Bioactive and luminescent indole and isatin based gold(i) derivatives

Abstract

A series of luminescent monometallic [AuL(PPh₃)] (1–3) and bimetallic [Au₂(μ-dppe)L₂] (4, 6, 8) and [Au₂(μ-dppp)L₂] (5, 7, 9) complexes, where L is either 4-cyano-indole, isatin, or 5,7-dimethyl-isatin, and dppe and dppp are 1,2-bis(diphenylphosphino)ethane and 1,3-bis(diphenylphosphino)propane, respectively, have been synthesised. X-ray diffraction confirmed the tendency to establish aurophillic interations for those complexes containing dppe. Luminescence studies and theoretical calculations revealed a different origin for both families, i.e. indole and isatin species. Thus, indole derivatives presented a ligand-to-ligand-charge-transfer transition (LLCT) from the indole to the PPh₃ fragment, whereas for the isatin derivatives an intraligand–charge-transfer transition (ILCT) within the isatin fragment is proposed. In both cases, the gold centre was slightly implicated as a ligand-to-metal-charge transfer transition (LMCT) (from the indole/isatin to Au(I)). Cell antiproliferative assays in lung cancer cells (A549), leukemia Jurkat-pLVTHM and Jurkat-shBak cells (cisplatin sensitive and resistant, respectively) showed excellent cytotoxic values (10.11–0.28 μM), showing the leukemia cells to be the most sensitive and the bimetallic species to be the most active agents. Preliminary studies associated the cytotoxicity with a combination of different factors, the metallic fragment being mainly responsible. Remarkably, these complexes are able to inhibit the cellular growth of cisplatin resistant Jurkat-shBak cells highlighting their promising future as an alternative anticancer agent.