新型有机小分子荧光探针的设计合成及其对光气的检测应用

【作者】 杨磊；

【导师】 孙志伟；

【作者基本信息】 曲阜师范大学 ， 分析化学， 2021， 硕士

【摘要】 光气（Phosgene）是一种剧毒气体,没有颜色并且味道与新割的干草十分相似,通常情况下不易被人察觉。光气曾在第一次世界大战和第二次世界大战中被部分军队作为化学武器使用,造成了人口的大量死亡。而在当下,光气作为许多工业上生产农药、医药、高分子材料和有机合成中间体的原料而同样被广泛地应用。此外,与其他化学战剂不同的是,光气的生产与销售不受法律的严格控制,一旦在使用时发生泄漏或被恐怖分子利用制成化学武器来进行恐怖活动,将会严重影响公众健康和安全。因此,鉴于光气越来越广泛的应用以及传统对光气检测的方法存在多种弊端的情况之下,我们结合有机小分子荧光探针的优越性设计合成出了多种检测光气的荧光探针,在本论文中,主要开展了以下几项工作:（1）第二章:基于7-硝基-2,1,3-苯并氧杂恶二唑（NBD）荧光团,我们设计合成了三个开启型的有机小分子光气荧光探针NBD-TACN、NBD-EDA和NBD-PZ。其中,探针NBD-TACN以能够提供多个N原子与孤对电子的1,4,7-三氮杂环壬烷作为识别基团,光气通过与三氮杂环壬烷结构中的4号和7号位亚氨基结合产生内部环化作用而阻断其对于NBD荧光团的PET作用,在525 nm处产生极强的绿色荧光开启;而探针NBD-EDA和探针NBD-PZ则以常见的乙二胺和哌嗪基团作为识别基团,其与光气结合后同样能够阻断其对NBD荧光团的PET作用,分别在530 nm和540 nm处产生极强的绿色荧光开启。在溶液中,三个探针均对光气的传感具有快速响应（20秒内完成）、高选择性和高灵敏度（检测限分别为1.2 n M、20.1 n M和27.4 n M）的优点。当然,在选择性和灵敏度方面,探针NBD-TACN要优于探针NBD-EDA和探针NBD-PZ。因此,我们基于探针NBD-TACN,进一步开发了用于实时检测气相中光气的便携式试纸条。（2）第三章:基于双苯并咪唑荧光团,我们设计合成了开启型的有机小分子光气荧光探针BBMMN,其可以与光气快速结合产生六元环状氨甲酰化产物BBMMN-Phos,在428 nm处产生极强的蓝色荧光发射,相对量子产率增加8.2倍。探针BBMMN对光气的响应具有快速（30秒内完成）、高选择性和高灵敏度（溶液中检测限低至3.3 n M）的良好特性。此外,基于此探针制造的便携式试纸条能够方便地对气态光气进行视觉和荧光检测。（3）第四章:基于苯并咪唑荧光团,我们首次提出了一种易于合成的双功能有机小分子荧光探针BMA用于光气和亚硝酸盐的检测。探针BMA在乙腈溶液（含10%DMSO）中对光气具有快速响应（1分钟内）、高选择性和灵敏度（检测限为1.27 n M）,表现为416 nm至480 nm的比率型荧光变化。而探针BMA在盐酸水溶液（含10%乙腈,p H=1）中对亚硝酸盐的响应同样具有很高的选择性和灵敏度（检测限为60.63 n M）,表现为485 nm处的关闭型荧光模式。此外,基于探针BMA我们还成功开发了两个便携式化学传感器（TLC板和试纸条）用于检测气相中的光气和溶液中的亚硝酸盐,均显示出良好的响应。最重要的是,探针BMA还能够检测出实际食品样品中的亚硝酸盐,并且通过添加标准亚硝酸盐溶液获得了良好的回收率（88.5%-107.2%）。（4）第五章:基于咪唑并[1,5-α]吡啶荧光团,我们设计合成了开启型有机小分子荧光探针PMPY-NH₂,其能够通过自身的ESIPT机理将分子结构转变为酮式结构从而对光气产生快速、高选择性和高灵敏度（检测限为2.68 n M）的响应。由于氨基与苯稠咪唑合环的反应使探针的共轭平面增大,表现为455 nm处高亮的天蓝色荧光开启,绝对量子产率增加将近5倍。此外,我们还基于探针PMPY-NH₂开发了便携式试纸条用于环境中气态光气的检测,该试纸条能够对低至1 ppm的气态光气产生响应,具有极高的灵敏度,对于气态光气的实际检测具有良好的应用潜力。更多还原

【Abstract】 Phosgene（COCl₂）is a highly toxic gas,which is not easy to be noticed because it has no color and tastes very similar to newly mown hay.Phosgene was also used as a chemical weapon in World War I and World War II,causing a large number of deaths.At present,phosgene is widely used as a raw material for the industrial production of many pesticides,medicines,polymer materials and organic synthesis intermediates.In addition,unlike other chemical warfare agents,the production and sales of phosgene are not strictly controlled by law.Once it leaks during use or is used by terrorists to make chemical weapons for terrorist activities,it will seriously affect public health and safety.Therefore,under the more and more widespread application of phosgene and the disadvantages of traditional phosgene detection methods,combined with the superiority of organic small molecule fluorescent probes,a variety of fluorescent probes for detecting phosgene have been born.In this paper,we mainly carried out the following work:（1）Chapter 2:Based on the 7-nitro-2,1,3-benzoxoxadiazole（NBD）fluorophore,we designed and synthesized three turn-on organic small molecule phosgene fluorescent probes NBD-TACN,NBD-EDA and NBD-PZ.The probe NBD-TACN uses1,4,7-triazacyclononane as the recognition group,which can provide multiple N atoms and lone pairs of electrons,and phosgene combined the 4 and 7 position-NH groups in triazacyclononane structure to produces internal cyclization and blocks its PET effect on the NBD fluorophore.The reaction between NBD-TACN and phosgene produces a strong green fluorescence at 525 nm.NBD-EDA and NBD-PZ are based the common ethylenediamine and piperazine groups to recognition groups,which can also block the PET effect on the NBD fluorophore after being combined with phosgene,and produce extremely strong green fluorescence at 530 nm and 540 nm,respectively.In solution,the three probes all have the advantages of fast response（completed within 20 s）,high selectivity and high sensitivity（the detection limits are1.2 n M,20.1 n M and 27.4 n M,respectively）for phosgene sensing.Of course,in terms of selectivity and sensitivity,NBD-TACN is superior to NBD-EDA and NBD-PZ.Therefore,we also successfully developed a portable test strip for real-time detection of phosgene in the gas phase based on the NBD-TACN.（2）Chapter 3:Based on the bis-benzimidazole fluorophore,we designed and synthesized a turn-on organic small molecule phosgene fluorescent probe BBMMN,which can quickly combine with phosgene to produce a six-membered cyclic carbamylation product BBMMN-Phos,produces extremely strong blue fluorescence emission at 428 nm and the relative quantum yield increases by 8.2 times.The response of BBMMN to phosgene is fast（completed within 30 s）,high selectivity and high sensitivity（the detection limit in solution is as low as 3.3 n M）.In addition,the portable test strip based on this probe can easily perform visual and fluorescent detection of gaseous phosgene.（3）Chapter 4:Based on the benzimidazole fluorophore,we first proposed a facile bifunctional organic small molecule fluorescent probe BMA for the detection of phosgene and nitrite.BMA had fast response（1 min）,high selectivity and sensitivity（the limit of detection was 1.27 n M）to phosgene in CH₃CN solution（containing 10%DMSO）,which manifested as a ratiometric fluorescent mode from 416 nm to 480 nm.The response of BMA to nitrite in HCl solution（p H=1,containing 10%CH₃CN）was also highly selective and sensitive（the limit of detection was 60.63 n M）,which shown as a turn-off fluorescent mode at 485 nm.In addition,two portable chemosensors（BMA-loaded TLC plates and test strips）had also been successfully manufactured for the detection of phosgene in the gas phase and nitrite in solution,which displayed good responses.Most importantly,BMA had also been successfully used for detection of nitrite in food samples,and a good recovery（88.5%-107.2%）was obtained by adding standard sodium nitrite.（4）Chapter 5:Based on the imidazo[1,5-α]pyridine fluorophore,we designed and synthesized a turn-on organic small molecule fluorescent probe PMPY-NH₂,which can be transformed into a ketone structure through the ESIPT mechanism to rapidly,high selectively and sensitively（detection limit is 2.68 n M）combine with phosgene.The conjugation plane of the probe is increased due to the formylation reaction between the amino group and the benzimidazole ring,which is manifested by the generation of bright sky blue fluorescence at 455 nm and the absolute quantum yield increases by nearly 5 times.In addition,we have also developed a portable test strips based on PMPY-NH₂for the detection of gaseous phosgene in the environment.The test strip can respond to gaseous phosgene as low as 1 ppm,which has extremely high sensitivity.So,PMPY-NH₂can be widely used in actual testing in the future.更多还原