基于Trityl自由基的高灵敏高选择性亚硝酰氢EPR探针的构建及生物成像应用研究
结题报告
批准号:
21967013
项目类别:
地区科学基金项目
资助金额:
39.0 万元
负责人:
刘文波
依托单位:
学科分类:
生物体系分子探针
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
刘文波
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中文摘要
作为一氧化氮(NO)的单电子还原产物,亚硝酰氢(HNO)是生物体内重要的信号分子,有着与一氧化氮(NO)截然不同的生物活性。实现活体组织内HNO水平的精确高效、特异性检测对于正确理解HNO的生物学功能和相关疾病的发病机制具有重要意义。电子顺磁共振(EPR)技术因其无创性、灵敏性及特异性,已发展为重要的检测及成像技术。但是由于缺少合适的顺磁性探针,该技术的体内应用受到限制。近年来,四硫取代三苯甲基(Trityl)自由基优越的波谱性质、高度的敏感性及稳定性使其在EPR检测和成像方面表现出极大的应用潜力。基于此,该项目首次设计一类基于Trityl结构的新型亚硝酰氢EPR探针;并进一步对其衍生化,构建高稳定、高灵敏、生物相容的细胞外/内的HNO探针;最后通过对探针物理化学性质的表征及在细胞和活体层面的性能测试,确定其最大使用剂量和体内分布等,总结出对HNO探针的设计与合成具有指导意义的规律。
英文摘要
Nitroxyl (HNO), as an electron reduced and protonated form of nitric oxide, is emerging as an important signaling molecule in many physiological processes,demonstrates a unique chemical and biological profile compared to NO. Accurate and efficient detection of HNO levels in living tissue is important for the correct understanding of the biological functions of HNO and the pathogenesis of related diseases. Although a wide variety of techniques have been developed to detect HNO, electron paramagnetic resonance (EPR) spectroscopy/imaging in tandem with the use of exogenous paramagnetic probes has been established as an important technique for the in vivo measurement and mapping of HNO. Unfortunately, the full potential of this technique has not been realized mainly due to lack of suitable paramagnetic probes. Recently, tetrathiatriarylmethyl (Trityl) radicals show great potential in the EPR measurement and imaging owing to their unique sharp EPR singlet, high sensitivity and biostability. To address these, the new EPR probes of HNO based on Trityl-Cu(II) skeleton with improved properties would be developed; then derivatize these Trityls as novel high sensitivity HNO probes with good biocompatibility for extracellular or intracellular HNO measurement; lastly physicochemically characterize and performance test in cell and living level of these new HNO probes, their maxim and distribution in vivo would be determined, and summarize the guiding principles of the design and synthesis of HNO probes.
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DOI:10.1039/d1ra07511j
发表时间:2022-05-23
期刊:RSC ADVANCES
影响因子:3.9
作者:Liu, Wenbo;Tao, Ouyang;Chen, Li;Ling, Yun;Zeng, Ming;Jin, Hongguang;Jiang, Dengzhao
通讯作者:Jiang, Dengzhao
DOI:10.3390/molecules28093676
发表时间:2023-04-24
期刊:Molecules (Basel, Switzerland)
影响因子:--
作者:Zeng M;Chen J;Li F;Li H;Zhao L;Jiang D;Dai J;Liu W
通讯作者:Liu W
DOI:--
发表时间:2022
期刊:NEW JOURNAL OF CHEMISTRY
影响因子:3.3
作者:Ming Zeng;Yi-xuan Liu;Jian-hui Zheng;Lan Zhao;Qi-han Zhu;Dengzhao Jiang;Yun Ling;Wenbo Liu;Shen-xin Zeng
通讯作者:Shen-xin Zeng
DOI:10.1039/d2ob00582d
发表时间:2022
期刊:Organic & Biomolecular Chemistry
影响因子:--
作者:Ming Zeng;Zixin Yuan;Linfei Wen;Dengzhao Jiang;Hui Lu;Wenbo Liu;Jun Dai;Shen-xin Zeng
通讯作者:Shen-xin Zeng
DOI:--
发表时间:2023
期刊:医药卫生
影响因子:--
作者:邹玉凤;徐 明;毛艺男;刘文波
通讯作者:刘文波
国内基金
海外基金