Identifying Health Effects of Exposure to Trichloroacetamide Using Transcriptomics and Metabonomics in Mice (Mus musculus)

Microarray-based transcriptomics and one-dimensional proton nuclear magnetic resonance (¹H NMR) based metabonomics approaches were employed to investigate the health effects of nitrogenous disinfection byproducts (N-DBPs) of trichloroacetamide (TCAcAm) on mice. Mice were exposed to TCAcAm at concentrations of 50, 500, and 5000 μg/L for 90 days, and hepatic transcriptome and serum metabonome and histopathological parameters were detected in comparison with those of control. TCAcAm esposures resulted in liver inflammation, weight loss (in 5000 ug/L TCAcAm group), and alterations in hepatic transcriptome and serum metabonome. Based on the differentially expressed genes and altered metabolites, several significant pathways were identified, which are associated with lipid, xenobiotics, amino acid and energy metabolism, and cell process. Moreover, integrative pathway analyses revealed that TCAcAm exposure in this study induced hepatotoxicity and cytotoxicity. These results also highlight the noninvasive prospect of transcriptomic and metabonomic approaches in evaluating the health risk of emerging N-DBPs

Multistate Redox-Switchable Ion Transport Using Chalcogen-Bonding Anionophores

Synthetic supramolecular transmembrane anionophores have emerged as promising anticancer chemotherapeutics. However, key to their targeted application is achieving spatiotemporally controlled activity. Herein, we report a series of chalcogen-bonding diaryl tellurium-based transporters in which their anion binding potency and anionophoric activity are controlled through reversible redox cycling between Te oxidation states. This unprecedented in situ reversible multistate switching allows for switching between ON and OFF anion transport and is crucially achieved with biomimetic chemical redox couples

Selective Potassium Chloride Recognition, Sensing, Extraction, and Transport Using a Chalcogen-Bonding Heteroditopic Receptor

Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M+ (M+ = K+, Rb+, Cs+) sandwich complex and bidentate ChB···X– formation. Extensive quantitative 1H NMR ion-pair affinity titration experiments, solid–liquid and liquid–liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor’s ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation–anion ion-pair binding observations for halides and oxoanions

Noncovalent Immobilization of a Pyrene-Modified Cobalt Corrole on Carbon Supports for Enhanced Electrocatalytic Oxygen Reduction and Oxygen Evolution in Aqueous Solutions

Efficient oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are the determinants of the realization of a hydrogen-based society, as sluggish OER and ORR are the bottlenecks for the production and utilization of H₂, respectively. A Co complex of 5,15-bis­(pentafluorophenyl)-10-(4)-(1-pyrenyl)­phenylcorrole (<b>1</b>) bearing a pyrene substituent was synthesized. When it was immobilized on multiwalled carbon nanotubes (MWCNTs), the <b>1</b>/MWCNT composite displayed very high electrocatalytic activity and durability for both OER and ORR in aqueous solutions: it catalyzed a direct four-electron reduction of O₂ to H₂O in 0.5 M H₂SO₄ with an onset potential of 0.75 V vs normal hydrogen electrode (NHE), and it catalyzed the oxidation of water to O₂ in neutral aqueous solution with an onset potential of 1.15 V (vs NHE, η = 330 mV). Control studies using a Co complex of 5,10,15-tris­(pentafluorophenyl)­corrole (<b>2</b>) demonstrated that the enhanced catalytic performance of <b>1</b> was due to the strong noncovalent π–π interactions between its pyrene moiety and MWCNTs, which were considered to facilitate the fast electron transfer from the electrode to <b>1</b> and also to increase the adhesion of <b>1</b> on carbon supports. The noncovalent immobilization of molecular complexes on carbon supports through strong π–π interactions appears to be a simple and straightforward strategy to prepare highly efficient electrocatalytic materials

Microcystin-LR Promotes Melanoma Cell Invasion and Enhances Matrix Metalloproteinase-2/‑9 Expression Mediated by NF-κB Activation

This study aimed to explore the molecular mechanisms behind the stimulation effects of microcystin-LR (a well-known cyanobacterial toxin produced in eutrophic lakes or reservoirs) on cancer cell invasion and matrix metalloproteinases (MMPs) expression. Boyden chamber assay showed that microcystin-LR exposure (>12.5 nM) evidently enhanced the invasion ability of the melanoma cells (MDA-MB-435). Tumor Metastasis PCR Array demonstrated that 24 h microcystin-LR treatment (25 nM) caused overexpression of eight genes involved in tumor metastasis, including MMP-2, MMP-9, and MMP-13. Quantitative real-time PCR, Western blotting and gelatin zymography consistently demonstrated that mRNA and protein levels of MMP-2/-9 were increased in the cells after microcystin-LR exposure (<i>P</i> < 0.05 each). Immunofluorescence assay and electrophoretic mobility shift assay revealed that microcystin-LR could activate nuclear factor kappaB (NF-κB) by accelerating NF-κB translocation into the nucleus and enhancing NF-κB binding ability. Furthermore, addition of NF-κB inhibitor in culture medium could suppress the invasiveness enhancement and MMP-2/-9 overexpression. This study indicates that microcystin-LR can act as a NF-κB activator to promote MMP-2/-9 expression and melanoma cell invasion, which deserves more environmental health concerns

Rhodium(III)-Catalyzed Oxidative Annulation of 2,2′-Bipyridine N‑Oxides with Alkynes via Dual C–H Bond Activation

Rh­(III)-catalyzed switchable annulation of 2,2′-bipyridine N-oxides with internal alkynes via dual C–H bond activation has been developed. Tuning the reaction conditions enabled the reaction pathway to be switched between rollover and nonrollover annulation, delivering 5,6-disubstituted-1,10-phenanthrolines and 5,6,7,8-tetrasubstituted-1-(pyridin-2-yl)­isoquinoline 2-oxides in high yields, respectively. The procedures feature excellent regioselectivity, broad substrate scope, and high tolerance of functional groups. The synthetic utilities of these obtained products were demonstrated in the catalytic reactions