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

doi:10.6023/cjoc201904020

有机化学 ›› 2019, Vol. 39 ›› Issue (10): 2835-2842.DOI: 10.6023/cjoc201904020 上一篇下一篇

所属专题：荧光探针-生物传感合辑；有机超分子化学合辑

研究论文

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)

文章分享

摘要/Abstract

利用生物硫醇独特的亲核性, 报道了基于香豆素的荧光传感器C1和C2, 可实现对半胱氨酸和同型半胱氨酸的检测. 化合物C1对Hcy/Cys表现出明显的荧光增强响应. 通过结构的微调, 设计并合成了比率荧光传感器C2. 在化合物C2的溶液中加入Hcy/Cys之后, 溶液的最大发射峰蓝移了近100 nm, 最大吸收光谱蓝移了近95 nm. 传感器C2具有较高的选择性, 对Hcy的响应远远大于对Cys、GSH及其他氨基酸的响应. 传感器C2对Hcy有较高的灵敏度, 检出限低达2.8×10 ^–7 mol/L. 并且, 化合物C2可以穿透细胞膜, 用于HeLa细胞中Hcy的比率荧光成像.

关键词: 化学传感器, 生物硫醇, 比率荧光, 分子内电荷转移, 细胞成像

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

引用此文

程晓红, 徐可, 屈少华, 阮志军. 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[J]. 有机化学, 2019, 39(10): 2835-2842.

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.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 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

参考文献 31

[1]	(a) An, L.; Tang, Y.; Wang, S.; Li, Y.; Zhu, D. Macromol. Rapid Commun. 2006, 27, 993.
	(b) Zhao, D.; Du, J.; Chen, Y.; Ji, X.; He, Z.; Chan, W. H. Macromolecules 2008, 41, 5373.
[2]	(a) Weerapana, E.; Wang, C.; Simon, G. M.; Richter, F.; Khare, S.; Dillon, M. B.; Bachovchin, D. A.; Mowen, K.; Baker, D.; Cravatt, B. F. Nature 2010, 468, 790. doi: 10.1038/nature09472
	(b) Reiser, J.; Adair, B.; Reinheckel, T. J. Clin. Invest. 2010, 120, 3421. doi: 10.1038/nature09472
	(c) Lin, J.; Lee, I. M.; Song, Y.; Cook, N. R.; Selhub, J.; Manson, J. E.; Buring, J. E.; Zhang, S.M. Cancer Res. 2010, 70, 2397. doi: 10.1038/nature09472
[3]	(a) Wang, J.; Hu, L. J.; Shen, J.; Jiang, J. Q.; Yu, K. Y. Sun, R.G. Chin. J. Org. Chem. 2018, 38, 760 (in Chinese).
	( 王军, 虎良军, 申婧, 姜吉泉, 郁科勇, 孙荣国, 有机化学, 2018, 38, 760 )
	(b) Ding, S.; Liu, M.; Hong, Y. Sci. China Chem. 2018, 61, 12.
	(e) Yin, C.; Huo, F.; Zhang, J.; Martinez-Manez, R.; Yang, Y.; Lv, H.; Li, S. Chem. Soc. Rev. 2013, 42, 6032.
	(f) Yang, Y.; Zhao, Q.; Feng, W.; Li, F. Chem. Rev. 2012, 113, 192.
[4]	(a) Zhang, M.; Xiao, H. F.; Han, Z. X.; Yang, L. Q.; Wu, X.Y. Chin. J. Org. Chem. 2018, 38, 926 (in Chinese).
	( 张敏, 肖慧丰, 韩志湘, 仰榴青, 吴向阳, 有机化学, 2018, 38, 926.)
	(b) Jiang, K.; Cao, L.; Hao, Z. F.; Chen, M. Y.; Cheng, J. L.; Li, X.; Xiao, Pi.; Chen, L.; Wang, Z.Y. Chin. J. Org. Chem. 2017, 37, 2221 (in Chinese).
	( 蒋凯, 曹梁, 郝志峰, 陈美燕, 程洁銮, 李晓, 肖萍, 陈亮, 汪朝阳, 有机化学, 2017, 37, 2221.)
	(c) Hou, S. H.; Qu, Z. G.; Zhong, K. L.; Bian, Y. J.; Tang, L.J. Chin. J. Org. Chem. 2016, 36, 768 (in Chinese).
	( 侯淑华, 曲忠国, 钟克利, 边延江, 汤立军, 有机化学, 2016, 36, 768 .)
	(d) Srikun, D.; Miller, E. W.; Domaille, D. W.; Chang, C.J. J. Am. Chem. Soc. 2008, 130, 4596.
	(e) Komatsu, K.; Urano, Y.; Kojima, H.; Nagano, T. J. Am. Chem. Soc. 2007, 129, 13447.
	(f) Tremblay, M. S.; Halim, M.; Sames, D. J. Am. Chem. Soc. 2007, 129, 7570.
[5]	Kimura, E.; Koike, T. Chem. Soc. Rev. 1998, 27, 179.
[6]	(a) Jung, H. S.; Han, J. H.; Pradhan, T.; Kim, S.; Lee, S. W.; Sessler, J. L.; Kim, T. W.; Kang, C.; Kim, J. S. Biomaterials 2012, 33, 945. doi: 10.1016/j.biomaterials.2011.10.040
	(b) Yuan, L.; Lin, W.; Yang, Y. Chem. Commun. 2011, 47, 6275. doi: 10.1016/j.biomaterials.2011.10.040
	(c) Jung, H. S.; Ko, K. C.; Kim, G. H.; Lee, A. R.; Na, Y. C.; Kang, C.; Lee, J. Y.; Kim, J.S. Org. Lett. 2011, 13, 1498. doi: 10.1016/j.biomaterials.2011.10.040
	(d) Kwon, H.; Lee, K.; Kim, H.-J. Chem. Commun. 2011, 47, 1773. doi: 10.1016/j.biomaterials.2011.10.040
	(e) Chen, X.; Ko, S. K.; Kim, M.J. Chem. Commun. 2010, 46, 2751. doi: 10.1016/j.biomaterials.2011.10.040
[7]	(a) Yang, T.; Guo, Z.; Shao, A.; Zhao, P.; Zhu, W. Chin. J. Appl. Chem. 2016, 33, 397 (in Chinese).
	( 杨婷婷, 郭志前, 邵安东, 赵平, 朱为宏, 应用化学, 2016, 33, 397 )
	(b) Lee, M. H.; Han, J. H.; Kwon, P. S.; Bhuniya, S.; Kim, J. Y.; Sessler, J. L.; Kang, C.; Kim, J.S. J. Am. Chem. Soc. 2016, 33, 397 .
	(c) Shao, J.; Sun, H.; Guo, H.; Ji, S.; Zhao, J.; Wu, W.; Yuan, X.; Zhang, C.; James, T.D. Chem. Sci. 2012, 3, 1049 .
	(d) Lim C. S.; Masanta, G.; Kim, H. J.; Han, J. H.; Kim, H. M.; Cho, B.R. J. Am. Chem. Soc. 2011, 133, 11132 .
	(e) Zhao, C.; Zhou, Y.; Lin, Q.; Zhu, L.; Feng, P.; Zhang, Y.; Cao, J. J. Phys. Chem. B. 2010, 115, 642 .
[8]	(a) Secor, K.; Plante, J.; Avetta, C.; Glass, T. J. Mater. Chem. 2005, 15, 4073.
	(b) Zhou, Y.; Won, J.; Lee, J. Y.; Yoon, J. Chem. Commun. 2011, 47, 1997.
[9]	(a) Xiong, L.; Zhao, Q.; Chen, H.; Wu, Y.; Dong, Z.; Zhou, Z.; Li, F. Inorg. Chem. 2010, 49, 6402.
	(b) Shiu, H. Y.; Chong, H. C.; Leung, Y. C.; Wong, M. K.; Che, C.M. Chem. Eur. J. 2010, 16, 3308.
	(c) Li, H.; Fan, J.; Wang, J.; Tian, M.; Du, J.; Sun, S.; Sun, P.; Peng, X. Chem. Commun. 2009, 45, 5904.
	(d) Lee, K. S.; Kim, T. K.; Lee, J. H.; Kim, H. J.; Hong, J.I. Chem. Commun. 2008, 44, 6173.
[10]	Tsai, M. S.; Hsu, Y. C.; Lin, J. T.; Chen, H. C.; Hsu, C.P. J. Phys. Chem. C 2007, 111, 18785.
[11]	Lee, K. S.; Kim, H. J.; Kim, G. H.; Shin, I.; Hong, J.I. Org. Lett. 2008, 10, 49.
[12]	Williams, A. T. R.; Winfield, S. A.; Miller, J. N. Analyst 1983, 108, 1067. doi: 10.1039/an9830801067
[13]	Wang, W.; Escobedo, J. O.; Lawrence, C. M.; Strongin, R.M. J. Am. Chem. Soc. 2004, 126, 3400.
[14]	Seshadri, S.; Beiser, A.; Selhub, J.; Jacques, P. F.; Rosenberg, I. H.; D’ Agostino, R. B.; Wilson, P. W. F.; Wolf, P.A. N. Engl. J. Med. 2002, 346, 476.
[15]	Dong, Y. S.; Liu, T. Q.; Wan, X. J.; Pei, H.; Wu, L. S.; Yao, Y.W. Sens. Actuator, B 2017, 241, 1139.
[16]	Yuan, L.; Lin, W. Y.; Yang, Y.T. Chem. Commun. 2011, 47, 6275.
[17]	Zhang, X.; Hang, Y. D.; Qu, W. S.; Yan, Y. C.; Zhao, P.; Hua, J.L. RSC Adv. 2016, 6, 20014. doi: 10.1039/C5RA25220B
[18]	Chen, F.; Chen, Z.; Sun, Y.; Liu, H.; Han, D.; He, H.; Zhang, X.; Wang, S. RSC Adv. 2017, 7, 16387. doi: 10.1039/C6RA28712C
[19]	Sun, Y.; Chen, M.; Liu, J.; Lv, X.; Li, J.; Guo, W. Chem. Commun. 2011, 47, 11029.
[20]	Li, H.; Jin, L.; Kan, Y.; Yin, B. Sens. Actuator, B 2014, 196, 546.
[21]	Qu, W. S.; Yang, L.; Hang, Y. D.; Zhang, X.; Qu, Y.; Hua, J.L. Sens. Actuator, B 2015, 211, 275.
[22]	Liu, X.; Niu, L.; Chen, Y.; Yang, Y.; Yang, Q. Biosens. Bioelectron. 2017, 90, 403.
[23]	Chen, X.; Ko, S. K.; Kim, M. J.; Shin, I.; Yoon, J. Chem. Commun. 2010, 46, 2751.
[24]	Jung, H. S.; Ko, K. C.; Kim, G. H.; Lee, A. R.; Na, Y. C.; Kang, C.; Lee, J. Y; Kim, J.S. . Org. Lett. 2011, 13, 1498.
[25]	Shao, J.; Guo, H.; Ji, S.; Zhao, J. Biosens. Bioelectron. 2011, 26, 3012.
[26]	Long, L.; Lin, W. Y.; Chen, B.; Gao, W.; Yuan, L. Chem. Commun. 2011, 47, 893.
[27]	(a) Zhang, S.; Wright, J. E. I.; Bansal, G.; Cho, P.; Uludag, H. Biomacromolecules 2005, 6, 2800. doi: 10.1021/bm050273s
	(b) Shiu, H. Y.; Wong, M. K.; Che, C.M. Chem. Commun. 2011, 47, 4367. doi: 10.1021/bm050273s
[28]	(a) Tatay, S.; Gavina, P.; Coronado, E.; Palomares, E. Org. Lett. 2006, 8, 3857.
	(b) Palomares, E.; Vilar, R.; Durrant, J.R. Chem. Commun. 2004, 40, 362.
[29]	(a) Delley, B. J. Chem.Phys. 1990, 92, 508.
	(b) Delley B. J. Chem.Phys. 2000, 113, 7756.
[30]	Lin, Y.; Lin, W. Y.; Song, J. Z.; Yang, Y.T. Chem. Commun. 2011, 47, 12691.
[31]	(a) Qian, Z.; Shan, X.; Chai, L.; Ma, J.; Chen, J.; Feng, H. ACS Appl. Mater. Interfaces 2014,6, 6797.
	(b) Meng, Z.; Wu, S.; Zhong, L.; Zeng, M.; Sun, X.; Li, L.; Zhang, S. RSC Adv. 2018,8, 38075.
	(c) Liao, S.; Zhao, X.; Zhu, F.; Chen, M.; Wu, Z.; Song, X.; Yang, H.; Chen, X. Talanta 2018,180, 300S.

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

RichHTML

PDF

可视化

摘要/Abstract

引用此文

分享此文

图/表 8

参考文献 31

相关文章 15

编辑推荐

相关统计

本文评价

[1]	杨敏, 夏丽丽, 周小琴, 贾程利, 吉民, 王鹏. 一种比率型荧光探针用于成像活细胞中的过氧化氢[J]. 有机化学, 2020, 40(9): 2888-2894.
[2]	申有名, 谷标, 刘歆, 唐裕才, 李海涛. 一种基于苯并噻唑衍生物的高选择性比率型高半胱氨酸荧光探针及生物成像[J]. 有机化学, 2020, 40(8): 2442-2449.
[3]	梅辉辉, 杨铭阳, 刘晓燕, 田玉平, 徐括喜. 一个基于菲咯啉的Pb(II)荧光探针[J]. 有机化学, 2020, 40(8): 2508-2512.
[4]	田雪琪, 左旻瓒, 牛蓬勃, 王开亚, 胡晓玉. 基于主客体作用构筑的聚集诱导发光型超分子组装体在生物医用领域的研究进展[J]. 有机化学, 2020, 40(7): 1823-1834.
[5]	钟克利, 周璐璐, 邓隆隆, 汤立军, 高雪, 刘秀英, 燕小梅. 新型7-羟基四氢喹喔啉-6-甲醛酰腙衍生物的合成及其对Al³⁺的识别[J]. 有机化学, 2020, 40(5): 1251-1256.
[6]	孟宪娇, 赵晋忠, 马文兵. 可用于连续识别Cu²⁺和阴离子、中性分子荧光探针的研究进展[J]. 有机化学, 2020, 40(2): 276-283.
[7]	陈宇, 毕克英, 郝瑞亭, 谢萍, 黄丽娜, 王玉敏, 张俊峰, 徐锐, 吴相华. 基于苯并吡喃腈-香豆素体系的近红外比率型荧光探针用于检测HeLa细胞中的过氧亚硝酸盐[J]. 有机化学, 2020, 40(2): 511-515.
[8]	胥稳智, 李雪, 韩孟楠, 周婷婷, 杨瑜涛, 李玮. 一种基于协同效应的肼荧光探针及其在细胞成像中的应用[J]. 有机化学, 2020, 40(1): 181-185.
[9]	常永新, 李白, 郭淼, 蔡永红, 徐括喜. 一种新型连续检测镉离子和焦磷酸阴离子的逻辑门荧光传感器及其细胞成像研究[J]. 有机化学, 2019, 39(9): 2485-2491.
[10]	刁璐, 王仁杰, 王念省, 刘刚, 蒲守智. 一种新型用于CN^-比色检测和Zn²⁺/H₂PO₄^-荧光识别的二芳烯探针[J]. 有机化学, 2019, 39(7): 1930-1938.
[11]	闫沛沛, 王婷, 张丹, 马晓雪. 巯基类荧光探针的研究进展[J]. 有机化学, 2019, 39(4): 916-928.
[12]	常永新, 李白, 高云帆, 徐括喜. 新型席夫碱Cr³⁺荧光探针及其细胞成像研究[J]. 有机化学, 2019, 39(4): 1023-1028.
[13]	周建平, 吴保庚, 周志宽, 田蒋为, 袁爱华. 基于新型萘环稠合硼氟二吡咯化合物(BODIPY)的氟离子荧光探针及其细胞成像研究[J]. 有机化学, 2019, 39(2): 406-411.
[14]	王晓芬, 魏超, 李雪艳, 郑雪阳, 耿晓维, 张平竹, 李小六. 一种溶酶体靶向双光子亚硝酰氢荧光探针的合成及细胞成像研究[J]. 有机化学, 2019, 39(2): 469-474.
[15]	周婷婷, 杨瑜涛, 周柯岩, 胥稳智, 李玮. 一种“关-开”型生物硫醇荧光探针和生物成像应用[J]. 有机化学, 2019, 39(12): 3498-3504.