The Emergence of Zerovalent Carbon Compounds from Structural Curiosities to Organocatalysts

Low-valent main group compounds have reactivity patterns and properties reminiscent of transition metals. While divalent carbon compounds such as carbenes are widely studied ligands and organocatalysts, zerovalent carbon species have received considerably less attention. This perspective highlights the properties and reactivity of zerovalent carbon compounds, focusing on their first applications as organocatalysts for small molecule reduction and polymerization reactions

7-Keto-Cholesterol and Cholestan-3beta, 5alpha, 6beta-Triol Induce Eryptosis through Distinct Pathways Leading to NADPH Oxidase and Nitric Oxide Synthase Activation

BACKGROUND/AIMS: We showed that patho-physiological concentrations of either 7-keto-cholesterol (7-KC), or cholestane-3beta, 5alpha, 6beta-triol (TRIOL) caused the eryptotic death of human red blood cells (RBC), strictly dependent on the early production of reactive oxygen species (ROS). The goal of the current study was to assess the contribution of the erythrocyte ROS-generating enzymes, NADPH oxidase (RBC-NOX), nitric oxide synthase (RBC-NOS) and xanthine oxido-reductase (XOR) to the oxysterol-dependent eryptosis and pertinent activation pathways. METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, reactive oxygen/nitrogen species (RONS) and nitric oxide formation from 2',7'-dichloro-dihydrofluorescein (DCF-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) -dependent fluorescence, respectively; Akt1, phospho-NOS3 Ser1177, and PKCζ from Western blot analysis. The activity of individual 7-KC (7 μM) and TRIOL (2, μM) on ROS-generating enzymes and relevant activation pathways was assayed in the presence of Diphenylene iodonium chloride (DPI), N-nitro-L-arginine methyl ester (L-NAME), allopurinol, NSC23766 and LY294002, inhibitors in this order of RBC-NOX, RBC-NOS, XOR and upstream regulatory proteins Rac GTPase and phosphoinositide3 Kinase (PI3K); hemoglobin oxidation from spectrophotometric analysis. RESULTS: RBC-NOX was the target of 7-KC, through a signaling including Rac GTPase and PKCζ, whereas TRIOL caused activation of RBC-NOS according to the pathway PI3K/Akt, with the concurrent activity of a Rac-GTPase. In concomitance with the TRIOL-induced .NO production, formation of methemoglobin with global loss of heme were observed, ascribable to nitrosative stress. XOR, activated after modification of the redox environment by either RBC-NOX or RBC-NOS activity, concurred to the overall oxidative/nitrosative stress by either oxysterols. When 7-KC and TRIOL were combined, they acted independently and their effect on ROS/RONS production and PS exposure appeared the result of the effects of the oxysterols on RBC-NOX and RBC-NOS. CONCLUSION: Eryptosis of human RBCs may be caused by either 7-KC or TRIOL by oxidative/nitrosative stress through distinct signaling cascades activating RBC-NOX and RBC-NOS, respectively, with the complementary activity of XOR; when combined, the oxysterols act independently and both concur to the final eryptotic effect

Spatiotemporal variability in the O-18-salinity relationship of seawater across the tropical Pacific Ocean

The relationship between salinity and the stable oxygen isotope ratio of seawater (δ18Osw) is of utmost importance to the quantitative reconstruction of past changes in salinity from δ18O values of marine carbonates. This relationship is often considered to be uniform across water masses, but the constancy of the δ18Osw-salinity relationship across space and time remains uncertain, as δ18Osw responds to varying atmospheric vapor sources and pathways, while salinity does not. Here we present new δ18Osw-salinity data from sites spanning the tropical Pacific Ocean. New data from Palau, Papua New Guinea, Kiritimati, and Galápagos show slopes ranging from 0.09 ‰/psu in the Galápagos to 0.32‰/psu in Palau. The slope of the δ18Osw-salinity relationship is higher in the western tropical Pacific versus the eastern tropical Pacific in observations and in two isotope-enabled climate model simulations. A comparison of δ18Osw-salinity relationships derived from short-term spatial surveys and multiyear time series at Papua New Guinea and Galápagos suggests spatial relationships can be substituted for temporal relationships at these sites, at least within the time period of the investigation. However, the δ18Osw-salinity relationship varied temporally at Palau, likely in response to water mass changes associated with interannual El Niño–Southern Oscillation (ENSO) variability, suggesting nonstationarity in this local δ18Osw-salinity relationship. Applying local δ18Osw-salinity relationships in a coral δ18O forward model shows that using a constant, basinwide δ18Osw-salinity slope can both overestimate and underestimate the contribution of δ18Osw to carbonate δ18O variance at individual sites in the western tropical Pacific.We are grateful for the dedicated water samplers who enabled this research: Lori J. Bell and Gerda Ucharm of the Coral Reef Research Foundation, Palau; Rosa Maritza Motoche Gonzalez and the Fuerza Aerea Ecuatoriana, Santa Cruz, Galapagos, Ecuador; Taonateiti Kabiri and the students of Tennessee Primary School, London, Kiritimati; and the Manus Weather Observers, U.S. Department of Energy ARM Climate Research Facility, Manus, Papua New Guinea. We would like to thank the Galapagos National Park, the Kiritimati Ministry of Environment Lands and Agricultural Development for sample permits, and the Charles Darwin Research Station for logistical support. Funding sources for this work includes NSF-AGS-PF 1049664 to J.L.C., NSF P2C2-1203785 to K.M.C., J.L.C., and D.N. This research was also supported by the Office of Biological and Environment Research of the U.S. Department of Energy as part of the Atmospheric Radiation Measurement Climate Research Facility. Isotope data are available as supporting information associated with the manuscript. (1049664 - NSF-AGS-PF; P2C2-1203785 - NSF; Office of Biological and Environment Research of the U.S. Department of Energy as part of the Atmospheric Radiation Measurement Climate Research Facility

Phenolic composition of hydrophilic extract of manna from sicilian Fraxinus angustifolia vahl and its reducing, antioxidant and anti-inflammatory activity in vitro

Manna, a very singular vegetable product derived from the spontaneous solidification of the sap of some Fraxinus species, has long been known for its mild laxative and emollient properties. In this work, a hydro-alcoholic extract of manna (HME) from Sicilian Fraxinus angustifolia Vahl was investigated using HPLC-DAD to find phenol components and using chemical and biological in vitro assays to determine its reducing, antioxidant and anti-inflammatory capacity. We identified elenolic acid, tyrosol, hydroxytyrosol, catechin, fraxetin, verbascoside, gallic acid, procyanidin-B1, and luteolin 3,7 glucoside, in order of abundance. Measurements of total antioxidant activity by Folin-Ciocalteu reaction and ferric reducing ability (FRAP), as well as of scavenger activity towards ABTS•+, DPPH•, and perferryl-myoglobin radicals, showed that the phytocomplex effectively reduced oxidants with different standard potentials. When compared with vitamin E, HME also behaved as an efficient chain-breaking antioxidant against lipoperoxyl radicals from methyl linoleate. In cellular models for oxidative stress, HME counteracted membrane lipid oxidation of human erythrocytes stimulated by tert-butyl hydroperoxide and prevented the generation of reactive oxygen species, as well as the GSH decay in IL-1β–activated intestinal normal-like cells. Moreover, in this in vitro intestinal bowel disease model, HME reduced the release of the pro-inflammatory cytokines IL-6 and IL-8. These findings may suggest that manna acts as an antioxidant and anti-inflammatory natural product in humans, beyond its well-known effects against constipation

Suicidal erythrocyte death in metabolic syndrome

Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted by the eryptotic process in the ED, the focus of the present review is to report and discuss the involvement of eryptosis within MetS, where vascular complications are utterly relevant. Current knowledge on the mechanisms leading to eryptosis in MetS-related conditions (hyperglycemia, dyslipidemia, hypertension and obesity) will be analyzed. Moreover, clinical evidence supporting or proposing a role for eryptosis in the ED, associated to MetS cardiovascular complications, will be discussed

Antioxidant Betalains from Cactus Pear (Opuntia Ficus Indica) inhibit endothelial ICAM-1 expression

It has been suggested that some pigments would have antioxidant properties and that their presence in dietary constituents would contribute to reduce the risk of oxidative stress\u2013correlated diseases. Among others, inflammatory response depends on redox status and may implicate oxidative stress. Vascular endothelial cells are a direct target of oxidative stress in inflammation. We have tested the impact of the free radical scavenger and antioxidant properties of betalains from the prickle pear in an in vitro model of endothelial cells. Here we show the capacity of betalains to protect endothelium from cytokine- induced redox state alteration, through ICAM-1 inhibition. KEYWORDS: endothelial cells; ICAM-1; betalains; antiinflammatory drug

Group 14 Metallocene Catalysts for Carbonyl Hydroboration and Cyanosilylation

A series of six Group 14 metallocene compounds (M = Ge, Sn, Pb) were studied as catalysts for carbonyl hydroboration and cyanosilylation reactions at room temperature. Both bis(pentamethylcyclopentadienyl) and tetramethyldisiloxa[3]metallocenophane compounds were compared. The tin and lead metallocenophanes exhibited the highest reactivity in hydroboration and cyanosilylation reactions. Hammett analysis of aldehyde hydroboration provided a ρ value of 0.73, suggesting a buildup of negative charge during the turnover-limiting step, consistent with the transition state for hydride transfer to the carbonyl center. NMR studies of Lewis acidity indicate that the Ge, Sn, and Pb tetramethyldisiloxa[3]metallocenophane compounds are weak Lewis acids

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells

Antioxidant phytochemicals are investigated as novel treatments for supportive therapy in b-thalassemia. The dietary indicaxanthin was assessed for its protective effects on human b-thalassemic RBCs submitted in vitro to oxidative haemolysis by cumene hydroperoxide. Indicaxanthin at 1.0\u201310 mMenhanced the resistance to haemolysis dose-dependently. In addition, it prevented lipid and haemoglobin (Hb) oxidation, and retarded vitamin E and GSH depletion. After ex vivo spiking of blood from thalassemia patients with indicaxanthin, the phytochemical was recovered in the soluble cell compartment of the RBCs. A spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb generated in solution from met-Hb and hydrogen peroxide (H2O2), more effectively than either Trolox or vitamin C. Collectively our results demonstrate that indicaxanthin can be incorporated into the redox machinery of b-thalassemic RBC and defend the cell from oxidation, possibly interfering with perferryl-Hb, a reactive intermediate in the hydroperoxidedependent Hb degradation. Opportunities of therapeutic interest for b-thalassemia may be considered

Crystal Structure of 2-(2,6-diiso­propyl­phen­yl)-N,N-diethyl-3,3-dimethyl-2-aza­spiro­[4.5]decan-1-amine: A Di­ethyl­amine Adduct of a Cyclic(alk­yl)(amino)­carbene (CAAC)

The structure of the title compound, C27H46N2, at 93 K has monoclinic (P21/n) symmetry. The title compound was prepared by treatment of 2-(2,6-diiso­propyl­phenyl)-3,3-dimethyl-2-aza­spiro­[4.5]dec-1-en-2-ium hydrogen dichloride with two equivalents of lithium di­ethyl­amide. Characterization of the title compound by single-crystal X-ray diffraction and 1H and 13C NMR spectroscopy is presented. Formation of the di­ethyl­amine adduct of the cyclic(alk­yl)(amino)­carbene (CAAC) was unexpected, as deprotonation using lithium diiso­propyl­amide results in free CAAC formation

Animal models of compulsive eating behavior

In industrialized nations, overeating is a significant problem leading to overweight, obesity, and a host of related disorders; the increase in these disorders has prompted a significant amount of research aimed at understanding their etiology. Eating disorders are multifactorial conditions involving genetic, metabolic, environmental, and behavioral factors. Considering that compulsive eating in the face of adverse consequences characterizes some eating disorders, similar to the way in which compulsive drug intake characterizes drug-addiction, it might be considered an addiction in its own right. Moreover, numerous review articles have recently drawn a connection between the neural circuits activated in the seeking/intake of palatable food and drugs of abuse. Based on this observation, “food addiction” has emerged as an area of intense scientific research and accumulating evidence suggests it is possible to model some aspects of food addiction in animals. The development of well-characterized animal models would advance our understanding of the etiologic neural factors involved in eating disorders, such as compulsive overeating, and it would permit to propose targeted pharmacological therapies. However, to date, little evidence has been reported of continued food seeking and intake despite its harmful consequences in rats and mice