Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

Abstract

Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2′-bipyridine-4,4′-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.

Two out of Three Musketeers Fight against Cancer: Synthesis, Physicochemical, and Biological Properties of Phosphino CuI, RuII, IrIII Complexes

“…An arrest in S-phase implies that the cell cannot duplicate its DNA. Other authors recently reported a similar effect for iridium(III)polypyridyl complexes [68,69]. Moreover, the percentage of the G2/M population also increases.…”

Donor moieties with D–π–a framing modulated electronic and nonlinear optical properties for non-fullerene-based chromophores

“…3 A literature review revealed that different classes of polycyclic aromatic hydrocarbons have been computed and they have shown promising nonlinear optical (NLO) and electronic properties. [1][2][3][4][5][6][7][8] In fact, the above-mentioned materials have attracted attention for their strong two-photon absorption properties in recent years. Their absorption properties may be affected by their molecular weight, symmetry, and solubility parameters.…”

“…FH) was selected as a reference compound for our NLO study, whose synthetic procedure was reported by Nailiang et al in 2020. 2 Such an NLO study for FH and its designed derivatives has not been performed so far. Therefore, a series of compounds named FHD1-FHD6 were designed using FH as the reference molecule.…”

“… 1 Although, research in PAHs has primarily been restricted to their synthesis and photoluminescence processes, it is currently being widened to organic electronics and frequently to their use as building block materials for opto-electronics. 2 Moreover, PAHs are also considered as promising scaffolds based on their various properties, including polarization, molecular wires, liquids crystals, organic electronics, and optical applications. 3 A literature review revealed that different classes of polycyclic aromatic hydrocarbons have been computed and they have shown promising nonlinear optical (NLO) and electronic properties.…”

“…Keeping in view the significant properties of non-fullerene compounds, the compound 2,2′-((2 Z ,2′ Z )-((4,4,7,7,12,12-hexamethyl-7,12-dihydro-4 H -thieno[2′′,3′′:1′,2′]indeno [5′,6′:5,6]- s -indaceno[1,2- b ]thien-2,9-diyl)bis(methaneylylidene))bis(3-oxo-2,3-dihydro-1 H -indene-2,1-diylidene))dimalononitrile (FH) was selected as a reference compound for our NLO study, whose synthetic procedure was reported by Nailiang et al in 2020. 2 Such an NLO study for FH and its designed derivatives has not been performed so far. Therefore, a series of compounds named FHD1–FHD6 were designed using FH as the reference molecule.…”