高选择性硒代半胱氨酸荧光探针的构建策略及成像

doi:10.6023/cjoc202305030

摘要/Abstract

硒代半胱氨酸(Sec)在维持生命系统运行中具有重要地位, 其浓度异常, 将导致多种生理疾病. 荧光探针具有高灵敏度、高时空分辨率、无损和可视化检测的优点. 然而, 由于生物硫醇的干扰, 用于体内成像的高选择性硒代半胱氨酸探针构建具有挑战性. 近年来, 为了提高探针选择性、准确性和荧光特性等, 人们采取了多种设计策略. 基于识别机制类型, 从设计原理、性能特点及成像应用几个方面对Sec荧光探针的研究进展进行了评述, 并展望了该领域面临的挑战和发展趋势.

关键词: 硒代半胱氨酸, 荧光探针, 设计策略, 选择性, 生物成像

Selenocysteine (Sec) is important in maintaining the functioning of living systems and its abnormal concentration will lead to a variety of physiological disorders. Fluorescent probes offer the advantages of high sensitivity, high spatial and temporal resolution, nondestructive and visual detection. However, the construction of highly selective selenocysteine probes for in vivo imaging is challenging due to the interference of biothiols. In recent years, various design strategies have been adopted to improve probe selectivity, accuracy and fluorescence properties. The research progress of Sec fluorescent probes in terms of design principles, performance characteristics and imaging applications based on the type of recognition mechanism is reviewed, and the challenges and development trends in this field are predicted.

Key words: selenocysteine, fluorescent probe, design strategies, selectivity, bioimaging

引用此文

张莹珍, 江丹丹, 李娟华, 王菁菁, 刘昆明, 刘晋彪. 高选择性硒代半胱氨酸荧光探针的构建策略及成像[J]. 有机化学, 2024, 44(1): 41-53.

Yingzhen Zhang, Dandan Jiang, Juanhua Li, Jingjing Wang, Kunming Liu, Jinbiao Liu. Construction Strategy and Imaging of Highly Selective Selenocysteine Fluorescent Probes[J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 41-53.

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图/表 28

图1. 基于2,4-二硝基苯磺基与Sec的反应机理

Figure 1. Reaction mechanism based on 2,4-dinitrophenylsulfonyl with Sec

图2. 基于荧光素骨架的探针1对Sec的选择性识别机理

Figure 2. Mechanism of selective recognition of Sec by fluorescein backbone based probe 1

图3. 生理条件下的探针2对Sec的识别机理及成像[26]

Figure 3. Recognition mechanism and imaging of Sec by probe 2 under physiological conditions[26]

图4. 比色/荧光双信号探针3对Sec的识别

Figure 4. Identification of Sec by colorimetric/fluorescent dual signal probe 3

图5. 高荧光量子产率的探针4对Sec的识别

Figure 5. Identification of Sec by probe 4 with high fluorescence quantum yield

图6. 基于四氢萘-氧杂蒽稠合染料骨架的探针5和6

Figure 6. Probes 5 and 6 based on tetrahydronaphthalene-oxanthene dyestuff backbone

图7. 识别位点区域性差异的异构体探针7和8

Figure 7. Isomeric probes 7 and 8 for regional differences in recognition sites

图8. 近红外染料骨架探针9对Sec的识别及成像[32]

Figure 8. Identification and imaging of Sec by NIR dye skeleton probe 9[32]

图9. 基于氧杂蒽染料骨架的近红外探针10

Figure 9. NIR probe 10 based on xanthene dye backbone

图10. 具有大斯托克斯位移的近红外探针11和12

Figure 10. NIR probes 11 and 12 with large Stokes shifts

图11. 基于ICT效应的近红外探针13

Figure 11. NIR probe 13 based on ICT effect

图12. 基于七甲基花菁骨架的近红外比率探针14

Figure 12. NIR ratio probe 14 based on heptamethanocyanine backbone

图13. 双响应型比率探针15对Sec的识别

Figure 13. Identification of Sec by dual response ratio probe 15

图14. 双光子探针16对Sec的识别[39]

Figure 14. Identification of Sec by two-photon probe 16 [39]

图15. 碳点探针17的合成及对Sec的识别[40]

Figure 15. Synthesis of carbon dot probe 17 and recognition of Sec[40]

图16. 基于苯醚与Sec硒解反应机理

Figure 16. Based on the reaction mechanism of selenolysis between phenyl ether and Sec

图17. 基于B-Bodipy骨架的探针18和19对Sec的选择性识别

Figure 17. Selective recognition of Sec by probes 18 and 19 based on the B-Bodipy backbone

图18. 比色/荧光双信号探针20对Sec的识别

Figure 18. Identification of Sec by colorimetric/fluorescent dual signal probe 20

图19. 基于FRET机理的双光子比率探针21对Sec的识别

Figure 19. Two-photon ratio probe 21 based on FRET mechanism for Sec identification

图20. 基于丙烯酸酯与Sec的加成-环化-裂解串联反应机理

Figure 20. Mechanism of addition-cyclization-cleavage tandem reaction based on acrylate and Sec

图21. 基于ICT机理的比率探针22对Sec的识别机理

Figure 21. Recognition mechanism of Sec by ratio probe 22 based on ICT mechanism

图22. 基于近红外七甲基花菁骨架的比率探针23对Sec的识别及成像[46]

Figure 22. Identification of Sec by ratio probe 23 based on NIR heptamethanocyanine skeleton and imaging[46]

图23. 基于二丙烯酸酯的探针24对Sec的识别及胱氨酸摄取[47]

Figure 23. Recognition of Sec and cystine uptake by diacrylate-based probe 24[47]

图24. 二硫键的硒解及氮-硒键的裂解机理

Figure 24. Mechanism of selenolysis of disulfide bond and cleavage of N—Se bond

图25. 基于二硫键的探针25对Sec的识别机理及细胞成像应用[50]

Figure 25. Mechanism of disulfide bond-based probe 25 for Sec recognition and cell imaging applications [50]

图26. 基于双光子荧光探针26对Sec的识别及细胞成像[51]

Figure 26. Identification and cellular imaging of Sec based on two-photon fluorescent probe 26 [51]

图27. 基于2,1,3-苯并硒二唑的探针27

Figure 27. Probe 27 based on 2,1,3-benzoselenadiazole

识别机制	探针编号	荧光骨架	线性范围/(μmol•L^－1)	检测限(LOD)/(nmol•L^－1)	响应时间/min	参考文献
芳香亲核取代反应	1	荧光素	—	—	10	[25]
	2	香豆素	0.5~100	—	3	[26]
	3	香豆素	0~80	47	30	[27]
	4	香豆素	0~100	18	6	[28]
	5	四氢萘-氧杂蒽	0~50	17	2	[29]
	6	四氢萘-氧杂蒽	0~32	11.2	3	[30]
	7	菲并咪唑	0~50	65.4	4	[31]
	8	菲并咪唑	0~50	84.7	3.5	[31]
	9	染料HD-NH₂	0~40	_—	10	[32]
	10	氧杂蒽染料	0~40	18.5	5	[33]
	11	二氰基甲基苯并吡喃荧光素	0.2~80	60	10	[34]
	12	二氰基槐酮	0~100	10	20	[35]
	13	染料NN	0~1	22	2.5	[36]
	14	七甲基花菁素	0~7	—	4	[37]
	15	香豆素	0~45	6.9	4	[38]
	16	2-(2-萘基)苯并噻唑	0~10	10.6	10	[39]
	17	黄绿色发光碳点	0~30	—	12	[40]
苯醚硒解反应	18	硼-二苯并吡喃甲烷染料	0~25	16	10	[41]
	19	硼-二苯并吡喃甲烷染料	0~10	9	10	[41]
	20	二腈基亚甲基苯并吡喃	0.2~80	62	5	[42]
	21	香豆素	0~50	7.88	10	[43]
加成-环化-裂解串联	22	4-羟基萘酰亚胺骨架	0~30	12	1	[45]
	23	七甲基花菁素	0~15	92	5	[46]
	24	荧光素	—	—	—	[47]
其他反应	25	七甲基花菁素	0~20	90	3	[50]
	26	TP-NN	—	—	—	[51]
	27	半花菁素染料	0~20	7	—	[53]

表1. 各类Sec探针性能比较

Table 1. Comparison of the performance of various Sec probes

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