Synthesis and Relaxivity of One Macrocyclic Binuclear Nonionic Magnetic Resonance Contrast Agent

doi:10.6023/cjoc202102009

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (7): 2767-2773.DOI: 10.6023/cjoc202102009 Previous Articles Next Articles

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一种大环类双核非离子型磁共振对比剂的合成及弛豫性能

周进^a^,^b, 孙宏顺^a^,^b^,^*(), 李玉龙^b, 蒋蕻^b, 郭成^a^,^*(), 沈临江^c

a 南京工业大学化学与分子工程学院南京 211816
b 南京科技职业学院江苏省磁共振靶向显像剂工程实验室南京 210048
c 南京工业大学数理科学学院南京 211816

收稿日期:2021-02-05 修回日期:2021-03-12 发布日期:2021-04-12
通讯作者: 孙宏顺, 郭成
作者简介:
† 共同第一作者(These authors contributed equally to this work).
基金资助:
江苏省自然科学基金(BK20181486); 江苏省高校自然科学基金(17KJB320001); 江苏省高校优秀中青年教师和校长境外研修计划和江苏省青蓝工程资助项目.

Synthesis and Relaxivity of One Macrocyclic Binuclear Nonionic Magnetic Resonance Contrast Agent

Jin Zhou^a^,^b, Hongshun Sun^a^,^b(), Yulong Li^b, Hong Jiang^b, Cheng Guo^a(), Linjiang Shen^c

a College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816
b Targeted MRI Contrast Agents Laboratory of Jiangsu Province, Nanjing Polytechnic Institute, Nanjing 210048
c School of Physical and Mathematical Sciences, Nanjing Tech University, Nanjing 211816

Received:2021-02-05 Revised:2021-03-12 Published:2021-04-12
Contact: Hongshun Sun, Cheng Guo
Supported by:
Natural Science Foundation of Jiangsu Province(BK20181486); Natural Science Foundation of the Jiangsu Higher Education Institutions(17KJB320001); Overseas Training Program for Excellent Young Teachers and Principals of Jiangsu Province and the Qing Lan Project of Jiangsu Province.

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Abstract

Magnetic resonance imaging (MRI) is widely employed in diagnostic medicine and soft tissue imaging. Contrast agents (CAs) can improve the specificity of enhanced MRI images. Herein, the design, synthesis and relaxivity of a novel binuclear nonionic Gd-based DOTA-hydrazide (DOTA=1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid) derived MRI contrast agents, (Gd-DOTAH)₂-SBDC, were reported. The improved longitudinal relaxivity was determined as 10.6 L•mmol^–1•s^–1 per molecule or 5.3 L•mmol^–1•Gd^–1•s^–1at 0.5 T, which is higher than that of the mononuclear clinical macrocyclic agent Gd-DOTA.In vitro MRI studies confirmed its suitability for use as a MRI contrast agent with improved diagnostic sensitivity and accuracy. Furthermore, the stilbene moiety endows it with myelin-targeting capabilities. In addition, two synthetic routes (A and B) for this contrast agent were compared, providing overall yields of 70% and 75%, respectivily, and route B was deemed superior.

Key words: magnetic resonance imaging, contrast agents, synthesis, relaxivity, DOTA-hydrazide, Gd-DOTA, myelin

Cite this article

Jin Zhou, Hongshun Sun, Yulong Li, Hong Jiang, Cheng Guo, Linjiang Shen. Synthesis and Relaxivity of One Macrocyclic Binuclear Nonionic Magnetic Resonance Contrast Agent[J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2767-2773.

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Fig. & Tab. 4

. Chart 1 Structures of some compounds concerned

Scheme 1. Synthetic routes (A and B) for complex 8 Reagents and conditions: (i) SOCl2, DMF; (ii) CH2Cl2, K2CO3; (iii) TFA, r.t, 24 h; (iv) GdCl3, 50 ℃, 24 h; (v) TFA, r.t, 24 h; (vi) GdCl3, 50 ℃, 24 h; (vii) DMF, K2CO3

Figure 1. MR relaxivities and T1-weighted MR images at 0.5 T r1 and r2 relaxivity curves of 8 (A, B); T1-weighted MR images at varying concentrations in the range of 0.25 to 2.0 mmol/L (C, D).

Entry	Gd-complexes	r₂/(L•mmol^–1•s^–1)	r₁/(L•mmol^–1•s^–1)	r₂/r₁	Ref.
1	(Gd-DOTAH)₂-SBDC	12.3	10.6	1.16	This work
2	Gd-DOTA	4.3	3.6	1.19	[26]
3	(Gd-DOTAH)₂-DYMB	13.2	11.4	1.16	[17]
4	(Gd-DOTAH)₂-DYMBP	14.0	11.7	1.20	[17]

Table 1. The r1 and r2 values and the ratios of r2/r1 of the synthesized complex at 0.5 Ta

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一种大环类双核非离子型磁共振对比剂的合成及弛豫性能

Synthesis and Relaxivity of One Macrocyclic Binuclear Nonionic Magnetic Resonance Contrast Agent

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References 29

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