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Mitochondrial‐DNA‐Targeted Ir III ‐Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells
Author(s) -
Li Xuezhao,
Wu Jinguo,
Wang Lei,
He Cheng,
Chen Liyong,
Jiao Yang,
Duan Chunying
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915281
Subject(s) - photodynamic therapy , chemistry , imine , dna , diamine , cancer cell , linker , covalent bond , stereochemistry , combinatorial chemistry , cancer , biochemistry , biology , polymer chemistry , organic chemistry , computer science , genetics , operating system , catalysis
The development of DNA‐targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear Ir III ‐containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine‐coupling chemistry between aldehyde end‐capped fac‐Ir(ppy) 3 handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd–even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis‐induction upon white‐light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA‐targeting Ir III ‐containing metallohelices as PDT agents.