CN109096299B - 5-苯基-2-邻甲苯基-2h-1,2,3-三氮唑-罗丹明b衍生物的合成及其应用 - Google Patents

5-苯基-2-邻甲苯基-2h-1,2,3-三氮唑-罗丹明b衍生物的合成及其应用 Download PDF

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CN109096299B
CN109096299B CN201811065096.4A CN201811065096A CN109096299B CN 109096299 B CN109096299 B CN 109096299B CN 201811065096 A CN201811065096 A CN 201811065096A CN 109096299 B CN109096299 B CN 109096299B
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何文英
吴禄勇
李建玲
刘艳萍
冯华杰
丁国华
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Abstract

本发明涉及一种5‑苯基‑2‑邻甲苯基‑2H‑1,2,3‑三氮唑‑罗丹明B衍生物的合成及其应用。所述衍生物具有式I所示结构：

Description

5-苯基-2-邻甲苯基-2H-1,2,3-三氮唑-罗丹明B衍生物的合 成及其应用
技术领域
本发明属于有机合成及细胞成像领域，具体涉及一种5-苯基-2-邻甲苯基-2H-1,2,3-三氮唑-罗丹明B衍生物的合成及其应用。
背景技术
随着工业的迅速发展，带来经济效应的同时，所带来的污染对环境也构成了极大的威胁。而重金属离子Hg2+的污染更是不容忽视。汞作为最具毒害的重金属离子之一，被排放到土壤或水体中，通过食物链富集生命体造成威胁，因此而引发的各类疾病如阿尔茨海默症、水俣病、肢端疼痛症、尿毒症，已严重影响到人们的生活。基于1,2,3-三氮唑-罗丹明的荧光探针已有报道，但是尚未有该系列探针应用于细胞成像的报道。本发明提供一种由罗丹明酰肼与三氮唑羧酸酯一步法制备高灵敏度的Hg2+离子识别探针，并将该探针应用于细胞成像。
发明内容
本发明提供一种式I结构的5-苯基-2-邻甲苯基-2H-1,2,3-三氮唑-罗丹明B衍生物，其特征在于式I结构如下：
Figure BDF0000010100080000011
本发明的另一实施方案提供上述式I化合物的制备方法，其特征在于包括如下步骤：
Figure BDF0000010100080000012
将化合物1与化合物2溶于CH2Cl2中，在Fe(acac)3和Et3N的作用下得到式I化合物；
其中化合物1与化合物2的摩尔比为1:0.8-1.0，Fe(acac)3的摩尔用量为化合物1的0.05-0.08倍，每毫摩尔化合物1使用CH2Cl2的体积为12-15mL，使用Et3N的体积为0.5-0.6mL。反应温度优选在室温下进行，反应时间优选20-24小时。
本发明的另一实施方案提供式I化合物在检测Hg2+中的应用。
本发明的另一实施方案提供式I化合物在HeLa细胞成像中的应用。
与现有技术相比，本发明的优点在于：本发明利用乙酰丙酮铁(Fe(acac)3)作为催化剂成功地实现了一步法合成5-苯基-2-邻甲苯基-2H-1,2,3-三氮唑-罗丹明B衍生物，且本发明合成的上述衍生物对Hg2+的检测灵敏度高，并能成功用于HeLa细胞成像。
附图说明
图1是式I化合物的13CNMR图；
图2是式I化合物对各离子的的荧光选择性光谱图，A：荧光选择性，B：
荧光强度增大倍数；
图3是式I化合物在不同pH下识别Hg2+的离子的荧光强度图；
图4是本发明实施例5的HeLa细胞活细胞荧光成像图。
具体实施方式
为了便于对本发明的进一步理解，下面提供的实施例对其做了更详细的说明。但是这些实施例仅供更好的理解发明而并非用来限定本发明的范围或实施原则，本发明的实施方式不限于以下内容。
实施例1
将化合物1(1.0mmol)与化合物2(1.0mmol)溶于CH2Cl2(15mL)中，室温下加入Fe(acac)3(0.08mmol)和Et3N(0.6mL)，搅拌反应20小时，TLC检测原料完全消失，反应液浓缩后，进行硅胶柱层析(200-300目硅胶)，用石油醚/乙酸乙酯(V:V＝3:1～4:1)为洗脱剂，得式I化合物640mg，产率为89.2％。如图1所示：1H NMR(400MHz,CDCl3)δ8.04(s,1H),7.99(d,J＝6.9Hz,1H),7.94–7.85(m,2H)，7.61(d,J＝7.5Hz,1H),7.55–7.44(m,3H),7.36–7.28(m,5H),7.17(d,J＝7.1Hz,1H),6.75(s,1H),6.73(s,1H),6.34(s,3H),6.33(s,1H),3.32(dd,J＝13.8,6.8Hz,8H),2.37(s,3H),1.13(t,J＝7.0Hz,12H)；13C NMR(100MHz,CDCl3)δ164.96,158.35,153.80,151.33,149.13,148.98,138.81,136.97,133.13,132.63,131.79,129.40,129.29,129.23,129.09,128.99,128.91,128.31,128.04,126.62,125.04,124.11,123.53,108.06,104.43,97.61,66.28,44.43,19.07,12.56.HRMS(ESI)(m/z):[M+H]+calcd forC44H44N7O3,718.3506；found,718.3507.
实施例2
将化合物1(1.0mmol)与化合物2(1.0mmol)溶于CH2Cl2(15mL)中，室温下加入Et3N(0.6mL)，搅拌反应20小时后，TLC显示除化合物1和2外，未产生新的点(即没有发生反应)。
实施例3式I化合物的荧光选择性光谱
如图2A所示，为检测在DMF-水(v/v＝1:1,Tris–HCl,pH＝7.4)溶液中，各离子(4×10-5mol/L)存在下式I化合物(1×10-5mol/L)的荧光选择性图，图中在562nm激发光照射下，Hg2+加入时在在577nm处出现了明显特征发射峰，而其他离子的均没有。如图2B，在该浓度下Hg2+加入后，荧光强度增大了538倍，对应的只有加入Hg2+的溶液伴有粉红色变化。
实施例4pH对式I化合物的影响
如图3所示，测定式I化合物在不同pH条件的DMF-水溶液的荧光强度(a)；及测定不同pH下加入Hg2+后的荧光强度变化(b)。图中式I化合物在pH＝4.0-10.0无荧光信号，加入Hg2+后，荧光强度在pH＝3.0-8.0明显增强，且在pH＝7.4为最强。
实施例5细胞成像应用
在37℃的CO2细胞培养箱中培养HeLa细胞24小时进行实验。如图4所示，A.在DMEM培养液下HeLa细胞的亮场成像；B.在DMEM培养液下HeLa细胞的荧光成像；C.式I化合物在HeLa细胞的亮场成像；D.式I化合物在HeLa细胞的荧光成像；E.式I化合物在HeLa细胞对Hg2+的亮场成像；F.式I化合物在HeLa细胞对Hg2+的荧光成像的效果。式I化合物的浓度为1.0×10-5mol/L，加入Hg2+的浓度为2.5×10-5mol/L。上述实验结果表明本发明的式I化合物可用于细胞成像。

Claims (1)

1.一种式I结构的5-苯基-2-邻甲苯基-2H-1,2,3-三氮唑-罗丹明B衍生物的制备方法，其特征在于包括如下步骤：
Figure FDA0002485351070000011
将化合物1与化合物2溶于CH2Cl2中，在Fe(acac)3和Et3N的作用下得到式I化合物；化合物1与化合物2的摩尔比为1:0.8-1.0，Fe(acac)3的摩尔用量为化合物1的0.05-0.08倍，每毫摩尔化合物1使用CH2Cl2的体积为12-15mL，使用Et3N的体积为0.5-0.6mL；反应温度选自在室温下进行，反应时间为20-24小时。
CN201811065096.4A 2018-09-12 2018-09-12 5-苯基-2-邻甲苯基-2h-1,2,3-三氮唑-罗丹明b衍生物的合成及其应用 Active CN109096299B (zh)

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