基于荧光素硫代酰肼类Hg2+荧光探针的合成及在生物成像中的应用

doi:10.7503/cjcu20180077

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (7): 1412.doi: 10.7503/cjcu20180077

基于荧光素硫代酰肼类Hg²⁺荧光探针的合成及在生物成像中的应用

刘大海¹, 张雪妍³, 冯玉沙², 杜显龙², 薛龙启², 杜建时¹(), 张桂荣³, 杨清彪², 李耀先²

1. 吉林大学中日联谊医院, 长春 130031
2. 吉林大学化学学院, 3. 生命科学学院, 长春 130021

收稿日期:2018-01-25 出版日期:2018-07-10 发布日期:2018-06-21
作者简介:联系人简介: 杜建时, 男, 博士, 教授, 主要从事纳米医学与纳米材料方面的研究. E-mail: dujianshi3043@163.com
基金资助:
吉林省自然科学基金(批准号: 20160101311JC, 20170101105JC)和吉林省科技厅重点项目(批准号: 20170204039GX).

Synthesis of Novel Fluorescein-Thiospirolactams Hg²⁺ Fluorescent Probes and Its Application in vivo^†

LIU Dahai¹, ZHANG Xueyan³, FENG Yusha², DU Xianlong², XUE Longqi², DU Jianshi^1,^*(), ZHANG Guirong³, YANG Qingbiao², LI Yaoxian²

1. Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun 130031, China
2. College of Chemistry, 3. College of Life Science, Jilin University, Changchun 130012, China

Received:2018-01-25 Online:2018-07-10 Published:2018-06-21
Contact: DU Jianshi E-mail:dujianshi3043@163.com
Supported by:
† Supported by the Natural Science Foundation of Jilin Province, China (Nos.20160101311JC, 20170101105JC) and the Science and Technology Key Program of Jilin Province, China(No.20170204039GX).

摘要/Abstract

摘要：

利用希夫碱反应, 在荧光素硫代酰肼中引入对羟基苯甲醛、吡咯甲醛等醛基化合物, 制得了能特异检测汞离子的3种荧光染料探针TFP3, TFP4及TFP5. 研究发现, 当加入7.5 μmol/L的Hg²⁺后, TFP3, TFP4和TFP5的荧光光谱530 nm处均出现了约高于30倍的荧光增强, 其检出限分别为7.22×10^-8, 1.03×10^-7和1.28×10^-8 mol/L. 另外, 细胞成像实验结果表明, 该探针具有良好的生物相容性和低毒性, 在生物体系中具有实际应用价值.

关键词: 硫代酰肼荧光素, 荧光探针, 二价汞离子, 细胞成像

Abstract:

The aldehyde compounds such as p-hydroxybenzaldehyde, pyrrole formaldehyde and acetaldehyd were introduced into the fluorescein thiohydrazide via the Schiff base reaction, the resulting compounds of TFP3, TFP4 and TFP5 could detect mercury with high selectivity and sensitivity. In further study, it was found that when the 7.5 μmol/L Hg²⁺was added, the fluorescence enhancement of TFP3, TFP4 and TFP5 at 530 nm of fluorescence spectrum appeared more than 30 times and the detection limits were 7.22×10^-8, 1.03×10^-7 and 1.28×10^-8 mol/L, respectively. In addition, the cellular imaging experiment exhibited that the probe had good biocompatibility and low toxicity, and may have practical application in the biological system.

Key words: Fluorescein thiohydrazide, Fuorescent probe, Mercury ion, Cellular imaging

中图分类号:

O657

TrendMD:

刘大海, 张雪妍, 冯玉沙, 杜显龙, 薛龙启, 杜建时, 张桂荣, 杨清彪, 李耀先. 基于荧光素硫代酰肼类Hg²⁺荧光探针的合成及在生物成像中的应用. 高等学校化学学报, 2018, 39(7): 1412.

LIU Dahai, ZHANG Xueyan, FENG Yusha, DU Xianlong, XUE Longqi, DU Jianshi, ZHANG Guirong, YANG Qingbiao, LI Yaoxian. Synthesis of Novel Fluorescein-Thiospirolactams Hg²⁺ Fluorescent Probes and Its Application in vivo^†. Chem. J. Chinese Universities, 2018, 39(7): 1412.

图/表 11

Scheme 1 Synthetic routes of probes TFP2, TFP3, TFP4 and TFP5

Fig.1 Selectivity of probes TFP2(A), TFP3(B), TFP4(C) and TFP5(D) for metal ions^Other ions include Cu2+, Mg2+, Na+, Mn2+, Cd2+, Co2+, Zn2+, Fe3+, Ni2+, Ba2+, K+, Ca2+, Pb2+, free.

Fig.2 UV absorption spectra of probe TFP3(5 μmol/L) in EtOH-HEPES (1∶1, volume ratio, pH=7.4) buffer solution upon the addition of different amounts of Hg2+ions(0—7.5 μmol/L)(A) and absorption enhancement at 509 nm as a function of Hg2+ concentration(B)

Fig.3 Fluorescence intensity of probe TFP3(5 μmol/L) in EtOH/HEPES(1∶1, volume ratio, pH=7.4) buffer solution upon the addition of different amounts of Hg2+ions(0—7.5 μmol/L)(λex=509 nm)(A), fluorescence enhancement at 530 nm as a function of Hg2+ concentration(B) and plot of emission intensity of TFP3 at 530 nm vs. Hg2+cation concentration(C)

Fig.4 Fluorescence intensity of TFP3(5 μmol/L) in the absence(a) and presence(b) of Hg2+(7.5 μmol/L) in EtOH-water(1∶1, volume ratio) solution under different pH conditions(λex=509 nm)

Fig.5 Fluorescence response of TFP3(5 μmol/L) in the presence of various metal ions in EtOH-HEPES (1∶1, volume ratio, pH=7.4) buffer solution(530 nm)^a. Hg2+; b. Cu2+; c. Mg2+; d. Na+; e. Mn2+; f. Cd2+; g. Co2+; h. Zn2+; i. Fe3+; j. Ni2+; k. Ba2+; l. K+; m. Ca2+; n. Pb2+.

Fig.6 Reversibility of Hg2+(5 μmol/L) coordination to TFP3 by Na2S

Fig.7 Job’s plot of TFP3 in EtOH-HEPES(1∶1, volume ratio, pH=7.4) buffer solution with a total concentration of [Hg2+]+[TFP3]=2×10-5 mol/L(λ=509 nm)

Fig.8 Benesi-Hildebrand plot(λex=509 nm) of 1/(F-F0) vs. 1/[Hg2+] for the association based on a 1∶2 association stoichiometry between TFP3 and Hg2+

Scheme 2 Proposed binding mechanism between the receptor probe TFP3 and Hg2+

Fig.9 Fluorescence images of Hg2+ ions in Hela cells with 20 μmol/L TFP3^ Bright-field transmission images(A, C) and fluorescence images(B, D) of Hela cells incubated with 0(A, B) and 40 μmol/L(C, D) of Hg2+ ions for 30 min.

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基于荧光素硫代酰肼类Hg²⁺荧光探针的合成及在生物成像中的应用

Synthesis of Novel Fluorescein-Thiospirolactams Hg²⁺ Fluorescent Probes and Its Application in vivo^†

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