Progress of Organic Radical Materials in Biomedical Applications

doi:10.6023/cjoc202508018

Abstract

Organic radical materials, due to their special open-shell electronic structure, possess unique magnetic, optical, and redox properties, and have been widely applied in the field of biomedicine. However, the lifetime of most radicals is too short to be separated, and only a few radicals can maintain their stable radical form via stereochemical strategies. Therefore, how to develop stable organic radical materials has been the focus and difficulty of research in recent years. This review summarizes the classification, molecular design, and fundamental properties of organic radical materials, and discusses their biomedical applications, particularly in bioimaging, photodynamic therapy, photothermal therapy, and synergistic therapy. Additionally, the article also discusses the various challenges and future opportunities that these organic radical materials are currently facing.

Key words: stable radical, bioimaging, photodynamic therapy, photothermal therapy, synergistic therapy

Cite this article

Jianye Yang, Pei Zhou, Qifei Shen, Peijuan Zhang, Yanzi Xu, Bingjie Zhao, Dongfeng Dang. Progress of Organic Radical Materials in Biomedical Applications[J]. Chinese Journal of Organic Chemistry, 2025, 45(11): 4013-4025.

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Fig. & Tab. 10

Figure 1. Schematic illustration of luminescence in (a) closed- shell molecules and (b) open-shell molecules

Figure 2. Classification of organic radical

Figure 3. Stable radical construction strategies

Figure 4. (a) Structural diagram of organic radical contrast agent (ORCA) and T1-weighted MRI of mouse 90 min after injection with ORCA; (b) Chemical structure of BASP-ORCAs and T2-weighted MRI before and after injection of BASP-ORCA; (c) Nitroxide radical network structure and MRI of mouse leg

Figure 5. (a) Chemical structure of HOPE71 and its stimulus-responsive EPR spectrum; (b) Interconversion structures between MCP and MCPH, and EPR imaging of MCP control group versus DEM-treated group

Figure 6. (a) Preparation process of P cation radical and mitochondrial co-localization imaging of P•+⊂CB[7] in different cells; (b) Chemical structures of P8 and P9 and in vivo fluorescence imaging of mice; (c) Chemical structure of TTM-Cz-Br and preparation of its nanoparticles

Figure 7. ROS production mechanisms of closed-shell and open-shell photosensitizers

Figure 8. Chemical structures of Cy-TEMPO and Cy-DENT; (b) Chemical structures of PTM-TPA and electron paramagnetic resonance spectra of PTM-TPA nanoparticles at different concentrations

Figure 9. Chemical structures of (a) BPDI3－, (b) NDI-2CB[7].－, (c) CRbio, (d) CR-(DPA)3-T, and (e) DRM; (f) Chemical structure of SFA-BTM and its application of radical nanoparticles in photothermal therapy

Figure 10. Chemical structures of (a) HTB, (b) TTMIndoOMe, and (c) 2PhNVDPP

References 88

[38]	Alcón, I.; Calogero, G.; Nick, A.; Song, K.; Cummings, A.; Brandbyge, M.; Roche, S. J. Am. Chem. Soc. 2022, 144, 8278. doi: 10.1021/jacs.2c02178
[39]	Plasser, F.; Pasalic, H.; Lischka, H. Angew. Chem. Int. Ed. 2013, 52, 2581. doi: 10.1002/anie.201207671 pmid: 23355507
[40]	Chen, Z. X.; Li, Y.; Huang, F. Chem 2022, 7, 288. doi: 10.1016/j.chempr.2020.09.024
[41]	Wang, X.; Xue, P.; Zhou, C.; Zhang, Y.; Li, P.; Chen, R. J. Mater. Chem. C 2022, 10, 18343. doi: 10.1039/D2TC03712B
[42]	Sindt, A. J.; DeHaven, B. A.; Goodlett, R. L.; Hartel, J. O.; Pooja, J. J. Am. Chem. Soc. 2019, 142, 502. doi: 10.1021/jacs.9b11518
[43]	Huo, G.; Shi, X.; Tu, Q.; Hu, Y.; Wu, G.; Yin, G.; Li, X.; Xu, L.; Ding, H.; Yang, H. J. Am. Chem. Soc. 2019, 141, 16014. doi: 10.1021/jacs.9b08149
[1]	Abe, M. Chem. Rev. 2013, 113, 7011. doi: 10.1021/cr400056a
[2]	Zhou, Z.; Song, J.; Nie, L.; Chen, X. Chem. Soc. Rev. 2016, 45, 6597. doi: 10.1039/C6CS00271D
[3]	Chen, X.; Wang, F.; Hyun, J.; Wei, T.; Ren, J.; Qiang, X.; Shin, I. Chem. Soc. Rev. 2016, 45, 2976. doi: 10.1039/C6CS00192K
[4]	Sheng, X. G.; Feng, L. Adv. Funct. Mater. 2023, 33, 2304291. doi: 10.1002/adfm.v33.48
[5]	Shadel, G. Horvath, T. Cell 2015, 163, 560. doi: 10.1016/j.cell.2015.10.001
[6]	Ai, X.; Chen, Y.; Feng, Y.; Li, F. Angew. Chem. Int. Ed. 2018, 57, 2869-2873. doi: 10.1002/anie.v57.11
[7]	Gomberg, M. J. Am. Chem. Soc. 1900, 22, 757. doi: 10.1021/ja02049a006
[8]	Gomberg, M. J. Am. Chem. Soc. 1901, 23, 496. doi: 10.1021/ja02033a015
[9]	Gomberg, M. J. Am. Chem. Soc. 1902, 24, 597. doi: 10.1021/ja02021a001
[10]	Lisa, C.; Mona, A.; Yonca, K.; Rémi, B.; Fedor, J.; Alexander, J. C. Adv. Opt. Mater. 2022, 10, 2102101. doi: 10.1002/adom.v10.7
[11]	Kenshiro, M.; Kazuhiro, N.; Minori, F.; Takuya, H.; Kosuke, K. A.; Ken, A. Chem. Commun. 2022, 58, 13443. doi: 10.1039/D2CC04481A
[12]	Bai, X.; Tan, W.; Abdurahman, A.; Li, X.; Li, F. Dye Pigm. 2022, 202, 110260. doi: 10.1016/j.dyepig.2022.110260
[13]	Cao, W.; Brédas, J.; Coropceanu, V.; Li, F. Adv. Mater. 2023, 35, 2208190. doi: 10.1002/adma.v35.6
[44]	Mu, Y.; Liu, Y.; Tian, H.; Ou, D.; Gong, L.; Zhao, J.; Zhang, Y.; Huo, Y.; Yang, Z.; Chi, Z. Angew. Chem. Int. Ed. 2021, 60, 6367. doi: 10.1002/anie.v60.12
[45]	Amali, S.; Subasinghe, S.; Allen, M. J. Chem. Commun. 2021, 57, 1770. doi: 10.1039/D0CC06400A
[46]	Meloni, M. M.; He, T. J. Mater. Chem. B 2017, 5, 5714. doi: 10.1039/c7tb01241a pmid: 32264204
[47]	Yu, L.; Zhang, K.; Zhang, Y.; Wang, X.; Dong, P.; Ge, Y.; Ni, G.; Liu, Z.; Zhang, Y. J. Mater. Chem. B 2024, 12, 2486.
[48]	Rajca, A.; Wang, Y.; Boska, M.; Paletta, J. T.; Olankitwanit, A.; Swanson, M. A.; Mitchell, D. G.; Eaton, S. S.; Eaton, G. R.; Rajca, S. J. Am. Chem. Soc. 2012, 134, 15724. doi: 10.1021/ja3079829
[49]	Nguyen, H.; Chen, Q.; Paletta, J.; Harvey, P.; Jiang, Y.; Zhang, H.; Boska, M. D.; Ottaviani, M. F.; Jasanoff, A.; Rajca, A.; Johnson, J. A. ACS Cent. Sci. 2017, 3, 800. doi: 10.1021/acscentsci.7b00253
[14]	Ding, J.; Dong, S.; Zhang, M.; Li, F. J. Mater. Chem. C 2022, 10, 14116. doi: 10.1039/D2TC03299F
[15]	Abdurahman, A.; Hele, T.; Gu, Q.; Zhang, J.; Peng, Q.; Zhang, M.; Friend, R. H.; Li, F.; Evans, E. W. Nat. Mater. 2020, 19, 1224. doi: 10.1038/s41563-020-0705-9
[16]	Maiju, S.; Kaisa, H.; Jani, O. M.; Marjut, T.; Jari, K.; Sami, H. Molecules 2018, 23, 1034. doi: 10.3390/molecules23051034
[17]	Zhou, J.; Zhu, W.; Miao, Z.; Yang, Q.; Ping, L.; Lin, F.; Peng, J.; Li, Y.; Huang, F.; Cao, Y. Sci. China Chem. 2019, 62, 1656. doi: 10.1007/s11426-019-9641-2
[18]	Chern, Y.; Zhang, S.; Ho, S.; Shao, Y.; Wang, Y.; Liou, G.-S. ACS Appl. Polym. Mater. 2024, 6, 5256. doi: 10.1021/acsapm.4c00432
[50]	Pena-Francesch, A.; Zhang, Z.; Sitti, M. Matter 2024, 7, 1. doi: 10.1016/j.matt.2023.12.009
[51]	Roessler, M. M.; Salvadori, E. Chem. Soc. Rev. 2018, 47, 2534. doi: 10.1039/c6cs00565a pmid: 29498718
[52]	Gluth, T.; Poncelet, M.; Gencheva, M.; Hoblitzell, E. H.; Khramtsov, V. V.; Eubank, T. D.; Driesschaer, B. Anal. Chem. 2023, 95, 946.
[53]	Emoto, M. C.; Sato-Akaba, H.; Matsuoka, Y.; Yamada, K. I.; Fujii, H. G. Neurosci. Lett. 2019, 960, 6.
[54]	Zhu, H.; Fan, J.; Du, J.; Peng, X. Acc. Chem. Res. 2016, 49, 2115. doi: 10.1021/acs.accounts.6b00292
[55]	Wang, S.; Ren, W. X.; Hou, J. T.; Won, M.; An, J.; Chen, X.; Shu, J.; Kim, J. S. Chem. Soc. Rev. 2021, 50, 8887.
[56]	Zhang, Z.; Fan, J.; Du, J.; Peng, X. Coord. Chem. Rev. 2021, 427, 213575. doi: 10.1016/j.ccr.2020.213575
[57]	Guo, H. Q.; Peng, Q. M.; Li, F. Nat. Mater. 2019, 18, 977. doi: 10.1038/s41563-019-0433-1
[58]	Hudson, J. M.; Hele, T. J. H.; Evans, E. W. J. Appl. Phys. 2021, 129, 180901. doi: 10.1063/5.0047636
[59]	Zheng, L.; Zhu, W.; Zhou, Z.; Liu, K.; Gao, M.; Tang, B. Z. Mater. Horiz. 2021, 8, 3082.
[60]	Dai, S.; Tao, M.; Zhong, Y.; Li, Z.; Liang, J.; Chen, D.; Liu, K.; Wei, B.; Situ, B.; Gao, M.; Tang, B. Adv. Mater. 2023, 35, 2209940.
[61]	Li, J.; Yu, X.; Jiang, Y.; He, S.; Zhang, Y.; Luo, Y.; Pu, K. Adv. Mater. 2021, 33, 2003458. doi: 10.1002/adma.v33.4
[19]	Tang, B.; Li, W.; Zhang, X. Angew. Chem. Int. Ed. 2019, 58, 15526. doi: 10.1002/anie.v58.43
[20]	Cui, Z.; Abdurahman, A.; Ai, X.; Li, F. CCS Chem. 2020, 2, 1129. doi: 10.31635/ccschem.020.202000210
[21]	Che, F.; Zhao, X.; Zhang, X.; Ding, Q.; Wang, X.; Li, P.; Tang, B. Acta Chim. Sinica 2023, 81, 1255 (in Chinese). doi: 10.6023/A23040191
	(车飞达, 赵晓茗, 张馨, 丁琪, 王昕, 李平, 唐波, 化学学报, 2023, 81, 1255.)
[22]	Ren, Y.; Li, X.; Han, Y. F. Acta Chim. Sinica 2023, 81, 735 (in Chinese). doi: 10.6023/A23040130
	(任妍妍, 李欣, 韩英锋, 化学学报, 2023, 81, 735.)
[23]	Zhu, Z.; Kuang, Z.; Shen, L.; Wang, S.; Ai, X.; Abdurahman, A.; Peng, Q. Angew. Chem. Int. Ed. 2024, 63, e202410552.
[24]	Ai, X.; Evans, E. W.; Dong, S.; Gillett, A. J.; Guo, H.; Chen, Y.; Hele, T. J. H.; Friend, R. H.; Li, F. Nature 2018, 563, 536. doi: 10.1038/s41586-018-0695-9
[62]	Li, D.; Liu, P.; Tan, Y.; Zhang, Z.; Kang, M.; Wang, D.; Tang, B. Z. Biosensors 2022, 12, 722.
[63]	Lucky, S.; Soo, K.; Zhang, Y. Chem. Rev. 2015, 115, 1990. doi: 10.1021/cr5004198
[64]	Lyu, Y.; Fang, Y.; Miao, Q.; Zhen, X.; Ding, D.; Pu, K. ACS Nano 2016, 10, 4472. doi: 10.1021/acsnano.6b00168
[65]	Zhang, C.; Zeng, Z.; Cui, D.; He, S.; Jiang, Y.; Li, J.; Huang, J.; Pu, K. Nat. Commun. 2021, 12, 2934. doi: 10.1038/s41467-021-23194-w pmid: 34006860
[66]	Wang, X.; Shi, G.; Wei, R.; Li, M.; Zhang, T.; Chen, C. F.; Zhang, Q.; Hu, H. Y. Chem. Sci. 2024, 15, 6421. doi: 10.1039/D3SC06826A
[25]	Ji, L.; Shi, J.; Wei, J.; Yu, T.; Huang, W. Adv. Mater. 2020, 32, 1908015. doi: 10.1002/adma.v32.32
[26]	Tan, G.; Wang, X. Acc. Chem. Res. 2006, 50, 1997. doi: 10.1021/acs.accounts.7b00229
[27]	Yang, Y.; Wang, J.; Li, D.; Yang, J.; Fang, M.; Li, Z. Adv. Mater. 2021, 33, 2104002. doi: 10.1002/adma.v33.43
[28]	Martinez-DelaHoz, J.; Konstantinov, I. Macromol. Theory Simul. 2016, 25, 475. doi: 10.1002/mats.201600023
[29]	Stanisavljev, D.; Milenkovic, M.; Mojovi, M. J. Phys. Chem. A 2011, 115, 7955. doi: 10.1021/jp203601w pmid: 21692499
[30]	Tebben, L.; Studer, A. Angew. Chem. Int. Ed. 2011, 50, 5034. doi: 10.1002/anie.v50.22
[31]	McClain, E.; Wortman, A.; Stephenson, C. J. Chem. Sci. 2022, 13, 12158.
[67]	Jiao, L.; Song, F.; Cui, J.; Peng, X. Chem. Commun. 2018, 54, 9198. doi: 10.1039/C8CC04582H
[68]	Xu, F.; Ge, H.; Xu, N.; Yang, C.; Yao, Q.; Long, S.; Sun, W.; Fan, J.; Xu, X.; Peng, X. Sci. China Chem. 2021, 64, 488. doi: 10.1007/s11426-020-9922-3
[69]	Cui, X.; Lu, G.; Dong, S.; Li, S.; Xiao, Y.; Zhang, J.; Liu, Y.; Meng, X.; Li, F.; Lee, C. S. Mater. Horiz. 2021, 8, 571. doi: 10.1039/d0mh01312a pmid: 34821273
[70]	Du, C.; Wu, X.; He, M.; Zhang, Y.; Zhang, R.; M. J. Mater. Chem. B 2021, 9, 1478. doi: 10.1039/D0TB02659J
[71]	Cao, Z. Y.; Feng, L. Z.; Zhang, G. B.; Wang, J. X.; Shen, S.; Li, D. D.; Yang, X. Z. Biomaterials 2018, 155, 103.
[32]	Zhang, H.; Xu, X.; Shou, X.; Liao, W.; Jin, C.; Chen, C.; Zhang, C.; Gao, W.; Zhang, J.; Ge, W.; Shi, L. Adv. Healthcare Mater. 2024, 13, 2401085. doi: 10.1002/adhm.v13.23
[33]	Lai, R.; Lu, E.; Samson, A. J. Chem. Phys. Lett. 1997, 275, 355. doi: 10.1016/S0009-2614(97)00775-6
[34]	Gallagher, N.; Ye, H.; Feng, S.; Lopez, J.; Zhu, Y.; Van Voorhis, T.; Shao-Horn, Y.; Feng, S. Angew. Chem. Int. Ed. 2020, 59, 3952. doi: 10.1002/anie.201915534 pmid: 31825136
[35]	Schroder, J.; Himmel, D.; Kratzert, D.; Radtke, V.; Richert, S.; Weber, S.; Bo¨ttcher, T. Chem. Commun. 2019, 55, 1322. doi: 10.1039/C8CC09700C
[36]	Liu, G.; Khlobystov, A. N.; Charalambidis, G. J. Am. Chem. Soc. 2012, 134, 1938. doi: 10.1021/ja209763u
[72]	Huang, J.; Wang, Z.; Zhu, W.; Li, Y. Aggregate 2024, 5, e426.
[73]	Zhang, H.; Yang, Y.; Huang, J.; Chen, L.; Cui, Y.; Lu, Z.; Shen, S.; Liu, Z.; Song, H.; Kuang, Z.; Dang, Q.; Li, Y. Adv. Sci. 2025, e13587.
[74]	Liu, T.; Zhu, Z.; Wang, S.; Shen, L.; Abdurahman, A.; Liu, X.; Lu, G. Light: Sci. Appl. 2025, 14, 289. doi: 10.1038/s41377-025-01993-w
[75]	Xu, Y.; Yin, D.; Wang, Y.; Chen, D.; Li, X.; Yan, L. Angew. Chem. Int. Ed. 2025, 64, e202509609.
[76]	Zhang, J.; Luo, H.; Ma, W.; Lv, J.; Wang, B.; Sun, F.; Chi, W.; Fang, Z.; Yang, Z. Adv. Sci. 2025, 12, 2500293. doi: 10.1002/advs.v12.17
[77]	Gao, Y.; Liu, Y.; Li, X.; Wang, H.; Yang, Y.; Luo, Y.; Wan, Y.; Lee, C.; Li, S.; Zhang, X. Nano-Micro Lett. 2024, 16, 21. doi: 10.1007/s40820-023-01219-x
[78]	Jiao, Y.; Liu, K.; Wang, G.; Wang, Y.; Zhang, X. Chem. Sci. 2015, 6, 3975. doi: 10.1039/C5SC01167A
[79]	Hu, H.; Zhang, Y.; Ma, H.; Yang, Y.; Mei, S.; Li, J.; Xu, J. F.; Zhang, X. Angew. Chem. Int. Ed. 2023, 62, e202308513.
[80]	Chen, G.; Sun, J.; Peng, Q.; Sun, Q.; Wang, G.; Cai, Y.; Gu, X.; Shuai, Z.; Tang, B. Z. Adv. Mater. 2020, 32, 1908537. doi: 10.1002/adma.v32.29
[81]	Sun, J.; Zhao, E.; Liang, J.; Li, H.; Zhao, S.; Wang, G.; Gu, X.; Tang, B. Z. Adv. Mater. 2022, 34, 2108048. doi: 10.1002/adma.v34.9
[82]	Yang, L.; Wang, G.; Zhang, Y.; Zhou, J.; Wu, R.; Qin, C.; Chang, Q.; Zhang, C.; Duan, S.; Gu, X. Angew. Chem. Int. Ed. 2025, 64, e202508821.
[83]	Zhu, X.; Li, L.; Tang, J.; Yang, C.; Yu, H.; Liu, K.; Zheng, Z.; Gu, X.; Yu, Q.; Xu, F.-J.; Gan, Z. Biomaterials 2022, 280, 121305. doi: 10.1016/j.biomaterials.2021.121305
[84]	Kong, X.; Liang, J.; Lu, M.; Zhang, K.; Zhao, E.; Kang, X.; Wang, G.; Yu, Q.; Gan, Z.; Gu, X. Adv. Mater. 2024, 36, 2409041. doi: 10.1002/adma.v36.48
[85]	Li, X.; Zhang, D.; Yin, C.; Lu, G.; Wan, Y.; Huang, Z.; Tan, J.; Li, S.; Luo, J.; Lee, C. S. ACS Appl. Mater. Interfaces 2021, 13, 15983. doi: 10.1021/acsami.0c21889
[37]	Alexander, H.; Jonas, B.; Frank, B.; Axel, S. Chem. Rev. 2023, 123, 16, 10468.
[86]	Zhao, Q.; Wu, C.; Gao, Y.; Long, J.; Zhang, W.; Chen, Y.; Yang, Y.; Luo, Y.; Lai, Y.; Zhang, H.; Chen, X.; Li, F.; Li, S. Adv. Sci. 2025, 12, 2411733. doi: 10.1002/advs.v12.15
[87]	Xu, Y.; Teng, C.; Dang, H.; Yin, D.; Yan, L. Talanta 2024, 266, 124948. doi: 10.1016/j.talanta.2023.124948
[88]	Feng, L.; Tuo, Y.; Wu, Z.; Zhang, W.; Li, C.; Yang, B.; Liu, L.; Gong, J.; Jiang, G.; Hu, W.; Tang, B.; Wu, L.; Wang, J. J. Am. Chem. Soc. 2024, 146, 32582. doi: 10.1021/jacs.4c11549

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