Citation: Hong RAO, Yang HU, Yicong MA, Chunxin LÜ, Wei ZHONG, Lihua DU. Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes[J]. Chinese Journal of Inorganic Chemistry, ;2024, 40(12): 2429-2437. doi: 10.11862/CJIC.20240275 shu

Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes

Hong RAO ¹ ,
Yang HU ² ,
Yicong MA ² ,
Chunxin LÜ ^2,, ,
Wei ZHONG ² ,
Lihua DU ^1,,

1.
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China
2.
College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, Zhejiang 314001, China

Corresponding author: Chunxin LÜ, chunxin.lu@mail.zjxu.edu.cn Lihua DU, orgdlh@zjut.edu.cn
Received Date: 21 July 2024
Revised Date: 18 October 2024

Figures(8)

A homobimetallic silver nitrogen heterocyclic carbene (NHC) complex NHC-Ag₂ and a heterobimetallic silver/gold NHC complex NHC-Ag/Au were synthesized using phenanthroline functionalized imidazole salt ((HL)PF₆, L=3-benzyl-1-(1, 10-phenanthrolin-2-yl)-imidazolylidene). NMR and elemental analysis characterized the NHC precursor and resultant NHC-metal complexes. Furthermore, X-ray diffraction analysis was conducted to examine the crystal structures of the two NHC-metal complexes. The results indicate that these two complexes share a similar structure wherein two phenanthrene-functionalized carbene ligands coordinate two metal center atoms. Within the homonuclear NHC-Ag₂, the two central silver ions exhibit distinct coordination modes, with an Ag—Ag distance of 0.282 87 nm. One silver ion is bis-coordinated by two carbene carbon atoms in a linear fashion, with C— Ag—C bond angle of 172.5°. In contrast, the other silver ion is coordinated with four nitrogen atoms from two phenanthrolines in a tetrahedral configuration. In the heteronuclear NHC-Ag/Au, the gold ion is coordinated linearly by two carbene carbon atoms, forming a C—Au—C bond angle of 176.2°, and the silver ion is coordinated in a distorted tetrahedral fashion by four nitrogen atoms from two phenanthrolines. The in vitro cytotoxic studies revealed that both NHC-Ag₂ and NHC-Ag/Au exhibited stronger antitumor activity compared to their NHC precursor and cisplatin. Specifically, in the case of LoVo cells, NHC-Ag₂ and NHC-Ag/Au demonstrated potent cytotoxicity with half inhibitory concentration (IC₅₀) values of (5.6±0.3) μmol·L^-1 and (6.4±0.3) μmol·L^-1, respectively, which were lower than that of cisplatin. Detailed mechanistic studies suggested that complexes NHC-Ag₂ and NHC-Ag/Au provoked mitochondrial membrane depolarization and intracellular reactive oxygen species (ROS) overproduction, which eventually resulted in cell membrane permeability and cell death.
- nitrogen heterocyclic carbene,
- silver and gold complexes,
- homo- and heterobimetallic complexes,
- in vitro anticancer activity
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