| 菲咯啉官能化的氮杂环卡宾同核和异核银/金配合物的合成及体外抗癌活性 | |
| Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes | |
| 摘要: 使用菲咯啉官能化咪唑盐配体((HL) PF6，L=3-苄基-1-[2-(1,10-菲咯啉)咪唑叶立德])分别合成了一个双核氮杂环卡宾(NHC)银配合物NHC-Ag2和一个异核的氮杂环卡宾银/金双金属配合物NHC-Ag/Au。通过NMR和元素分析对NHC前体和金属配合物进行了表征。单晶衍射分析表明，这2个配合物具有类似的结构，2个金属中心原子分别由2个配体的4个菲咯啉氮原子和2个卡宾碳原子配位，呈四面体和直线型构型。体外细胞毒性研究表明，配合物NHC-Ag2和NHC-Ag/Au具有比它们的前体咪唑盐配体和顺铂更强的抗癌活性。如在结肠癌LoVo细胞中，NHC-Ag2和NHC-Ag/Au的IC50值(半抑制浓度)分别为(5.6±0.3)μmol·L-1和(6.4±0.3)μmol·L-1，均优于顺铂的细胞毒性。机制研究表明，配合物NHC-Ag2和NHC-Ag/Au引起了LoVo细胞内线粒体膜电位变化和活性氧(ROS)的过度产生，最终导致细胞膜通透性增加和细胞死亡。 | |
| 关键词: 氮杂环卡宾 银和金配合物 同核和异核双金属配合物 体外抗癌活性 | |
| 基金项目: 嘉兴市科技计划项目(No.2022AY10025)和浙江省大学生科技创新活动计划(新苗人才计划)(No.2024R417A012)资助。 | |
| Abstract: 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. | |
| Keywords: nitrogen heterocyclic carbene silver and gold complexes homo- and heterobimetallic complexes in vitro anticancer activity | |
| 投稿时间：2024-07-21 修订日期：2024-10-18 | |
| 摘要点击次数: 365 | |
| 全文下载次数: 625 | |
| 饶宏,胡杨,马艺聪,吕春欣,钟伟,杜理华.菲咯啉官能化的氮杂环卡宾同核和异核银/金配合物的合成及体外抗癌活性[J].无机化学学报,2024,40(12):2429-2437. | |
| 查看全文 查看/发表评论 下载PDF阅读器 | |
| Support information: 相关附件： 20240275_Support_Information.doc | |
|
| |
|
| |
|
| |