Preparation and Crystallization Kinetics of New Structurally Well

Biomacromolecules 2005, 6, 2236-2247

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Preparation and Crystallization Kinetics of New Structurally Well-Defined Star-Shaped Biodegradable Poly(L-lactide)s Initiated with Diverse Natural Sugar Alcohols Qinghui Hao,† Faxue Li,†,‡ Qiaobo Li,† Yang Li,† Lin Jia,†,§ Jing Yang,† Qiang Fang,† and Amin Cao*,† Laboratory for Polymer Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China, College of Textiles, Donghua University, 1882 Yan-an west Road, Shanghai 200051, China, and Department of Chemistry, Northwest University, 229 North Taibai Road, Xi’an, Shanxi 710069, China Received March 22, 2005; Revised Manuscript Received April 25, 2005

This study presents syntheses, structural characterization, and crystallization kinetic investigation of new structurally well-defined star-shaped poly(L-lactide)s (PLLAs). First, a series of new 3- to 6-arm star-shaped PLLAs were synthesized through SnOct2 catalyzed ring-opening polymerization of (L)-lactide with natural sugar alcohols of glycerol, erythritol, xylitol, and sorbitol as the favorable initiators. Subsequently, their chemical structures were characterized by means of GPC, NMR, and viscometer with respect to the starshaped structures, demonstrating the well-defined arm structures as evidenced on the g1/2/g′ values, where g and g′ denote the ratios of mean-square radius of gyration and intrinsic viscosity of a star-shaped polymer to those of a linear structural reference with similar absolute molecular weight. Furthermore, spherulite morphologies and growth rates were studied by a polarized microscopy (POM) for the synthesized starshaped PLLAs with different molecular weights, and it was found that the more arms of a star-shaped PLLA finally resulted in a lower spherulite growth rate. With regard to the crystallization kinetics of these star-shaped PLLAs, isothermal and nonisothermal crystallization were examined by differential scanning calorimeter (DSC). It was found that Avrami exponent n values of isothermal crystallization were almost independent of the isothermal crystallization temperature Tc for different series of star-shaped PLLAs. In contrast, the values of Avrami exponent n were observed to strongly depend on the star-shaped structures with different arms, implying their distinct nucleation mechanisms, and the more arms of a star-shaped PLLA led to a slower isothermal crystallization rate. On the basis of a modified Avrami equation, new light was shed on the nonisothermal crystallization kinetics for the star-shaped PLLAs, and the activation energies were found to vary from 146.86 kJ/mol for the linear PLLA EG-3 to 221.23 kJ/mol of the star-shaped S-3, demonstrating much decreased crystallizabilities of star-shaped PLLAs with more arms. Introduction In the past decades, there has been a steadily increasing interest in fundamental research and application of biodegradable and biocompatible polymers. Among them, poly(L-lactide) (PLLA) derived from renewable biomass has been extensively studied due to its bioresorbability and good physical properties;1 thus, nowadays it has been widely applied as an important kind of biomaterial in biomedicine,2 surgical suture,3 tissue engineering,4 and drug delivery systems.5-6 On the other hand, linear structural PLLA as rigid plastics with a glass transition temperature over 50 °C has also been known to have some drawbacks, like excessive brittleness and lower thermal stability under processing, and for instance, high melt viscosity of linear structural PLLA would result in thermal degradation during production of * To whom correspondence should be addressed. Phone: +86-21-54925303. Fax: +86-21-6416-7152. E-mail: [email protected]. † Chinese Academy of Sciences. ‡ Donghua University. § Northwest University.

fiber and bone plates,7 and these indeed impeded a more broad spectrum of its possible applications. To date, to improve physical properties of the linear structural aliphatic polyesters, numerous functional copolymers and new branched structural biodegradable polyesters have been rationally designed and synthesized; in particular, star-shaped polymers have been found to exhibit interesting morphologies and rheological properties significantly different from their linear structural counterparts.8 So far, it has been known that chemical preparation of the star-shaped functional polymers could be accomplished generally in two important synthetic strategies, namely the “arm-first” and an alternative “core-first” approach.9-11 Ring opening polymerization has usually been employed with a suitable catalyst in the “core-first” approach. In the meantime, the final functional polymer structures inherently depend on the polyfunctional “core” applied as the true “initiators”. Until now, there have been a number of works published on the syntheses of the star-shaped biodegradable polyesters with various polyhydroxyl initiators, 12-13 such as penta-

10.1021/bm050213m CCC: $30.25 © 2005 American Chemical Society Published on Web 05/25/2005

Preparation and Kinetics of Star-Shaped PLLAs

erythritol,7,14a-g trimethylol propane,14c-e,15 polyglycerine,14f dipentaerythritol,15 di(trimethylol propane),15 dendritic polyols,16 and so forth. In this way, Kim et al.7,14a prepared 4-arm star-shaped biodegradable PLLAs with the pentaerythritol initiator and thereby revealed that their second virial coefficients and intrinsic viscosities are lower than those of linear structural PLLAs in solution. Furthermore, using trimethylol propane or pentaerythritol as the initiator, new 3- or 4-arm star-shaped polyesters and structurally well-defined block copolyesters were further synthesized.14c-d In addition, Seppa¨la¨ et al.14f have preliminarily investigated the polymerization kinetics for the 4-, 6-, and 10-arm star-shaped PLLAs and concluded that polymerization rate of the PLLA arms apparently increased with the hydroxyl functionalities under a fixed molar ratio of monomer to the initiator. Recently, structurally more complicated star-shaped PLLAs have been synthesized with various dendritic synthetic precursors such as PAMAM-OH as the macroinitiators.16 In view of most of the published works, it can however be found that most of the true initiators as the “cores” for preparation of star-shaped biodegradable PLLAs are not favorable natural products; thus, after complete biodegradation of PLLA, the nonbioresorbable residual “core” compounds might be problematic particularly for the specific in vivo applications. On the other hand, sugar alcohols such as sorbitol and glycerol have been known as important low/ nontoxic natural products. Employing the sorbitol and glycerol as the ROP initiators, 3- and 6-arm star-shaped PLLA were synthesized and investigated concerning their crystallization and degradation behavior17a,18a and thereby found a strong molecular weight dependence of melting temperature, crystallization rate, and degradation behavior. Furthermore, with respect to the 3-arm star-shaped PLLAs prepared with the glycerol core, Tsuji et al.18c most recently revealed that the 3-arm star-shaped PLLAs showed lower melting temperature, crystallinity, and spherulite growth rate than those of the linear PLLA. In general, although there have already been several studies on the star-shaped PLLAs synthesized with the sugar alcohols as glycerin or sorbitol, to our knowledge, few systematical studies have been published concerning structural elucidation and crystallization kinetics of the structurally well-defined star-shaped PLLAs initiated by diverse sugar alcohols. In this study, a series of natural sugar alcohols of glycerol, erythritol, xylitol, and sorbitol have been employed as the initiators to systematically prepare new star-shaped biodegradable PLLAs with corresponding 3- to 6-arm structures. Subsequently, their macromolecular architectures and their thermal and crystallization behaviors were examined by means of GPC, NMR, viscometer, polarized microscope (POM), and thermal analytical instruments. Finally, the starshape structure dependence of isothermal and nonisothermal crystallization kinetics was intensively studied and discussed for the new structurally well-defined star-shaped poly(lactide)s. Experimental Section Materials. L-Lactide monomer was kindly provided by Mr. X. Pan of Synica Chemical Ltd. (Shanghai, China) and

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was routinely purified four times via recrystallization in ethyl acetate. Stannous octoate supplied from Aldrich Chemical was distilled under reduced pressure, and then dissolved in dehydrated m-xylene prior to use. Solvent of m-xylene was allowed to be purified with distillation in metallic sodium and benzophenone. Sorbitol (AR grade) was recrystallized twice in ethanol. Erythritol and xylitol of AR grade were purchased from Acros Organics and further dried under ambient temperature in a vacuum oven. Glycerol and ethylene glycol of analytical grade were dehydrated over calcium oxide and then were distilled under reduced pressure. In addition, all of the other reagents of analytical grade were used as-received. Preparation of New Star-Shaped Biodegradable PLLAs. In this study, 3- to 6-arm star-shaped biodegradable PLLAs as well as linear PLLA were synthesized through SnOct2 catalyzed ring-opening polymerization of (L)-lactide monomer with corresponding sugar alcohols as true initiators. Typically, a glass tube was flame-dried and then was degassed and purged with nitrogen, and the process was repeated three times. Thereafter, predetermined amounts of initiator, catalyst, lactide monomer, and solvent of m-xylene were in turn placed into the reaction tube, and the tube was immersed in a preset oil-bath under an appropriate temperature. Subsequently, the reaction mixture was periodically sampled out and was monitored by1H NMR. When a certain monomer conversion approached, the reaction mixture was cooled and precipitated in an excess amount of dry cold methanol. Finally, the collected white precipitates were washed several times with methanol and then were dried under ambient temperature in a vacuum oven for 24 h before further characterization. Analytical Procedures GPC Characterization. Molecular weights of the synthesized star-shaped PLLA as well as the linear counterpart were measured under 40 °C on a Perkin-Elmer 200 series gel permeation chromatograph equipped with a refractive index detector (RI) and a network chromatography interface NCI 900. Two PLgel 5 µm mixed-D type of GPC columns (300 × 7.5 mm, Polymer Laboratories Ltd., UK) were set in series with chloroform as the eluent at 1.0 mL/min. Polystyrene standards with extremely narrow molecular weight distribution were commercially supplied from Showa Denko Ltd., Japan, and were employed to calibrate the recorded GPC elution traces. As a result, the molecular weights and their distributions were thus evaluated. NMR Characterization. NMR spectra were recorded at ambient temperature on a Bruker AMX-300 and a Varian VXR-300 Fourier transform nuclear magnetic resonance spectrometer operating at 300.0 and 75.5 MHz for corresponding 1H and 13C nuclei, respectively. Meanwhile, tetramethylsilane (TMS) was applied as the internal chemical shift reference. Measurements of Intrinsic Viscosity. Viscosities of the synthesized star-shaped PLLA as well as linear poly(lactide) were measured under 25 °C with a 1836 Ubbelohde viscometer in chloroform solution. Under a series of PLLA

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concentrations, special viscosities (ηsp) and relative viscosities (ηr) were measured and evaluated. Furthermore, intrinsic viscosities ([η]) were estimated via the extrapolation of the ηr vs polymer concentration plot for the synthesized polyesters. Polarized Microscope (POM). Spherulite morphologies and crystal growth rates were characterized under various crystallization temperatures for the star-shaped PLLA samples on an Olympus BX51 polarized microscope with an attached hot stage. First, a synthesized PLLA sample was sandwiched between two thin glass cover slides. Subsequently, the sample was allowed to heat up over their corresponding melting temperatures and further kept for 1 min. Finally, the sample temperature was allowed to rapidly decrease to a predetermined crystallization temperature for crystallization kinetic and spherulite morphological studies. Thermal Characterization. Thermal properties of the synthesized PLLAs were characterized on a Perkin-Elmer Pyris 1 differential scanning calorimeter (DSC) and a thermal gravimetrical analyzer (TGA). A total of 2.0∼3.0 mg of a synthesized PLLA sample was first encapsulated in an aluminum pan, then heated to 180 °C to remove its thermal history, and further kept under 60 °C for more than 3 weeks to prompt equilibrium crystallization. Then the sample was scanned from the room temperature to 180 °C at 20 °C/min. The melting point (Tm) and enthalpy of fusion (∆Hm) were estimated as the first peak top temperature and the integral of endothermic trace, respectively. With respect to isothermal crystallization kinetics, a sample was first melted at 180 °C for 0.5 min and then rapidly cooled to the preset crystallization temperature (Tc), and the DSC trace was thus recorded as a function of isothermal crystallization time. In a similar way, a PLLA sample was first melt at 180 °C for 1 min and then cooled to 65 °C at various cooling rates of 4, 8, and 16 °C/min, and the DSC trace for nonisothermal crystallization was recorded and further analyzed. In addition, thermal gravimetric analyses (TGA) were carried out at a heating rate of 10 °C/min from 50 to 500 °C under a flowing nitrogen atmosphere (45 mL/min). Peak top temperatures (Td) of the differentiated TGA trace (dTGA) were employed to characterize thermal decomposition and stabilities for the linear and new star-shaped PLLAs with diverse natural sugar alcohols as the “cores”. Results and Discussion Syntheses of New Star-Shaped Biodegradable PLLAs with Diverse Natural Sugar Alcohols. To prepare new starshaped PLLAs, in this study, the ring opening polymerization of enantiomeric (L)-lactide was catalyzed by the SnOct2 with the aid of diverse natural sugar alcohols as the initiators. At first, an experimental condition dependence of new starshaped polymer preparation was investigated, and the synthetic results are generalized in Table 1, where the series of samples denoted as S, X, E, G, and EG represent new structural PLLAs synthesized with corresponding sugar alcohol initiators of sorbitol (S), xylitol (X), erythritol (E), glycerol (G), and ethylene glycol (EG), respectively. With

Hao et al. Table 1. Results for the New Star-Shaped PLLAs Synthesized at Various Polymerization Temperatures in m-Xylene Solution initiator to monomer feeding ratio, temp. conv(%) conv(%) MnNMR (°C) at 1.5 hb at 5.0 hb (KDa)b Mw/Mnc sample [I]:[LLA]a S-1 S-2 X-1 X-2 E-1 E-2 G-1 G-2 EG-1

1:60 1:60 1:50 1:50 1:40 1:40 1:30 1:30 1:20

130 100 130 100 130 100 130 100 130

60.3 19.4 81.7 20.6 81.6 28.1 89.2 47.1 94.9

94.6 62.3 97.4 65.8 95.6 69.8 94.7 89.0 96.2

8.2 8.1 7.0 7.0 5.5 5.8 5.8 2.8 2.8

1.09 1.06 1.17 1.08 1.16 1.08 1.19 1.16 1.25

a The values express feeding molar ratios of sugar alcohol to LLA monomer. b The LLA monomer conversions (%) were evaluated by 1H NMR, and molecular weights of PLLAs were evaluated on the monomer conversions. c Mw/Mn (PDI) was characterized by GPC in chloroform with PS standards.

Figure 1. Polymerization time dependence of LLA monomer conversion in m-xylene solution at 130 °C under a fixed [LLA]/[sorbitol] equal to 60 and various molar ratios of SnOct2 catalyst to hydroxyl functional groups of sorbitol.

respect to the ROP reactions in solution, it was experimentally found that the ROP polymerization in m-xylene solution seemed better, and a polymerization temperature of 130 °C was more favorable when a good balance between the apparent polymerization rate and the well-tailored star-shaped architecture was taken into consideration. Figure 1 depicts the LLA monomer conversions under 130 °C and a fixed molar ratio of LLA to sorbitol initiator equal to 60 in m-xylene solution as a function of feeding molar ratio of SnOct2 catalyst to sorbitol hydroxyl functional group ([C]/[OH]). It could be obviously seen that the higher values of [C]/[OH] of reaction systems with a fixed [I]/[LLA] would apparently lead to faster ROP polymerization rates, and narrow molecular weight distributions with PDI ) Mw/Mn values lower than 1.23 as seen in Table 2 were observed for the final PLLA products as analyzed by GPC. Under a molar ratio of catalyst to the sorbitol hydroxyl functional group equal to 0.01, much narrow molecular weight distribution of the final PLLA product and suitable polymerization rate could be hereby realized; therefore, the value of [C]/[OH] equal to 0.01 was tentatively applied as the optimized


Preparation and Kinetics of Star-Shaped PLLAs Table 2. Ring-Opening Polymerization of LLA Initiated with Sugar Alcohol Sorbitol under Various Catalyst to Hydroxyl Molar Ratios in m-Xylene Solution at 130 °C

sample a

feeding catalyst to hydroxyl molar ratios, [C]/[OH]b

LLA conv. (%)c

MnNMR (KDa) c

Mw/Mnd

S-50 S-100 S-200 S-400

1:50 1:100 1:200 1:400

96.0 97.0 92.0 87.3

8.3 8.4 8.0 7.5

1.23 1.09 1.16 1.08

a All samples were synthesized under a fixed feeding molar ratio of LLA monomer to sorbitol equal to 60. b The [C]/[OH] Values express initial feeding molar ratios of catalyst to hydroxyl of sorbitol. c The LLA monomer conversions (%) were evaluated by 1H NMR, and molecular weights of PLLAs were evaluated on the monomer conversions. d Mw/Mn (PDI) was characterized by GPC in chloroform with PS standards.

polymerization condition for synthesizing diverse new starshaped PLLAs. Up to date, the structure-physical property relations were often discussed in most of the published works with an ideal hypothesis that arm structures of the star-shaped PLLAs initiated by sugar alcohols were perfect. Practically, the arm defects of the prepared star-shaped PLLAs were reported to possibly stem from the presence of less reactive secondary hydroxyl functional groups in the applied sugar alcohol initiators.14f In this study, for the low molecular weight PLLAs synthesized with various sugar alcohols, NMR and GPC were employed to elucidate their fine structures. As seen in the 1H and 13C NMR spectra, the characteristic proton (HO-CH2-, -CH(OH)-) and carbon (HO-CH2-, -CH(OH)-) resonance signals of methylene and methine directly neighboring hydroxyl functional groups of different sugar alcohols completely disappeared, and in the meantime new proton and carbon resonance signals originating from corresponding methylene and methine could be obviously detected; thus, these results unambiguously confirmed the efficient initiation of either primary or secondary hydroxyl functional group of the applied sugar alcohols. Furthermore, GPC traces exhibited extremely narrow and symmetrical elution peaks for all PLLA samples prepared with different sugar alcohol initiators, implying there was no appreciable ROP initiated by the impurities such as water, alcohol, and so forth. On these evidences, it could therefore be concluded that new star-shaped PLLAs bearing 3 to 6 arms as seen in Scheme 1 were synthesized with the initiation of various natural sugar alcohols. On the other hand, to make clear the fine structures of the synthesized star-shaped PLLAs, a series of star-shaped PLLAs were designed bearing diverse arms but similar theoretical absolute molecular weights and were efficiently prepared with various reduced sugar alcohols. Furthermore, their intrinsic viscosities [η] were measured at 25 °C in chloroform by means of Ubbelohde viscometer, and the ratios (g′) of intrinsic viscosities of the star-shaped PLLAs to that of linear structural PLLA bearing similar absolute molecular weight could be experimentally estimated in accordance with eq 1 g′ ) [η]star/[η]linear

(1)

For a star-shaped polymer with perfect arm structures, there will be an important relationship of g1/2 ) g′ or g1/2/g′ ) 1.0 as proposed by Zimm and Kilb,19 and the parameter (g) was defined as the ratio of mean-square radius of gyration of a star-shaped polymer to that of a linear counterpart with similar absolute molecular weight, and could be calculated according to eq 2,20 where the parameter f means arm number of the star-shaped polymer g ) 6f/[(f + 1)(f + 2)]

(2)

Table 3 summarized the calculated values of g1/2/g′ for the PLLAs prepared with the initiators of glycerol, erythritol, xylitol, sorbitol, and ethylene glycol and similar theoretical absolute molecular weights equal to 34.6 KDa. It could be seen that the g1/2/g′ values of 0.99-0.95 were very close to 1.00 for an ideal star-shaped polymer with perfect arm architecture, implying that the prepared star-shaped PLLAs had fewer arm defects and that the less hydroxyl functional groups in a sugar alcohol would lead to more perfect arm structures. To shed a new light on the initiation activities for the different sugar alcohols, Figure 2 shows the LLA monomer conversion as a function of ROP reaction time under 130 °C in m-xylene solution with fixed [C]/[OH] ) 0.01 and [LLA]/[OH] ) 10. It was seen that after 1.5 h that the conversion of LLA initiated by glycerol approached 90%, whereas the conversion was just near 60% for the sorbitol, indicating that the more hydroxyl functional groups were in a sugar alcohol like sorbitol, xylitol, the lower ROP polymerization rate could be apparently observed, similar to that as reported by Seppa¨la¨ et al.14f This result could be reasonably accounted for the larger steric hindrance stemming from high-densely packed PLLA chains for a sugar alcohol initiator bearing more secondary hydroxyl functionalities. Thermal Characterization. To examine the macromolecular structure dependence of thermal properties for the synthesized 3- to 6-arm star-shaped PLLAs with less arm defects, DSC and TGA were hereby employed. First, a series of PLLAs with different molecular weights were prepared with various molar ratios of sorbitol initiator to LLA monomer, and the synthetic results are summarized in Table 4, and much narrow molecular weight distributions could be detected. As compared to the S-1 sample, the molecular weight distribution for the S-4 synthesized under a lower [LLA]/[I] feeding molar ratio equal to 30 was detected to be more broad, and this may be suggested for the reason that the difference in initiation reactivity between the primary and secondary hydroxyl groups of sorbitol would become more obvious since a lower [LLA]/[I] feeding molar ratio would result in a faster complete conversion of the LLA monomer. Table 4 summarized thermal properties for S-1, S-3, and S-4, and it could be found that both their melting temperatures and enthalpies of fusion tended to increase with increasing molecular weight, indicating a tendency similar to those as reported.17a,18a The higher molecular weight of star-shaped PLLAs would lead to longer PLLA arms, and the longer PLLA arms were capable of organizing more perfect PLLA crystal lattices, and thus, they exhibited higher

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Scheme 1. Chemical Preparation of New Star-Shaped PLLAs Initiated with Diverse Reduced Sugar Alcohols

Table 3. Results for Syntheses of Diverse Star-Shaped PLLAs with Similar Theoretical Molecular Weights (34.6 KDa) in m-Xylene sample

initiator

feeding molar ratio, [I]: [LLA]a

LLA conv. (%)b

MnNMR (KDa)b

Mw/Mnc

[η] (ml/g)d

g′ e

g1/2f

g1/2/g′

S-3 X-3 E-3 G-3 EG-3

sorbitol xylitol erythritol glycerol ethylene glycol

1:240 1:240 1:240 1:240 1:240

96.8 96.1 96.8 96.3 97.0

33.5 33.2 33.5 33.3 33.6

1.16 1.15 1.16 1.46 1.86

35.8 36.4 38.7 40.9 42.5

0.84 0.86 0.91 0.96 1.00

0.80 0.84 0.89 0.95 1.00

0.95 0.98 0.98 0.99 1.00

a Values indicate the initiator to LLA monomer feeding molar ratios. b The LLA monomer conversions (%) were evaluated by 1H NMR, and molecular weights of PLLAs were evaluated on the monomer conversions. c Mw/Mn (PDI) was characterized by GPC in chloroform with PS standards. d The intrinsic viscosity [η] was measured in chloroform at 25 °C by 1836 Ubbelohde viscometer. e g′ ) [η]star/[η]linear. f g ) 6f/[(f + 1)(f + 2)], and the value of f means the number of arms.

Figure 2. Reaction time dependence of LLA monomer conversion under 130 °C in m-xylene solution with [catalyst]/[OH] ) 1/100 and [LLA]/[OH] ) 10 in the presence of different natural sugar alcohol initiators of sorbitol, xylitol, erythritol, glycerol, as well as ethylene glycol.

values of Tm and heat of fusion. Meanwhile, thermal stabilities were studied by TGA for the synthesized starshaped PLLAs, indicating that the thermal stabilities became higher with increasing molecular weights due to the decreased population of free chain ends.

Furthermore, Table 5 depicts thermal analytical results of the new star-shaped PLLAs with a diverse number of arms but similar theoretical absolute molecular weights equal to 8.6 KDa. Tm values of the star-shaped PLLAs were observed to be much lower than that of the linear structural EG-4 (Tm ) 143.7 °C). When taking the factor of macromolecular architecture into consideration, the lower melting points of various star-shaped PLLAs might be suggested for the fact that, under the similar absolute molecular weight (8.6 KDa), the more arms of a star-shaped PLLA would result in more chain ends and shorten each arm length, accompanying with more densely packed chains near the sugar “cores”, thus finally lead to less perfectness in the ordered PLLA crystallites. Crystal Morphologies for the Star-Shaped PLLAs. To date, the crystal morphologies of linear structural PLLAs had been extensively studied.18c,21-22 Figure 3 shows the spherulites recorded by a polarized microscope at an isothermal crystallization time of 4 min under 110 °C for the synthesized samples of EG-4, G-4, E-4, X-4, and S-1. Among them, the linear structural EG-4 exhibited a common spherulitic structure with a diameter of 62.39 µm at an isothermal crystallization time of 4 min. With increasing arm number of the synthesized new star-shaped PLLA, the observed



Table 4. Thermal Properties for the New Star-Shaped PLLAs Initiated by Sugar Alcohol Sorbitol under Various Sorbitol to Monomer Molar Ratios in m-Xylene at 130 °C sample

initiator to monomer feeding molar ratioa

conversion (%)b

MnNMR (KDa)b

Mw/Mnc

Mntheo (KDa)d

Tm (°C)e

∆Hm (J/g)e

Td (°C)f

S-4 S-1 S-3

1:30 1:60 1:240

99.4 96.2 95.2

4.3 8.3 32.9

1.21 1.09 1.16

4.5 8.8 34.8

112.2 124.5 158.8

0.6 34.8 51.9

193.5 216.3 277.5

a The values mean sorbitol initiator to LLA monomer feeding molar ratios. b The LLA monomer conversions (%) were evaluated by 1H NMR, and molecular weights of PLLAs were evaluated on the monomer conversions. c Mw/Mn (PDI) was characterized by GPC in chloroform with PS standards. d M e f ntheo ) [LLA]/[I] × 144.13 + Minitiator. Tm and ∆Hm were measured by the DSC scan at 20 °C/min. Data of Td were evaluated from the dTGA traces recorded at 10°C/min under nitrogen atmosphere.

Table 5. Thermal Properties of the Star-Shaped PLLAs Synthesized with Various Sugar Alcohol Initiators with Similar Theoretical Molecular Weights (8.6 KDa) LLA monomer MnNMR sample conversion (%)a (KDa)a Mw/Mnb S-1 X-4 E-4 G-4 EG-4

98.3 95.7 96.3 99.7 96.5

8.5 8.3 8.3 8.6 8.3

1.09 1.10 1.12 1.19 1.41

Tm (°C)c

∆Hm (J/g)c

Td (°C)d

114.8 113.1 112.5 126.6 143.7

36.4 39.4 42.3 43.5 52.7

223.4 211.3 217.1 227.0 205.8

a The LLA monomer conversions (%) were evaluated by 1H NMR, and molecular weights of PLLAs were evaluated on the monomer conversions. b M /M (PDI) was characterized by GPC in chloroform with PS standards. w n c T and ∆H were measured by the first DSC scan at 20 °C/min. d The m m values of Td were evaluated from the dTGA traces measured at 10 °C/ min.

Figure 4. Isothermal crystallization time dependence of spherulite diameters under 130 °C for the prepared star-shaped EG-3, G-3, E-3, X-3, and S-3.

rates, showing the lower crystallization rates for the starshaped PLLAs with the sugar alcohol “core” bearing more arms, a result in agreement with that reported for 3-arm PLLA system.18c Isothermal Crystallization Kinetics. As for the 3-arm star-shaped biodegradable PLLAs, Arvanitoyannis et al.18a have studied their molecular weight dependence of isothermal crystallization kinetics by DSC. In this study, isothermal crystallization kinetics of the new star-shaped PLLAs with various arms was investigated. Here, the relative degree of crystallinity denoted as Xt can be calculated according to eq 3

Xt )

( ) ∫ ( ) ∫0t

∞

0

Figure 3. Morphologies for the isothermally crystallized spherulites under 110 °C after 4 min for the synthesized EG-4 (a), G-4 (b), E-4 (c), X-4 (d), and S-1 (e).

spherulites became less ordered and were detected to organize crystals with much lower spherulite growth rates. Moreover, Figure 4 depicts the isothermal crystallization time dependence of spherulite diameters under 130 °C for another series of synthesized EG-3, G-3, E-3, X-3, and S-3 with similar theoretical absolute molecular weights equal to 34.6 KDa. The slopes of these linear plots reflect spherulite growth

dHt dt dt dHt dt dt

(3)

where dHt means enthalpy of crystallization generated during a period of dt, and the limits of t and ∞ denote the elapsed times during the course of crystallization and at the end of crystallization process, respectively. Figure 5 shows the plots of relative degree of crystallinity Xt versus the isothermal crystallization time t for the samples of EG-3 (a), G-3 (b), E-3 (c), X-3 (d), and S-3 (e) under various isothermal crystallization temperatures Tc, respectively. It could be obviously seen that a-e profiles exhibited a similar tendency that the higher Tc resulted in slower crystallization rate and a longer crystallization time to

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Figure 5. Plots of relative degree of crystallinity (Xt) as a function of isothermal crystallization time under various crystallization temperatures for the star-shaped PLLA EG-3 (a), G-3 (b), E-3 (c), X-3 (d), and S-3 (e).

approach the final equilibrium state, demonstrating an apparent PLLA structure dependence of isothermal crystallization. Furthermore, at a fixed Tc equal to 118 °C, the isothermal crystallization results of the star-shaped G-3, E-3, X-3, and S-3 were plotted as well as EG-3 in Figure 6. It was observed that the crystallization rate monotonically decreased with an increase in arm number of the star-shaped PLLA, and this phenomenon could be attributed to the decrease in arm length and the effect of star-shaped architecture.

For the isothermal crystallization, the Avrami equation (4) can accordingly be employed to study the melt-crystallization kinetics 23-24 1 - Xt ) exp (-Ktn )

(4)

where n is the Avrami exponent which is a function of the nucleation and crystal growth process and K is the isothermal crystallization rate constant depending on nucleation and crystal growth process. Commonly, the n should be a value



Figure 6. Plots of relative degree of crystallinity (Xt) versus isothermal crystallization time for star-shaped PLLAs bearing different sugar alcohol “cores” under 118 °C.

of integer between 1 and 4 corresponding to different isothermal crystallization mechanisms. Practically, the experimentally obtained values of the Avrami exponent were often found to be not an integer, and other complex factors might be concurrently involved.25 It has been known that the Avrami equation in a simple form can only represent unimpeded crystal growth in an ideal state, but in practice, the polymer sample cannot reach complete crystallization. Hence, with a hypothesis of complete crystallization, the relative degree of crystallinity Xt can be used, and eq 4 could be further deduced as log(-ln(1 - Xt )) ) log K + n log t

(5)

Thus the values of n and K at each isothermal crystallization temperature Tc can be determined from the linear plots of log(ln(1 - Xt)) against log t. On the basis of K and n, another important parameter of half-crystallization time (t1/2) can further be estimated in accordance with eq 6 t1/2 )

(lnK2)

1/n

(6)

Figure 7 depicts the log(ln(1 - Xt)) versus log t plots for the 3- to 6-arm star-shaped PLLAs of G-3, E-3, X-3, and S-3 at different Tc along with the EG-3, and linear relationships could be observed, regardless of their quite different numbers of arms and molecular architectures. The linear correlation coefficients R of plots for each star-shaped PLLA as well as the EG-3 were greater than 0.99, demonstrating the isothermal crystallization process in well agreement with the Avrami equation. In the meantime, there was little deviation simultaneously detected in the linear plots, and this could be accounted for possible occurrence of secondary crystallization. As a result, the parameters of K, n, and t1/2 were thus determined for the above PLLA samples and generalized in Table 6. It seemed that the obtained n values were not so obviously dependent on the as-applied Tc for individual star-shaped PLLA, resembling the results as reported.18a However, the calculated Avrami exponent n values at Tc ) 118 °C varied from 2.55 (E-3) to 3.43 (linear structural EG-3), demonstrating that the nucleation mechanism strongly depended on the architectures of the synthesized star-shaped PLLAs. Miyata et al.22 have reported the

Avrami exponent n of isothermal crystallization equal to 4.0 for linear structural PLLA. According to the Avrami theory, the obtained experimental n results implied that the new starshaped G-3, E-3, X-3, and S-3 tended to crystallize via heterogeneous nucleation. On the other hand, in a view of the K results in Table 6, it could be found that the K values decreased with increasing the isothermal crystallization temperature Tc for both linear EG-3 and a star-shaped PLLA, and the more arms of a starshaped PLLA finally led to a relative lower K under the same crystallization temperature Tc. Moreover, when increasing degree of supercooling, the results of half-crystallization times t1/2 tended to decrease, implying the faster crystallization rate for the prepared PLLAs similar to that as reported by Arvanitoyannis.18a On the evidences of t1/2 results, the star-shaped PLLAs bearing less arms exhibited faster crystallization rates. Nonisothermal Crystallization Kinetics. In practice, during polymer processing such as extrusion, injection, molding, and so forth, crystallization has been known to proceed under nonisothermal conditions.25 Therefore, it seems extremely meaningful to shed a new light on nonisothermal crystallization kinetics for the synthesized new starshaped PLLAs. According to the widely accepted method reported by Ozawa,26 the nonisothermal crystallization can be studied with a modified Avrami method as 1 - Xv ) exp[-K(T)/qn]

(7)

in which K(T) and q represent the cooling crystallization function and cooling rate, respectively, and Xv denotes the crystalline volume fraction. Taking the function of K(T) as a constant under the range of the designated temperature, the values of exponent n have been successfully determined for several semicrystalline polymers.26,27 However, the function of K(T) was practically found to depend not only on the degree of supercooling but also on the crystallization onset temperature.28 Recently, Caze´ et al.29have suggested an exponential increase of K(T) with T upon cooling as ln(K(T)) ) a(T - T1)

(8)

where a and T1 denote the empirical constants. If the extreme point in the dXv/dT curve occurs at T ) Tq, i.e., (∂2XV/∂T2) ) 0, there will exist a correlation as K(Tq) ) qn

(9)

Combining eqs 7-9 will yield ln[-ln(1 - Xv)] ) a(T - Tq)

(10)

Hence, through the linear plot of ln[-ln(1 - Xv)] against T, the values of a and Tq could be obtained. Furthermore, When T ) Tq, there will be another correlation as Tq ) (n/a) ln(q) + T1

(11)

where T1 means the Tq at a cooling rate of q ) 1 K/min. As a result, the parameters of n and T1 could be obtained in the Tq versus ln(q)/a plot.

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Figure 7. Avrami plots for isothermal crystallization of the synthesized star-shaped PLLA EG-3 (a), G-3 (b), E-3 (c), X-3 (d), and S-3 (e) at different crystallization temperatures.

Via integrating the partial areas in the DSC exothermic trace, the crystalline weight fraction Xw could be evaluated, and the value of Xv could further be calculated according to eq 12 Xv) Xw(Fa/Fc)[1 - (1 - Fa/Fc)Xw]-1

(12)

where Fa and Fc express the corresponding densities of a semicrystalline polymer in the pure amorphous and crystalline states, respectively. Taking the temperature effect into the consideration of Fa/Fc ratio, the empirical rules were here

applied as RaTg ) 0.16 and RcT 0m ) 0.11,28 where Ra and Rc denote thermal expansion coefficients of the semicrystalline polymer in the pure amorphous and crystalline states, respectively, Tg and T 0m express the glass transition temperature and equilibrium melting point, and the corresponding values of Tg and T 0m for the PLLA were applied as 328 and 480 K as referred.1 Hence, the value of Fa/Fc could be determined according to Fa/Fc ) (Fa0/Fc0) exp[(T - Tr)(0.11/T 0m - 0.16/Tg)] (13)



Figure 8. Relative degree of crystallinity (Xv) versus temperature (T) during nonisothermal melt crystallization process at different cooling rates for the new star-shaped PLLA EG-3 (a), G-3 (b), E-3 (c), X-3 (d), and S-3 (e).

where Tr ) 298 K and Fa0/Fc0 denote the density ratio at 298 K, which was further applied as 0.969 as referred.30 With aid of the eqs 12 and 13, the values of Xv could thus be calculated on the basis of measured Xw values. Figure 8 shows the plots of the relative degree of crystallinity (Xv) against the nonisothermal crystallization temperature (T) for the synthesized EG-3, G-3, E-3, X-3, and S-3 under different cooling rates q, respectively, and linear plots of ln [-ln(1 -

Xv)] vs T could further be obviously detected; thus, the a and Tq parameters were obtained. Moreover, Figure 9 illustrates the plots of Tq against ln(q)/a for the above five PLLAs with the linear correlation coefficients R higher than 0.97, and the parameters of T1 and n were accordingly evaluated and are summarized in Table 7. It could be found that the obtained Avrami exponent n varied from 2.14 (S-3) to 2.42 (EG-3), indicating that the crystallites of these

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Table 6. Avrami Exponent (n), Kinetic Rate Constant (K), and Half-Time of Crystallization (t1/2) for Various PLLAs Synthesized with Similar Theoretical Molecular Weights sample

Tc (°C)

K × 102 (min-1)

t1/2 (min)

n

Ra

EG-3

115 118 121 124 127 106 109 112 115 118 106 109 112 115 118 106 109 112 115 118 106 109 112 115 118

15.18 2.70 0.94 0.28 0.26 5.46 4.42 3.15 2.51 1.39 4.82 2.64 1.86 1.49 1.01 1.56 1.78 1.05 0.99 0.44 1.69 1.40 1.27 0.75 0.35

1.41 2.57 3.53 5.08 5.30 2.26 2.49 3.00 3.38 3.97 3.06 3.46 4.13 4.62 5.26 3.56 3.86 4.25 4.76 5.80 3.45 3.83 4.21 4.81 5.93

4.41 3.43 3.41 3.39 3.35 3.11 3.01 2.82 2.72 2.83 2.38 2.63 2.55 2.51 2.55 2.98 2.71 2.90 2.73 2.87 3.00 2.91 2.80 2.88 2.96

0.9990 0.9996 0.9998 0.9999 0.9999 0.9982 0.9974 0.9992 0.9963 0.9987 0.9998 0.9995 0.9998 0.9999 0.9999 1.0000 0.9999 0.9999 0.9998 1.0000 0.9987 0.9992 0.9997 0.9996 0.9997

G-3

E-3

X-3

S-3

a R denotes the linear correlation coefficient for Avrami plots in Figure 7.

Figure 9. Linear plots of Tq versus ln q/a for the nonisothermal crystallization of different new star-shaped PLLAs.

polymers preferentially grew in two dimensions and that the nonisothermal crystallization underwent heterogeneous nucleation for these synthesized PLLAs. Meanwhile, the results of T1 values were found to slightly decrease with increasing arm number of the star-shaped PLLAs, demonstrating a relatively lower crystallizability for a star-shaped PLLA bearing many arms such as S-3. Proposing that the heat of crystallization at the peak of crystallization exothermic trace is practically constant and consequently independent of the cooling rate,31 the Arrhenius equation (K ) A exp(-Ea/RT)) could be deduced as -ln(q) ) A′ - Ea/RTp

(14)

Table 7. Kinetics Parameters for Nonisothermal Crystallization of Diverse Star-Shaped PLLAs Synthesized with Similar Theoretical Molecular Weights sample EG-3

G-3

E-3

X-3

S-3

n 2.42 2.29 2.15 2.24 2.14 T1 (K) 391.04 390.62 385.84 385.39 382.71 R1a 1.0000 0.9999 0.9757 0.9731 0.9910 ∆E (kJ/mol) 146.86 150.07 164.17 221.42 221.23 R2b 0.9999 0.9981 0.9991 0.9743 0.9904 b

a R denotes the linear correlation coefficient for the plots in Figure 9. 1 R2 denotes the linear correlation coefficient for the plots in Figure 10.

Figure 10. Linear plots of -ln(q) versus 1/Tp for the nonisothermal crystallization of different star-shaped PLLAs.

in which R, Ea, q, and Tp express universal gas constant, activation energy of the nonisothermal crystallization process, the cooling rate, and the crystallization peak temperature, respectively. Thus, the activation energy of the nonisothermal crystallization of the above PLLA samples could be further evaluated by varying the factor of nonisothermal crystallization peak temperature Tp with the cooling rate. As seen in Figure 10, the plots of -ln(q) against 1/Tp obviously exhibited good linear correlation for both the linear structural EG-3 and the star-shaped PLLAs of G-3, E-3, X-3, and S-3 (R > 0.97), and from the slopes the values of crystallization, activation energies Ea were determined and are summarized in Table 7. It could be found that the Ea from 146.86 kJ/mol (EG-3) to 221.23kJ /mol (S-3) values tended to increase with increasing arm number of the star-shaped PLLAs, indicating a result very consistent with the results provided in the crystallization kinetic study. Conclusions In this study, G, E, X, and S series of new star-shaped PLLAs bearing well-defined 3- to 6-arm structures were systematically synthesized through SnOct2 catalyzed ROP of (L)-lactide in m-xylene solution with glycerol, erythritol, xylitol, and sorbitol as the initiator, respectively. NMR analytical results demonstrated the efficient initiation of primary and secondary hydroxyl functional groups of each sugar alcohol, and symmetric GPC elution traces with narrow PDI substantiated successful preparation of the star-shaped


PLLAs with diverse arms. To shed a new light on perfectness of the prepared star-shaped structures, intrinsic viscosities were measured in chloroform solution for the star-shaped PLLAs G-3, E-3, X-3, and S-3 along with the linear structural PLLA reference EG-3 bearing similar theoretical absolute molecular weights (34.6 KDa). Further the g1/2/g′ ratios of 0.99-0.95 close to 1.00 of ideal star-shaped polymer demonstrated star-shaped structures with fewer arm defects, and the more arms of a sugar alcohol core would lead to more arm defects of the star-shaped PLLA products. Regarding the ROP reaction, it was revealed that, under a fixed monomer to hydroxyl group of the sugar alcohol initiator, more secondary hydroxyl groups in the core like sorbitol would obviously lead to slower polymerization rate, indicating the star-shaped structure dependence of polymerization kinetics due to its densely packed “core”. On the other hand, crystal morphologies and spherulitic growth rates of the 3to 6-arm star-shaped PLLAs strongly depended on their molecular weights and sugar alcohol core structures. Isothermal crystallization kinetic study on these star-shaped PLLAs indicated that their Avrami exponent n values were hardly dependent on the isothermal crystallization temperature. In contrast, the values of the Avrami exponents n for the star-shaped PLLAs with various kinds of sugar alcohol cores were significantly influenced by their core structures, implying a nucleation mechanism different from that of the linear PLLA reference. Furthermore, the evidences of halfcrystallization time t1/2 indicated faster crystallization rates for the prepared PLLAs bearing fewer arms. In addition, their nonisothermal crystallization kinetic studies demonstrated a trend of crystallization rates consistent with that of the isothermal crystallization. The activation energies of nonisothermal crystallization were calculated to be 146.86 (EG-3) to 221.23 kJ/mol (S-3) for the prepared 3- to 6-arm starshaped PLLAs, demonstrating lower crystallizability of the star-shaped PLLA bearing more arms such as S-3. In addition, due to the presence of different initiation reactivities between the primary and secondary hydroxyl functional groups of these sugar alcohols, therefore, it might be interesting to explore a new alternative route to efficiently prepare hetero-arm star-shaped functional polymers with selective initiation of primary or secondary hydroxyl functionality of a sugar alcohol core, and it is now ongoing in this lab. Acknowledgment. The authors are grateful for the partial financial support from the Hundreds of Talents Project, Chinese Academy of Sciences (CAS), National Science Foundation of China (Contract No. 20204019), and Rising Star Project No. 04QMX1445 of science and technology committee of Shanghai municipality. The authors are also grateful to Prof. Y. Inoue of the Tokyo Institute of Technology and Dr. T. Masuda of AIST, Japan for their kind encouragements.


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Preparation and Crystallization Kinetics of New Structurally Well

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