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Synthesis and characterization of biodegradable aliphatic polyesters using dibutylmagnesium as initiator
Chinese Chemical Letters 18 (2007) 744–746 www.elsevier.com/locate/cclet
Synthesis and characterization of biodegradable aliphatic polyesters using dibutylmagnesium as initiator Lian Liu a,*, Zhi Yong Wei b, Min Qi b a
Electromechanics and Materials Engineering College, Dalian Maritime University, Dalian 116026, China b School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, China Received 22 January 2007
Abstract Aliphatic polyesters were synthesized via the ring opening polymerization of the corresponding lactones initiated with dibutylmagnesium both in bulk and in solution. The resulting polymers were characterized by 1H, 13C NMR, GPC and XRD. The results indicated that dibutylmagnesium is an effective initiator for the ring opening polymerization of lactones. # 2007 Lian Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Aliphatic polyesters; Lactones; Dibutylmagnesium; Biodegradable; Biomaterials
Aliphatic polyesters such as poly(L-lactide) (PLLA), poly(e-caprolactone) (PCL) and poly(3-hydroxybutyrate) (PHB) are of great interest as biodegradable medical materials. Continuous efforts have been devoted to the development of new catalysts and initiators for the ring opening polymerization (ROP) of lactones. Stannous octoate has been frequently used as one of the effective catalyst. However, like many other catalysts, the cytotoxicity and difficulties in removal of the catalyst from the resulting polymer have limited its use in many cases [1,2]. For some medical and pharmaceutical applications, the synthetic polymers without containing any toxic heavy metal ions are reasonably desirable and high molecular weights are always unnecessary and even undesirable [3]. A nontoxic alternative may be magnesium compounds [3–6], since magnesium ion is a rather harmless ion. Biodegradable copolymers were also extensively investigated. Copolymerization was usually performed to improve the processability, mechanical and thermal properties of these biodegradable polymers. In the present paper, we report dibutylmagnesium (Bu2Mg, purchased from Aldrich Chemical Co.) as initiator for the ROP of lactones to prepare aliphatic polyesters. Monomers, such as b-butyrolactone (BL, Tokyo Kasei Kogyo), e-caprolactone (CL, Acros Organics) and L-lactide (LLA, Purac Biochem), and 1,4-dioxane were dried in anhydrous form prior to use. Random copolymers were synthesized from Bu2Mg-initiated copolymerization of BL, CL and LLA in bulk at 110 8C; block copolymers were obtained by sequential polymerization in 1,4-dioxane at 70 8C. The copolymer compositions and chain microstructure were measured by 1H and 13C NMR. Molecular weights and its distributions were determined by GPC. The results are summarized in Tables 1 and 2.
* Corresponding author. E-mail address: [email protected] (L. Liu). 1001-8417/$ – see front matter # 2007 Lian Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2007.04.011
L. Liu et al. / Chinese Chemical Letters 18 (2007) 744–746
745
Table 1 Bu2Mg-initiated BL, CL and LLA copolymerization in bulk at 110 8Ca Copolymers
Yield (%)
In feed b
Observedc
Mwd
Mw/Mn d
P(BL-co-CL) P(CL-co-LLA) P(LLA-co-BL)
98 89 85
51.0/49.0 50.5/49.5 50.6/49.4
47.4/52.6 45.3/54.7 56.1/43.9
17 500 45 300 21 300
2.31 2.45 2.29
a b c d
Monomer to initiator molar ratio = 100, 24 h. Molar ratio in the comonomers feed. Molar ratio in the copolymer by 1H NMR. Measured by GPC using polystyrene standard calibration, THF as an eluent at 40 8C.
Table 2 Bu2Mg-initiated BL, CL and LLA sequential polymerization in 1,4-dioxane at 70 8Ca Copolymers
Total yield (%)
In feed b
Observedc
Mwd
Mw/Mn d
PCL-b-PLLA PLLA-b-PCL PCL-b-PBL PBL-b-PCL
88 86 72 57
50.4/49.6 48.8/51.2 49.7/50.3 48.6/51.4
64.3/35.7 66.2/33.8 74.5/25.5 77.8/22.2
20,400 25,600 18,700 10,300
1.89 1.32 1.93 1.46
a b c d
Monomer to initiator molar ratio = 100, 24 + 24 h. Molar ratio in the comonomers feed. Molar ratio in the copolymer by 1H NMR. Measured by GPC using polystyrene standard calibration, THF as an eluent at 40 8C.
The random copolymer compositions calculated from 1H NMR were similar to the feeding ratio. In contrast, the ratio of the first monomer to the second in the block copolymer in Table 2 was larger than that of the comonomers feed. Molecular weights of all synthetic copolyesters are more than 10 000 Da and sufficient for most pharmaceutical applications. These results indicate that Bu2Mg is an effective initiator for the ROP of lactones. Comparison of carbonyl signals in 13C NMR for the random and block copolymers was shown in Fig. 1. The random copolymer spectrum contains two other triads peaks than expected from the superposition of the spectrum of each homopolymer. In contrast, for block copolymers, no intermediate resonance can be detected between the two homo-PCL and PLLA carbonyl signals, indicating no significant occurrence of transesterification side reactions during the sequential solution polymerization. The X-ray diffraction patterns for the random and block copolymers (Fig. 2) were approximately the superposition of both the PCL and PLLA homo-polymers. This indicated that there are two separated crystalline micro-domains consisting of the PCL and PLLA blocks in these copolymers, respectively.
Fig. 1. Expanded carbonyl resonance region in
13
C NMR spectra of the synthetic copolymers.
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L. Liu et al. / Chinese Chemical Letters 18 (2007) 744–746
Fig. 2. X-ray diffraction patterns for the synthetic copolymers.
In conclusion, the Bu2Mg-initiated lactones polymerization could afford the synthesis of the aliphatic polyesters for medical and pharmaceutical applications, especially, using as drug delivery carriers. Therefore, Bu2Mg is an attractive initiator for the polymerization of lactones, due to Mg2+ ions are fully compatible with the metabolism of the human body. Acknowledgment This work was supported by the National Natural Science Foundation of China (No. 30470521). References [1] [2] [3] [4] [5] [6]
H.R. Kricheldorf, Chemospere 43 (2001) 49. M. Okad, Prog. Polym. Sci. 27 (2002) 87. H.R. Kricheldorf, S.-R. Lee, Polymer 36 (1995) 2995. B.M. Chamberlain, M. Cheng, D.R. Moore, et al. J. Am. Chem. Soc. 123 (2001) 3229. M.H. Chischolm, K. Phomphrai, Inorgan. Chim. Acta 350 (2003) 121. Z. Li, J.Y. Hao, M.L. Yuan, et al. Eur. Polym. J. 39 (2003) 313.
Synthesis and characterization of biodegradable aliphatic polyesters using dibutylmagnesium as initiator Lian Liu a,*, Zhi Yong Wei b, Min Qi b a
Electromechanics and Materials Engineering College, Dalian Maritime University, Dalian 116026, China b School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, China Received 22 January 2007
Abstract Aliphatic polyesters were synthesized via the ring opening polymerization of the corresponding lactones initiated with dibutylmagnesium both in bulk and in solution. The resulting polymers were characterized by 1H, 13C NMR, GPC and XRD. The results indicated that dibutylmagnesium is an effective initiator for the ring opening polymerization of lactones. # 2007 Lian Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Aliphatic polyesters; Lactones; Dibutylmagnesium; Biodegradable; Biomaterials
Aliphatic polyesters such as poly(L-lactide) (PLLA), poly(e-caprolactone) (PCL) and poly(3-hydroxybutyrate) (PHB) are of great interest as biodegradable medical materials. Continuous efforts have been devoted to the development of new catalysts and initiators for the ring opening polymerization (ROP) of lactones. Stannous octoate has been frequently used as one of the effective catalyst. However, like many other catalysts, the cytotoxicity and difficulties in removal of the catalyst from the resulting polymer have limited its use in many cases [1,2]. For some medical and pharmaceutical applications, the synthetic polymers without containing any toxic heavy metal ions are reasonably desirable and high molecular weights are always unnecessary and even undesirable [3]. A nontoxic alternative may be magnesium compounds [3–6], since magnesium ion is a rather harmless ion. Biodegradable copolymers were also extensively investigated. Copolymerization was usually performed to improve the processability, mechanical and thermal properties of these biodegradable polymers. In the present paper, we report dibutylmagnesium (Bu2Mg, purchased from Aldrich Chemical Co.) as initiator for the ROP of lactones to prepare aliphatic polyesters. Monomers, such as b-butyrolactone (BL, Tokyo Kasei Kogyo), e-caprolactone (CL, Acros Organics) and L-lactide (LLA, Purac Biochem), and 1,4-dioxane were dried in anhydrous form prior to use. Random copolymers were synthesized from Bu2Mg-initiated copolymerization of BL, CL and LLA in bulk at 110 8C; block copolymers were obtained by sequential polymerization in 1,4-dioxane at 70 8C. The copolymer compositions and chain microstructure were measured by 1H and 13C NMR. Molecular weights and its distributions were determined by GPC. The results are summarized in Tables 1 and 2.
* Corresponding author. E-mail address: [email protected] (L. Liu). 1001-8417/$ – see front matter # 2007 Lian Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2007.04.011
L. Liu et al. / Chinese Chemical Letters 18 (2007) 744–746
745
Table 1 Bu2Mg-initiated BL, CL and LLA copolymerization in bulk at 110 8Ca Copolymers
Yield (%)
In feed b
Observedc
Mwd
Mw/Mn d
P(BL-co-CL) P(CL-co-LLA) P(LLA-co-BL)
98 89 85
51.0/49.0 50.5/49.5 50.6/49.4
47.4/52.6 45.3/54.7 56.1/43.9
17 500 45 300 21 300
2.31 2.45 2.29
a b c d
Monomer to initiator molar ratio = 100, 24 h. Molar ratio in the comonomers feed. Molar ratio in the copolymer by 1H NMR. Measured by GPC using polystyrene standard calibration, THF as an eluent at 40 8C.
Table 2 Bu2Mg-initiated BL, CL and LLA sequential polymerization in 1,4-dioxane at 70 8Ca Copolymers
Total yield (%)
In feed b
Observedc
Mwd
Mw/Mn d
PCL-b-PLLA PLLA-b-PCL PCL-b-PBL PBL-b-PCL
88 86 72 57
50.4/49.6 48.8/51.2 49.7/50.3 48.6/51.4
64.3/35.7 66.2/33.8 74.5/25.5 77.8/22.2
20,400 25,600 18,700 10,300
1.89 1.32 1.93 1.46
a b c d
Monomer to initiator molar ratio = 100, 24 + 24 h. Molar ratio in the comonomers feed. Molar ratio in the copolymer by 1H NMR. Measured by GPC using polystyrene standard calibration, THF as an eluent at 40 8C.
The random copolymer compositions calculated from 1H NMR were similar to the feeding ratio. In contrast, the ratio of the first monomer to the second in the block copolymer in Table 2 was larger than that of the comonomers feed. Molecular weights of all synthetic copolyesters are more than 10 000 Da and sufficient for most pharmaceutical applications. These results indicate that Bu2Mg is an effective initiator for the ROP of lactones. Comparison of carbonyl signals in 13C NMR for the random and block copolymers was shown in Fig. 1. The random copolymer spectrum contains two other triads peaks than expected from the superposition of the spectrum of each homopolymer. In contrast, for block copolymers, no intermediate resonance can be detected between the two homo-PCL and PLLA carbonyl signals, indicating no significant occurrence of transesterification side reactions during the sequential solution polymerization. The X-ray diffraction patterns for the random and block copolymers (Fig. 2) were approximately the superposition of both the PCL and PLLA homo-polymers. This indicated that there are two separated crystalline micro-domains consisting of the PCL and PLLA blocks in these copolymers, respectively.
Fig. 1. Expanded carbonyl resonance region in
13
C NMR spectra of the synthetic copolymers.
746
L. Liu et al. / Chinese Chemical Letters 18 (2007) 744–746
Fig. 2. X-ray diffraction patterns for the synthetic copolymers.
In conclusion, the Bu2Mg-initiated lactones polymerization could afford the synthesis of the aliphatic polyesters for medical and pharmaceutical applications, especially, using as drug delivery carriers. Therefore, Bu2Mg is an attractive initiator for the polymerization of lactones, due to Mg2+ ions are fully compatible with the metabolism of the human body. Acknowledgment This work was supported by the National Natural Science Foundation of China (No. 30470521). References [1] [2] [3] [4] [5] [6]
H.R. Kricheldorf, Chemospere 43 (2001) 49. M. Okad, Prog. Polym. Sci. 27 (2002) 87. H.R. Kricheldorf, S.-R. Lee, Polymer 36 (1995) 2995. B.M. Chamberlain, M. Cheng, D.R. Moore, et al. J. Am. Chem. Soc. 123 (2001) 3229. M.H. Chischolm, K. Phomphrai, Inorgan. Chim. Acta 350 (2003) 121. Z. Li, J.Y. Hao, M.L. Yuan, et al. Eur. Polym. J. 39 (2003) 313.