blocks can also crystallize in PEG5000-PCL30 600 that consists of only 14% PEG, 6% less than the lowest content observed by Gan et al.18 for PEG blocks to crystallize in PEG-PCL diblock copolymer. The mutual influence between PCL and PEG blocks is dependent on the relative length. As shown in Table 2, with the length of the PEG block fixed (Mn ) 5000), the crystallization temperature of the PCL block rises gradually from 1 to about 35 °C while that of the PEG block drops from 36 to -6.6 °C with increasing length of the PCL block. At the same time, the melting temperature of the PCL block goes up from 30 to 60 °C, while that of the PEG block declines from 60 to 41 °C. Polarized Optical Microscopy (POM). Figures 6 and 7 show the optical micrographs of spherulites of the seven copolymers and the homopolymers of PCL and PEG observed under crossed polarizers. In Figure 6, both PEG5000-PCL2070 and PEG5000-PCL3020 show spherulite morphology similar to that of PEG homopolymer shown in Figure 7a. And samples PEG5000-PCL15 200, PEG5000PCL30 600, and PEG2000-PCL33 000 (Figure 6e-g) show similar spherulite patterns to that of homo-PCL (Figure 7b). These similarities allow us to assign the former two and the latter three patterns to PEG spherulites and to PCL spherulites, respectively. For PEG5000-PCL5000, as shown in Figure 6c, bright central spherulites are embedded in dark outer spherulites. The bright region can be further divided into a bright center, a dark ring around it, and a bright wide ring outside. In Figure 6d for PEG5000-PCL7990, more alternative bright and dark rings are observed, but the dark outer spherulites shown in Figure 6c are not seen.

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Figure 6. POM micrographs of spherulites of diblock copolymers, crystallized at 42 °C.

Figure 7. POM micrographs of spherulites of (a) PEG and (b) PCL homopolymers, crystallized at 42 °C.

Real-Time Observation. To explain the above results, three typical samples were melted at 80 °C and then quenched to 36 °C. The real-time morphology changes were observed under crossed polarizers. The results are shown in Figures 8-10. It is known that the growth of PEG spherulites is much quicker than that of PCL.22,23 The spherulites of PEG5000-PCL3020 grew as quickly as that of pure PEG as shown in Figure 8, whereas those of PEG5000PCL15 200 grew as slowly as that of pure PCL, as shown in Figure 10. Therefore, the spherulites in Figure 8 can be assigned to PEG while those in Figure 10 can be assigned

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Figure 8. Real-time POM micrographs of the PEG5000-PCL3020 (melted at 80 °C for 5 min followed by quenching to 36 °C).

Figure 9. Real-time POM micrographs of the PEG5000-PCL5000 (melted at 80 °C for 5 min followed by quenching to 36 °C).

to PCL. As for sample PEG5000-PCL5000, a complicated crystallization process was observed. As shown in Figure 9, at the beginning, there appeared several bright crystalline nuclei on the black background and they grew quite slowly. About 25-30 s later, some of these spherulites became brighter quickly from their center to around and then began to grow out at the same speed in the direction at right angles to the circle boundaries until the entire area was occupied, but the brightness was less than that of the central part. Considering the above nucleation times and growth rates, we assign the interior bright center to PCL and the exterior darker area to PEG. In addition, the brightening process of the interior spherulites can be attributed to the growth of PEG crystallization in the free space of the PCL spherulites. That is to say, at 36 °C, PCL nucleates earlier but its crystals grow slower whereas PEG nucleates later but its crystals grow faster. The sudden appearance of the PEG phase prevents the PCL phase from further growing, leading to the sharp boundary of the PCL phase.

He et al.

Figure 10. Real-time POM micrographs of the PEG5000-PCL15 200 (melted at 80 °C for 5 min followed by quenching to 36 °C).

Fortunately, Figure 9 (at 60 s) look like Figure 6c although they were obtained at 36 and 42 °C, respectively. Therefore, we may make the same assignment for Figure 6c. With the same argument, we assign the bright center and bright wide rings in Figure 6d to PCL, but the assignment of the dark thin rings has not been clear yet. The difference between parts c and d of Figure 6 is caused by the relative length and the relative supercooling degree of the PCL block. Obviously, this mechanism for the concentric spherulites in PEG-PCL is different from those for poly(dioxolane)24 and for PCL blends.25,26 Here, it should be mentioned that POM patterns are the optical images of the spherulites. All the samples examined by POM were cooled to room temperature prior to observation, so both PEG and PCL crystals should coexist. From the above discussion, it is concluded that only the crystals that were formed at the isothermal crystallization temperature are reflected in POM images. This is because the postcrystallization of PCL blocks (in samples PEG5000PCL2070 and PEG5000-PCL3020) or PEG blocks (in samples PEG5000-PCL15 200, PEG5000-PCL30 600, and PEG2000-PCL33 000) only takes place in the free space left after the isothermal crystallization and does not change the overall morphology or internal spatial distribution of the spherulites. Conclusions PEG-PCL diblock copolymers with fixed PEG block length and various PCL block lengths were synthesized by using calcium ammoniate as the catalyst. In all the copolymers, microphase separation was observed because the PCL and PEG blocks like to crystallize themselves. The relative block length determines which block crystallizes first. When the length of the PEG block is longer it crystallizes first and leads to imperfect crystallization of the PCL block and vice versa. With the length of PEG block fixed, the crystallization temperature of PCL block rises gradually from 1 to about 35 °C with increasing length of PCL block, while that of PEG block drops from 36 to -6.6 °C. At the same time, the

PEG-PCL Synthesis, Crystallization, and Morphology

melting temperature of PCL block goes up from 30 to 60 °C, while that of PEG block declines from 60 to 41 °C. In this study, a unique morphology of concentic spherulites for PEG5000-PCL5000 was observed by POM. On the basis of the real-time observation of the crystallization process, these concentric POM images are assigned as follows: bright center and bright wide rings are due to PCL crystallization, and the outer darker part is due to PEG crystallization. They can be observed by POM at 36 °C because the PCL block nucleates earlier but its crystals grow slowly while the PEG block nucleates later but its crystals grow quickly, and eventually both crystalline phases are formed at 36 or 42 °C. In other isothermally prepared samples, only the crystalline phases formed at the crystallization temperature are detected by POM. Acknowledgment. This project is financially supported by the National Natural Science Foundation of China, Project No. 50173027, 20274048, 50373043, and the “863” Project (2002AA326100) from the Ministry of Science and Technology of China. References and Notes (1) Masahiko, O. Prog. Polym. Sci. 2002, 27, 87. (2) Kathryn, E. U.; Scott, M. C.; Robert, S. L.; Kevin, M. S. Chem. ReV. 1999, 99, 3181. (3) Jeong, B. M.; Bae, Y. H.; Lee, D. S.; Kim, S. W. Nature 1997, 388, 860. (4) Chiellini, E.; Solaro, R. AdV. Mater. 1996, 8, 305. (5) Robert, L. Science 1993, 260, 920. (6) Rashokv, I., II; Espartero, J. L.; Manolova, N.; Vert, M. Macromolecules 1996, 29, 57.

Biomacromolecules, Vol. 5, No. 5, 2004 2047 (7) Cerrai, P.; Guerra, G. D.; Lelli, L.; Tricoli, M. J Mater. Sci.: Mater. Med. 1994, 5, 33. (8) Youxin, L.; Kissel, T. J. Controlled Release 1993, 27, 247. (9) Jedlinski, Z.; Kurcok, P.; Walach, W.; Janeczek, H.; Radecka, I. Makromol. Chem. 1993, 194, 1681. (10) Kricheldorf, H. R.; Meier-Haack, J. Makromol. Chem. 1993, 194, 715. (11) Piao, L. H.; Dai, Z. L.; Deng, M. X.; Chen, X. S.; Jing, X. B. Polymer 2003, 44, 2025. (12) Piao, L. H.; Deng, M. X.; Chen, X. S.; Jiang, L. S.; Jing, X. B. Polymer 2003, 44, 2331. (13) Tang, Z. H.; Chen, X. S.; Liang, Q. Z.; Bian, X. C.; Yang, L. X.; Piao, L. H.; Jing, X. B. J. Polym. Sci., Part A: Polym. Chem. 2003, 41, 1934. (14) Rong, G. Z.; Deng, M. X.; Deng, C.; Tang, Z. H.; Piao, L. H.; Chen, X. S.; Jing, X. B. Biomacromolecules 2003, 4, 1800. (15) Perret, R.; Skoulios, A. Makromol. Chem. 1972, 162, 147. (16) Perret, R.; Skoulios, A. Makromol. Chem. 1972, 162, 163. (17) Nojima, S.; Ono, M.; Ashida, T. Polym. J. 1992, 24, 1272. (18) Gan, Z. H.; Jiang, B. Z.; Zhang, J. J. Appl. Polym. Sci. 1996, 59, 961. (19) Gan, Z. H.; Zhang, J.; Jiang, B. Z. J. Appl. Polym. Sci. 1997, 63, 1793. (20) Wunderlich, B. Macromolecular Physics, Crystal Nucleation, Growth, Annealing; Academic Press: New York, 1976; Vol. 2, p 168. (21) Bogdanov, B.; Vidts, A.; Van Den Bulcke, A.; Verbeeck, R.; Schacht, E. Polymer 1997, 39, 1631. (22) Bogdanov, B.; Vidts, A.; Schacht, E. Macromolecules 1999, 32, 726. (23) Shiomi, T.; Imai, K.; Takenaka, K.; Takeshita, H.; Hayashi, H.; Tezuka, Y. Polymer 2001, 42, 3233. (24) Geil, P. H. Polymer single crystals; Interscience: New York, 1963; Chapter IV, p 284. (25) Ma, D. Z.; Luo, X. L.; Zhang, R. Y.; Nishi, T. Polymer 1996, 37, 1575. (26) Ma, D. Z.; Xu, X.; Luo, X. L.; Nishi, T. Polymer 1997, 38, 1131.

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