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

作　　者：饶宏 胡杨 马艺聪 吕春欣 钟伟 杜理华[1] RAO Hong;HU Yang;MA Yicong;LÜChunxin;ZHONG Wei;DU Lihua(College of Pharmaceutical Sciences,Zhejiang University of Technology,Hangzhou 310014,China;College of Biological,Chemical Sciences and Engineering,Jiaxing University,Jiaxing,Zhejiang 314001,China)

机构地区：[1]浙江工业大学药学院,杭州310014 [2]嘉兴大学生物与化学工程学院,嘉兴314001

出　　处：《无机化学学报》2024年第12期2429-2437,共9页Chinese Journal of Inorganic Chemistry

基　　金：嘉兴市科技计划项目(No.2022AY10025);浙江省大学生科技创新活动计划(新苗人才计划)(No.2024R417A012)资助。

摘　　要：使用菲咯啉官能化咪唑盐配体((HL)PF_(6),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-Ag_(2)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-Ag_(2)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-Ag_(2)和NHC-Ag/Au的IC_(50)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-Ag_(2)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。A homobimetallic silver nitrogen heterocyclic carbene(NHC)complex NHC‑Ag_(2) and a heterobimetallic silver/gold NHC complex NHC‑Ag/Au were synthesized using phenanthroline‑functionalized imidazole salt((HL)PF_(6),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‑Ag_(2),the two central silver ions exhibit distinct coordination modes,with an Ag—Ag distance of 0.28287 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‑Ag_(2) and NHC‑Ag/Au exhibited stronger antitumor activity compared to their NHC precursor and cisplatin.Specifically,in the case of LoVo cells,NHC‑Ag_(2) and NHC‑Ag/Au demonstrated potent cytotoxicity with half inhibitory concentration(IC_(50))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‑Ag_(2) 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.CCDC:2326924,NHC‑Ag_(2);2326925,NHC‑Ag/Au.

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 

分 类 号：O614.122[理学—无机化学] O614.123[理学—化学]