Mitochondria specific highly cytoselective iridium(iii)–Cp* dipyridophenazine (dppz) complexes as cancer cell imaging agents

Abstract

Cancer is the most incurable pernicious disease to date after cardiovascular disease with an immeasurable rate of mortality. However, effective cancer medication and therapy are still castles in the sky to researchers. Therefore, in search of an appropriate strategy to annihilate cancer, we have designed a set of Ir(III)–Cp* dipyridophenazine complexes as luminescent anticancer agents combining the cancer inhibiting potency of the planar dipyridophenazine (dppz) moiety through DNA interaction and mitochondrial dysfunction with the wonderful photoluminescence ability and target specificity of iridium metal. Hence, with the synergy of these dual aspects in the same system, we have aspired to emphasize the theranostic approach of cancer treatment in the present study by preparing effective, aqueous-soluble, mitochondria-targeting, highly cytoselective, luminescent, cancer cell-permeable scaffolds, enabling diagnosis as well as the healing of cancer cells in the body. Here, the presence of the cyclopentadienyl (Cp*) moiety in association with the fluorine group has boosted the lipophilic character of the complexes. Also, the cytotoxicity screening of the prepared Cp*Ir(III)-dipyridophenazine complexes (IrL1–IrL7) against colorectal adenocarcinoma cells (Caco-2) and human epitheloid cervix carcinoma cells (HeLa) clearly identified them as potential anticancer agents and imaging studies unveiled their superb cellular imaging properties. Among them, the complex [(η⁵-Cp*)IrCl(11-fluorodipyrido[3,2-a:2′,3′-c]phenazine)] (IrL6) achieved the best cytoselectivity. However, the superiority of the anticancer potency of [(η⁵-Cp*)IrCl(benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine)] (IrL3) was also corroborated by its activity against the most aggressive colorectal carcinoma cell line (HT-29), whereas (η⁵-Cp*)IrCl(11-(trifluoromethyl)dipyrido[3,2-a:2′,3′-c]phenazine (IrL5) came into the limelight as the best theranostic agent as it showed remarkable cytoselectivity as well as significant cellular imaging properties, endowing it with the highest quantum yield value among all the complexes.