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<p>Herein, we reported the synthesis and characterization of two new iridium(III) complexes [Ir(ppy)<sub>2</sub>(fpp)](PF<sub>6</sub>) (Ir1a, ppy = 2-phenylpyridine, fpp = 2-(2,2-difluorobenzo[1,3]dioxol-5-yl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(bzq)<sub>2</sub>(fpp)](PF<sub>6</sub>) (Ir1b, bzq = benzo[h]quinoline) through high resolution mass&#xa0;spectrometry (HRMS), <sup>1</sup>H NMR and <sup>13</sup>C NMR. The cytotoxicity in vitro of Ir1a and Ir1b on normal NIH3T3 cells and cancer SGC-7901, A549, SK-Hep1 cells was tested using MTT (3-(4,5-dimethylthiazole-2-yl)-diphenyltetrazolium bromide) method. Ir1a exhibits high cytotoxicity on SGC-7901 cells (IC<sub>50</sub> = 2.7 ± 0.7&#xa0;µM), whereas Ir1b shows moderate cytotoxicity toward the selected cancer cells. The ROS content was investigated using a fluorescence probe of 2′,7′-dichlorodihydrofluorescein diacetate (DCHF-DA), the results show that Ir1a and Ir1b elevate ROS content. The co-localization and the change of mitochondrial membrane potential were explored. Apoptotic studies using Annex V/PI double staining method demonstrate that Ir1a and Ir1b can efficiently cause apoptosis. Ir1a and Ir1b inhibit the cell proliferation at the G2/M period. Additionally, lipid peroxidation and downregulation of ferritin protein suggest that Ir1a and Ir1b can trigger ferroptosis.</p>

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Synthesis, characterization and studies of iridium (III) complexes inducing cell death via apoptosis and ferroptosis

  • 期刊论文

  • 发表日期：

    2025年2月14日

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  • Qiying Feng,
  • Lin Zhou,
  • Shuang Tian,
  • Jiawan Yang,
  • Yunjun Liu

摘要

Herein, we reported the synthesis and characterization of two new iridium(III) complexes [Ir(ppy)2(fpp)](PF6) (Ir1a, ppy = 2-phenylpyridine, fpp = 2-(2,2-difluorobenzo[1,3]dioxol-5-yl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(bzq)2(fpp)](PF6) (Ir1b, bzq = benzo[h]quinoline) through high resolution mass spectrometry (HRMS), 1H NMR and 13C NMR. The cytotoxicity in vitro of Ir1a and Ir1b on normal NIH3T3 cells and cancer SGC-7901, A549, SK-Hep1 cells was tested using MTT (3-(4,5-dimethylthiazole-2-yl)-diphenyltetrazolium bromide) method. Ir1a exhibits high cytotoxicity on SGC-7901 cells (IC50 = 2.7 ± 0.7 µM), whereas Ir1b shows moderate cytotoxicity toward the selected cancer cells. The ROS content was investigated using a fluorescence probe of 2′,7′-dichlorodihydrofluorescein diacetate (DCHF-DA), the results show that Ir1a and Ir1b elevate ROS content. The co-localization and the change of mitochondrial membrane potential were explored. Apoptotic studies using Annex V/PI double staining method demonstrate that Ir1a and Ir1b can efficiently cause apoptosis. Ir1a and Ir1b inhibit the cell proliferation at the G2/M period. Additionally, lipid peroxidation and downregulation of ferritin protein suggest that Ir1a and Ir1b can trigger ferroptosis.