Citation: Jiao Chen, Zihan Zhang, Guojin Sun, Yudi Cheng, Aihua Wu, Zefan Wang, Wenwen Jiang, Fulin Chen, Xiuying Xie, Jianli Li. Benzo[4,5]imidazo[1,2-a]pyrimidine-based structure-inherent targeting fluorescent sensor for imaging lysosomal viscosity and diagnosis of lysosomal storage disorders[J]. Chinese Chemical Letters, ;2024, 35(11): 110050. doi: 10.1016/j.cclet.2024.110050 shu

Benzo[4,5]imidazo[1,2-a]pyrimidine-based structure-inherent targeting fluorescent sensor for imaging lysosomal viscosity and diagnosis of lysosomal storage disorders

Jiao Chen ^{a, b, 1} ,
Zihan Zhang ^{a, 1} ,
Guojin Sun ^a ,
Yudi Cheng ^{a, b} ,
Aihua Wu ^a ,
Zefan Wang ^{a, b} ,
Wenwen Jiang ^a ,
Fulin Chen ^{b, *,} ,
Xiuying Xie ^{a, c} ,
Jianli Li ^{a, *,}

a.
Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, Xi'an Key Laboratory of Functional Supramolecular Structure and Materials, College of Chemistry & Materials Science, Northwest University, Xi'an 710127, China
b.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Biomedicine Key Laboratory of Shaanxi Province, Lab of Tissue Engineering, the College of Life Sciences, Faculty of Life Science & Medicine, Northwest University, Xi'an 710069, China
c.
The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China

chenfl@nwu.edu.cn

lijianli@nwu.edu.cn

Received Date: 16 May 2024
Revised Date: 22 May 2024
Accepted Date: 24 May 2024
Available Online: 28 May 2024

Figures(6)

Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines, pesticides, tracers and photoelectric materials. However, their synthesis approach still needs to be optimized, and their fluorescent properties in intracellular microenvironment are unclear. Here, a Cu(Ⅱ)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions, broad substrate scopes and high yields. After a system study, we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement (102-fold) for glycerol at 490 nm. Particularly, 4aa possessed excellent structure-inherent targeting (SIT) capability for lysosome (P = 0.95) with high pH stability and large Stokes shift. Importantly, 4aa was validated for its effectiveness in diagnosing lysosomal storage disorders (LSD) in living cells. The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish. This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives, reveals this skeleton has excellent SIT features for lysosome, but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.
- Fluorescent sensor,
- Benzo[4,5]imidazo[1,2-a]pyrimidine,
- Lysosome,
- Viscosity,
- Lysosomal storage disorders,
- Structure-inherent targeting,
- Fluorescence imaging
1. [1]
  S.R. Bonam, F. Wang, S. Muller, Nat. Rev. Drug Discov. 18 (2019) 923–948. doi: 10.1038/s41573-019-0036-1
2. [2]
  C. Settembre, R.M. Perera, Nat. Rev. Mol. Cell Biol. 25 (2024) 223–245. doi: 10.1038/s41580-023-00676-x
3. [3]
  L. Wang, Y. Xiao, W. Tian, L. Deng, J. Am. Chem. Soc. 135 (2013) 2903–2906. doi: 10.1021/ja311688g
4. [4]
  H. Song, W. Zhang, Y. Zhang, et al., Chem. Eng. J. 445 (2022) 136448. doi: 10.1016/j.cej.2022.136448
5. [5]
  J. Ma, R. Sun, K. Xia, et al., Chem. Rev. 124 (2024) 1738–1861. doi: 10.1021/acs.chemrev.3c00573
6. [6]
  D. Su, C.L. Teoh, L. Wang, et al., Chem. Soc. Rev. 46 (2017) 4833–4844. doi: 10.1039/C7CS00018A
7. [7]
  D. Li, T. Shen, X. Xue, et al., Sci. China Chem. 66 (2023) 2329–2338. doi: 10.1007/s11426-023-1661-6
8. [8]
  J. Devany, K. Chakraborty, Y. Krishnan, Nano Lett. 18 (2018) 1351–1359. doi: 10.1021/acs.nanolett.7b05040
9. [9]
  X. Wang, L. Wang, T. Jin, et al., Sens. Actuators B: Chem. 375 (2023) 132935. doi: 10.1016/j.snb.2022.132935
10. [10]
  J.J. Chao, H. Zhang, Z.Q. Wang, et al., Anal. Chim. Acta 1285 (2024) 342024. doi: 10.1016/j.aca.2023.342024
11. [11]
  L. Hu, J. Yang, C. Zhang, et al., Sens. Actuators B: Chem. 398 (2024) 134776. doi: 10.1016/j.snb.2023.134776
12. [12]
  L. Lian, R. Zhang, S. Guo, et al., Chin. Chem. Lett. 34 (2023) 108516. doi: 10.1016/j.cclet.2023.108516
13. [13]
  L. Zhang, W. Wang, Y.-Q. Zhao, et al., Chin. Chem. Lett. (2024), doi:10.1016/j.cclet.2024.109798. doi: 10.1016/j.cclet.2024.109798
14. [14]
  Y.Q. Zhou, Z.Z. Liu, G.M. Qiao, et al., Chin. Chem. Lett. 32 (2021) 3641–3645. doi: 10.1016/j.cclet.2021.04.035
15. [15]
  F. Zheng, R. Xiao, S. Huang, et al., Chin. Chem. Lett. (2024), doi:10.1016/j.cclet.2024.109876. doi: 10.1016/j.cclet.2024.109876
16. [16]
  H. Fang, Y. Chen, Z. Jiang, et al., Acc. Chem. Res. 56 (2023) 258–269. doi: 10.1021/acs.accounts.2c00643
17. [17]
  Q. Fu, X. Yang, M. Wang, et al., ACS Nano 18 (2024) 3916–3968. doi: 10.1021/acsnano.3c10659
18. [18]
  Y. Yang, M. Ma, L. Shen, et al., Angew. Chem. Int. Ed. 62 (2023) e202310408. doi: 10.1002/anie.202310408
19. [19]
  X. Li, J. Wang, F. Huo, C. Yin, Coord. Chem. Rev. 506 (2024) 215713. doi: 10.1016/j.ccr.2024.215713
20. [20]
  Y. Cheng, X. Wang, J. Chen, et al., Chin. Chem. Lett. 35 (2024) 109156. doi: 10.1016/j.cclet.2023.109156
21. [21]
  S.-S. Tseng, J.W. Epstein, H.J. Brabander, G. Francisco, J. Heterocycl. Chem. 24 (1987) 837–843. doi: 10.1002/jhet.5570240357
22. [22]
  R. Alajarin, J.J. Vaquero, J. Alvarez-Builla, et al., Bioorg. Med. Chem. 2 (1994) 323–329. doi: 10.1016/S0968-0896(00)82188-4
23. [23]
  A.J. Marcus, I. Iezhitsa, R. Agarwal, et al., Eur. J. Pharmacol. Sci. 114 (2018) 245–254. doi: 10.1016/j.ejps.2017.12.015
24. [24]
  S.B. Bharate, T.R. Mahajan, Y.R. Gole, et al., Bioorg. Med. Chem. 16 (2008) 7167–7176. doi: 10.1016/j.bmc.2008.06.042
25. [25]
  N.A. White, K. Clagg, L.E. Sirois, et al., Org. Lett. 21 (2019) 9527–9531. doi: 10.1021/acs.orglett.9b03702
26. [26]
  M. Rawat, D.S. Rawat, Tetrahedron Lett. 59 (2018) 2341–2346. doi: 10.1016/j.tetlet.2018.05.005
27. [27]
  J. Wu, H. Luo, T. Wang, et al., Tetrahedron 75 (2019) 1052–1063. doi: 10.1016/j.tet.2019.01.009
28. [28]
  Z. Qin, R. Zhang, S. Ying, Y. Ma, Org. Chem. Front. 9 (2022) 5624–5630. doi: 10.1039/d2qo01008a
29. [29]
  M. Guo, X. Huang, S. Li, et al., J. Org. Chem. (2023), doi:10.1021/acs.joc.3c01227. doi: 10.1021/acs.joc.3c01227
30. [30]
  J. Liu, W. Zhang, C. Zhou, et al., J. Am. Chem. Soc. 144 (2022) 13586–13599. doi: 10.1021/jacs.2c03832
31. [31]
  A. Zheng, H. Liu, X. Gao, et al., Anal. Chem. 93 (2021) 9244–9249. doi: 10.1021/acs.analchem.1c01511
32. [32]
  G. Parenti, G. Andria, A. Ballabio, Ann. Rev. Med. 66 (2015) 471–486. doi: 10.1146/annurev-med-122313-085916
33. [33]
  F.M. Platt, A. D'azzo, B.L. Davidson, et al., Nat. Rev. Dis. Primers 4 (2018) 27. doi: 10.1038/s41572-018-0025-4
34. [34]
  M. Li, J. Fan, H. Li, et al., Biomaterials 164 (2018) 98–105. doi: 10.1016/j.biomaterials.2018.02.044
35. [35]
  I. Hamer, M. Jadot, Exp. Cell Res. 309 (2005) 284–295. doi: 10.1016/j.yexcr.2005.06.006
36. [36]
  M. Samarani, N. Loberto, G. Soldà, et al., FASEB J. 32 (2018) 5685–5702. doi: 10.1096/fj.201701512rr
1. [1]
  Lanyun Zhang , Weisi Wang , Yu-Qiang Zhao , Rui Huang , Yuxun Lu , Ying Chen , Liping Duan , Ying Zhou . Mechanism study of the molluscicide candidate PBQ on Pomacea canaliculata using a viscosity-sensitive fluorescent probe. Chinese Chemical Letters, 2025, 36(1): 109798-. doi: 10.1016/j.cclet.2024.109798
2. [2]
  Fan Zheng , Runsha Xiao , Shuai Huang , Zhikang Chen , Chen Lai , Anyao Bi , Heying Yao , Xueping Feng , Zihua Chen , Wenbin Zeng . Accurate visualization colorectal cancer by monitoring viscosity variations with a novel mitochondria-targeted fluorescent probe. Chinese Chemical Letters, 2025, 36(2): 109876-. doi: 10.1016/j.cclet.2024.109876
3. [3]
  Shuangying Li , Qingxiang Zhou , Zhi Li , Menghua Liu , Yanhui Li . Sensitive measurement of silver ions in environmental water samples integrating magnetic ion-imprinted solid phase extraction and carbon dot fluorescent sensor. Chinese Chemical Letters, 2024, 35(5): 108693-. doi: 10.1016/j.cclet.2023.108693
4. [4]
  Gongcheng Ma , Qihang Ding , Yuding Zhang , Yue Wang , Jingjing Xiang , Mingle Li , Qi Zhao , Saipeng Huang , Ping Gong , Jong Seung Kim . Palladium-free chemoselective probe for in vivo fluorescence imaging of carbon monoxide. Chinese Chemical Letters, 2024, 35(9): 109293-. doi: 10.1016/j.cclet.2023.109293
5. [5]
  Du Liu , Yuyan Li , Hankun Zhang , Benhua Wang , Chaoyi Yao , Minhuan Lan , Zhanhong Yang , Xiangzhi Song . Three-in-one erlotinib-modified NIR photosensitizer for fluorescence imaging and synergistic chemo-photodynamic therapy. Chinese Chemical Letters, 2025, 36(2): 109910-. doi: 10.1016/j.cclet.2024.109910
6. [6]
  Lijia Xu , Tong Zhong , Wei Zhao , Bing Yao , Lin Ding , Huangxian Ju . Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia. Chinese Chemical Letters, 2024, 35(4): 108760-. doi: 10.1016/j.cclet.2023.108760
7. [7]
  Jia-Mei Qin , Xue Li , Wei Lang , Fu-Hao Zhang , Qian-Yong Cao . An AIEgen nano-assembly for simultaneous detection of ATP and H₂S. Chinese Chemical Letters, 2024, 35(6): 108925-. doi: 10.1016/j.cclet.2023.108925
8. [8]
  Jiajia Lv , Jie Gao , Hongyu Li , Zeli Yuan , Nan Dong . Rational design of hydroxytricyanopyrrole-based probes with high affinity and rapid visualization for amyloid-β aggregates in vitro and in vivo. Chinese Chemical Letters, 2024, 35(5): 108940-. doi: 10.1016/j.cclet.2023.108940
9. [9]
  Yiqiao Chen , Ao Liu , Biwen Yang , Zhenzhen Li , Binggang Ye , Zhouyi Guo , Zhiming Liu , Haolin Chen . Photoluminescence and photothermal conversion in boric acid derived carbon dots for targeted microbial theranostics. Chinese Chemical Letters, 2024, 35(9): 109295-. doi: 10.1016/j.cclet.2023.109295
10. [10]
  Fengkai Zou , Borui Su , Han Leng , Nini Xin , Shichao Jiang , Dan Wei , Mei Yang , Youhua Wang , Hongsong Fan . Red-emissive carbon quantum dots minimize phototoxicity for rapid and long-term lipid droplet monitoring. Chinese Chemical Letters, 2024, 35(10): 109523-. doi: 10.1016/j.cclet.2024.109523
11. [11]
  Zhipeng Li , Qincong Feng , Jianliang Shen . A β-lactamase-activatable photosensitizer for the treatment of resistant bacterial infections. Chinese Chemical Letters, 2024, 35(11): 109602-. doi: 10.1016/j.cclet.2024.109602
12. [12]
  Hui-Juan Wang , Wen-Wen Xing , Zhen-Hai Yu , Yong-Xue Li , Heng-Yi Zhang , Qilin Yu , Hongjie Zhu , Yao-Yao Wang , Yu Liu . Cucurbit[7]uril confined phenothiazine bridged bis(bromophenyl pyridine) activated NIR luminescence for lysosome imaging. Chinese Chemical Letters, 2024, 35(6): 109183-. doi: 10.1016/j.cclet.2023.109183
13. [13]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
14. [14]
  Yiling Li , Zekun Gao , Xiuxiu Yue , Minhuan Lan , Xiuli Zheng , Benhua Wang , Shuang Zhao , Xiangzhi Song . FRET-based two-photon benzo[a] phenothiazinium photosensitizer for fluorescence imaging-guided photodynamic therapy. Chinese Chemical Letters, 2024, 35(7): 109133-. doi: 10.1016/j.cclet.2023.109133
15. [15]
  Kaimin WANG , Xiong GU , Na DENG , Hongmei YU , Yanqin YE , Yulu MA . Synthesis, structure, fluorescence properties, and Hirshfeld surface analysis of three Zn(Ⅱ)/Cu(Ⅱ) complexes based on 5-(dimethylamino) isophthalic acid. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1397-1408. doi: 10.11862/CJIC.20240009
16. [16]
  You Zhou , Li-Sheng Wang , Shuang-Gui Lei , Bo-Cheng Tang , Zhi-Cheng Yu , Xing Li , Yan-Dong Wu , Kai-Lu Zheng , An-Xin Wu . I₂-DMSO mediated tetra-functionalization of enaminones for the construction of novel furo[2′,3′:4,5]pyrimido[1,2-b]indazole skeletons via in situ capture of ketenimine cations. Chinese Chemical Letters, 2025, 36(1): 109799-. doi: 10.1016/j.cclet.2024.109799
17. [17]
  Hao Cai , Xiaoyan Wu , Lei Jiang , Feng Yu , Yuxiang Yang , Yan Li , Xian Zhang , Jian Liu , Zijian Li , Hong Bi . Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(4): 108946-. doi: 10.1016/j.cclet.2023.108946
18. [18]
  Junying LI , Xinyan CHEN , Xihui DIAO , Muhammad Yaseen , Chao CHEN , Hao WANG , Chuansong QI , Wei LI . Chiral fluorescent sensor Tb³⁺@Cd-CP based on camphoric acid for the enantioselective recognition of R- and S-propylene glycol. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2497-2504. doi: 10.11862/CJIC.20240084
19. [19]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
20. [20]
  Huamei Zhang , Jingjing Liu , Mingyue Li , Shida Ma , Xucong Zhou , Aixia Meng , Weina Han , Jin Zhou . Imaging polarity changes in pneumonia and lung cancer using a lipid droplet-targeted near-infrared fluorescent probe. Chinese Chemical Letters, 2024, 35(12): 110020-. doi: 10.1016/j.cclet.2024.110020

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(160)
HTML views(6)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142