Strategies for the Synthesis of High-Efficiency Aggregation-Induced Emission Photosensitizers

doi:10.6023/cjoc202503003

Abstract

Aggregation-induced emission (AIE) photosensitizers have emerged as a new generation of candidates for photodynamic therapy (PDT) owing to their ability to maintain strong fluorescence and efficiently generate reactive oxygen species (ROS) in polymerized and aggregated states. Focusing on the recent research progress in molecular electronic structure and molecular motion regulation strategies, synthetic methodologies for constructing donor-acceptor (D-A) frameworks (such as Suzuki-Miyaura coupling, Stille coupling, Buchwald-Hartwig coupling, Sonogashira coupling, and Knoevenagel condensation), strategies for tuning π-conjugated backbones (such as the Heck reaction and Vilsmeier-Haack reaction), methods for enhancing spin-orbit coupling (SOC) including Menshutkin reactions, click chemistry, and metal coordination reaction, as well as motion-restricting strategies, including polymer encapsulation and nanoparticle loading, are mainly summarized. Through synergistic multidimensional molecular design and materials engineering, AIE photosensitizers have achieved significant improvements in near-infrared imaging and deep-tissue PDT efficacy. Looking forward, machine learning-assisted molecular screening and multimodal delivery platforms accelerate their clinical translation toward precision phototherapy of deep solid tumors.

Key words: aggregation-induced emission, photosensitizer, donor-acceptor framework, near-infrared phototherapy, reactive oxygen species

Cite this article

Hongyu Dai, Honghong Sun, Peifa Wei, Weijiang Guan. Strategies for the Synthesis of High-Efficiency Aggregation-Induced Emission Photosensitizers[J]. Chinese Journal of Organic Chemistry, 2025, 45(11): 4128-4142.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 15

Scheme 1. Synthesis of conjugated polymers 3~5

Scheme 2. Synthesis of compound 6

Scheme 3. Synthesis of compound 8

Scheme 4. Synthesis of compound 9 and chemical structures of compounds 10~12

Scheme 5. Synthesis of compounds 13 and 14

Scheme 6. Synthesis of compounds 20 and 21

Figure 1. Chemical structure of compound 24

Scheme 7. Synthesis of compounds 27 and 28

Figure 2. Chemical structures of compounds 29~32

Figure 3. Chemical structures of compounds 33~36

Scheme 8. Synthesis of compound 37, and chemical structures of compounds 38~43

Scheme 9. Synthesis of compound 45

Figure 4. Chemical structures of compounds 47 and 48

Figure 5. Schematic illustration of the synthesis of AIE-NFs with different peptides

Figure 6. (A) Chemical structure of QMC12, (B) self-assembly of YNP-QMC, and (C) preparation procedure of core-shell AD-Cu- DOX-HA

References 45

[46]	Li, Q. H.; Feng, S. M.; Feng, G. Q. Sens. Actuators, B 2025, 422, 136229.
[47]	Shen, C. J.; Xie, M. T.; Pan, L. Y.; Wu, B. B.; Zhang, W. X.; Yuan, Y. Y.; Chen, Y.; Quan, Y. Y.; Ye, X. X.; Huang, Z. S. Mater. Des. 2023, 228, 111838. doi: 10.1016/j.matdes.2023.111838
[48]	Liu, S. S.; Wang, B. N.; Yu, Y. W.; Liu, Y. B.; Zhuang, Z. Y.; Zhao, Z. J.; Feng, G. X.; Qin, A. J.; Tang, B. Z. ACS Nano 2022, 16, 9130. doi: 10.1021/acsnano.2c01206
[49]	Wang, J. J.; Zhu, X. J.; Zhang, J.; Wang, H. Y.; Liu, G.; Bu, Y. C.; Yu, J. H.; Tian, Y. P.; Zhou, H. P. ACS Appl. Mater. Interfaces 2020, 12, 1988. doi: 10.1021/acsami.9b15577
[50]	Wang, J. L.; Xia, F. W.; Wang, Y.; Shi, H. Z.; Wang, L. J.; Zhao, Y.; Song, J. X.; Wu, M. Y.; Feng, S. ACS Appl. Mater. Interfaces 2023, 15, 17433. doi: 10.1021/acsami.2c18835
[51]	Ghosal, K.; Bhattacharyya, S. K.; Mishra, V.; Zuilhof, H. Chem. Rev. 2024, 124, 13216. doi: 10.1021/acs.chemrev.4c00251
[52]	Li, C. Y.; Liu, J. K.; Hong, Y. J.; Lin, R. F.; Liu, Z. C.; Chen, M.; Lam, J. W. Y.; Ning, G. H.; Zheng, X. L.; Qin, A. J.; Tang, B. Z. Angew. Chem., Int. Ed. 2022, 61, e202202005.
[53]	Wang, Y. B.; Xu, S. D.; Shi, L. L.; Teh, C.; Qi, G. B.; Liu, B. Angew. Chem., Int. Ed. 2021, 60, 14945. doi: 10.1002/anie.v60.27
[54]	Zhang, L. P.; Li, Y. Y.; Che, W. L.; Zhu, D. X.; Li, G. F.; Xie, Z. G.; Song, N.; Liu, S.; Tang, B. Z.; Liu, X. M.; Su, Z. M.; Bryce, M. R. Adv. Sci. 2019, 6, 1802050. doi: 10.1002/advs.v6.5
[55]	Liu, L. L.; Zhu, T.; Cai, C. T.; Wang, L. K.; Li, S. L.; Lian, X.; Feng, Y.; Tian, Y. P.; Zhang, Q. Dalton Trans. 2022, 51, 16915. doi: 10.1039/D2DT02410A
[56]	Wei, L.; He, X. D.; Zhao, D. M.; Kandawa-Shultz, M.; Shao, G. Q.; Wang, Y. H. Eur. J. Med. Chem. 2024, 264, 115985. doi: 10.1016/j.ejmech.2023.115985
[1]	Teng, K. X.; Niu, L. Y.; Yang, Q. Z. J. Am. Chem. Soc. 2023, 145, 4081. doi: 10.1021/jacs.2c11868
[2]	Huang, Y.; Qiu, F.; Chen, R. J.; Yan, D. Y.; Zhu, X. Y. J. Mater. Chem. B 2020, 8, 3772. doi: 10.1039/d0tb00262c pmid: 32219270
[3]	Almeida, A.; Faustino, M. A. F.; Tomé, J. P. C. Future Med. Chem. 2015, 7, 1221. doi: 10.4155/fmc.15.59
[4]	Feng, H. T.; Li, Y. Y.; Duan, X. C.; Wang, X. X.; Qi, C. X.; Lam, J. W. Y.; Ding, D.; Tang, B. Z. J. Am. Chem. Soc. 2020, 142, 15966. doi: 10.1021/jacs.0c06872
[5]	Fan, W. P.; Huang, P.; Chen, X. Y. Chem. Soc. Rev. 2016, 45, 6488. doi: 10.1039/C6CS00616G
[6]	Liu, S. S.; Feng, G. X.; Tang, B. Z.; Liu, B. Chem. Sci. 2021, 12, 6488. doi: 10.1039/D1SC00045D
[7]	Piksa, M.; Lian, C.; Samuel, I. C.; Pawlik, K. J.; Samuel, I. D. W.; Matczyszyn, K. Chem. Soc. Rev. 2023, 52, 1697. doi: 10.1039/D0CS01051K
[8]	Liu, Y. H.; Chen, X. Q.; Liu, X. T.; Guan, W. J.; Lu, C. Chem. Soc. Rev. 2023, 52, 1456. doi: 10.1039/D2CS01021F
[57]	Wang, T.; He, X.; Xu, J.; Shen, D.; Mei, L.; Xu, G.; Wei, P.; Tang, B. Z. CCS Chem. 2025, 7, 105. doi: 10.31635/ccschem.024.202404130
[58]	Xiong, X.; Liu, J.; Wu, L.; Xiong, S.; Jiang, W.; Wang, P. Coord. Chem. Rev. 2024, 510, 215863. doi: 10.1016/j.ccr.2024.215863
[59]	Mao, L.; Huang, H.; Hu, D.; Ma, H.; Tian, M.; Zhang, X.; Wei, Y. Dyes Pigm. 2021, 194, 109521. doi: 10.1016/j.dyepig.2021.109521
[60]	Kamya, E.; Yi, S.; Hussain, Z.; Lu, Z.; Li, W.; Yan, J.; Ma, F.; Ullah, I.; Cao, Y.; Pei, R. ACS Macro Lett. 2023, 12, 1549. doi: 10.1021/acsmacrolett.3c00500
[61]	Zeng, W.; Xu, Y.; Yang, W.; Liu, K.; Bian, K.; Zhang, B. Adv. Healthcare Mater. 2020, 9, 2000560. doi: 10.1002/adhm.v9.17
[62]	Wang, H.; Wang, Y.; Zheng, Z.; Yang, F.; Ding, X.; Wu, A. J. Mater. Chem. B 2022, 10, 1418. doi: 10.1039/D1TB02610K
[63]	Wu, X.; Zhu, Z.; Liu, Z.; Li, X.; Zhou, T.; Zhao, X.; Wang, Y.; Shi, Y.; Yu, Q.; Zhu, W.-H.; Wang, Q. Molecules 2022, 27, 7981. doi: 10.3390/molecules27227981
[64]	Chen, D.; Long, Z.; Zhong, C.; Chen, L.; Dang, Y.; Hu, J.-J.; Lou, X.; Xia, F. ACS Appl. Bio Mater. 2021, 4, 5231. doi: 10.1021/acsabm.1c00398
[65]	Cao, B.; Ma, Y. F.; Zhang, J.; Wang, Y. N.; Wen, Y.; Li, Y.; Wang, R.; Cao, D. H.; Zhang, R. P. Mater. Today Bio 2024, 26, 101091.
[66]	Guo, K.; Zhang, M.; Cai, J.; Ma, Z.; Fang, Z.; Zhou, H.; Chen, J.; Gao, M.; Wang, L. Small 2022, 18, 2108030. doi: 10.1002/smll.v18.17
[67]	Song, A.; Wang, Y.; Xu, J.; Wang, X.; Wu, Y.; Wang, H.; Yao, C.; Dai, H.; Zhang, Y.; Wang, Q.; Wang, C. Nano Today 2024, 54, 102109. doi: 10.1016/j.nantod.2023.102109
[9]	Pan, J.; Li, W. L.; Wang, M. Y.; Peng, C. P.; Dong, J. H.; Zhou, Q. T.; Xia, F. Chem. Mater. 2024, 36, 11721. doi: 10.1021/acs.chemmater.4c02176
[10]	Wang, X. N.; Ramamurthy, G.; Shirke, A.; Walker, E.; Mangadlao, J.; Wang, Z.; Wang, Y.; Shan, L. P.; Schluchter, M.; Dong, Z. P.; Brady-Kalnay, S. M.; Walker, N. K.; Gargesha, M.; MacLennan, G.; Luo, D.; Sun, R.; Scott, B.; Roy, D.; Li, J.; Basilion, J. P. Cancer Res. 2020, 80, 156. doi: 10.1158/0008-5472.CAN-19-0201
[11]	Pham, T. C.; Nguyen, V. N.; Choi, Y.; Lee, S.; Yoon, J. Chem. Rev. 2021, 121, 13454. doi: 10.1021/acs.chemrev.1c00381
[12]	Dang, J. J.; He, H.; Chen, D. L.; Yin, L. C. Biomater. Sci. 2017, 5, 1500. doi: 10.1039/C7BM00392G
[13]	Dichiara, M.; Prezzavento, O.; Marrazzo, A.; Pittalà, V.; Salerno, L.; Rescifina, A.; Amata, E. Eur. J. Med. Chem. 2017, 142, 459. doi: S0223-5234(17)30681-5 pmid: 28943196
[14]	Nguyen, V. N.; Yan, Y. X.; Zhao, J. Z.; Yoon, J. Y. Acc. Chem. Res. 2021, 54, 207. doi: 10.1021/acs.accounts.0c00606
[15]	Bonnett, R. Chem. Soc. Rev. 1995, 26, 19.
[16]	Luo, J.; Xie, Z.; Lam, J. W. Y.; Cheng, L.; Tang, B. Z.; Chen, H.; Qiu, C.; Kwok, H. S.; Zhan, X.; Liu, Y.; Zhu, D. Chem. Commun. 2001, 1740.
[17]	Tang, X. F.; Zhu, Y. P.; Guan, W. J.; Lu, C. Aggregate 2023, 4, e348.
[18]	Zhou, C. C.; Ding, Z. Y.; Guan, W. J.; Tang, B. Z. Aggregate 2023, 4, e366.
[19]	Mei, J.; Hong, Y. N.; Lam, J. W. Y.; Qin, A. J.; Tang, Y. H.; Tang, B. Z. Adv. Mater. 2014, 26, 5429. doi: 10.1002/adma.v26.31
[20]	Qi, J.; Chen, C.; Zhang, X. Y.; Hu, X. L.; Ji, S. L.; Kwok, R. T. K.; Lam, J. W. Y.; Ding, D.; Tang, B. Z. Nat. Commun. 2018, 9, 12. doi: 10.1038/s41467-017-02416-0
[21]	Wang, H. P.; Chen, X.; Qi, Y. L.; Huang, L. W.; Wang, C. X.; Ding, D.; Xue, X. Adv. Drug Delivery Rev. 2021, 179, 114028. doi: 10.1016/j.addr.2021.114028
[22]	Wang, Y. B.; Shi, L. L.; Wu, W. B.; Qi, G. B.; Zhu, X. Y.; Liu, B. Adv. Funct. Mater. 2021, 31, 2010241. doi: 10.1002/adfm.v31.16
[23]	Li, L. Q.; Shao, C.; Liu, T.; Chao, Z. C.; Chen, H. L.; Xiao, F.; He, H. M.; Wei, Z. X.; Zhu, Y. L.; Wang, H.; Zhang, X. D.; Wen, Y. T.; Yang, B.; He, F.; Tian, L. L. Adv. Mater. 2020, 32, 2003471. doi: 10.1002/adma.v32.45
[24]	Lu, B. L.; Wang, L. Y.; Tang, H.; Cao, D. R. J. Mater. Chem. B 2023, 11, 4600. doi: 10.1039/D3TB00545C
[25]	Maluenda, I.; Navarro, O. Molecules 2015, 20, 7528. doi: 10.3390/molecules20057528 pmid: 25919276
[26]	Li, Y.; Zhang, D.; Yu, Y.; Zhang, L.; Li, L.; Shi, L.; Feng, G.; Tang, B. Z. ACS Nano 2023, 17, 16993. doi: 10.1021/acsnano.3c04256
[68]	Wang, L.; Chen, Y.; Han, Z.; Wang, E.; Zhang, J.; Wang, B.; Yang, X. J. Anal. Test. 2023, 7, 215. doi: 10.1007/s41664-023-00261-3
[69]	Yan, S.; Sun, P.; Niu, N.; Zhang, Z.; Xu, W.; Zhao, S.; Wang, L.; Wang, D.; Tang, B. Z. ACS Nano 2022, 16, 9785. doi: 10.1021/acsnano.2c03550
[27]	Xue, B.; Hou, A.; Du, Y.; Qi, Y.; Jiang, H.; Zhou, H.; Zhou, Z.; Chen, H. Surf. Interfaces 2023, 39, 102996.
[28]	Li, C. L.; Li, J.; Pang, Y. D.; Mei, L. C.; Xu, W. H.; Zhang, Z. P.; Han, C. P.; Sun, Y. Chem. Eng. J. 2024, 498, 155471. doi: 10.1016/j.cej.2024.155471
[29]	Hu, Y.; Yin, S. Y.; Liu, W.; Li, Z.; Chen, Y.; Li, J. Aggregate 2023, 4, e256.
[30]	Wu, W. B.; Mao, D.; Xu, S. D.; Kenry; Hu, F.; Li, X. Q.; Kong, D. L.; Liu, B. Chem 2018, 4, 1937. doi: 10.1016/j.chempr.2018.06.003
[31]	Chishiro, A.; Konishi, M.; Inaba, R.; Yumura, T.; Imoto, H.; Naka, K. Dalton Trans. 2021, 51, 95. doi: 10.1039/D1DT02955J
[32]	Li, D.; Chen, X. H.; Wang, D. L.; Wu, H. Z.; Wen, H. F.; Wang, L.; Jin, Q.; Wang, D.; Ji, J.; Tang, B. Z. Biomaterials 2022, 283, 121476. doi: 10.1016/j.biomaterials.2022.121476
[33]	Xiao, Y.; Yuan, Y.; Liang, M.; Ni, J.; Yu, L.; Huang, Z. S.; Du, B.; Quan, Y. Y. Dyes Pigm. 2023, 220, 111765. doi: 10.1016/j.dyepig.2023.111765
[34]	Heravi, M. M.; Kheilkordi, Z.; Zadsirjan, V.; Heydari, M.; Malmir, M. J. Organomet. Chem. 2018, 861, 17. doi: 10.1016/j.jorganchem.2018.02.023
[35]	Wang, Q.; Li, C. B.; Song, Y. C.; Shi, Q. K.; Li, H.; Zhong, H.; Wang, J. G.; Hu, F. Chem. Sci. 2023, 14, 684. doi: 10.1039/D2SC05454J
[36]	Zhang, W. G.; Kang, M. M.; Li, X.; Pan, Y. Z.; Li, Z. R.; Zhang, Y. B.; Liao, C. R.; Xu, G. X.; Zhang, Z. J.; Tang, B. Z.; Xu, Z. R.; Wang, D. Adv. Mater. 2024, 36, 2410142. doi: 10.1002/adma.v36.47
[37]	Zhang, Z. J.; Xu, W. H.; Xiao, P. H.; Kang, M. M.; Yan, D. Y.; Wen, H. F.; Song, N.; Wang, D.; Tang, B. Z. ACS Nano 2021, 15, 10689. doi: 10.1021/acsnano.1c03700
[38]	Huang, H. Y.; Xie, W. S.; Wan, Q.; Mao, L. C.; Hu, D. N.; Sun, H.; Zhang, X. Y.; Wei, Y. Adv. Sci. 2022, 9, 2104101. doi: 10.1002/advs.v9.4
[39]	Zhang, Z. J.; Xu, W. H.; Kang, M. M.; Wen, H. F.; Guo, H.; Zhang, P. F.; Xi, L.; Li, K.; Wang, L.; Wang, D.; Tang, B. Adv. Mater. 2020, 32, 2003210. doi: 10.1002/adma.v32.36
[40]	Liu, L. Q.; Wang, X.; Wang, L. J.; Guo, L. Q.; Li, Y. B.; Bai, B.; Fu, F.; Lu, H. G.; Zhao, X. W. ACS Appl. Mater. Interfaces 2021, 13, 19668. doi: 10.1021/acsami.1c02260
[41]	Zhuang, J. B.; Wang, B.; Chen, H.; Zhang, K. Y.; Zhao, N.; Li, N.; Tang, B. Z. ACS Nano 2023, 17, 9110. doi: 10.1021/acsnano.2c12319
[42]	Hu, Y. C.; Yin, S. Y.; Deng, T.; Li, J. S. Chem. Commun. 2024, 60, 3047. doi: 10.1039/D3CC06247C
[43]	Bai, H. Y.; Xiong, Z.; Zhou, F. F.; Qin, J. M.; Wen, S. L.; Li, Z. M.; Chen, Y.; Cao, Q. Y. Dyes Pigm. 2022, 206, 110652. doi: 10.1016/j.dyepig.2022.110652
[44]	Sun, Z. C.; Wang, J. X.; Xiao, M. H.; Wu, K. Y.; Wang, C.; Fu, H.; Lv, S. Y.; Shi, L. Q.; Zhu, C. L. Chem. Eng. J. 2024, 499, 155782. doi: 10.1016/j.cej.2024.155782
[45]	Xue, J.; Zhang, Y. S.; Huan, Z.; Yang, J. D.; Cheng, J. P. J. Org. Chem. 2022, 87, 15539. doi: 10.1021/acs.joc.2c02085

高效聚集诱导发光光敏剂的合成策略