文献类型：期刊文献

英文题名：A Domino-Synthesized Dicoordinate Copper(I) Bis-imidazopyridine Complex Triggering Cuproptosis/Ferroptosis for Enhanced Cancer Immunotherapy

作者：Tian, Ning[1];Ju, Haoyu[2];Liu, Yu[1];Huang, Jinmei[1];Luan, Zhenggang[1];Hou, Qifeng[1];Chen, Qing[3];Zhang, Bin[1];Huang, Jin[2];Zeng, Ming- Hua[1,4]

机构：[1]Guangxi Normal Univ, Sch Chem & Pharmaceut Sci, Key Lab Chem & Mol Engn Med Resources,Minist Educ, Guangxi Key Lab Chem & Mol Engn Med Resources, Guilin, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, State Key Lab Bioreactor Engn,Shanghai Key Lab New, Shanghai, Peoples R China;[3]Guangxi Univ Chinese Med, Inst Tradit Chinese & Zhuang Yao Ethn Med, Coll Pharm, Nanning, Peoples R China;[4]Shantou Univ, Dept Chem & Chem Engn, Key Lab Preparat & Applicat Ordered Struct Mat Gua, Shantou, Peoples R China

年份：2026

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20262721048826);Scopus(收录号：2-s2.0-105043749923);WOS:【SCI-EXPANDED(收录号:WOS:001810601800001)】；

基金：This work was supported by the BAGUI Talent Program of Guangxi Province (Grants No. 2019AC26001), the National Natural Science Foundation of China (Grants No. U23A2080, 22171075, 82373913, 82574463), the STU Scientific Research Initiation Grant (Grants No. NTF26016T), the Shanghai Oriental Talent Plan Outstanding Project (Grants No. BJJY2024021), and the Translational Medicine National Science and Technology Infrastructure (Shanghai) 2024 Open Research Project (Grants No. TMSK-2024-102).

语种：英文

外文关键词：copper complex; cuproptosis; domino reaction; ferroptosis; immunogenic cell death

摘要：Novel synthetic methods offer significant potential to accelerate drug development, yet there remains a largely unexplored area for efficiently synthesizing metal-based anticancer agents. Herein, we report a novel solvothermal domino reaction of pyridine-2-methylamine (and its 4-OCH3-substituted derivative), benzaldehyde, and CuCl2 center dot 2H2O, which simultaneously achieves ligand synthesis and coordination assembly in one pot and facilely affords innovative dinuclear dicoordinate copper(I) complexes (Cu1 and Cu2) with the in situ-formed bulky steric-hindering tetraarylethane ligands featuring the bis-imidazo[1,5-a]pyridine scaffold. The unique geometry of Cu1 and Cu2 confers physiological stability and vacant coordination sites for efficiently catalyzing Fenton-like reactions. Further studies reveal that Cu2 effectively elevates intracellular copper ion levels to induce cuproptosis, concurrently disrupting cellular redox homeostasis to trigger ferroptosis. The concurrent cuproptosis-ferroptosis activation finally elicits significantly enhanced immunogenic cell death (ICD), which facilitates the antitumor activity of Cu2. Moreover, in combination with immune checkpoint inhibitor alpha PD-1, Cu2 exhibits improved immunotherapy effects. This work introduces the first small-molecule copper complex that achieves immunotherapy potentiation through cuproptosis-ferroptosis-ICD induction and provides a new pathway for accessing innovative metal-based antitumor agents through such a rationally designed domino reaction.