可X射线显影的新型碘代聚碳酸酯的设计与合成

doi:10.7503/cjcu20190231

摘要/Abstract

摘要：

以丝氨醇、 4-碘苯甲酰氯和氯甲酸乙酯为原料, 通过酰胺化和分子内关环两步反应合成了一种新型的碘代环碳酸酯功能单体——4-碘-N-(2-氧代-1,3-二噁烷-5-基)苯甲酰胺(IBTMC). 以异戊醇为引发剂, 1,5,7-三叠氮双环(4.4.0)癸-5-烯(TBD)为催化剂, 使IBTMC与三亚甲基碳酸酯(TMC)进行开环共聚, 合成了一系列具有X射线不透过性的碘代聚碳酸酯材料, 并采用核磁共振氢谱( ¹H NMR)、凝胶渗透色谱(GPC)、差示扫描量热仪(DSC)、热重分析(TGA)和X射线计算机断层成像系统(Micro-CT)表征了其化学结构与组成、分子量与分子量分布、热力学性能及X射线不透过性. 研究结果表明, 本文合成的碘代聚碳酸酯具有较窄的分子量分布、良好的热稳定性及可调的X射线不透过性. 小鼠体内埋置实验结果表明, 碘代聚碳酸酯具备体内X射线成像的能力.

关键词: 聚碳酸酯, X射线不透过性, 碘代环碳酸酯功能单体, 开环聚合

Abstract:

Biodegradable polymeric materials with X-ray opacity are unique in various biomedical studies in vivo, yet the available polymers, in particular functionalized monomers, are very limited. Herein, a novel iodinated cyclic carbonate monomer, 4-iodo-N-(2-oxo-1,3-dioxan-5-yl)benzamide(IBTMC), was designed and synthesized by amidation and subsequent intramolecular cyclization using 2-amino-1,3-propanediol, 4-iodobenzoyl chloride and ethyl chloroformate as raw materials. Then, a series of iodinated polycarbonates with inherent X-ray opacity were obtained via ring-opening copolymerization of IBTMC and trimethylene cyclic carbonate(TMC) using 1,5,7-triazabicyclo[4.4.0]dec-5-ene(TBD) as the catalyst. Their chemical structures and compositions, molar mass dispersity, thermal properties and radiopacity were characterized via proton nuclear magnetic resonance( ¹H NMR), gel permeation chromatography(GPC), differential scanning calorimetry(DSC), thermogravimetric analysis(TGA) and micro-computed tomography(Micro-CT). The results illustrated that the iodinated polycarbonates had good thermal stability and outstanding X-ray opacity. Finally, a subcutaneous implantation experiment in ICR mice demonstrated the potential of the synthesized iodinated polycarbonates for in vivo deep tissue imaging.

Key words: Polycarbonate, X-Ray opacity, Iodinated cyclic carbonate monomer, Ring-opening polymerization

中图分类号:

O631

TrendMD:

马前,吴晓慧,俞麟,丁建东. 可X射线显影的新型碘代聚碳酸酯的设计与合成. 高等学校化学学报, 2019, 40(10): 2233.

MA Qian,WU Xiaohui,YU Lin,DING Jiandong. Design and Synthesis of Novel Iodinated Polycarbonates with Inherent X-Ray Opacity ^†. Chem. J. Chinese Universities, 2019, 40(10): 2233.

图/表 10

Scheme 1 Synthesis of N-(1,3-dihydroxypropan-2-yl)-4-iodobenzamide(IBT)

Scheme 2 Synthesis of 4-iodo-N-(2-oxo-1,3-dioxan-5-yl)benzamide(IBTMC)

Scheme 3 Synthesis of P(TMC-co-IBTMC)

Fig.1 1H NMR spectra of IBT(a) and IBTMC(b) in DMSO-d6

Fig.2 Stability of functionalized monomer IBTMC at room temperature in the presence of light for 0(a) and 6 months(b)

Fig.3 Polymerization kinetics of copolymer P4 The polymerization temperature was set at 25 ℃. Mn and D ˉ M were obtained from GPC analysis.

Table 1 Ring-opening polymerization of IBTMC with TMC catalyzed by TBD using isopentanol as the initiatora

Sample	n(TMC)∶n(IBTMC) in feed	n(TMC)∶n(IBTMC) in P(TMC-co-IBTMC)^b	$T d c$	$T g d$ /℃	$M n, NMR b$	$M n, GPC e$	$D ˉ M e$	$F NMR b$ (%)
P1	100∶0	100∶0	/	-58	7100	2500	1.33	0
P2	95∶5	94∶6	182	-39	12200	2100	1.60	6
P3	90∶10	91∶9	190	-31	9800	2300	1.55	9
P4	62.5∶37.5	60∶40	200	44	18800	4000	1.26	40

Table 1 Ring-opening polymerization of IBTMC with TMC catalyzed by TBD using isopentanol as the initiatora

Sample	n(TMC)∶n(IBTMC) in feed	n(TMC)∶n(IBTMC) in P(TMC-co-IBTMC)^b	$T d c$	$T g d$ /℃	$M n, NMR b$	$M n, GPC e$	$D ˉ M e$	$F NMR b$ (%)
P1	100∶0	100∶0	/	-58	7100	2500	1.33	0
P2	95∶5	94∶6	182	-39	12200	2100	1.60	6
P3	90∶10	91∶9	190	-31	9800	2300	1.55	9
P4	62.5∶37.5	60∶40	200	44	18800	4000	1.26	40

Fig.4 1H NMR spectrum of P4 in CDCl3

Fig.5 Tg of polycarbonates as a function of molar fraction of repeating unit of functionalized monomer IBTMC(FNMR)

Fig.6 In vitro Micro-CT images on the z-axis of the indicated samples(A) and in vivo X-ray imaging analysis using in vivo Xtreme after subcutaneous implantation of P1 and P4 into the buttock of ICR rat(B) (A) The color represents the X-ray opacity of the samples and the inserted numbers are the average grayscale values of the corresponding samples; (B) one rat without treatment(the left) was used as the control.

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