Volcano relationships and a new activity descriptor of 2D transition metal-Fe layered double hydroxides for efficient oxygen evolution reaction.

Iron (Fe) sites play a critical role in boosting the catalytic activity of transition metal layered double hydroxide (LDH) electrocatalysts for the oxygen evolution reaction (OER), but the contribution of the Fe content to the catalysis of Fe-doped LDHs is still not well understood. Herein, a series of two-dimensional (2D) Fe-doped MFe-LDHs (M = Co, Ni, Cu, and Mn) was synthesized via a general molecular self-assembly method to track the role of Fe in their electrocatalytic OER activities. Besides the revelation of the intrinsic activity trend of NiFe > CoFe > MnFe > CuFe, volcano-shaped relationships among the catalytic activity descriptors, i.e., overpotential, Tafel slope, and turnover frequency (TOF), and the Fe-content in MFe-LDHs, were identified. Specifically, a ∼20% Fe content resulted in the highest OER performance for the LDH, while excess Fe compromised its activity. A similar volcano relationship was determined between the intermediate adsorption and Fe content via operando impedance spectroscopy (EIS) measurements, and it was shown that the intermediate adsorption capacitance (CPEad) can be a new activity descriptor for electrocatalysts. In this work, we not only performed a systematic study on the role of Fe in 2D Fe-doped LDHs but also offer some new insights into the activity descriptors for electrocatalysts.

Physico-chemical properties of sediments governing the bioavailability of heavy metals in urban waterways.

Bioavailability is a critical facet of metal toxicity. Although past studies have investigated the individual role of sediment physico-chemical properties in relation to the bioavailability of heavy metals, their collective effects are little-known. Further, limited knowledge exists on the contribution of nutrients to metal bioavailability. In this study, the influence of physico-chemical properties of sediments, including total organic carbon (TOC), total phosphorus (TP), total nitrogen (TN), cation exchange capacity (CEC), specific surface area (SSA), and mineralogical composition to metal bioavailability is reported. The weak-acid extraction method was used to measure Cd, Cr, Cu, Ni, Pb and Zn as the potentially bioavailable fraction in sediments in an urban creek. The results confirmed that Cu has strong selectivity for organic matter (r = 0.814, p < 0.01). Cr bioavailability was influenced by either sediment mineralogy, nutrients, CEC or SSA. Zn, Ni and Pb showed strong affinity to mineral oxides, though their preferred binding positions were with nutrients, particularly organic matter (r = 0.794, 0.809, and 0.753, p < 0.01, respectively). The adsorption of Cd was strongly influenced by the competition with other metals and its bioavailability was weakly influenced by ion exchange (CEC: r = 0.424, p < 0.01). The study results indicate that nitrogen and phosphorus compounds can elevate metal bioavailability due to complexation reactions. Generally, the estuarine area was more favourable for the adsorption of weakly-bound metals. This is concerning as estuaries generate high biogeochemical activity and are economically important.

Lewis Acid Catalyzed Atom-Economic Synthesis of C2-Substituted Indoles from o-Amido Alkynols.

Herein we have disclosed a Zn(OTf)2 catalyzed synthesis of C2-alkyl substituted indole derivatives via unprecedented carbonyl group migration from o-amido alkynols. The key features of this protocol involve N,O-carbonyl group migration, broad substrate scope with varied functionality tolerance, moderate to good yields, and 100% atom economy. The crossover experiments proved that the migration is happening via an intramolecular pathway.

Analysing Sr isotopes in low-Sr samples such as single insects with inductively coupled plasma tandem mass spectrometry using N2 O as a reaction gas for in-line Rb separation.

RATIONALE: Strontium isotopes are valuable markers of provenance in a range of disciplines. Limited amounts of Sr in low-mass samples such as insects mean that conventional Sr isotope analysis precludes their use for geographic origins in many ecological studies or in applications such as biosecurity. Here we test the viability of using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) with N2 O as a reaction gas for accurately determining Sr isotopes in insects with Sr < 100 ng. METHODS: Strontium isotopes were determined in solution mode using ICP-MS/MS with 0.14 L/min N2 O as a reaction gas to convert Sr+ into SrO+ for in-line separation of 87 Sr from 87 Rb. The Sr isotope reference standards NIST SRM 987, NIST SRM 1570a and NIST SRM 1547 were used to assess accuracy and reproducibility. Ten insect species collected from the wild as a proof-of-principle application were analysed for Sr concentration and Sr isotopes. RESULTS: Using ICP-MS/MS we show for the first time that internal mass bias correction of 87 Sr16 O/86 Sr16 O based on 88 Sr16 O/86 Sr16 O works to give for NIST SRM 987 a 87 Sr/86 Sr ratio of 0.7101 ± 0.012 (RSD = 0.17%) and for NIST SRM 1570a a 87 Sr/86 Sr ratio of 0.7100 ± 0.009 (RSD = 0.12%), which are within error of the accepted values. The first 87 Sr/86 Sr ratio of NIST SRM 1547 is 0.7596 ± 0.0014. Strontium analyses were run on 0.8 mL of 0.25-0.5 ppb Sr, which equates to 2-4 ng of Sr. Strontium isotope analysis with a precision of >99.8% can be achieved with in-line separation of 87 Sr from 87 Rb at least up to solutions with 25 ppb Rb. CONCLUSIONS: A minimum of 5 mg of insect tissue is required for Sr isotope analysis. This new ICP-MS/MS method enables Sr isotope analysis in single insects, allowing population-scale studies to be feasible and making possible applications with time-critical uses such as biosecurity.

High Energy Capacitors Based on All Metal-Organic Frameworks Derivatives and Solar-Charging Station Application.

High energy and efficient solar charging stations using electrochemical capacitors (ECs) are a promising portable power source for the future. In this work, two kinds of metal-organic framework (MOF) derivatives, NiO/Co3 O4 microcubes and Fe2 O3 microleaves, are prepared via thermal treatment and assembled into electrochemical capacitors, which deliver a relatively high specific energy density of 46 Wh kg-1 at 690 W kg-1 . In addition, a solar-charging power system consisting of the electrochemical capacitors and monocrystalline silicon plates is fabricated and a motor fan or 25 LEDs for 5 and 30 min, respectively, is powered. This work not only adds two novel materials to the growing categories of MOF-derived advanced materials, but also successfully achieves an efficient solar-ECs system for the first time based on all MOF derivatives, which has a certain reference for developing efficient solar-charge systems.

A Turn-on Fluorescence Sensor for Heparin Detection Based on a Release of Taiwan Cobra Cardiotoxin from a DNA Aptamer or Adenosine-Based Molecular Beacon.

This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the fluorescent signal of the aptamer or MB 5'-end labeled with carboxyfluorescein (FAM) and 3'-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid (DABCYL) was observed upon the addition of CTX3. The presence of heparin and formation of the CTX3-heparin complex caused CTX3 detachment from the MB or aptamer, and restoration of FAM fluorescence of the 5'-FAM-and-3'-DABCYL-labeled MB and aptamer was subsequently noted. Moreover, the detection of heparin with these CTX3-aptamer and CTX3-MB sensors showed high sensitivity and selectivity toward heparin over chondroitin sulfate and hyaluronic acid regardless of the presence of plasma. The limit of detection for heparin in plasma was determined to be 16 ng/mL and 15 ng/mL, respectively, at a signal-to-noise ratio of 3. This study validates the practical utility of the CTX3-aptamer and CTX3-MB systems for determining the concentration of heparin in a biological matrix.

Photodynamic Therapy Using Indolines-Fused-Triazoles Induces Mitochondrial Apoptosis in Human Non-Melanoma BCC Cells.

BACKGROUND/AIM: Cancer is one of the most dreadful diseases in humans and among them non-melanoma skin cancer (NMSC) is an increasing problem in the world, that occurs more frequently in people with fair skin. Photodynamic therapy (PDT), a non-invasive treatment is widely used for the prevention and treatment of BCC cells. We previously reported an efficient synthesis of novel indolines-fused-triazoles and studied their photophysical studies. This study delineated the signaling pathways involved in the PDT effect of triazoles on BCC cells under UVA irradiation. MATERIALS AND METHODS: Cell survival was evaluated by the MTT assay. The uptake of 1j in BCC cells was determined by using its fluorescence properties. Intracellular ROS and mitochondrial membrane potential (ΔΨmt) were measured using DCFH-DA probe and DiOC6 dye, respectively. Cytochrome c release was determined using immunofluorescent staining. RESULTS: Our data disclosed that treatment of BCC cells with 1j-UVA resulted in increased ROS generation, loss of mmp (ΔΨmt), decreased levels of Bcl-2 and Bcl-xL, increased levels of Bax and Bad, cytochrome c release, and caspase-3/PARP degradation to identify apoptotic cell death. CONCLUSION: The present study suggest that 1j-PDT may serve as a potential ancillary modality for the treatment of NMSC.

Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon.

This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5'- and 3'-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A2-coralyne-A2 coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs.

Iodine-promoted cyclization of N-propynyl amides and N-allyl amides via sulfonylation and sulfenylation.

An iodine-promoted regioselective cyclization of N-propynyl/allyl amides with sulfonyl hydrazides has been developed for the synthesis of 5-methyl-arylsulfonyloxazoles and 5-methyl-arylthiooxazolines via sulfonylation and sulfenylation reactions. The notable features of this reaction are the formation of new C-S and C-O bonds, the broad functional group tolerance, and its applicability to alkyl sulfonyl hydrazides as well as internal alkynes.

BF3-Etherate-Promoted Cascade Reaction of 2-Alkynylanilines with Nitriles: One-Pot Assembly of 4-Amido-Cinnolines.

A BF3-etherate-promoted cascade reaction of nitriles with 2-alkynylanilines is described. This method achieves the formation of two new C-N bonds through a reaction sequence of diazotization with t-BuONO, nucleophilic addition of the alkyne to the BF3-coordinated diazonium ion, followed by nitrile addition to the intermediary vinyl cation and hydrolysis. The method provides efficient and general access to a variety of 4-amido-cinnolines. Notable features of the method include its broad functional group tolerance and avoidance of transition metals.

DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins.

Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electrophoretic mobility of aptamers against α-Bgt. Analysis of the changes in the fluorescence intensity of carboxyfluorescein-labeled aptamers upon binding toxin molecules revealed that CTX3 and α-Bgt could bind the tested aptamers. Moreover, the aptamers inhibited the membrane-damaging activity and cytotoxicity of CTX3. In addition to CTX3, other N. atra CTX isotoxins also bound to the aptamer against α-Bgt. Taken together, our data indicate that aptamers against α-Bgt show cross-reactivity with CTXs. The findings that aptamers against α-Bgt also suppress the biological activities of CTX3 highlight the potential utility of aptamers in regard to the broad inhibition of snake venom three-fingered proteins.

Design and synthesis of pyrrolobenzodiazepine-gallic hybrid agents as p53-dependent and -independent apoptogenic signaling in melanoma cells.

A new class of pyrrolo[2,1-c][1,4]benzodiazepine-Gallic hybrid agents (PBD-GA) conjugated through alkyl spacers has been designed and synthesized. The combination of these two core pharmacophores with modification in the C-8 position of the PBD ring with alkyl spacers afforded oxygen-tethered compounds 5a-5d and amide-tethered analogues 11a-11d with improved anticancer activity for two melanoma cell lines, A375 and RPMI7951, differing in their p53 status. The agents 5a-5d were cytotoxic in melanoma compared to agents 11a-11d. In particular, compounds 5b and 5c were found to possess the most potent activity compared with other hybrid agents and were proved with the help of quantitative structure activity relationship studies (QSAR). These PBD conjugates caused S phase arrest for the A375 cell line via increased reactive oxygen species (ROS) generation, deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (ATM)/ATM-Rad3-related (ATR) and checkpoint kinases 1 (Chk1) activation. Moreover, the PBD-GA induced A375 apoptotic cell death followed through p53 (ATM downstream target) increase, B-cell leukemia-xL (Bcl-xL) and mitochondrial membrane potential (ΔΨmt) decrease, cytochrome c release, and caspase-3/Poly Adp Ribose Polymerase (PARP) cleavage. On the other hand, mutant p53 RPMI7951 cell death occurred by PBD-GA-mediated mitochondria- and caspase-dependent pathways via lysosomal membrane permeabilization (LMP), but not through p53 signaling. Finally, compound 5b was shown to reduce murine melanoma size in a mouse model. These results suggest that the PBD-GA could be used as a useful chemotherapeutic agent in melanoma with activated p53 or mutant p53.

The Association Between p38 MAPK-Mediated TNF-α/TNFR2 up-Regulation and 2-(4-Aminophenyl)-7-Methoxybenzothiazole-Induced Apoptosis in Human Leukemia U937 Cells.

The primary cause of treatment failures in acute myeloid leukemia is usually associated with defects in the apoptotic pathway. Several studies suggest that 2-(4-aminophenyl)-7-methoxybenzothiazole (7-OMe-APBT) may potentially induce apoptosis of cancer cells. Thus, the present study was conducted to explore the cytotoxic effect of 7-OMe-APBT on human leukemia U937 cells. The apoptosis of human leukemia U937 cells induced by 7-OMe-APBT was characterized by an increase in mitochondrial membrane depolarization, procaspase-8 degradation, and tBid production. Down-regulation of FADD blocked 7-OMe-APBT-induced procaspase-8 degradation and rescued the viability of 7-OMe-APBT-treated cells, suggesting the involvement of a death receptor-mediated pathway in 7-OMe-APBT-induced cell death. Increased TNF-α expression, TNFR2 expression, and p38 MAPK phosphorylation were noted in 7-OMe-APBT-treated cells. Pretreatment with a p38 MAPK inhibitor abolished 7-OMe-APBT-induced TNF-α and TNFR2 up-regulation. 7-OMe-APBT stimulated p38 MAPK/c-Jun-mediated transcriptional up-regulation of TNFR2, while the increased TNF-α mRNA stability led to TNF-α up-regulation in 7-OMe-APBT-treated cells. Treatment with 7-OMe-APBT up-regulated protein phosphatase 2A catalytic subunit α (PP2Acα) expression via the p38 MAPK/c-Jun/ATF-2 pathway, which, in turn, promoted tristetraprolin (TTP) degradation. Pretreatment with a protein phosphatase 2A inhibitor or TTP over-expression abrogated TNF-α up-regulation in 7-OMe-APBT-treated cells. Abolishment of TNF-α up-regulation or knock-down of TNFR1/TNFR2 by siRNA restored the viability of 7-OMe-APBT-treated cells. Taken together, our data indicate a connection between p38 MAPK-mediated TNF-α and TNFR2 up-regulation and 7-OMe-APBT-induced TNF-α-mediated death pathway activation in U937 cells. The same pathway also elucidates the mechanism underlying 7-OMe-APBT-induced death of human leukemia HL-60 cells.

Bis(phenylidenebenzeneamine)-1-disulfide Derivatives Induce Autophagy in Melanoma Cells Through a Mitochondria-mediated Pathway.

We have previously reported the efficient synthesis of bis(phenylidenebenzeneamine)-1-disulfide derivatives 1-8. In the present article, we delineated the signaling pathways involved in the anticancer effects of compound 2 on melanoma cells. The treatment of melanoma cells with compound 2 resulted in ROS generation, a decrease in ΔΨmt, ATP, and protein expression of mitochondrial respiratory chain subunits. In addition, no significant apoptotic or necrotic effect was seen following compound 2 treatment using an annexin V and propidium iodide (PI) double-staining. Nevertheless, autophagy-related proteins LC3 and Beclin 1 were enhanced by compound 2. Furthermore, compound 2 was also shown to reduce murine melanoma size in a mouse model. We revealed a novel bio-evaluation of bis(phenylidenebenzeneamine)-1-disulfide derivatives anti-tumor proliferation mechanism and suggest that these agents may have potential chemotherapeutic activity for melanoma cells.

Palladium(II)-catalysed regioselective synthesis of 3,4-disubstituted quinolines and 2,3,5-trisubstituted pyrroles from alkenes via anti-Markovnikov selectivity.

A novel strategy has been identified for the regioselective synthesis of 3,4-disubstituted quinolines and 2,3,5-trisubstituted pyrroles from simple alkenes via anti-Markovnikov selectivity under palladium catalysis. The salient features are synthesis of two different heterocycles, readily available starting materials, broad substrate scope, moderate to good yields and use of molecular oxygen as a terminal oxidant.

Au(I)-catalyzed synthesis of 8-oxabicyclo[3.2.1]oct-2-enes and 9-oxabicyclo[3.3.1]nona-2,6-dienes from enynol via oxonium/Prins-type cyclization.

A sustainable and simple Au(I) catalytic system to synthesise 8-oxabicyclo[3.2.1]oct-2-enes and 9-oxabicyclo[3.3.1]nona-2,6-dienes from enynol via oxonium/Prins-type cyclization is described. The key advantages of this reaction are selectivity, good functional group tolerance and a new approach for synthesis of oxabicyclic and oxatricyclic systems.

I2-TBHP-catalyzed oxidative cross-coupling of N-sulfonyl hydrazones and isocyanides to 5-aminopyrazoles.

I2-TBHP-catalyzed oxidative cross coupling of N-sulfonyl hydrazones with isocyanides has been realized for the synthesis of 5-aminopyrazoles through formal [4 + 1] annulation via in situ azoalkene formation. Notable features are the metal/alkyne-free strategy, C-C and C-N bond formation, atom economy, catalytic I2, broad functional group tolerance, good reaction yields, shorter time, and also applicability to one-pot methodology.

Palladium(0)-catalyzed single and double isonitrile insertion: a facile synthesis of benzofurans, indoles, and isatins.

A palladium(0)-catalyzed cascade process consisting of isonitrile insertion and α-Csp(3)-H cross-coupling can be achieved for the synthesis of benzofurans and indoles. The construction of isatins by a Pd-catalyzed cascade reaction incorporating double isonitrile insertion, amination, and hydrolysis has also been achieved. The key features of this work include diverse heterocycle synthesis, phosphine-ligand-free reaction conditions, a one-pot procedure, simple and commercially available starting materials, broad functional-group compatibility, and moderate to good reaction yields.

Modulated mechanism of phosphatidylserine on the catalytic activity of Naja naja atra phospholipase A2 and Notechis scutatus scutatus notexin.

Phosphatidylserine (PS) externalization is a hallmark for apoptotic death of cells. Previous studies showed that Naja naja atra phospholipase A2 (NnaPLA2) and Notechis scutatus scutatus notexin induced apoptosis of human cancer cells. However, NnaPLA2 and notexin did not markedly disrupt the integrity of cellular membrane as evidenced by membrane permeability of propidium iodide. These findings reflected that the ability of NnaPLA2 and notexin to hydrolyze membrane phospholipids may be affected by PS externalization. To address that question, this study investigated the membrane-interacted mode and catalytic activity of NnaPLA2 and notexin toward outer leaflet (phosphatidylcholine/sphingomyelin/cholesterol, PC/SM/Chol) and inner leaflet (phosphatidylserine/phosphatidylethanolamine/cholesterol, PS/PE/Chol) of plasma membrane-mimicking vesicles. PS incorporation promoted enzymatic activity of NnaPLA2 and notexin on PC and PC/SM vesicles, but suppressed NnaPLA2 and notexin activity on PC/SM/Chol and PE/Chol vesicles. PS incorporation increased the membrane fluidity of PC vesicles but reduced membrane fluidity of PC/SM, PC/SM/Chol and PE/Chol vesicles. PS increased the phospholipid order of all the tested vesicles. Moreover, PS incorporation did not greatly alter the binding affinity of notexin and NnaPLA2 with phospholipid vesicles. Acrylamide quenching studies and trinitrophenylation of Lys residues revealed that membrane-bound mode of notexin and NnaPLA2 varied with the targeted membrane compositions. The fine structure of catalytic site in NnaPLA2 and notexin in all the tested vesicles showed different changes. Collectively, the present data suggest that membrane-inserted PS modulates PLA2 interfacial activity via its effects on membrane structure and membrane-bound mode of NnaPLA2 and notexin, and membrane compositions determine the effect of PS on PLA2 activity.