State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116012, China.
Department of Pharmacy, Dalian University of Technology, Dalian, 116012, China.
Angew Chem Int Ed Engl. 2020 Apr 16;59(16):6420-6427. doi: 10.1002/anie.201915281. Epub 2020 Feb 25.
The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear Ir -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) 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 -containing metallohelices as PDT agents.
用于癌症治疗的 DNA 靶向光动力疗法 (PDT) 试剂的开发引起了广泛关注。本文报道了设计和合成具有可调 PDT 疗效的双核铱配合物发光金属螺旋体，该螺旋体靶向癌细胞中的线粒体 DNA。金属螺旋体是通过醛端封 fac-Ir(ppy) 手柄与线性烷二胺间隔物之间的动态亚胺偶联化学制备的，然后还原亚胺键。二胺烷基间隔物的长度和奇偶特性决定了立体化学（螺旋体与中孔体）。与螺旋体相比，中孔体在白光照射下表现出更好的诱导细胞凋亡能力。分子对接研究表明，具有适当长度二胺间隔物的中孔体对 DNA 小沟具有更强的亲和力。这项研究强调了 DNA 靶向含铱金属螺旋体作为 PDT 试剂的潜力。
