去甲肾上腺素（NE）、多巴胺（DA）、谷氨酸（Glu）神经递质的特异性荧光探针设计及其神经成像

Neurological diseases and the abuse of neuropathic drugs, both seriously affect the stability of society. The occurrence of neurological disorders is that some neurotransmitters in the organization of the level of abnormal causes of its messenger function failure. Among them, catechols and amino acid neurotransmitters were much concerned in recent years, because they play a leading role in neurological function attention. Above the neurotransmitter structure similarity or containing the same functional groups, today's fluorescent probes developed being lack of specific detection of neurotransmitters, have been greatly limited in the field of biological, medical applications. In view of these problems, the project intends to carry out the following work: first, for catecholamines, the introduction of supramolecules, through the cavity size and their assembly, the regulation of fluorescence, to distinguish recognition; second, the introduction of aldehydes in the probe for the ammonia Acid amide binding sites, with divalent zinc ions as a fluorescent switch to achieve glutamic acid near-infrared specific fluorescence recognition; third, to study the release and neurotransmission of neurotransmitters under drugs stimulation (amphetamine, caffeine and nicotine, etc.), and promote the development of low toxic, high efficacy neuropathic drugs.

神经性疾病和神经性药物的滥用，两者严重影响到社会的安定。神经性疾病的产生就是某些神经递质在组织中的水平异常导致其信使功能出现故障。其中儿茶酚类和氨基酸类神经递质，由于他们在神经性功能中起着主导作用近年来备受关注。以上神经递质结构相似性或者含有相同的官能团，使得当今发展起来的荧光探针因为对神经递质缺乏特异性检测，在生物、医学领域中的应用受到了极大的限制。针对这些问题，本项目拟开展以下工作：第一、针对儿茶酚胺，引入超分子，通过空腔大小与它们发生组装，调控荧光，实现区分识别；第二、在探针中引入醛基为谷氨酸氨基结合位点，以二价锌离子配位为荧光开关，实现谷氨酸的近红外特异性荧光识别；第三，研究药物（安非他民、咖啡因和尼古丁等）刺激下神经递质释放、信号传递过程，为开发毒副性小，疗效高的神经药物提供理论基础。

按计划完成本项目，发表SCI论文17篇，包括J Am Chem Soc, Anal Chem, Chem commun, Sens Actuators B.等。另外，会议论文6篇，授权国家发明专利5项。项目组两名教师美国访学，6名研究生美国、西班牙访学。举办全国学术会议1次（中国化学会第十五届生物无机化学会议暨金属化学生物学学术会议，2021.10.22-10.25, 山西太原），参加学术会议多次，项目主持人做6次邀请报告。培养博士生4名，硕士生10名，培养山西省青年学术带头人一名、山西省三晋英才3名，培养副教授2名，引进青年教师1名，阴彩霞荣获2010年CCL优秀青年学者，2名博士荣获宝钢优秀学生奖。项目针对儿茶酚胺神经递质特异性检测的科学问题开展研究，本项目中成功实现了NE特异性荧光检测，另外对它们的干扰物质活性硫化物进行了荧光检测和生物成像的研究。实验与理论结合取得的具体成果：完成去甲肾上腺素特异性荧光探针的构建与脑组织标记；完成去甲肾上腺素胞吐过程和药物干预可视化；揭示了抑郁症与去甲肾上腺素胞吐过程的相关性；通过光控原位激活反应位点，时空精准解析了气体信使分子SO2；实现了儿茶酚胺神经递质干扰物质谷胱甘肽代谢SO2可视化示踪；实现了儿茶酚胺神经递质干扰物质半胱氨酸线粒体内代谢SO2可视化示踪。