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| Tuning the stability and cytotoxicity of fac-[Fe(CO)3I3]- anion by its counter ions: From aminiums to inorganic cations |
| Author Name | Affiliation | E-mail | | JIN Jing | Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314001, China | | | GUO Zhuming | College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, Zhejiang 314001, China | | | XIAO Zhiyin | College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, Zhejiang 314001, China | zhiyin.xiao@zjxu.edu.cn | | JIANG Xiujuan | College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, Zhejiang 314001, China | | | HE Yi | Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314001, China | heyi@zjxu.edu.cn | | LIU Xiaoming | College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, Zhejiang 314001, China | |
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| Abstract: Five inorganic monoiron(Ⅱ) carbonyl salts 1-5, fac-M[Fe(CO)3I3]n (Mn+=Na+ (1), K+ (2), Mg2+ (3), Ca2+ (4), NH4+ (5)) were prepared from the reactions of cis‐[Fe(CO)4I2] precursor with the iodo salts (MIn), and developed as CO-releasing molecules (CORMs) for CO therapy of cancer. The decomposition of salts 1-5 with CO-release in DMSO, D2O, saline, and phosphonate buffer solution was investigated by the Fourier transform infrared (FTIR) spectroscopic monitoring. The corresponding kinetics for the decomposing of these salts were estimated by abiding by a first-order model. Cytotoxicity of the five salts was assessed on a bladder cancer cell line (RT112) by the methyl thiazolyl tetrazolium (MTT) assays for 24 h, with the half maximal inhibitory concentration (IC50) values of 25-43 μmol·L-1. Notably, varying a counter ion of fac-[Fe(CO)3I3]-anion from an organic aminium to an inorganic cation unambiguously affects its stability and thus the cytotoxicity. Moreover, a mechanistic probing into the cytotoxicity of fac-[Fe(CO)3I3]- anion was paved. Interestingly, not only the produced iodine radicals but also the gaseous CO from the decomposition contributed to its cytotoxicity. Particularly, it was found that, with the treatment of the anion, the reactive oxygen species (ROS) level in the mitochondria significantly enhanced, and the mitochondria-related protein expression of Parkin was extremely upregulated. The ferroptosis inhibitor assays of Ferrostatin-1 and Liproxstatin-1 confirmed that these complexes evoked a ferroptosis-involved pathway to contribute to their cytotoxicity. Therefore, a mechanistic understanding of the cytotoxicity of fac-[Fe(CO)3I3]- anion is proposed, which is stimulated by the decomposing of the anion, and thus manufactures the mitochondria-relevant activities such as fission, energy metabolism, and mitophagy, and evokes a pathway of ferroptosis, to lead severe cellular damage even death. |
| Keywords: iron carbonyl iodine counter ion effect CO release kinetics cytotoxicity ferroptosis |
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| JIN Jing,GUO Zhuming,XIAO Zhiyin,JIANG Xiujuan,HE Yi,LIU Xiaoming.Tuning the stability and cytotoxicity of fac-[Fe(CO)3I3]- anion by its counter ions: From aminiums to inorganic cations[J].Chinese Journal of Inorganic Chemistry,2024,40(5):991-1004. |
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