Ratiometric Fluorescent Probe for Homocysteine and CysteineBased on the Aldehyde Functionalized Coumarin and SuccessfulBioimaging Application

doi:10.6023/cjoc201904020

Chinese Journal of Organic Chemistry ›› 2019, Vol. 39 ›› Issue (10): 2835-2842.DOI: 10.6023/cjoc201904020 Previous Articles Next Articles

Special Issue: 荧光探针-生物传感合辑；有机超分子化学合辑

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基于香豆素的比率荧光传感器对同型半胱氨酸/半胱氨酸的检测及生物成像

程晓红^a^*(), 徐可^a, 屈少华^a, 阮志军^b

^a 湖北文理学院低维光电材料与器件湖北省重点实验室湖北襄阳 441053
^b 黄冈师范学院化学化工学院湖北黄冈 438000

收稿日期:2019-04-09 修回日期:2019-05-14 发布日期:2019-06-06
通讯作者: 程晓红 E-mail:chengxiaohong0807@126.com
基金资助:
国家自然科学基金(21704032);湖北省自然科学基金(2018CFB454);“机电汽车”湖北省优势特色学科群开放基金资助项目(XKQ2019038)

Ratiometric Fluorescent Probe for Homocysteine and CysteineBased on the Aldehyde Functionalized Coumarin and SuccessfulBioimaging Application

Cheng Xiaohong^a^*(), Xu Ke^a, Qu Shaohua^a, Ruan Zhijun^b

^a Hubei Key Laboratory of Low Dimensional Optoelectronic Materials and Devices, Hubei University ofArts and Science, Xiangyang 441053, Hubei
^b College of chemistry and Chemical Engineering, Huanggang Normal University,Huanggang 438000, Hubei

Received:2019-04-09 Revised:2019-05-14 Published:2019-06-06
Contact: Cheng Xiaohong E-mail:chengxiaohong0807@126.com
Supported by:
Project supported by the National Natural Science Foundation of China(21704032);The Natural Science Foundation of Hubei Province(2018CFB454);The Hubei Superior and Distinctive Discipline Group of “Mechatronics and Automobiles”(XKQ2019038)

Novel reactive probes (C1 and C2) towards homocysteine/cysteine (Hcy/Cys) were designed and synthesized, based on the unique nucleophilic nature of bio-thiols. In the presence of Hcy/Cys, probe C1 displayed remarkable fluorescence enhancement. Meanwhile, ratiometric fluorescent probe C2 was designed through subtle structure adjustment. Differently, compound C2 displayed dramatic blue-shift in both fluorescence (100 nm) and absorption (95 nm) spectra upon the addition of Hcy/Cys. By virtue of the specific nucleophilic reaction, probe C2 had outstanding selectivity towards Hcy over Cys, GSH and other amino acids. The detection limit of probe C2 was calculated to be as low as 2.8×10 ^–7 mol/L. Moreover, C2 was successfully applied to microscopic imaging for the detection of Hcy in HeLa cells with ratiometric fluorescent methods.

Key words: chemosensor, bio-thiols, ratiometric fluorescence, intramolecular charge transfer, cell imaging

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Cheng Xiaohong, Xu Ke, Qu Shaohua, Ruan Zhijun. Ratiometric Fluorescent Probe for Homocysteine and CysteineBased on the Aldehyde Functionalized Coumarin and SuccessfulBioimaging Application[J]. Chinese Journal of Organic Chemistry, 2019, 39(10): 2835-2842.

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Fig. & Tab. 8

Scheme 1. Structure of probe C2 and its sensing process towards Hcy

Scheme 2. Synthetic route of compounds C1~C4

Figure 1. Fluorescent emission spectra of C1 (10–5 mol?L–1, DMSO/HEPES=1/9) in the presence of different concentrations of Hcy excited at 380 nm Inset: structure of probe C1 and fluorescent photograph of C1 and C1+Hcy

Figure 2. Fluorescent emission spectra of C2 (10–5 mol?L–1, DMSO/HEPES=1/9) in the presence of different concentrations of Hcy [Hcy]/(10–5 mol/L): 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2, 2.5, 3.0. Inset: plot of emission intensity of probe C2 (10–5 mol?L–1) centered at 450/550 nm in the presence of different concentrations of Hcy; fluorescent photograph of C2 and C2+Hcy

Figure 3. Fluorescent intensity change profile of C2 (10 μmol/L, DMSO/HEPES=1/9) in the presence of various amino acid Inset: Photograph of C2 in the presence of various amino acid. Hcy: 30 mol?L–1, Cys: 30 μmol/L, others: 300 μmol/L. a~v: C2+Ala, Arg, Asn, Asp, Val, Glu, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Thr, Tyr, GSH, Cys and Hcy

Figure 4. Image of HeLa cells incubated with C2 (a~c) and pre-treated with C2 and then further incubated with 30 μmol/L Hcy (d~f) for 20 min (a, d) fluorescence at the blue emission channel, (b, e) fluorescence at the green emission channel, and (c, f) bright field images. Scale bar: 20 μm

Figure 5. Calculated HOMOs and LUMOs of compound C2 (left) and C2+Hcy (right)

Figure 6. 1H NMR spectra of C2 (a) and the reaction mixture of C2 and Hcy (b) in CDCl3

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基于香豆素的比率荧光传感器对同型半胱氨酸/半胱氨酸的检测及生物成像

Ratiometric Fluorescent Probe for Homocysteine and CysteineBased on the Aldehyde Functionalized Coumarin and SuccessfulBioimaging Application

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