谷氨酸赖氨酸无规共聚物和谷氨酸精氨酸无规共聚物的合成及性能

doi:10.7503/cjcu20160190

摘要/Abstract

摘要：

采用氨基酸-N-内羧酸酐(氨基酸-NCA)开环聚合的方法, 并通过改变开环聚合时谷氨酸-N-内羧酸酐(BLG-NCA)与赖氨酸-N-内羧酸酐[Lys(Z)-NCA]的投料比以及BLG-NCA与鸟氨酸-N-内羧酸酐[Orn(Z)-NCA]的投料比, 经过脱保护和胍基化反应得到一系列谷氨酸赖氨酸无规共聚物Poly(E,K)和谷氨酸精氨酸无规共聚物Poly(E,R). 核磁共振氢谱(¹H NMR)和核磁共振定量碳谱(¹³C NMR)分析结果表明, 合成了无规共聚物Poly(E,K)和Poly(E,R), 且二者中不同氨基酸的摩尔比接近开环聚合时相应NCA的投料比. 动态光散射(DLS)测定结果表明, 无规共聚物在pH=7.4的正常生理环境中形成的胶束粒径均一、尺寸小于200 nm. Zeta电位表征结果表明, 无规共聚物Poly(E,K)和Poly(E,R)的Zeta电位值随着溶液pH值的变化而变化, 具有pH敏感性.

关键词: 开环聚合, 无规共聚物, pH敏感

Abstract:

A series of random copolymers Poly(E,K) and Poly(E,R) was synthesized by the ring-opening polymerization of amino acid-N-carboxyanhydride(amino acid-NCA), along with changing the feed ratio of glutamin acid-N-carboxyanhydride(BLG-NCA) and lysine(benzyloxycarbonyl)-N-carboxyanhydride[Lys(Z)-NCA] as well as BLG-NCA and ornithine(benzyloxycarbonyl)-N-carboxyanhydride[Orn(Z)-NCA] and by the subsequent deprotection and guanidination. These random copolymers were confirmed by nuclear magnetic resonance(¹H NMR and ¹³C NMR), and the molar ratios of different amino acids in the copolymers were close to the feed ratios of corresponding NCA in the ring-opening polymerization. Dynamic light scattering(DLS) test showed that the random copolymers assemble to uniform micelles with less than 200 nm diameter at pH of 7.4. The zeta potential of the random copolymers could change with the pH of solution, suggesting that the copolymers are pH-sensitive.

Key words: Ring-opening polymerization, Random copolymer, pH-Sensitive

中图分类号:

O631

TrendMD:

王慧洁, 于海洋, 张大为, 汤朝晖, 曹琪. 谷氨酸赖氨酸无规共聚物和谷氨酸精氨酸无规共聚物的合成及性能. 高等学校化学学报, 2017, 38(1): 165.

WANG Huijie, YU Haiyang, ZHANG Dawei, TANG Zhaohui, CAO Qi. Synthesis and Characterization of Poly(E,K) and Poly(E,R)^†. Chem. J. Chinese Universities, 2017, 38(1): 165.

图/表 10

Scheme 1 Synthesis routes of Poly(E,K)

Fig.1 1H NMR spectra of Poly[E(Bn),K(Cbz)](A) and Poly(E,K)(B) in TFA-d (A) a. Poly[E(Bn),K(Cbz)]1; b. Poly[E(Bn),K(Cbz)]2; c. Poly[E(Bn),K(Cbz)]3. (B) a. Poly(E,K)1; b. Poly(E,K)2; c. Poly(E,K)3.

Fig.2 Quantitative 13C NMR spectra of Poly(E,K) in TFA-da. Poly(E,K)1; b. Poly(E,K)2; c. Poly(E,K)3.

Scheme 2 Synthesis routes of Poly(E,R)

Fig.3 1H NMR spectra of Poly[E(Bn),O(Cbz)](A), Poly(E,O)(B) and Poly(E,R)(C) in TFA-d (A) a. Poly[E(Bn),O(Cbz)]1; b. Poly[E(Bn),O(Cbz)]2; c. Poly[E(Bn),O(Cbz)]3. (B) a. Poly(E,O)1; b. Poly(E,O)2; c. Poly(E,O)3. (C) a. Poly(E,R)1; b. Poly(E,R)2; c. Poly(E,R)3.

Fig.4 Quantitative 13C NMR spectra of Poly(E,O)(A) and Poly(E,R)(B) in D2O/NaOD (A) a. Poly(E,O)1; b. Poly(E,O)2; c. Poly(E,O)3. (B) a. Poly(E,R)1; b. Poly(E,R)2; c. Poly(E,R)3.

Fig.5 GPC curves of Poly[E(Bn),K(Cbz)](A), Poly[E(Bn),O(Cbz)](B), Poly(E,K)(C), Poly(E,O)(D) and Poly(E,R)(E) (A) a. Poly[E(Bn),K(Cbz)]1; b. Poly[E(Bn),K(Cbz)]2; c. Poly[E(Bn),K(Cbz)]3. (B) a. Poly[E(Bn),O(Cbz)]1; b. Poly[E(Bn),O(Cbz)]2; c. Poly[E(Bn),O(Cbz)]3. (C) a. Poly(E,K)1; b. Poly(E,K)2. (D) a. Poly(E,O)1; b. Poly(E,O)2. (E) Poly(E,R)1.

Table 1 Characterization of copolymers

Copolymer	Feed molar ratio	Resultant molar ratio	10^-3 $M n h$	PDI^h	Conversion ratio(%)
Poly[E(Bn),K(Cbz)]₁	2:1^a	2.2:1.0^c	20.4	1.30	86
Poly[E(Bn),K(Cbz)]₂	1:1^a	1.1:1.0^c	16.6	1.25	87
Poly[E(Bn),K(Cbz)]₃	1:2^a	1.0:1.8^c	12.9	1.26	81
Poly(E,K)₁	2:1^a	2.2:1.0^d	5.5	1.33	95
Poly(E,K)₂	1:1^a	1.0:1.0^d	6.0	1.38	96
Poly(E,K)₃	1:2^a	1.0:1.8^d			93
Poly[E(Bn),O(Cbz)]₁	2:1^b	2.2:1.0^e	16.2	1.37	84
Poly[E(Bn),O(Cbz)]₂	1:1^b	1.2:1.0^e	11.9	1.28	83
Poly[E(Bn),O(Cbz)]₃	1:2^b	1.0:1.9^e	10.5	1.29	87
Poly(E,O)₁	2:1^b	2.0:1.0^f	7.9	1.41	96
Poly(E,O)₂	1:1^b	1.0:1.0^f	6.1	1.45	94
Poly(E,O)₃	1:2^b	1.0:2.0^f			93
Poly(E,R)₁	2:1^b	2.2:1.0^g	15.9	1.43	95
Poly(E,R)₂	1:1^b	1.2:1.0^g			93
Poly(E,R)₃	1:2^b	1.0:1.9^g			92

Table 1 Characterization of copolymers

Copolymer	Feed molar ratio	Resultant molar ratio	10^-3 $M n h$	PDI^h	Conversion ratio(%)
Poly[E(Bn),K(Cbz)]₁	2:1^a	2.2:1.0^c	20.4	1.30	86
Poly[E(Bn),K(Cbz)]₂	1:1^a	1.1:1.0^c	16.6	1.25	87
Poly[E(Bn),K(Cbz)]₃	1:2^a	1.0:1.8^c	12.9	1.26	81
Poly(E,K)₁	2:1^a	2.2:1.0^d	5.5	1.33	95
Poly(E,K)₂	1:1^a	1.0:1.0^d	6.0	1.38	96
Poly(E,K)₃	1:2^a	1.0:1.8^d			93
Poly[E(Bn),O(Cbz)]₁	2:1^b	2.2:1.0^e	16.2	1.37	84
Poly[E(Bn),O(Cbz)]₂	1:1^b	1.2:1.0^e	11.9	1.28	83
Poly[E(Bn),O(Cbz)]₃	1:2^b	1.0:1.9^e	10.5	1.29	87
Poly(E,O)₁	2:1^b	2.0:1.0^f	7.9	1.41	96
Poly(E,O)₂	1:1^b	1.0:1.0^f	6.1	1.45	94
Poly(E,O)₃	1:2^b	1.0:2.0^f			93
Poly(E,R)₁	2:1^b	2.2:1.0^g	15.9	1.43	95
Poly(E,R)₂	1:1^b	1.2:1.0^g			93
Poly(E,R)₃	1:2^b	1.0:1.9^g			92

Fig.6 Sizes of copolymer micelles determined by DLS(A) Poly(E,K)1; (B) Poly(E,K)2; (C) Poly(E,K)3; (D) Poly(E,R)1; (E) Poly(E,R)2; (F) Poly(E,R)3.

Fig.7 Zeta potentials of Poly(E,K)(A) and Poly(E,R)(B) at different pH(A) a. Poly(E,K)1; b. Poly(E,K)2; c. Poly(E,K)3. (B) a. Poly(E,R)1; b. Poly(E,R)2; c. Poly(E,R)3.

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