CN114437120A - 一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的设计与合成 - Google Patents

一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的设计与合成 Download PDF

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CN114437120A
CN114437120A CN202011199708.6A CN202011199708A CN114437120A CN 114437120 A CN114437120 A CN 114437120A CN 202011199708 A CN202011199708 A CN 202011199708A CN 114437120 A CN114437120 A CN 114437120A
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叶亚熙
曾尚明珠
俞雅文
陈新月
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Institute Of Artificial Intelligence Biomedical Technology Nanjing University
Nanjing Carbon Silicon Artificial Intelligence Biomedical Technology Research Institute Co ltd
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Abstract

本发明公开了一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的制备方法，结构如式所示，

Description

一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱 导荧光探针的设计与合成
技术领域
本发明属于荧光探针领域
背景技术
癫痫是一种慢性神经退行性疾病，越来越多的证据表明其病理进展与过氧亚硝酸盐(ONOO-)密切相关。然而，由于缺乏用于癫痫脑内ONOO-测定的体内成像探针，对其功能的理解仍然具有挑战性。
在众多的检测方法中，荧光法因具有灵敏度高，选择性好，对生物组织基本无侵入性，实时原位成像，时空分辨率高等优点，被广泛应用于化学传感和成像等领域.其中，基于化学反应型的聚集诱导发光(AIE)荧光传感器因克服了传统荧光探针广泛存在的聚集诱导猝灭(ACQ)现象而成为研究热点。
血脑屏障是指脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障和由脉络丛形成的血浆和脑脊液之间的屏障，这些屏障能够阻止某些物质(多半是有害的)由血液进入脑组织。血液中多种溶质从脑毛细血管进入脑组织，有难有易；有些很快通过，有些较慢，有些则完全不能通过，这种有选择性的通透现象使人们设想可能有限制溶质透过的某种结构存在，这种结构可使脑组织少受甚至不受循环血液中有害物质的损害，从而保持脑组织内环境的基本稳定，对维持中枢神经系统正常生理状态具有重要的生物学意义。
发明内容
本发明提供用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的合成方法，以解决现有问题，以及提供一种上述化合物在荧光成像方面的应用。
技术方案：用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的合成，其具有如式所示的结构，
Figure BSA0000223361550000021
一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的合成方法，具体如下：
Figure BSA0000223361550000022
Reagents and conditions：(i)1-(2-hydroxyethyl)-4-methylpyridin-1-ium，MeCN，piperidine，80℃，overnight；
(ii)2-(4-(bromomethyl)phenyl)-4，4，5，5-tetramethyl-1，3，2-dioxaborolane，MeCN，piperidine，80℃，avoid light，overnight
具体实施方式
步骤1.称取A(355.1mg，1mmol)，B(265.1mg，1mmol)加入50mL乙腈作溶剂，50μL哌啶催化，80℃反应过夜。停止反应后，旋蒸去除溶剂，用乙醚清洗得到紫红色固体C，产率85％m.p.138-139℃1H NMR(600MHz，Chloroform-d)δ8.81(d，J＝9.23HZ，2H)，7.94(d，J＝8.54Hz，2H)，7.84(d，J＝7.26Hz，4H)，7.37(d，J＝7.26Hz，2H)，7.21(m，J＝8.5Hz，5H).7.20(m，J＝7.8HZ，5H)，6.90(s，1H)，6.6(s，1H)，4.38(t，J＝1.53HZ，2H)，3.73(t，J＝1.52HZ，2H).MS EI+：602.5(C31H27IN2OS，[M]+).
步骤2.称取C(602mg，1mmol)，D(297mg，1mmol)加入50mL乙腈作溶剂，50μL哌啶催化，80℃避光反应过夜。停止反应后，用二氯甲烷萃取，用无水硫酸钠除水，硅胶柱层析(洗脱剂V二氯甲烷∶V甲醇＝20∶1)，得到最终的结构式如E所示的化合物产率20％，m.p.201-202℃1H NMR(600MHz，Chloroform-d)δ8.81(d，J＝9.23HZ，2H)，7.94(d，J＝8.54Hz，2H)，7.84(m，J＝7.26Hz，6H)，7.37(m，J＝7.26Hz，4H)，7.21(m，J＝8.5Hz，5H).7.20(m，J＝7.8HZ，5H)，6.90(s，1H)，6.6(s，1H)，4.38(t，J＝1.53HZ，2H)，4.24(m，J＝1.57HZ，2H)3.73(t，J＝1.52HZ，2H)，1.20(s，12H)，MS EI+：818.6(C44H44BIN2O3S，[M]+).。
Figure BSA0000223361550000031
以上详细描述了本发明的优选实施方式，但是，本发明并不限于上述实施方式中的具体细节，在本发明的技术构思范围内，可以对本发明的技术方案进行多种等同变换，这些等同变换均属于本发明的保护范围。另外需要说明的是，在上述具体实施方式中所描述的各个具体技术特征，在不矛盾的情况下，可以通过任何合适的方式进行组合。为了避免不必要的重复，本发明对各种可能的组合方式不再另行说明。此外，本发明的各种不同的实施方式之间也可以进行任意组合，只要其不违背本发明的思想，其同样应当视为本发明所公开的内容。

Claims (2)

1.一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的结构
Figure FSA0000223361540000011
2.一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的制备方法，结构如下
Figure FSA0000223361540000012
制备方法包括如下步骤，
步骤1.称取A(355.1mg，1mmol)，B(265.1mg，1mmol)加入50mL乙腈作溶剂，50μL哌啶催化，80℃反应过夜。停止反应后，旋蒸去除溶剂，用乙醚清洗得到紫红色固体C。
步骤2.称取C(602mg，1mmol)，D(297mg，1mmol)加入50mL乙腈作溶剂，50μL哌啶催化，80℃避光反应过夜。停止反应后，用二氯甲烷萃取，用无水硫酸钠除水，硅胶柱层析(洗脱剂V二氯甲烷∶V甲醇＝20∶1)，得到最终的结构式如E所示的化合物。
Figure FSA0000223361540000021
CN202011199708.6A 2020-10-30 2020-10-30 一种用于癫痫模型中实时监测过氧化亚硝酸盐波动的聚集诱导荧光探针的设计与合成 Pending CN114437120A (zh)

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CN110256413A (zh) * 2019-06-11 2019-09-20 天津大学 一种新型aie荧光探针分子及该探针分子、纳米胶束和囊泡的制备方法
CN110964044A (zh) * 2019-12-13 2020-04-07 山东省科学院生物研究所 一种基于双香豆素衍生物的过氧化亚硝酸盐荧光探针、制备方法与应用
CN111072632A (zh) * 2019-12-27 2020-04-28 山东大学 一种利用荧光图像显示细胞膜电位两种状态的荧光探针及其应用
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CN101100465A (zh) * 2007-06-12 2008-01-09 山东大学 阳离子咔唑类化合物及其作为双光子核酸荧光探针的应用
CN107033177A (zh) * 2017-04-05 2017-08-11 济南大学 一种以硼酸频哪醇酯为识别受体的超灵敏高选择过氧化亚硝酸盐比色比率荧光探针
CN111263751A (zh) * 2017-10-24 2020-06-09 香港科技大学 具有聚集诱导发光特性的水溶性化合物
CN109942609A (zh) * 2019-03-20 2019-06-28 南京师范大学 一种过氧亚硝酸盐近红外荧光探针onp及其制备方法和应用
CN110256413A (zh) * 2019-06-11 2019-09-20 天津大学 一种新型aie荧光探针分子及该探针分子、纳米胶束和囊泡的制备方法
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CN111072632A (zh) * 2019-12-27 2020-04-28 山东大学 一种利用荧光图像显示细胞膜电位两种状态的荧光探针及其应用

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