👤 Harris HH.

Ruthenium(III) complexes with Schiff base ligands bearing diverse functional groups remain extensively underexplored, despite their promising potential in therapeutic applications. To address this gap, we designed and synthesized a new series of mononuclear octahedral Ru(III) complexes with the general formula [RuL^1-3], where L¹, L², and L³ are deprotonated Schiff bases derived from functionalized aromatic precursors. These complexes were characterized through a suite of physicochemical and spectroscopic techniques, including FT-IR, ¹H-NMR, UV-Vis spectroscopy, mass spectrometry, TGA, and elemental analysis, to confirm their structural features and coordination environment. To complement experimental findings, density functional theory (DFT/B3LYP) calculations were conducted, revealing stable, distorted octahedral geometries and supporting the proposed molecular configurations. Building upon the structural insights, we evaluated the biological activity of the complexes through in vitro cytotoxicity assays against HCT-116 (colorectal), MCF-7 (breast), and HepG2 (liver) cancer cell lines. Among them, RuL² exhibited the most potent activity against HCT-116 (IC₅₀ = 4.97 µg/mL), comparable to the standard drug Vinblastine. Finally, molecular docking simulations were employed to investigate the interaction of these complexes with key biological targets from Escherichia coli (PDB IDs: 4BJP and 1BNA), offering further insights into their potential modes of action. Together, these results demonstrate the importance of ligand design in tuning the coordination behavior and bioactivity of ruthenium complexes, highlighting their promise in anticancer and antimicrobial drug development. Show less

A new series of Zr(IV), V(IV), Ru(III), and Cd(II) complexes with the ligand N-((5-hydroxy-4-oxo-4H-pyran-3-yl)methylene)-2-(p-tolylamino)acetohydrazide (H₂L) have been prepared. FT-IR, ¹H-NMR, electronic spectra, powder X-ray, and thermal behavior methods were applied to elucidate the structural composition of new compounds. Geometry optimization for all synthesized compounds was conducted using the Gaussian09 program via the DFT method, to obtain optimal structures and essential parameters. Moreover, the antibacterial and antitumor activity of the ligand and its complexes were studied, where the Cd(II) complex acquires probably the best antibacterial activity followed by the Ru(III) complex towards bacterial species than others when using ampicillin and gentamicin were used as standard drugs. The complexes exhibited interestingly antitumor potential against the MCF-7 breast cancer cell line. The cytotoxicity of the new complexes has been arranged to follow the order: Ru(III) complex > Cd(II) complex > Zr(IV) complex > V(IV) complex > ligand. Molecular docking was performed on the active site of ribosyltransferase and obtained good results. Structure-based molecular docking is used to identify a potential therapeutic inhibitor for NUDT5. Show less

Three iridium (III) polypyridine complexes [Ir(bzq)₂(maip)](PF₆) (Ir1，bzq = benzo[h]quinoline, maip = 3-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(bzq)₂(apip)](PF₆) (Ir2, apip = 2-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(bzq)₂(paip)](PF₆) (Ir3, paip = 4-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The cytotoxic activities of the three complexes against human osteosarcoma HOS, U2OS, MG63 and normal LO2 cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The results showed that Ir1-3 exhibited moderate antitumor activity against HOS with IC₅₀ of 21.8 ± 0. 4 μM,10.5 ± 1.8 μM and 7.4 ± 0.4 μM, respectively. We found that Ir1-3 can effectively inhibit HOS cells growth and blocked the cell cycle at the G0/G1 phase. Further studies revealed that complexes can increase intracellular reactive oxygen species (ROS) and Ca²⁺, which accompanied by mitochondria-mediated intrinsic apoptosis pathway. In addition, autophagy was also investigated. Taken together, the complexes induce HOS apoptosis through a ROS-mediated mitochondrial dysfunction pathway and inhibition of the PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway. This study provides useful help for understanding the anticancer mechanism of iridium (III) complexes toward osteosarcoma treatment. Show less

Two iridium (III) polypyridine complexes [Ir(ppy)₂(BIP)]PF₆ (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)₂(BIP)]PF₆ (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC₅₀ value of 5.8 ± 0.2 μM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways. Show less

In this work, we demonstrate bioorthogonal control of the phosphorescence and singlet oxygen photosensitisation properties of new iridium(iii) tetrazine complexes by different reaction partners; the system was exploited for organelle-specific staining and modulated photocytotoxic activity applications. Show less

A new class of luminescent Ir^III antitumor agents, namely, [Ir(CP1)(PY1)₂] (Ir-1), [Ir(CP1)(PY2)₂] (Ir-2), [Ir(CP1)(PY4)₂] (Ir-3), [Ir(CP2)(PY1)₂] (Ir-4), [Ir(CP2)(PY4)₂] (Ir-5), [Ir(CP3)(PY1)₂]⋅CH₃OH (Ir-6), [Ir(CP4)(PY4)₂]⋅CH₃OH (Ir-7), [Ir(CP5)(PY2)₂] (Ir-8), [Ir(CP5)(PY4)₂]⋅CH₃OH (Ir-9), [Ir(CP6)(PY1)₂] (Ir-10), [Ir(CP6)(PY2)₂]⋅CH₃OH (Ir-11), [Ir(CP6)(PY3)₂] (Ir-12), [Ir(CP6)(PY41)₂] (Ir-13), and [Ir(CP7)(PY1)₂] (Ir-14), supported by 8-oxychinolin derivatives and 1-phenylpyrazole ligands was prepared. Compared with SK-OV-3/DDP and HL-7702 cells, the Ir-1-Ir-14 compounds exhibited half maximal inhibitory concentration (IC₅₀) values within the high nanomolar range (50 nM-10.99 μM) in HeLa cells. In addition, Ir-1 and Ir-3 accumulated and stained the mitochondrial inner membrane of HeLa cells with high selectivity and exhibited a high antineoplastic activity in the entire cervical HeLa cells, with IC₅₀ values of 1.22 ± 0.36 μM and 0.05 ± 0.04 μM, respectively. This phenomenon induced mitochondrial dysfunction, suggesting that these cyclometalated Ir^III complexes can be potentially used in biomedical imaging and Ir(III)-based anticancer drugs. Furthermore, the high cytotoxicity activity of Ir-3 is correlated with the 1-phenylpyrazole (H-PY4) secondary ligands in the luminescent Ir^III antitumor complex. Show less

This paper reports the synthesis, structure characterization, and anticancer properties of 13 organometallic Ru(ii)-arene complexes: [Ru(η6-p-cymene)Cl-(L1)] (1), [Ru(η6-p-cymene)Cl-(L2)] (2), [Ru(η6-p-cymene)Cl-(L3)] (3), [Ru(η6-p-cymene)Cl-(L4)] (4), [Ru(η6-p-cymene)Cl-(L5)] (5), [Ru(η6-p-cymene)I-(L1)] (6), [Ru(η6-p-cymene)I-(L2)] (7), [Ru(η6-p-cymene)I-(L3)] (8), [Ru(η6-p-cymene)I-(L4)] (9), [Ru(η6-p-cymene)I-(L5)] (10), [Ru(η6-p-cymene)I-(L6)] (11), [Ru(η6-p-cymene)I-(L7)] (12), and [Ru(η6-p-cymene)Cl-(L8)] (13) respectively containing deprotonated 5,7-dichloro-2-methyl-8-quinolinol (H-L1), 5,7-dibromo-2-methyl-8-quinolinol (H-L2), 5-chloro-7-iodo-8-hydroxy-quinoline (H-L3), 5,7-dibromo-8-quinolinol (H-L4), 5,7-diiodo-8-hydroxyquinoline (H-L5), 8-hydroxy-2-methylquinoline (H-L6), 2,8-quinolinediol (H-L7), or 6,7-dichloro-5,8-quinolinedione (H-L8). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that 13 organometallic Ru(ii)-arene complexes 1-13 are more selective for HeLa cells than normal HL-7702 cells. In addition, 1, 2, 5, and 6, which contain the active ligands H-L1 and H-L2, showed remarkable cell cytotoxicity, giving the respective IC50 values of 2.00 ± 0.20 nM, 0.89 ± 0.62 μM, 25.00 ± 0.30 nM, and 2.18 ± 0.35 μM on HeLa cancer cells. These values indicated higher activity than 6,7-dichloro-5,8-quinolinedione and other 8-hydroxyquinoline derivative Ru(ii)-arene complexes. Interestingly, all these Ru(ii)-arene complexes 1-13 were significantly less toxic to human hepatic (HL-7702) cells. Moreover, 1- and 2-induced HeLa cell apoptosis was mediated by the inhibition of telomerase activity and dysfunction of mitochondria, and resulted in DNA damage and increased anti-migration activity on HeLa cells. The organometallic Ru(ii)-arene complex 1 exhibited evident priority to the antitumor activity compared to 2, which should be highly associated with the key roles of the 5,7-dichloro substituted groups in the L1 ligand of organometallic Ru(ii)-arene complexes 1. Remarkably, 1 showed higher inhibitory activity against the xenograft tumor growth of human cervical cells (HeLa) in vivo (tumor growth inhibition rate (TGIR) = 58.5%) than cisplatin. This study was the first to show that the 5,7-dihalogenated-2-methyl-8-quinolinol organometallic Ru(ii)-arene complexes 1 and 2 are novel Ru(ii) anticancer drug candidates. Show less

A new ligand PFPIP (PFPIP=2-(2,3,4,5,6-pentafluorophenyl)[4,5-f]imadazo [1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes [Ru(NN)₂(PFPIP)](ClO₄)₂ (NN=dmb: 4,4'-dimethyl-2,2'-bipyridine, 1; bpy: 2,2'-bipyridine, 2; phen: 1,10-phenanthroline, 3; dmp: 2,9-dimethyl-1,10-phenanthroline, 4) were synthesized and characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated using MTT method (MTT=(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Complexes 1, 3 and 4 show moderate cytotoxic effect on the cell growth in BEL-7402 cells with IC₅₀ values of 32.1±0.9, 37.9±1.7 and 42.1±3.0μM, respectively. The apoptosis in BEL-7402 cell was investigated with AO/EB and Hoechst 33,258 staining methods. The autophagy in BEL-7402 cell induced by complexes was assayed using MDC staining cell nuclei. The cell invasion, reactive oxygen species (ROS), mitochondrial membrane potential, cell cycle arrest, cellular uptake, comet assay and wound healing were studied under a fluorescent microscope. The complexes can cause autophagy and inhibit the cell invasion, and increase the ROS levels and induce a decrease in the mitochondrial membrane potential. The expression of the proteins related with apoptosis induced by the complexes was assayed by western blot analysis. Show less

As one of the major cell regulated center, mitochondria are closely associated with cell proliferation, apoptosis of tumor cell. In this work, four new ruthenium (II) polypyridyl complexes [Ru(bpy)₂(FTTP)](ClO₄)₂ (1) (FTTP=11-(3-fluoro-naphthalen-2-yloxy)-4,5,9,14-tetraaza-benzo[b]triphenylene, bpy=2,2'-bipyridine), [Ru(phen)₂(FTTP)](ClO₄)₂ (2) (phen=1,10-phenanthroline), [Ru(bpy)₂(PTTP)](ClO₄)₂ (3) (PTTP=2-phenoxy-1,4,8,9-tetraazatriphenylene) and [Ru(phen)₂(PTTP)](ClO₄)₂ (4) were synthesized and characterized by elemental analysis, ESI-MS, ¹H NMR and ¹³C NMR. The cytotoxic activity, ability of inhibiting cell invasion, cell cycle arrest and apoptosis-inducing mechanism of these Ru(II) complexes have been investigated in detail by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method, invasion assay, comet assay as well as western blotting techniques. Notably, complexes 1-4 displayed high cytotoxic activity against liver carcinoma HepG2 cells and the IC₅₀ values of complexes 1-4 against HepG2 cells are 10.4±1.2, 9.3±0.6, 29.1±1.5 and 5.6±1.2μM, respectively. The comet assay showed that the complexes can induce DNA damage. The acridine orange (AO) and ethidium bromide (EB) staining method indicated that the complexes can cause apoptosis in HepG2 cells. Further studies showed that complexes 1-4 caused cell cycle arrest at G0/G1 phase and induced HepG2 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which involved an increase in the levels of reactive oxygen species (ROS), a decrease in the mitochondrial membrane potential, activation of caspases and Bcl-2 family proteins. Show less

The cytotoxic activity of two Ru(II) complexes against A549, BEL-7402, HeLa, PC-12, SGC-7901 and SiHa cell lines was investigated by MTT method. Complexes 1 and 2 show moderate cytotoxicity toward BEL-7402 cells with an IC50 value of 53.9 ± 3.4 and 39.3 ± 2.1 μM. The effects of the complexes inducing apoptosis, cellular uptake, reactive oxygen species and mitochondrial membrane potential in BEL-7402 cells have been studied by fluorescence microscopy. The percentages of apoptotic and necrotic cells and cell cycle arrest were studied by flow cytometry. The BSA-binding behaviors were investigated by UV/visible and fluorescent spectra. Show less

A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10-phenanthroline, NMIP = 2'-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4',5'-f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.6 ± 2.6 µM) and MC3T3-e1 (IC50 = 41.6 ± 2.8 µM) cell lines. The morphological studies show that the complex can induce apoptosis in HOS cells and cause an increase of reactive oxygen species levels and a decrease in the mitochondrial membrane potential. The cell cycle distribution demonstrates that the complex inhibits the cell growth at S phase. Additionally, the antitumor activity in vivo reveals that the complex can induce a decrease in tumor weight. Show less

A rhodium(iii) complex, [Rh(MQ)(DMSO)₂Cl₂] (1), with 8-hydroxy-2-methylquinoline as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC₅₀ values in the micromolar range (6.52-17.86 μM). Various experiments on the Hep-G2 cells showed that complex 1 caused cell cycle arrest at the S phase, downregulation of cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53. Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced apoptosis was achieved via disruption of the mitochondrial function, which led to a significant loss of the mitochondrial membrane potential, an increase in the cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a fluctuation of the intracellular Ca²⁺ concentration. Taken altogether, complex 1 can trigger cancer cell death by inducing apoptosis through a mitochondrial dysfunction pathway. Show less

Radiation has large influence on the cytotoxicity, apoptosis and cell cycle arrest. The bioactivity of ruthenium(II) complex [Ru(dmb)2(DBHIP)](ClO4)2 (Ru1) (DBHIP=2-(3,5-dibromo-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) was investigated in the absence and presence of radiation. The cytotoxicity of Ru1 against MG-63 cells was evaluated by CCK-8 method. Ru1 shows high cytotoxicity upon radiation. Radiation can enhance the cytotoxicity of Ru1 on MG-63 cells. The apoptosis was studied by Hoechst 33258 staining method and flow cytometry. The reactive oxygen species, mitochondrial membrane potential, cell cycle arrest and western blot analysis were investigated in detail. The complex induces the apoptosis in MG-63 cells through ROS-mediated mitochondrial dysfunction pathway. Show less

Three new ruthenium(II) polypyridyl complexes [Ru(bpy)(2)(BHIP)](2+) 1, [Ru(phen)(2)(BHIP)](2+) 2, and [Ru(dip)(2)(BHIP)](2+) 3 were synthesized and characterized. The cytotoxicity of the three complexes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis induced by the complexes was studied by cell morphology and flow cytometry. The results showed that the percentage of apoptotic cells is 7.19%, 75.58%, and 3.51% in the presence of complexes 1, 2, and 3, respectively. The cellular uptakes were also performed and the results indicated that complexes 1, 2, and 3 can enter into the cytoplasm and also into the nucleus. The studies on antiproliferative mechanism showed the induction of S-phase arrest by complexes 1, 2, and 3. DNA-binding constants of these complexes with calf thymus DNA (CT-DNA) were determined to be 1.07 (± 0.47) × 10(5) M(-1) (s = 2.04), 1.21 (± 0.32) × 10(5) M(-1) (s = 1.88), and 2.75 (± 0.27) × 10(5) M(-1) (s = 2.17), respectively. Upon irradiation at 365 nm, complexes 1, 2, and 3 can induce cleavage of pBR322 DNA. Show less