CN110483512A - 一种喹啉酰亚胺类探针分子及其合成方法与应用、喹啉酰亚胺类探针分子络合物及其应用 - Google Patents

一种喹啉酰亚胺类探针分子及其合成方法与应用、喹啉酰亚胺类探针分子络合物及其应用 Download PDF

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CN110483512A
CN110483512A CN201910839615.6A CN201910839615A CN110483512A CN 110483512 A CN110483512 A CN 110483512A CN 201910839615 A CN201910839615 A CN 201910839615A CN 110483512 A CN110483512 A CN 110483512A
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张宇
王金平
张悦
郭祥峰
贾丽华
张宇涵
温雅婷
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Abstract

本发明提供了一种喹啉酰亚胺类探针分子及其制备方法与应用、喹啉酰亚胺类探针分子络合物及应用,属于有机合成技术领域,本发明提供的喹啉酰亚胺类探针分子具有如下所示结构。本发明提供的喹啉酰亚胺类探针分子将5‑烷基‑5H‑苯并[de][2,6]萘啶‑4,6‑二酮与2,2'‑二吡啶甲基胺结合,使该类探针分子可以高选择性、灵敏度荧光猝灭检测Cu2+。当所述喹啉酰亚胺类探针分子与Cu2+络合形成络合物后,该络合物能够高选择性地荧光增强识别各种环境下的半胱氨酸。依次交替加入Cu2+和半胱氨酸,该类喹啉酰亚胺分子形成“关‑开‑关”荧光循环回路,据此可以构建分子水平的、具有“读‑写‑读‑擦除”功能的可逆分子器件。

Description

一种喹啉酰亚胺类探针分子及其合成方法与应用、喹啉酰亚 胺类探针分子络合物及其应用
技术领域
本发明涉及有机合成技术领域,尤其涉及一种喹啉酰亚胺类探针分子及其合成方法与应用、喹啉酰亚胺类探针分子络合物及其应用。
背景技术
众所周知,Cu2+是人体内第三丰富的过渡金属,在人体的基本生理过程中发挥至关重要的作用。同时,作为一种重要的环境污染物,过量的Cu2+摄入会改变细胞的稳态,导致神经退行性疾病。另外,半胱氨酸(Cys),作为一种含硫醇的氨基酸,在氧化还原反应和细胞解毒等许多生理过程中起着关键作用。Cys在细胞内含量与许多疾病,如阿尔茨海默病、艾滋病和癌症等密切相关。因此,能够有效监测细胞内Cu2+和Cys的分析方法有助于阐明两者在健康和疾病状态下的行为。荧光检测技术由于有操作简单、灵敏度高和响应速度快等优势,被广泛用于Cu2+及Cys的检测。
喹啉酰亚胺类化合物具有喹啉和萘酰亚胺基团的嵌合结构,并且其荧光性能优于喹啉和萘酰亚胺基团。与喹啉基团相比,喹啉酰亚胺类化合物的激发和发射波长均红移至可见光区,避免了喹啉基团需用紫外光激发分子发射荧光的弊端;而与萘酰亚胺基团相比,N原子的引入不仅使发射波长红移,还能够增加化合物的水溶性。然而,尽管喹啉酰亚胺类化合物的合成于2004 年就已经被报道(M.F.A.Gradillas,A.Gómez,N.Acero,F.Llinares,D. -Mingarro,C.Abradelo,F.Rey-Stolle,M.Yuste,J.Campos,Gallo,A. Espinosa,Synthesis,biological activity and quantitative structure-activity relationship study of azanaphthalimide and arylnaphthalimidederivatives,J.Med. Chem.2004,47,2236-2242)。但目前为止,仅有两篇文献描述了此类化合物的荧光性能(J.A.González-Vera,F.Fueyo-González,I.Alkorta,M.Peyressatre,M.C.Morris,R.Herranz,Highly solvatochromic and tunable fluorophores based ona 4,5-quinolimide scaffold:novel CDK5 probes,Chem.Commun.2016,52, 9652-9655;Y.Zhang,X.Guo,M.Zheng,R.Yang,H.Yang,L.Jia,M.Yang,A 4,5-quinolimide-basedfluorescent sensor for the turn-on detection of Cd2+with live-cell imaging,Org.Biomol.Chem.2017,15,2211-2216),未见喹啉酰亚胺类化合物其他功能的报道。
发明内容
有鉴于此,本发明的目的在于提供一种喹啉酰亚胺类探针分子及其合成方法与应用、喹啉酰亚胺类探针分子络合物及其应用。本发明提供的喹啉酰亚胺类探针分子能够高选择性地检测Cu2+
为了实现上述发明目的,本发明提供以下技术方案:
本发明提供了一种喹啉酰亚胺类探针分子,其结构如式I所示:
其中,R为C1-C4直链烷基。
本发明还提供了上述技术方案所述的喹啉酰亚胺类探针分子的合成方法,包括以下步骤:
将2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮、2,2'-二吡啶甲基胺和有机溶剂混合,在氮气保护下回流,得到所述喹啉酰亚胺类探针分子;
所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮中的烷基为C1-C4直链烷基。
优选地,所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮和2,2'-二吡啶甲基胺的摩尔比1:3~6。
优选地,所述有机溶剂为包括乙腈或乙二醇甲醚。
优选地,所述回流的时间为36~72h。
优选地,回流结束后,还包括将所得回流产物旋干,将所得旋干产物经硅胶柱色谱分离,得到所述喹啉酰亚胺类探针分子。
优选地,所述硅胶柱色谱分离用洗脱剂为二氯甲烷和甲醇的混合物,所述洗脱剂中二氯甲烷和甲醇的体积比为20~30:1。
本发明将上述技术方案所述的喹啉酰亚胺类探针分子应用于检测Cu2+
本发明提供了一种喹啉酰亚胺类探针分子络合物,包括权利要求1所述的喹啉酰亚胺类探针分子和Cu2+,所述喹啉酰亚胺类探针分子络合物中喹啉酰亚胺类探针分子和Cu2 +的摩尔比为1:1。
本发明将上述技术方案所述的喹啉酰亚胺类探针分子络合物应用于检测半胱氨酸。
本发明提供了一种喹啉酰亚胺类探针分子,其结构如式I所示。本发明提供的喹啉酰亚胺类探针分子将5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮与2,2'-二吡啶甲基胺结合。由于2,2'-二吡啶甲基胺具有高的生物兼容性和Cu2+亲和力,使得该探针分子能够识别Cu2+。实施例的数据表明:当溶液中存在多种金属离子时,本发明的喹啉酰亚胺类探针分子能够有选择性地、高灵敏度地检测 Cu2+
本发明还提供了上述技术方案所述的喹啉酰亚胺类探针分子的制备方法,本发明提供的制备方法简单、易操作,且反应条件温和,能够得到高产率和高纯度的喹啉酰亚胺类探针分子。
本发明还提供了一种喹啉酰亚胺类探针分子络合物,所述络合物中包括喹啉酰亚胺类探针分子和Cu2+,由于半胱氨酸对络合物中的Cu2+的亲和力高于喹啉酰亚胺类探针分子,使得半胱氨酸可以竞争络合Cu2+,导致喹啉酰亚胺类探针分子荧光恢复,所以,使得该络合物能够高选择性地识别各种环境下的半胱氨酸,能够应用于检测半胱氨酸。
附图说明
图1为实施例1所得喹啉酰亚胺类探针分子在加入不同金属离子前后的荧光光谱变化图;
图2为实施例1所得喹啉酰亚胺类探针分子在加入等摩尔金属离子与 Cu2+后的荧光强度柱状图;
图3为实施例1所得喹啉酰亚胺类探针分子对不同浓度Cu2+的荧光光谱变化图;
图4为实施例1所得喹啉酰亚胺类探针分子对不同浓度Cu2+的荧光强度变化曲线;
图5为实施例1所得喹啉酰亚胺类探针分子Cu2+络合物在加入不同含硫氨基酸前后的荧光光谱变化图;
图6为实施例1所得喹啉酰亚胺类探针分子Cu2+络合物对不同浓度Cys 的荧光光谱变化图;
图7为实施例1所得喹啉酰亚胺类探针分子Cu2+络合物对不同浓度Cys 的荧光强度变化曲线;
图8为实施例1所得喹啉酰亚胺类探针分子在交替加入Cu2+和Cys后的荧光强度可逆曲线;
图9为实施例1所得喹啉酰亚胺类探针分子在依次加入Cu2+和Cys后利用荧光强度变化构造的、具有“读-写-读-擦除”功能的可逆分子器件示意图;
图10为实施例1所得喹啉酰亚胺类探针在细胞内依次加入Cu2+和Cys后荧光显微成像和明场图。
具体实施方式
本发明提供了一种喹啉酰亚胺类探针分子,其结构如式I所示:
其中,R为C1-C4直链烷基。
在本发明中,当R为甲基时,所述喹啉酰亚胺类探针分子的结构如式II 所示:
在本发明中,当R为乙基时,所述喹啉酰亚胺类探针分子的结构如式III 所示:
在本发明中,当R为丙基时,所述喹啉酰亚胺类探针分子的结构如式IV 所示:
在本发明中,当R为正丁基时,所述喹啉酰亚胺类探针分子的结构式如式V所示:
本发明还提供了上述技术方案所述的喹啉酰亚胺类探针分子的合成方法,包括以下步骤:
将2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮、2,2'-二吡啶甲基胺和有机溶剂混合,在氮气保护下回流,得到所述喹啉酰亚胺类探针分子;
所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮中的烷基为C1-C4直链烷基。
在本发明中,所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮和2,2'-二吡啶甲基胺的摩尔比优选为1:3~6,进一步优选为1:5。在本发明中,所述有机溶剂优选为乙腈或乙二醇甲醚,进一步优选为乙腈;本发明对所述有机溶剂的量不做具体限定,只要能够将2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮和2,2'-二吡啶甲基胺充分溶解即可。本发明对所述2-氯-5-烷基-5H-苯并 [de][2,6]萘啶-4,6-二酮和2,2'-二吡啶甲基胺的来源不做具体限定,本领域技术人员根据现有文献自行制备即可。
在本发明中,所述回流的时间优选为36~72h,进一步优选为48h。
回流结束后,本发明优选还包括将所得回流产物旋干,将所得旋干产物经硅胶柱色谱分离,得到所述喹啉酰亚胺类探针分子。
在本发明中,所述硅胶柱色谱分离用洗脱剂优选为二氯甲烷和甲醇的混合物,所述洗脱剂中二氯甲烷和甲醇的体积比优选为20~30:1,进一步优选为25:1。
在本发明中,所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮和2,2'-二吡啶甲基胺生成喹啉酰亚胺类探针分子的反应机理如式VI所示:
本发明还提供了将上述技术方案所述的喹啉酰亚胺类探针分子应用于检测Cu2+。在本发明中,所述喹啉酰亚胺类探针分子应用于检测Cu2+时,所述 Cu2+所处的环境优选为水、甲醇、DMSO、DMF、乙腈溶剂或其混合溶剂、细胞。
在本发明中,当检测的物质中存在Cu2+时,当加入本发明的喹啉酰亚胺类探针分子时,Cu2+能够猝灭所述喹啉酰亚胺类探针分子的荧光,而Cu2+浓度与喹啉酰亚胺类探针分子荧光强度猝灭程度之间在一定区间内呈现线性关系,因此,可以用来定量检测Cu2+
本发明还提供了一种喹啉酰亚胺类探针分子络合物,所述喹啉酰亚胺类探针分子络合物包括上述技术方案所述的喹啉酰亚胺类探针分子和Cu2+;在本发明中,所述喹啉酰亚胺类探针分子络合物中喹啉酰亚胺类探针分子和Cu2+的摩尔比优选为1:1。
在本发明中,所述喹啉亚酰胺类探针分子Cu2+络合物的结构式如式VII 所示:
在本发明中,所述喹啉酰亚胺类探针分子络合物的制备方法优选包括以下步骤:
将喹啉酰亚胺类探针分子和Cu2+溶于含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,得到所述喹啉酰亚胺类探针分子络合物。在本发明中,所述喹啉酰亚胺类探针分子和Cu2+的摩尔比优选为1:3。
在本发明中,所述喹啉酰亚胺类探针分子络合物并非单独存在,均是在使用时直接配制,然后将喹啉酰亚胺类探针分子络合物储存在上述含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中。
本发明还提供了将上述技术方案所述的喹啉酰亚胺类探针分子络合物应用于检测半胱氨酸;在本发明中,当所述喹啉酰亚胺类探针分子络合物应用于检测半胱氨酸时,所述半胱氨酸所处的环境优选为水、甲醇、DMSO、DMF、乙腈溶剂或其混合溶剂、细胞。
在本发明中,所述喹啉亚酰胺类探针分子络合物识别半胱氨酸的示意图如式VIII所示:
在本发明中,当所需要检测的物质中含有半胱氨酸时,加入本发明的喹啉酰亚胺类探针分子络合物后,由于半胱氨酸对络合物中的Cu2+的亲和力高于喹啉酰亚胺类探针分子,使得半胱氨酸可以竞争络合Cu2+,导致喹啉酰亚胺类探针分子荧光恢复。也就是说,半胱氨酸能够使喹啉酰亚胺类探针分子络合物的荧光增强,同时喹啉酰亚胺类探针分子络合物的荧光增强幅度与半胱氨酸的浓度在一定区间内成线性关系,因此,可以利用本发明的喹啉酰亚胺类探针分子络合物来定量检测半胱氨酸。
下面结合实施例对本发明提供的喹啉酰亚胺类探针分子及其合成方法与应用、喹啉酰亚胺类探针分子络合物及其应用进行详细的说明,但是不能把它们理解为对本发明保护范围的限定。
实施例1
将2-氯-5-丁基-5H-苯并[de][2,6]萘啶-4,6-二酮(100mg,0.35mmol)、2,2'- 二吡啶甲基胺(348mg,1.75mmol)加入至20mL乙腈中,在氮气保护下回流48h,将回流反应液旋干,将所得旋干液溶于二氯甲烷和甲醇按体积比25: 1混合而成的洗脱剂中,然后经硅胶柱色谱分离,得喹啉酰亚胺类探针分子,产量85mg,收率为54%,mp:136.1~137.6℃。
1H NMR(600MHz,CDCl3):8.54(d,J=4.8Hz,2H),8.03(d,J=8.4Hz,1H), 7.88(d,J=9.0Hz,1H),7.82(s,1H),7.77(t,J=7.8Hz,1H),7.74(t,J=7.2Hz, 2H),7.40(d,J=7.8Hz,2H),7.28(t,J=6.0Hz,2H),5.17(N(CH2Py)2,s,4H), 3.96(CH2CH2CH2CH3,t,J=7.2Hz,2H),1.56(CH2CH2CH2CH3,m,2H),1.31 (CH2CH2CH2CH3,m,2H),0.90(CH2CH2CH2CH3,t,J=7.5Hz,3H).13C NMR(150MHz,CDCl3):163.38,163.27,158.13,157.72,149.76,146.83,137.38, 131.64,131.03,125.03,122.88,122.64,122.03,121.82,117.57,112.10,54.37,40.55,30.01,20.22,14.15。
实施例2
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸 (0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,分别加入各种常见的金属离子(Na+、K+、 Mg2+、Ca2+、Cr3+、Fe3+、Co2+、Ni2+、Cu2+、Zn2+、Ag+、Cd2+、Hg2+、Pb2+、 Al3+),金属离子浓度均为50μM,测定其荧光光谱。图1为实施例1所得喹啉酰亚胺类探针分子在加入不同金属离子前后的荧光光谱变化图。从图1可以看出:空白探针分子在552nm处发射荧光,仅Cu2+导致探针分子在552nm处的荧光显著猝灭,猝灭幅度达70%以上。由此可见,本发明的提供的喹啉酰亚胺类探针分子可高选择性荧光猝灭识别Cu2+
实施例3
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸 (0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,分别加入等摩尔各种常见的金属离子(1:无离子、2:Na+、3:K+、4:Mg2+、5:Ca2+、6:Cr3+、7:Fe3 +、8:Co2+、9: Ni2+、10:Zn2+、11:Ag+、12:Cd2+、13:Hg2+、14:Pb2+、15:Al3+)和Cu2+,金属离子浓度均为50μM时,测定其荧光强度。图2为实施例1所得喹啉酰亚胺类探针分子在加入等摩尔金属离子与Cu2+后的荧光强度柱状图。从图2 可以看出:当等摩尔的Cu2+与各种常见的金属离子共存时,常见金属离子的加入均不干扰探针分子对Cu2+的检测,其荧光强度与溶液中仅存Cu2+时相似。由此可见,本发明的喹啉酰亚胺类探针分子对Cu2+检测具有较强的抗其他金属干扰能力。
实施例4
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,研究不同Cu2+溶度对喹啉酰亚胺类探针分子荧光光谱的影响。图3为实施例1所得喹啉酰亚胺类探针分子对不同浓度 Cu2+的荧光光谱变化图;图4为实施例1所得喹啉酰亚胺类探针分子对不同浓度Cu2+的荧光强度变化曲线。从图3和图4可以看出:随着Cu2+的加入 (0~30μM),探针分子在552nm处的荧光强度逐渐下降,下降幅度达70%以上;而当Cu2+浓度超过30μM时,其荧光强度基本保持不变。探针分子对Cu2+的检出限为0.44μM,与Cu2+形成1:1型络合物时的结合常数为4.5×103M-1。在Cu2+浓度0.44~20μM范围内,探针分子的荧光强度与Cu2+浓度呈良好的线性关系,线性方程为y=-3.69x+117.11,其线性相关系数R2=0.9940。由此可见,本发明的喹啉酰亚胺类探针分子可以定量检测Cu2+
实施例5
将实施例1所得喹啉酰亚胺类探针分子和Cu2+溶于含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,Cu2+浓度为30μM,分别加入不同含硫氨基酸(半胱氨酸Cys、蛋氨酸Met、胱氨酸Cyst),含硫氨基酸浓度均为50μM,测定喹啉酰亚胺类探针分子Cu2+络合物荧光光谱。由于Cyst易溶于酸性介质,而本实施例是在中性条件下进行,Cyst不溶于该测量体系,因此无法准确测定Cyst对喹啉酰亚胺类探针分子Cu2+络合物荧光光谱的影响。图5为实施例 1所得喹啉酰亚胺类探针分子Cu2+络合物在加入不同含硫氨基酸前后的荧光光谱变化图。从图5可以看出:喹啉酰亚胺类探针分子Cu2+络合物在552nm 发射荧光较弱,加入Met后喹啉酰亚胺类探针分子Cu2+络合物荧光光谱基本保持不变;而Cys导致喹啉酰亚胺类探针分子Cu2+络合物荧光显著上升,增强约3.5倍。由此可见,本发明的喹啉酰亚胺类探针分子Cu2+络合物可在含硫氨基酸中高选择性荧光增强识别Cys。
实施例6
将实施例1所得喹啉酰亚胺类探针分子和Cu2+溶于含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,Cu2+浓度为30μM,研究不同Cys浓度对喹啉酰亚胺类探针分子Cu2+络合物荧光光谱的影响。图6为实施例1所得喹啉酰亚胺类探针分子Cu2+络合物对不同浓度Cys的荧光光谱变化图;图7 为实施例1所得喹啉酰亚胺类探针分子Cu2+络合物对不同浓度Cys的荧光强度变化曲线。从图6和图7可以看出:随着Cys的加入(0~30μM),喹啉酰亚胺类探针分子Cu2+络合物在552nm处的荧光强度逐渐上升,增强约3.5倍;而当Cys浓度超过30μM时,其荧光强度基本保持不变。喹啉酰亚胺类探针分子Cu2+络合物对Cys的检出限为1.5μM,与Cys形成1:1型络合物时的结合常数为3.2×104M-1。在Cys浓度1.5~14μM范围内,喹啉酰亚胺类探针分子 Cu2+络合物的荧光强度与Cys浓度呈良好的线性关系,线性方程为 y=1.19x+32.39,其线性相关系数R2=0.9912。由此可见,本发明的喹啉酰亚胺类探针分子Cu2+络合物可以定量检测Cys。
实施例7
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,交替加入30μM的Cu2+和Cys,重复3次,测定其荧光强度。图8为实施例1所得喹啉酰亚胺类探针分子在交替加入Cu2+和Cys后的荧光强度可逆曲线。从图8可以看出:在三个周期内,溶液在552nm 处的荧光强度显现交替猝灭和增强,并且其荧光效率损失几乎可以忽略,进一步验证了本发明的探针分子荧光响应的可逆性。
实施例8
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸 (0.01M)缓冲溶液(pH=7.20)的乙腈和水(乙腈和水的体积比1:4)的混合溶液中,探针分子浓度为10μM,依次加入30μM的Cu2+和Cys,测定其荧光强度。图9为实施例1所得喹啉酰亚胺类探针分子在依次加入Cu2+和Cys 后利用荧光强度变化构造的、具有“读-写-读-擦除”功能的可逆分子器件示意图;表1为实施例1所得喹啉酰亚胺类探针分子在依次加入Cu2+和Cys后利用荧光强度变化构造的逻辑门数据表。从图9和表1可以看出:根据依次加入Cu2+和Cys后溶液荧光“关-开-关”性质,通过测量溶液在552nm处的荧光强度,开发了一种符合二进制逻辑功能的“读-写-读-擦除”逻辑门电路。喹啉酰亚胺类探针分子溶液荧光在存在Cu2+(输入1)的情况下处于“关”状态(由于Cu2+的加入能够猝灭喹啉酰亚胺类探针分子的荧光,使溶液荧光很弱),视为二进制“0”;加入Cys(输入2)后,溶液荧光增强,处于“开”状态(由于Cys的加入竞争络合Cu2+,能够使喹啉酰亚胺类探针分子溶液荧光恢复),视为二进制“1”,即溶液荧光“关”可以通过加入Cys“擦除”为荧光“开”。在循环回路中“关”和“开”状态之间,通过可逆逻辑操作,本发明的喹啉酰亚胺类探针分子利用552nm处的输出信号显示了“读-写-读-擦除”行为。
表1实施例1所得喹啉酰亚胺类探针分子在依次加入Cu2+和Cys后利用荧光强度变化构造的逻辑门数据
实施例9
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸(0.01M)缓冲溶液(pH=7.20)的乙腈和湖水(乙腈和湖水的体积比1:4) 的混合溶液中,探针分子浓度为10μM,加入一定量的Cu2+,测定其荧光强度,根据图4所示的标准曲线计算溶液中Cu2+的回收率,结果如表2所示。从表2 可以看出:实验测得的Cu2+含量与溶液中存在的Cu2+含量基本一致,回收率良好。由此可见,本发明的探针分子可用于实际样品中Cu2+的检测。
表2实施例1所得喹啉酰亚胺类探针分子对湖水中Cu2+回收率数据
实施例10
将实施例1所得喹啉酰亚胺类探针分子溶于含4-羟乙基哌嗪乙磺酸 (0.01M)缓冲溶液(pH=7.20)的DMSO和水(DMSO和水的体积比1:4) 的混合溶液中,探针分子浓度为10μM,Cu2+和Cys浓度均为30μM。图10为实施例1所得喹啉酰亚胺类探针在细胞内依次加入Cu2+和Cys后荧光显微成像和明场图。从图10可以看出:将细胞利用本发明的探针分子染色0.5h后荧光成像,细胞发出较强的黄绿色荧光;向上述细胞内加入Cu2+,细胞内荧光猝灭;继续加入Cys,细胞内黄绿色荧光恢复。由此可见,本发明的喹啉酰亚胺类探针分子在细胞内可依次荧光成像检测Cu2+和Cys。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。

Claims (10)

1.一种喹啉酰亚胺类探针分子,其特征在于,其结构如式I所示:
其中,R为C1-C4直链烷基。
2.权利要求1所述的喹啉酰亚胺类探针分子的合成方法,其特征在于,包括以下步骤:
将2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮、2,2'-二吡啶甲基胺和有机溶剂混合,在氮气保护下回流,得到所述喹啉酰亚胺类探针分子;
所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮中的烷基为C1-C4直链烷基。
3.根据权利要求2所述的合成方法,其特征在于,所述2-氯-5-烷基-5H-苯并[de][2,6]萘啶-4,6-二酮和2,2'-二吡啶甲基胺的摩尔比1:3~6。
4.根据权利要求2所述的合成方法,其特征在于,所述有机溶剂包括乙腈或乙二醇甲醚。
5.根据权利要求2所述的合成方法,其特征在于,所述回流的时间为36~72h。
6.根据权利要求2或5所述的合成方法,其特征在于,回流结束后,还包括将所得回流产物旋干,将所得旋干产物经硅胶柱色谱分离,得到所述喹啉酰亚胺类探针分子。
7.根据权利要求6所述的合成方法,其特征在于,所述硅胶柱色谱分离用洗脱剂为二氯甲烷和甲醇的混合物,所述洗脱剂中二氯甲烷和甲醇的体积比为20~30:1。
8.权利要求1所述的喹啉酰亚胺类探针分子应用于检测Cu2+
9.一种喹啉酰亚胺类探针分子络合物,其特征在于,包括权利要求1所述的喹啉酰亚胺类探针分子和Cu2+,所述喹啉酰亚胺类探针分子络合物中喹啉酰亚胺类探针分子和Cu2+的摩尔比为1:1。
10.权利要求9所述的喹啉酰亚胺类探针分子络合物应用于检测半胱氨酸。
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YU ZHANG等: "A 4,5-quinolimide-based fluorescent sensor for the turn-on detection of Cd2+ with live-cell imaging", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 *
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Publication number Priority date Publication date Assignee Title
CN112625024A (zh) * 2020-11-26 2021-04-09 华东理工大学 一种用于细胞膜快速免洗成像的双亲性荧光探针
CN112625024B (zh) * 2020-11-26 2022-09-20 华东理工大学 一种用于细胞膜快速免洗成像的双亲性荧光探针

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