Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo-and heterobimetallic silver/gold complexes
Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo-and heterobimetallic silver/gold complexes
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 exam-ine 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.With-in the homonuclear NHC-Ag2,the two central silver ions exhibit distinct coordination modes,with an Ag—Ag dis-tance 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 phen-anthrolines 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 distort-ed 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 cispla-tin.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 even-tually resulted in cell membrane permeability and cell death.CCDC:2326924,NHC-Ag2;2326925,NHC-Ag/Au.
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