基于香豆素荧光团的新型极性检测荧光探针的开发及其成像应用

doi:10.6023/A22060261

化学学报 ›› 2022, Vol. 80 ›› Issue (9): 1217-1222.DOI: 10.6023/A22060261 上一篇下一篇

研究论文

基于香豆素荧光团的新型极性检测荧光探针的开发及其成像应用

宋思睿^a, 唐永和^a, 孙良广^b, 郭锐^a, 姜冠帆^a, 林伟英^a^,^*()

a 广西电化学能源材料重点实验室广西大学光功能材料与化学生物学研究院广西大学化学化工学院南宁 530004
b 广西农业职业技术大学南宁 530007

投稿日期:2022-06-13 发布日期:2022-08-24
通讯作者: 林伟英
基金资助:
国家自然科学基金(21672083); 国家自然科学基金(21877048); 国家自然科学基金(22077048); 国家自然科学基金(22104019); 广西省自然科学基金(2021GXNSFDA075003); 广西省自然科学基金(AD21220061); 广西省自然科学基金(2019GXNSFBA245068); 广西大学启动基金(A3040051003)

Development of a Novel Fluorescent Probe Based on Coumarin Fluorophore for Polarity Detection and Its Imaging Applications

Sirui Song^a, Yonghe Tang^a, Liangguang Sun^b, Rui Guo^a, Guanfan Jiang^a, Weiying Lin^a()

a Guangxi Key Laboratory of Electrochemical Energy Materials, Institute of Optical Materials and Chemical Biology, School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
b Guangxi Agricultural Vocational University, Nanning 530007, China

Received:2022-06-13 Published:2022-08-24
Contact: Weiying Lin
Supported by:
National Natural Science Foundation of China(21672083); National Natural Science Foundation of China(21877048); National Natural Science Foundation of China(22077048); National Natural Science Foundation of China(22104019); Natural Science Foundation of Guangxi Province(2021GXNSFDA075003); Natural Science Foundation of Guangxi Province(AD21220061); Natural Science Foundation of Guangxi Province(2019GXNSFBA245068); Startup Fund of Guangxi University(A3040051003)

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摘要/Abstract

极性是生物微环境的重要参数之一, 在很大程度上, 生物体内许多生命活动都受到极性变化的影响, 本工作通过改变香豆素母体上的推-拉电子基团, 设计并合成了一种具有较大斯托克斯位移的新型极性荧光探针COM-PO, 该探针的荧光强度和波长会随着测试体系的极性变化而发生改变. 当极性增加时, COM-PO的激发态能量会通过偶极-偶极的相互作用散失在溶剂中, 荧光发射强度降低, 而在低极性溶剂中荧光发射强度增强, 利用这种特性实现了对极性的检测. 本工作通过荧光光谱、荧光成像实验表明COM-PO能够在样品中实现极性检测, 该探针有望实现与极性相关的疾病的早期诊断.

关键词: 极性, 香豆素, 荧光探针, 荧光成像

Polarity is one of the important factors in cell microenvironment. Polarity, to a large extent, is involved in various physiological activities and has an important influence on many life activities of organisms. Studies show that many metabolic diseases in the body can cause polarity changes, such as diabetes, fatty liver, atherosclerosis, and so on. Therefore, it is important to detect polarity changes in living organisms. In this paper, a novel polar fluorescent probe COM-PO with large Stokes-shift was designed and synthesized by altering the push and pull electron groups on coumarin to alter the intramolecular charge transfer (ICT). The fluorescence intensity and wavelength of the probe changed with the polarity of the test system. In polar solvents, the excited state energy of COM-PO dissipates in the solvent through dipole-dipole interaction, and its fluorescence emission intensity decreases. On the contrary, the fluorescence emission intensity of the probe increases significantly in low polar solvents. Since the probe has a large Stokes shift, it can avoid the relatively high signal-to-noise ratio and the serious fluorescence self-extinguishing in the imaging process. Therefore, we applied the probe to cell diagnosis and in vivo disease diagnosis. It is well known that cancer cells are less polar than normal cells, and when the probe enters cancer cells, their fluorescence intensity increases by two to three times compared to normal cells. The fluorescence intensity of the probe COM-PO was also twice as high as that of the normal mice. The COM-PO probe was tested by solution spectroscopy, cell imaging, tissue imaging and mouse in vivo imaging. The experimental results show that the probe COM-PO has the advantages of high polarity sensitivity, high selectivity, strong pH adaptability and good biocompatibility, and can detect the polarity changes of abnormal states of cells, tissues and even livers, which is expected to realize the early diagnosis of polarity related diseases.

Key words: polarity, coumarin, fluorescent probe, fluorescence imaging

引用此文

宋思睿, 唐永和, 孙良广, 郭锐, 姜冠帆, 林伟英. 基于香豆素荧光团的新型极性检测荧光探针的开发及其成像应用[J]. 化学学报, 2022, 80(9): 1217-1222.

Sirui Song, Yonghe Tang, Liangguang Sun, Rui Guo, Guanfan Jiang, Weiying Lin. Development of a Novel Fluorescent Probe Based on Coumarin Fluorophore for Polarity Detection and Its Imaging Applications[J]. Acta Chimica Sinica, 2022, 80(9): 1217-1222.

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图/表 9

图式1. COM-PO的反应机理

Scheme 1. The mechanism of COM-PO

图式2. COM-PO的合成路线

Scheme 2. Synthetic route of COM-PO Reagents and conditions: (i) Compound 1, compound 2, ethanol, 85 ℃, 4 h. (ii) Compound 3, compound 4, ethanol, 85 ℃, 8 h

图1. (A) COM-PO (10 μmol•L-1)在不同极性溶剂中的紫外可见吸收光谱. (B) COM-PO (10 μmol•L-1)在不同极性溶剂中的荧光发射光谱

Figure 1. (A) UV absorption spectra of COM-PO (10 μmol•L-1) in different polarity solvents. (B) Fluorescence emission spectra of COM-PO (10 μmol•L-1) in different polarity solvents

Solvent	ε/(mol•L^-1•cm^-1)	λ_b/λ_a (nm)	Δλ_s(斯托克斯位移)/nm
1,4-Dioxane	5.45×10³	460/564	96
THF	2.36×10³	465/590	125
MeOH	5.78×10⁴	475/620	145
DMSO	8.25×10⁴	480/625	145
Acetonitrile PBS	7.77×10³ 6.73×10³	468/580 479/627	112 148

表1. 探针COM-PO在不同溶剂中的光谱特性

Table 1. The spectroscopic characteristics of the probe COM-PO in different solvents

图2. COM-PO(10 μmol•L-1)在1,4-二氧六环-PBS混合溶剂体系中的荧光发射光谱(百分数代表混合溶剂中1,4-二氧六环的体积分数)

Figure 2. Fluorescence emission spectra of COM-PO (10 μmol•L-1) in dioxane-water mixed solvent system (percentage represents volume fraction of dioxane content in mixed solvent)

图3. COM-PO(10 μmol•L-1)在不同无机离子和氨基酸的荧光发射柱状图

Figure 3. Fluorescence emission histograms of COM-PO (10 μmol•L-1) in different inorganic ions and amino acids The numbers represent: 1. CaCl2; 2. NaClO; 3. CuSO4; 4. L-Cys; 5. NaF; 6. GSH; 7. H2O2; 8. DL-Hcy; 9. KI; 10. MgCl2; 11. MnCl2; 12. Na2S; 13. Na2SO4; 14. ZnCl2; 15. L-Met; 16. TBHP; 17. L-Arg; 18. L-Lys; 19. L-Val; 20. Na2SO3 (p<0.05)

图4. (a~c)用探针 COM-PO (10 μmol•L-1)处理后的3T3细胞成像图; (d~f) 用探针COM-PO (10 μmol•L-1)处理后的4T1细胞成像图; (g~i) 用探针COM-PO (10 μmol•L-1)处理后的HL-7702细胞成像图; (j~l) 用探针COM-PO (10 μmol•L-1)处理后的Hela细胞成像图; (m) 四组细胞成像的荧光强度对比图(*p<0.05)

Figure 4. (a~c) Imaging plots of 3T3 cells treated with probe COM-PO (10 μmol•L-1); (d~f) imaging plots of 4T1 cells treated with probe COM-PO (10 μmol•L-1); (g~i) imaging plots of HL-7702 cells treated with probe COM-PO (10 μmol•L-1); (j~l) imaging plots of Hela cells treated with probe COM-PO (10 μmol•L-1); (m) comparison of the fluorescence intensity of the four groups of cells imaged (*p<0.05)

图5. 探针COM-PO在(a)正常肝脏和(b)脂肪肝中不同的荧光强度的成像图; (c) 探针COM-PO在不同肝脏中荧光强度对比图

Figure 5. Different fluorescence intensities of probe COM-PO when using in (a) normal liver and (b) fatty liver; (c) comparative diagram of the fluorescence intensity of probe COM-PO in different livers

图6. 探针COM-PO在活体小鼠体内的荧光成像. (A) 注射COM-PO的肝炎小鼠模型; (B) 注射COM-PO的正常小鼠模型; (C) 探针COM-PO在不同小鼠体内荧光强度对比图(λex=480 nm, λem=570 nm)

Figure 6. Fluorescence imaging of living mice. (A) The image of hepatitis mouse injected with COM-PO; (B) the normal mouse model injected with COM-PO; (C) the relative fluorescence intensities of mouse model (λex=480 nm, λem=570 nm)

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基于香豆素荧光团的新型极性检测荧光探针的开发及其成像应用

Development of a Novel Fluorescent Probe Based on Coumarin Fluorophore for Polarity Detection and Its Imaging Applications

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