Cytotoxicity of silver(I), gold(I) and gold(III) complexes of a pyridine wingtip substituted annelated N-heterocyclic carbene

Abstract

Starting from the proligand 1-methyl-2-pyridin-2-yl-2H-imidazo[1,5-a]pyridin-4-ylium chloride (1 HCl), three novel complexes [Ag(1)Cl] (2), [Au(1)Cl] (3) and [Au(1)Cl3] (4) were synthesized and characterized using various spectroscopic techniques. In addition, the structure of 2 was elucidated using single crystal X-ray diffraction analysis, which revealed that the carbene nucleus and the chloride ion bound to the silver(I) were nearly linear (165.37(9)°). The gold(I)-NHC complex 3 was synthesized via transmetallation from the aforementioned silver complex 2. Similarly, treatment of 3 with Au(SMe2)Cl afforded 4, ostensibly via a disproportionation process. The cytotoxicities of complexes 2, 3, and 4 were examined against HepG2 (human hepatocellular carcinoma), HCT 116 (human colorectal carcinoma), A549 (human lung adenocarcinoma), and MCF-7 (human breast adenocarcinoma) cells. Au(I)-NHC complex 3 exhibited a cytotoxicity that was similar to that of cisplatin towards all the four cancer cell lines tested; by comparison, Ag(I) NHC complex 2 and Au(III) NHC complex 4 appeared relatively less potent. Complex 3 was found to induce apoptosis in HepG2 cells.