A High Photostability Mitochondrial Targeted Near-Infrared Dye with Large Stokes Shift and Cell Imaging Application

doi:10.6023/cjoc202112012

Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (6): 1687-1693.DOI: 10.6023/cjoc202112012 Previous Articles Next Articles

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一种具有大斯托克斯位移和高光学稳定性的线粒体靶向近红外染料及其细胞成像应用

周红梅, 唐永和, 卢辉旭, 张倩, 林伟英^*()

广西大学化学化工学院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有色金属及材料加工新技术教育部重点实验室广西有色金属及特色材料加工重点实验室广西南宁 530004

收稿日期:2021-12-06 修回日期:2022-02-17 发布日期:2022-03-21
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)

A High Photostability Mitochondrial Targeted Near-Infrared Dye with Large Stokes Shift and Cell Imaging Application

Hongmei Zhou, Yonghe Tang, Huixu Lu, Qian Zhang, Weiying Lin()

Guangxi Key Laboratory of Electrochemical Energy Materials, Institute of Optical Materials and Chemical Biology, MOE Key Laboratory of New Processing Technology for Nonferrous Metals and Materials,Guangxi Key Laboratory of Processing for Non-ferrous Metals and Featured Materials,School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004

Received:2021-12-06 Revised:2022-02-17 Published:2022-03-21
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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Abstract

Mitochondrial dysfunction is closely related to serious diseases such as Alzheimer’s disease (AD), hypertension, diabetes and neurodegenerative diseases. The development of a fluorescent dye that can be highly targeted to mitochondria is essential for studying the physiological functions of mitochondria. However, the Stokes shift of the mitochondrial dyes on the market is very small and is easily affected by the self-absorption effect. Herein, a new mitochondria targeted dye was designed, named as Mito-ql, based on the properties of mitochondrial membrane potential. The dye Mito-ql has excellent optical properties such as large Stokes shift (about 165 nm), good chemical and photo stability, and low cytotoxicity. In addition, the cell imaging experiments demonstrated that the dye Mito-ql has excellent mitochondrial localization ability, which is not affected by changes in mitochondrial membrane potential.

Key words: large Stokes shift, fluorescent imaging, mitochondria, fluorescent dye

Cite this article

Hongmei Zhou, Yonghe Tang, Huixu Lu, Qian Zhang, Weiying Lin. A High Photostability Mitochondrial Targeted Near-Infrared Dye with Large Stokes Shift and Cell Imaging Application[J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1687-1693.

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Fig. & Tab. 10

Scheme 1. Stokes shifts and structures of commercial mitochondria dye MTG, MTO, MTR, MTDR and Mito-ql

Scheme 2. Synthesis routes of the dye Mito-ql Reagents and conditions: (i) diethylmalonate, piperidine, ethanol, 80 ℃, 6 h; acetic acid and HCl (V∶V=1∶1), 120 ℃, 8 h; (ii) DMF and POCl3 (V∶V=1∶1), 0 ℃, 30 min; Compound 2, DMF, 60 ℃, 12 h; (iii) iodomethane, 0 ℃, 48 h; (iv) Compound 3, piperidine, ethanol, reflux, overnight

Figure 1. (a) Normalized absorption of Mito-ql (5 μmol/L) in different solvents; (b) normalized Fluorescence intensity of the dye Mito-ql (5 μmol/L) in different solvents

Solvent	ε/(mol•L^–1•cm^–1)	λ_b/λ_a	Δλ_s/nm	Φ_Fl/%
Toluene	4.32×10⁴	542/669	127	3.09
1,4-Dioxane	4.42×10⁴	532/661	129	1.28
Acetic acid	4.84×10⁴	545/696	151	19.56
EtOH	4.95×10⁴	545/700	165	20.22
Acetone	4.69×10⁴	542/712	170	7.96
DMSO	4.34×10⁴	549/721	172	13.77
PBS	2.75×10⁴	525/703	178	0.25

Table 1. Spectroscopic characteristics of Mito-ql probe in different solvent

Figure 2. Fluorescence intensities of Mito-ql (5 μmol/L) and related ions at λem=700 nm and related biological species (100 μmol/L) 1, Only probe; 2, AD-glucose; 3, L-Arg; 4, L-ascorbic acid; 5, Gly; 6, GSH; 7, TBHP; 8, Hcy; 9, Cys; 10, Sodium pyruvate; 11, NO; 12, NaClO; 13, H2O2; 14, HCHO; 15, Na2S; 16, Na2SO3; 17, CaCl2; 18, NaNO2; 19, RNA; 20, DNA.

Figure 3. (a) Fluorescence intensity changes of the dye Mito-ql (5 μmol/L) at different pH values (3.01~10.07); (b) photostability profiles of the dye Mito-ql (5.0 μmol/L) at different voltages (λex=550 nm)

Figure 4. Colocalization of the dye Mito-ql (200 nmol/L) and commercial organelle tracker dyes in HeLa cells (A) The HeLa cells incubated with Mito-ql and Hoechst; (B) the HeLa cells incubated with Mito-ql and ETB; (C) the HeLa cells incubated with Mito-ql and LTG; (D) the HeLa cells incubated with Mito-ql and MTG Scale bar=30 μm. λex=550 nm, λem=650~750 nm

Figure 5. Colocalization of the dye Mito-ql (200 nmol/L) and MTG in 7702 cells and RAW cells Scale bar=30 μm. λex=550 nm, λem=650~750 nm.

Figure 6. (a) Fluorescence images of HeLa cells incubated with Mito-ql acquired at different time; (b) fluorescence intensities of the cells incubated with Mito-ql (200 nmol/L) in the red channel at different times Excitation wavelength: 550 nm, scale bar=30 μm. λex=550 nm, λem=650~750 nm.

Figure 7. Colocalization of the dye Mito-ql (200 nmol/L) and MTG in HeLa cells treated with CCCP Scale bar=30 μm. λex=550 nm, λem=650~750 nm.

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一种具有大斯托克斯位移和高光学稳定性的线粒体靶向近红外染料及其细胞成像应用

A High Photostability Mitochondrial Targeted Near-Infrared Dye with Large Stokes Shift and Cell Imaging Application

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