📋 Browse Articles

Functionalized carbon nanotubes are interesting, promising and unique delivery systems for anticancer drugs, which are now in the spotlight of nanomedicine. Connecting nanotubes with anticancer drugs or new compounds with anticancer properties aims at improving their stability, efficiency and reduces the toxic side effects of cancer treatment. In our research, we are interested in connecting functionalized MWCNTs-NH2 with [InH][trans-RuCl4(In)2], (KP1019) which is one of the most promising anticancer ruthenium(iii) drug candidates, known mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers. As a result of the amidation of MWCNTs (1), MWCNTs-NH2 (2) were obtained. Then, they were modified with [InH][RuCl4(In)2] (4) and the nanosystem [MWCNT-NH3+][RuCl4(In)2-] (3) was obtained. The characterization of the resulting products was performed using IR, Raman spectroscopy, thermal gravimetric, XRD, STEM-EDX, ESI-MS, ICP-MS, and XPS analyses. The cytotoxic activity has been tested on human lung carcinoma (A549), chronic myelogenous leukemia (K562) and human cervix carcinoma (HeLa) cells which showed the higher toxicity of the nanosystem than the ruthenium complex. Show less

Glioblastomas (GBs) are highly aggressive and malignant brain tumors, which are highly resistant to conventional multimodal treatments, leading to their abysmal prognosis. Herein, we designed two organometallic half-sandwich Ru(ii)-η6-p-cymene complexes containing Schiff bases derived from 3-aminoquinoline and 2-hydroxy-benzaldehyde (L1) and 2-hydroxy-naphthaldehyde (L2), namely [Ru(η6-p-cymene)(L1)Cl] (1) and [Ru(η6-p-cymene)(L2)Cl] (2), respectively, and studied their activity on GB cells. Both complexes were structurally characterized using single-crystal X-ray diffraction, which exhibited their half-sandwich three-legged piano-stool geometry. Furthermore, we studied their physicochemical behavior, solution speciation, aquation kinetics, and photo-substitution reactions using various spectroscopic methods. The complexes exhibited a moderate binding affinity with calf-thymus (CT)-DNA (Kb ∼ 105 M-1). The complexes effectively interacted with human serum albumin (HSA) (K ∼ 105 M-1) with preferential tryptophan binding, as determined via synchronous fluorescence studies. The in vitro studies showed their significant antiproliferative activity against an aggressive human GB cell line, LN-229 (IC50 = 22.8 μM), with moderate selectivity relative to normal mouse fibroblast L929 cells. Notably, [Ru(η6-p-cymene)(L1)Cl] (1) exhibited a higher selectivity index (S.I.) than [Ru(η6-p-cymene)(L2)Cl] (2) and cisplatin. We evaluated the clonogenic potential of the GB cells using a colony formation assay in the presence of complex 1. Excitingly, it showed ∼75% inhibition of the clonogenic potential of GB cells at the IC50 concentration. Complex 1 also effectively lowered the migratory potential of the GB cells, as assessed by the wound healing assay. The studied compound led to the apoptosis of GB cells, as evidenced by nuclear condensation, blebbing, and enhanced caspase 3/7 activity, and thus has anticipated utility in the treatment of GBs using photochemotherapy. Show less

Platinum-based chemotherapies, including oxaliplatin, are a mainstay in the management of solid tumors and induce cell death by forming intrastrand dinucleotide DNA adducts. Despite their common use, they are highly toxic, and approximately half of cancer patients have tumors that are either intrinsically resistant or develop resistance. Previous studies suggest that this resistance is mediated by variations in DNA repair levels or net drug influx. Here, we aimed to better define the roles of nucleotide excision repair and DNA damage in platinum chemotherapy resistance by profiling DNA damage and repair efficiency in seven oxaliplatin-sensitive and three oxaliplatin-resistant colorectal cancer cell lines. We assayed DNA repair indirectly as toxicity and directly measured bulky adduct formation and removal from the genome by slot blot and repair capacity in an excision assay, and used excision repair sequencing (XR-seq) to map repair events genome-wide at single-nucleotide resolution. Using this combinatorial approach and proxies for oxaliplatin-DNA damage, we observed no significant differences in repair efficiency that could explain the relative sensitivities and chemotherapy resistances of these cell lines. In contrast, the levels of oxaliplatin-induced DNA damage were significantly lower in the resistant cells, indicating that decreased damage formation, rather than increased damage repair, is a major determinant of oxaliplatin resistance in these cell lines. XR-seq-based analysis of gene expression revealed up-regulation of membrane transport pathways in the resistant cells, and these pathways may contribute to resistance. In conclusion, additional research is needed to characterize the factors mitigating cellular DNA damage formation by platinum compounds. Show less

This work describes the synthesis of three new ruthenium(ii) complexes with gallic acid and derivatives of the general formula [Ru(L)(dppb)(bipy)]PF₆, where L = gallate (GAC), benzoate (BAC), and esterified-gallate (EGA), bipy = 2,2'-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane. The complexes were characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis and IR spectroscopy, and two of them by X-ray crystallography. Cell viability assays show promising results, indicating higher cytotoxicity of the complexes in MDA-MB-231 cells, a triple-negative breast cancer (TNBC) cell line, compared with the hormone-dependent MCF-7 cell line. Studies in vitro with the MDA-MB-231 cell line showed that only Ru(BAC) and Ru(GAC) interacted with BSA. Besides that, the Ru(GAC) complex, which has a polyphenolic acid, interacted in an apo-Tf structure and function dependent manner and it was able to inhibit the formation of reactive oxygen species. Ru(GAC) was able to cause damage to the cellular cytoskeleton leading to inhibition of some cellular processes of TNBC cells, such as invasion, migration, and adhesion. Show less

The potential chemotherapeutic properties coupled to photochemical transitions make the family of fac-[Re(CO)₃(N,N)X]^0/+ (N,N = a bidentate diimine such as 2,2'-bipyridine (bpy); X = halide, H₂O, pyridine derivatives, PR₃, etc.) complexes of special interest. We have investigated reactions of the aqua complex fac-[Re(CO)₃(bpy)(H₂O)](CF₃SO₃) (1) with potential anticancer activity with the amino acid L-cysteine (H₂Cys), and its derivative N-acetyl-L-cysteine (H₂NAC), as well as the tripeptide glutathione (H₃A), under physiological conditions (pH 7.4, 37 °C), to model the interaction of 1 with thiol-containing proteins and enzymes, and the impact of such coordination on its photophysical properties and cytotoxicity. We report the syntheses and characterization of fac-[Re(CO)₃(bpy)(HCys)]·0.5H₂O (2), Na(fac-[Re(CO)₃(bpy)(NAC)]) (3), and Na(fac-[Re(CO)₃(bpy)(HA)])·H₂O (4) using extended X-ray absorption spectroscopy, IR and NMR spectroscopy, electrospray ionization spectrometry, as well as the crystal structure of {fac-[Re(CO)₃(bpy)(HCys)]}₄·9H₂O (2 + 1.75 H₂O). The emission spectrum of 1 displays a variance in Stokes shift upon coordination of L-cysteine and N-acetyl-L-cysteine. Laser excitation at λ = 355 nm of methanol solutions of 1-3 was followed by measuring their ability to produce singlet oxygen (¹O₂) using direct detection methods. The cytotoxicity of 1 and its cysteine-bound complex 2 was assessed using the MDA-MB-231 breast cancer cell line, showing that the replacement of the aqua ligand on 1 with L-cysteine significantly reduced the cytotoxicity of the Re(I) tricarbonyl complex. Probing the cellular localization of 1 and 2 using X-ray fluorescence microscopy revealed an accumulation of 1 in the nuclear and/or perinuclear region, whereas the accumulation of 2 was considerably reduced, potentially explaining its reduced cytotoxicity. Replacing the aqua ligand with cysteine in the antitumor active fac-[Re(CO)₃(bpy)(H₂O)](CF₃SO₃) complex significantly reduced its cellular accumulation and cytotoxicity against the MDA-MB-213 breast cancer cell line, shifted its maximum emission to considerably higher energies, and decreased its fluorescence quantum yield. Show less

Oxidation of guanine generates several types of DNA lesions, such as 8-oxoguanine (8OG), 5-guanidinohydantoin (Gh), and spiroiminodihydantoin (Sp). These guanine-derived oxidative DNA lesions interfere with both replication and transcription. However, the molecular mechanism of transcription processing of Gh and Sp remains unknown. In this study, by combining biochemical and structural analysis, we revealed distinct transcriptional processing of these chemically related oxidized lesions: 8OG allows both error-free and error-prone bypass, whereas Gh or Sp causes strong stalling and only allows slow error-prone incorporation of purines. Our structural studies provide snapshots of how polymerase II (Pol II) is stalled by a nonbulky Gh lesion in a stepwise manner, including the initial lesion encounter, ATP binding, ATP incorporation, jammed translocation, and arrested states. We show that while Gh can form hydrogen bonds with adenosine monophosphate (AMP) during incorporation, this base pair hydrogen bonding is not sufficient to hold an ATP substrate in the addition site and is not stable during Pol II translocation after the chemistry step. Intriguingly, we reveal a unique structural reconfiguration of the Gh lesion in which the hydantoin ring rotates ∼90° and is perpendicular to the upstream base pair planes. The perpendicular hydantoin ring of Gh is stabilized by noncanonical lone pair-π and CH-π interactions, as well as hydrogen bonds. As a result, the Gh lesion, as a functional mimic of a 1,2-intrastrand crosslink, occupies canonical -1 and +1 template positions and compromises the loading of the downstream template base. Furthermore, we suggest Gh and Sp lesions are potential targets of transcription-coupled repair. Show less

Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh3)) (1) or triethylphosphine (Au(pben)(PEt3)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC50) was determined. 1 and 2 showed an IC50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms. Show less

Cell death can be executed through different subroutines. Since the description of ferroptosis as an iron-dependent form of non-apoptotic cell death in 2012, there has been mounting interest in the process and function of ferroptosis. Ferroptosis can occur through two major pathways, the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway. Ferroptosis is caused by a redox imbalance between the production of oxidants and antioxidants, which is driven by the abnormal expression and activity of multiple redox-active enzymes that produce or detoxify free radicals and lipid oxidation products. Accordingly, ferroptosis is precisely regulated at multiple levels, including epigenetic, transcriptional, posttranscriptional and posttranslational layers. The transcription factor NFE2L2 plays a central role in upregulating anti-ferroptotic defense, whereas selective autophagy may promote ferroptotic death. Here, we review current knowledge on the integrated molecular machinery of ferroptosis and describe how dysregulated ferroptosis is involved in cancer, neurodegeneration, tissue injury, inflammation, and infection. Show less

Combination therapy targeting both tumor growth and vascularization is considered to be a cornerstone for colorectal carcinomas (CRC) treatment. However, the major obstacles of most clinical anticancer drugs are their weak selective activity towards cancer cells and inherent inner organs toxicity, accompanied with fast drug resistance development. In our effort to discover novel selective and non-toxic agents effective against CRC, we designed, synthesized and characterized a series of rhenium(I) tricarbonyl-based complexes with increased lipophilicity. Two of these novel compounds were discovered to possess remarkable anticancer, anti-angiogenic and antimetastatic activity in vivo (zebrafish-human HCT-116 xenograft model), being effective at very low doses (1-3 μM). At doses as high as 250 μM the complexes did not provoke toxicity issues encountered in clinical anticancer drugs (cardio-, hepato-, and myelotoxicity). In vivo assays showed that the two compounds exceed the anti-tumor and anti-angiogenic activity of clinical drugs cisplatin and sunitinib malate, and display a large therapeutic window. Show less

In the fight against cancer, photodynamic therapy is generating great interest thanks to its ability to selectively kill cancer cells without harming healthy tissues. In this field, ruthenium(II) polypyridyl complexes, and more specifically, complexes with dipyrido[3,2-a:2',3'-c]phenazine (dppz) as a ligand are of particular interest due to their DNA-binding and photocleaving properties. However, ruthenium(II) polypyridyl complexes can sometimes suffer from low lipophilicity, which hampers cellular internalisation through passive diffusion. In this study, four new [Ru(dppz-X₂ )₃ ]²⁺ complexes (X=H, F, Cl, Br, I) were synthesized and their lipophilicity (logP), cytotoxicity and phototoxicity on cancerous and noncancerous cell lines were assessed. This study shows that, counterintuitively, the phototoxicity of these complexes decreases as their lipophilicity increases; this could be due solely to the atomic radius of the halogen substituents. Show less

The most common applications of artificial intelligence (AI) in drug treatment have to do with matching patients to their optimal drug or combination of drugs, predicting drug-target or drug-drug interactions, and optimizing treatment protocols. This review outlines some of the recently developed AI methods aiding the drug treatment and administration process. Selection of the best drug(s) for a patient typically requires the integration of patient data, such as genetics or proteomics, with drug data, like compound chemical descriptors, to score the therapeutic efficacy of drugs. The prediction of drug interactions often relies on similarity metrics, assuming that drugs with similar structures or targets will have comparable behavior or may interfere with each other. Optimizing the dosage schedule for administration of drugs is performed using mathematical models to interpret pharmacokinetic and pharmacodynamic data. The recently developed and powerful models for each of these tasks are addressed, explained, and analyzed here. Show less

Two water-soluble amphiphilic Ru(ii) polypyridyl complexes containing N-1,10-phenanthrolin-5-yldocosanamide and 1,10-phenanthroline (phen) or 1,4,5,8-tetraazaphenanthrene (TAP) as ligands were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and displayed phototoxicity against HeLa cervical cancer cells. Show less

A cryo-EM structure of mitochondrial complex I from Yarrowia lipolytica reveals structured waters involved in proton relays and energy transfer, with insights into the ‘deactive transition’ in mammalian systems. Show less

On the 14-15th November 2019, the first workshop on Metals in Medicine took place in Paris at Chimie ParisTech, PSL University. Organised with the aim of having invited speakers share their experience in bringing metal-based drugs to (pre-)clinical trials, this event gathered 135 attendees from six continents to Paris. A special collection on this event has now been published in ChemBioChem, combining more than 20 articles on different topics related to metals in medicine. Show less

Ruthenium(ii) diclofenac-based complexes of the general formula [Ru(dicl)(P-P)(bpy)]PF6 [dicl = diclofenac, bpy = 2,2'-bipyridine, and P-P = 1,4'-bis(diphenylphosphino)butane (dppb) (1), 1,2'-bis(diphenylphosphino)ethane (dppe) (2), 1,3'-bis(diphenylphosphino)propane (dppp) (3) and 1,1'-bis(diphenylphosphino)ferrocene (dppf) (4)] are synthesized. The complexes (1-4) are characterized by elemental analyses, infrared, NMR, and UV-vis spectroscopy and (3) and (4) are characterized by single crystal X-ray diffraction. The DNA binding of complexes (1-4), studied by circular dichroism (CD) and Hoechst 33 258 staining assay, indicates their binding with the minor grooves. The complexes interact with BSA with binding constants (Kb) in the range of 2.5 × 103-5.5 × 104 M-1. The complexes exhibit high cytotoxicity against the tumor cell lines A549, MDA-MB-231, and MCF-7 with IC50 values ranging from 0.56 to 15.28 μM. The complexes are more selective for the hormone-dependent MCF-7 breast tumor cell line and complex (1) is the most potent one. The study demonstrates the anticancer activity of ruthenium(ii)/diclofenac-based complexes. Show less

A rise in atmospheric carbon dioxide levels, following years of burning fossil fuels, has brought about increase in global temperatures and climate change due to the green-house effect. As such, recent efforts aimed at addressing this problem have been directed to the use of carbon dioxide as an inexpensive and non-toxic single carbon source for making chemical products. Herein, we report the use of tetrazolyl complexes as catalysts precursors for hydrogenation of carbon dioxide. Specifically, tetrazolyl compounds bearing phosphorus-sulfur bonds have been synthesized with the view of using these as phosphorus-nitrogen bidentate tetrazolyl ligands that can coordinate to iridium(III) thereby forming heteroatomic five-member complexes. Interestingly, reacting the phosphorus-nitrogen bidentate tetrazolyl ligands with iridium dimer led to serendipitous isolation of chiral-at-metal iridium(III) half-sandwich complexes instead. The complexes were obtained via prior formation non-chiral iridium half-sandwich complexes. The complexes undergo initial phosphorus-sulfur bond heterolysis of the precursor ligands, which then ultimately results in new half-sandwich iridium complexes featuring monodentate phosphine co-ligands with proton responsive functionalities. Conditions necessary to significantly affect the rate of phosphorus-sulfur bond heterolysis in the precursor ligand and the subsequent coordination to iridium have been reported. The complexes served as catalyst precursors and exhibited activity in carbon dioxide and bicarbonate hydrogenation in excellent catalytic activity, at low catalyst loadings, producing concentrated formate solutions exclusively. Catalyst precursors with proton responsive phosphines were found to influence catalytic activity when present as racemates, while ease of dissociation of the ligand from the iridium centre was observed to influence activity in spite of the presence of electron-donating ligands. A test for homogeneity indicated that hydrogenation of carbon dioxide proceeded by homogenous means. Subsequently, the mechanism of the reaction by the iridium catalyst precursors was studied using proton NMR techniques. This revealed that a chiral-at-metal iridium hydride species generated in situ, served as the active catalyst. Show less

A new mitochondria-targeted probe MitoCLox was designed as a starting compound for a series of probes sensitive to cardiolipin (CL) peroxidation. Fluorescence microscopy reported selective accumulation of MitoCLox in mitochondria of diverse living cell cultures and its oxidation under stress conditions, particularly those known to cause a selective cardiolipin oxidation. Ratiometric fluorescence measurements using flow cytometry showed a remarkable dependence of the MitoCLox dynamic range on the oxidation of the sample. Specifically, MitoCLox oxidation was induced by low doses of hydrogen peroxide or organic hydroperoxide. The mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenyl-phosphonium (SkQ1), which was shown earlier to selectively protect cardiolipin from oxidation, prevented hydrogen peroxide-induced MitoCLox oxidation in the cells. Concurrent tracing of MitoCLox oxidation and membrane potential changes in response to hydrogen peroxide addition showed that the oxidation of MitoCLox started without a delay and was complete during the first hour, whereas the membrane potential started to decay after 40 minutes of incubation. Hence, MitoCLox could be used for splitting the cell response to oxidative stress into separate steps. Application of MitoCLox revealed heterogeneity of the mitochondrial population; in living endothelial cells, a fraction of small, rounded mitochondria with an increased level of lipid peroxidation were detected near the nucleus. In addition, the MitoCLox staining revealed a specific fraction of cells with an increased level of oxidized lipids also in the culture of human myoblasts. The fraction of such cells increased in high-density cultures. These specific conditions correspond to the initiation of spontaneous myogenesis in vitro, which indicates that oxidation may precede the onset of myogenic differentiation. These data point to a possible participation of oxidized CL in cell signalling and differentiation. Show less

Cancer is one of the main causes of death worldwide. Chemotherapy, despite its severe side effects, is to date one of the leading strategies against cancer. Metal-based drugs present several potential advantages when compared to organic compounds and they have gained trust from the scientific community after the approval on the market of the drug cisplatin. Recently, we reported the ruthenium complex ([Ru(DIP)₂ (sq)](PF₆ ) (where DIP is 4,7-diphenyl-1,10-phenantroline and sq is semiquinonate) with a remarkable potential as chemotherapeutic agent against cancer, both in vitro and in vivo. In this work, we analyse a structurally similar compound, namely [Ru(DIP)₂ (mal)](PF₆ ), carrying the flavour-enhancing agent approved by the FDA, maltol (mal). To possess an FDA approved ligand is crucial for a complex, whose mechanism of action might include ligand exchange. Herein, we describe the synthesis and characterisation of [Ru(DIP)₂ (mal)](PF₆ ), its stability in solutions and under conditions that resemble the physiological ones, and its in-depth biological investigation. Cytotoxicity tests on different cell lines in 2D model and on HeLa MultiCellular Tumour Spheroids (MCTS) demonstrated that our compound has higher activity than cisplatin, inspiring further tests. [Ru(DIP)₂ (mal)](PF₆ ) was efficiently internalised by HeLa cells through a passive transport mechanism and severely affected the mitochondrial metabolism. Show less

The well-documented cytotoxic activity of coordinatively saturated and substitutionally inert polypyridyl Ru(ii) complexes substantiates their high potency as antiproliferative agents against primary tumors. However, the primary cause of cancer morbidity and mortality responsible for about 90% of cancer deaths is the occurrence of metastasis. Therefore, scientists have to concentrate their efforts on designing compounds affecting not only the primary tumor, but also efficiently inhibiting metastasis. Herein, we report two families of Ru(ii) polypyridyl complexes bearing 2,2'-bipyridine substituted by a semicarbazone 2-formylopyridine moiety as one of the ligands and 4,4'-di-tert-butyl-2,2'-dipyridyl or 4,7-diphenyl-1,10-phenanthroline as auxiliary ligands. These complexes strengthen cells' adherent properties and inhibit the activity of metalloproteinases (MMPs) in vitro, which is relevant in anti-metastatic treatment. The in vitro studies were performed on human lung adenocarcinoma (A549) and human pancreatic cancer (PANC-1) cells, which have a well-documented invasive potential. The induced alteration of the tumor cells' adhesion properties correlated with the high cytotoxic effect exerted by the complexes and their excellent cellular uptake. It was also proved that both complexes directly inhibit M-MP2 and M-MP9 enzyme activities, which are essential for the development of tumor metastasis. The results of this study indicate that the biological properties of polypyridyl Ru(ii) complexes extend beyond the standard cytotoxic activity and represent an important step towards designing new anti-metastatic agents. Show less

Cytochrome c (cyt c) is known for its role in the electron transport chain but transitions to a peroxidase-active state upon exposure to oxidative species. The peroxidase activity ultimately results in the release of cyt c into the cytosol for the engagement of apoptosis. The accumulation of oxidative modifications that accompany the onset of the peroxidase function are well-characterized. However, the concurrent structural and conformational transitions of cyt c remain undercharacterized. Fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry is a protein footprinting technique used to structurally characterize proteins. FPOP coupled with native ion mobility separation shows that exposure to H2O2 results in the accumulation of a compact state of cyt c. Subsequent top-down fragmentation to localize FPOP modifications reveals changes in heme coordination between conformers. A time-resolved functional assay suggests that this compact conformer is peroxidase active. Altogether, combining FPOP, ion mobility separation, and top-down and bottom-up mass spectrometry allows us to discern individual conformations in solution and obtain a better understanding of the conformational ensemble and structural transitions of cyt c as it transitions from a respiratory role to a proapoptotic role. Show less

The stability in water and at pH = 7.2, substitution reactions with Tu, 5’-GMP, GSH andl-Met, DNA/BSA interactions, cytotoxicity, DFT and molecular docking of gold(iii) complexes with phenanthroline derivatives as inert ligands were studied. Show less

In this study, we newly designed and synthesized a small library of ten structurally related C,N-cyclometalated ruthenium(II) complexes containing various pyridine-functionalized NHC ligand and chelating bipyridyl ligands (e.g., 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, and 1,10-phenanthroline (phen)). The complexes were well characterized by NMR, electrospray ionization-mass spectrometry, and single-crystal X-ray structure analyses. Among the new ruthenium(II) derivatives, we identified that the complex Ru8 bearing bulky moieties (i.e., phen and pentamethyl benzene) had the most potent cytotoxicity against all tested cancer cell lines, generating dose- and cell line-dependent IC₅₀ values at the range of 3.3-15.0 μm. More significantly, Ru8 not only efficiently inhibited the metastasis process against invasion and migration of tumor cells but also exhibited potent antivascular effects by suppressing HUVEC cells migration and tube formation in vitro and blocking vessel generation in vivo (chicken chorioallantoic membrane model). In a metastatic A2780 tumor xenograft-bearing mouse model, administration of Ru8 outperformed antimetastatic agent NAMI-A and clinically approved cisplatin in terms of antitumor efficacy and inhibition of metastases to other organs. Overall, these data provided compelling evidence that the new cyclometalated ruthenium complex Ru8 is an attractive agent because of synergistically suppressing bulky tumors and metastasized tumor nudes. Therefore, the complex Ru8 deserves further investigations. Show less

The automatic recognition of chemical structure diagrams from the literature is an indispensable component of workflows to re-discover information about chemicals and to make it available in open-access databases. Here we report preliminary findings in our development of Deep lEarning for Chemical ImagE Recognition (DECIMER), a deep learning method based on existing show-and-tell deep neural networks, which makes very few assumptions about the structure of the underlying problem. It translates a bitmap image of a molecule, as found in publications, into a SMILES. The training state reported here does not yet rival the performance of existing traditional approaches, but we present evidence that our method will reach a comparable detection power with sufficient training time. Training success of DECIMER depends on the input data representation: DeepSMILES are superior over SMILES and we have a preliminary indication that the recently reported SELFIES outperform DeepSMILES. An extrapolation of our results towards larger training data sizes suggests that we might be able to achieve near-accurate prediction with 50 to 100 million training structures. This work is entirely based on open-source software and open data and is available to the general public for any purpose. Show less

A new application for bis(cyclometalated) iridium(III) species containing ancillary acyclic diaminocarbene ligands, viz. for sensing of mercury(II) ions, is disclosed. A family of bis(cyclometalated) iridium(III) species supported by both parent isocyanide and acyclic diaminocarbene ligands was prepared, and their electrochemical and photophysical properties were evaluated, revealing efficient blue-green phosphorescence in solution with quantum yields of up to 55%. We uncovered that the photophysical properties of these complexes are dramatically altered by the presence of metal ions and that the complex [Ir(ppy)₂(CN){C(NH₂)(NHC₆H₄-4-X)}] with an ADC ligand reacts selectively with Hg²⁺ ions, enabling its use for sensing of mercury(II) ions in solution. The limit of detection was as low as 2.63 × 10^-7 M, and additional mechanistic studies indicated the formation of an unusual dinuclear iridium(III) cyclometalated intermediate, bridged by a mercury dicyano fragment as a driving force of mercury sensing. Show less