Design and Synthesis of Novel Iodinated Polycarbonates with Inherent X-Ray Opacity †

doi:10.7503/cjcu20190231

Abstract

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

CLC Number:

O631

TrendMD:

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

Figures/Tables 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.

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

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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