Anti-inflammatory effect of Spiranthera odoratissima A. St.-Hil. leaves involves reduction of TNF-alpha

Spiranthera odoratissima A. St.-Hil., 'manaca', is a medicinal species used in Brazil, especially in central region, for the treatment of several diseases such as pain and inflammation. In this study, the methanol/aqueous phase of the ethanol extract of the leaves of 'manaca' (MAP), at the doses of 50, 150 and 500 mg/kg was used to evaluate the anti-inflammatory and/or antinociceptive effects and the possible anti-inflammatory mechanism. The antinociceptive and anti-inflammatory activities of MAP were assessed using formalin test, carrageenan-induced paw oedema. The myeloperoxidase activity, capillary permeability, leukocyte migration and tumour necrosis factor alpha (TNF-alpha) levels were evaluated in pleural exudate. The MAP reduced the licking time only in the later phase of formalin test, and showed anti-inflammatory activity by reducing the paw oedema, migration cell, myeloperoxidase activity, capillary permeability and TNF-alpha levels. In conclusion, we confirmed the inflammatory activity of MAP and affirm that this effect involves the reduction of TNF-alpha level.

Graphene based electrode materials for solar cell and electrochemical oxygen reduction

Diese Arbeit hat viele beispiellose synthetische Ansätze für neuartige Verbundwerkstoffe Graphen-und stickstoffhaltigen graphitischen Materialien erforscht. Die erhaltenen Materialien wurden als den transparenten Elektroden der Solarzellen, die freistehenden Elektroden mit verbesserter mechanischer Festigkeit, und die Kathoden der Brennstoffzellen der Sauerstoffreduktion aufgebracht.rnAlle Ergebnisse haben eindeutig das große Potenzial von Graphen basierenden Materialien und stickstoffhaltigen graphitische Kohlenstoffe als neuartige Elektrodenmaterialien für neue Energie-Geräten demonstriert.

Role of catechol in the radical reduction of B-alkylcatecholboranes in presence of methanol

Mechanistic investigations on the previously reported reduction of B-alkylcatecholboranes in the presence of methanol led to the disclosure of a new mechanism involving catechol as a reducing agent. More than just revising the mechanism of this reaction, we disclose here the surprising role of catechol, a chain breaking antioxidant, which becomes a source of hydrogen atoms in an efficient radical chain process

Homo-DNA templated chemistry and its application to nucleic acid sensing

We have investigated the homo-DNA templated Staudinger reduction of the profluorophore rhodamine azide and have applied this reaction to the detection of natural DNA with a hybrid homo-DNA/DNA molecular beacon. In this system the sensing and the reporting unit are bioorthogonal to each other which facilitates sequence design and increases fidelity.

Exploratory studies on coordination chemistry of a redox-active bridging ligand: synthesis, properties and solid state structures of the complexes

The explorative coordination chemistry of the bridging ligand TTF-PPB is presented. Its strong binding ability to Co(II) and then to Ni(II) or Cu(II) in the presence of hexafluoroacetylacetonate (hfac(-)), forming new mono-and dinuclear complexes 1-3, is described. X-ray crystallographic studies have been conducted in the case of the free ligand TTF-PPB as well as its complexes [Co(TTF-PPB)(hfac)(2)] (1) and [Co(hfac)(2)(mu-TTF-PPB)Ni(hfac)(2)] (2). Each metal ion is bonded to two bidentate hfac-anions through their oxygen atoms and two nitrogen atoms of the PPB moiety with a distorted octahedral coordination geometry. Specifically, nitrogen donor atoms of TTF-PPB adopt a cis-coordination but not in the equatorial plane, which is quite rare. Electronic absorption, photoinduced intraligand charge transfer ((1)ILCT), and electrochemical behaviour of 1-3 have been investigated. UV-Vis spectroscopy shows very strong bands in the UV region consistent with ligand centred pi-pi* transitions and an intense broad band in the visible region corresponding to a spin-allowed pi-pi* (1)ILCT transition. Upon coordination, the (1)ILCT band is bathochromically shifted by 3100, 6100 and 5900 cm(-1) on going from 1 to 3. The electrochemical studies reveal that all of them undergo two reversible oxidation and one reversible reduction processes, ascribed to the successive oxidations of the TTF moiety and the reduction of the PPB unit, respectively.

The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line

This study investigated the uptake, kinetics and cellular distribution of different surface coated quantum dots (QDs) before relating this to their toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads (PBs) were also examined (50 microg ml(-1)). The potential for uptake of QDs was examined by both fixed and live cell confocal microscopy as well as by flow cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages. Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was observed following 3D reconstruction of fixed cells, as well as by flow cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed only a small amount of uptake in a relatively small number of cells. This uptake was insufficient to be detected by flow cytometry. Imaging of fixed cells was not possible due to a loss in cell integrity related to cytotoxicity. A significant reduction (p<0.05) in the fluorescent intensity in a cell-free environment was found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative of an endosome) after 2 h, suggesting reduced stability. No evidence of exocytosis was found over 2 h. These findings confirm that surface coating has a significant influence on the mode of NP interaction with cells, as well as the subsequent consequences of that interaction.

Sulfoxides as an intramolecular sulfenylating agent for indoles and diverse applications of the sulfide-sulfoxide redox cycle in organic chemistry

This dissertation involves study of various aspects of sulfoxide chemistry. Specifically designed t-butyl and propanenitrile sulfoxides tethered to indole-2-carboxamide were used as a source of intramolecular sulfenylating agents to synthesize novel indolo[3,2-b]-1-5-benzothiazepinones which are structurally analogous to the other biologically active benzothiazepinones. This study reveals that the intramolecular cyclization of sulfoxide follows an electrophilic sulfenylation (Sulfoxide Electrophilic Sulfenylation, SES) reaction pathway. Evidence of the absence of sulfenic acid as a transient reactive intermediate in such intramolecular cyclization is also provided. In another study, sulfoxide was used as a “protecting group” of thioether to synthesize 8-membered, indole substituted, thiazocine-2-acetic acid derivative via Ring Closing Metathesis (RCM). Protection (oxidation) of inert (to RCM) sulfide to sulfoxide followed by RCM produced cyclized product in good yields. Deprotection (reduction) of sulfoxide was achieved using Lawessons Reagent (L.R.). Application of the sulfide-sulfoxide redox cycle to solve the existing difficulties in using RCM methodology to thioethers is illustrated. A new design of a “molecular brake”, based on the sulfide-sulfoxide redox cycle is described. N-Ar rotation in simple isoindolines is controlled by the oxidation state of the proximate sulfur atom. Sulfide [S(II)] shows “free” [brake OFF] N-Ar rotation whereas sulfoxide displayed hindered [brake ON] N-Ar rotation. The semi-empirical molecular orbital (PM3) calculations revealed concerted pyramidalization of amidic nitrogen with N-Ar rotation.

Convenient synthesis of substituted α-methylene--valerolactones in aqueous medium using Baylis-Hillman chemistry

A mild and convenient synthesis of substituted α-methylene--valerolactones was achieved by SN2 nucleophilic substitution of the acetates of the Baylis-Hillman adducts with acetyl acetone followed by one-pot saponification of the ester, reduction of the keto group and subsequent intramolecular ring closure in aqueous medium.

Studies on the reduction of the nitro group in 3-aryl-2-methylene-4-nitro-alkanoates afforded by the Baylis-Hillman adducts: Synthesis of 4-aryl-3-methylene-2-pyrrolidinones and 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylates

The formation of substituted 2-pyrrolidinones and indoles by the reduction of the secondary nitro group in appropriate 3-aryl-2-methylene-4-nitroalkanoates afforded by Baylis-Hillman chemistry via different reducing agents is described. The 3-aryl-2-methylene-4-nitroalkanoate obtained from SN2 nucleophilic reaction between the acetate of Baylis-Hillman adducts and ethyl nitroacetate upon reduction with indium-HCl furnishes a mixture of cis and trans substituted phenyl-3-methylene-2-pyrrolidinones. In contrast, similar reductions of analogous substrates derived from nitroethane stereoselectively furnished only the trans substituted phenyl-3-methylene-2-pyrrolidinones. On the other hand the SnCl2.2H2O-promoted reductions of substrates derived from nitro ethylacetate give oxime derivatives while the ones obtained from nitroethane yield a mixture of cis and trans 4-aryl-3-methylene-2-pyrrolidinones. Alternatively, the SnCl2.2H2O-promoted reduction of substituted 2-nitrophenyl-2-methylene-alkanoate furnished from ethyl nitroacetate yields 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylate while indium-promoted reaction of this substrate leads to a complex mixture. Analogous reactions with SnCl2.2H2O of substituted 2-nitrophenyl-2-methylene-alkanoate obtained from nitroethane yield 4-alkyl-3-methylene-2-quinolones in moderate yields

An alternate approach to quinoline architecture via Baylis-Hillman chemistry: SnCl2-mediated tandem reaction toward synthesis of 4-(substituted vinyl)-quinolines

An alternate approach to densely substituted quinolines from the products of SN2 nucleophilic substitution reaction between the acetyl derivatives of the Baylis-Hillman adducts obtained from 2-nitrobenzaldehydes and the carbonyl group containing carbon nucleophiles is described. Treatment of these compounds with SnCl2, trigger a tandem reaction wherein reduction of the nitro group is followed by a remarkably regioselective intramolecular cyclization and subsequent dehydrogenation to afford 4-(substituted vinyl)-quinolines.

Forcing of stratospheric chemistry and dynamics during the Dalton Minimum

The response of atmospheric chemistry and dynamics to volcanic eruptions and to a decrease in solar activity during the Dalton Minimum is investigated with the fully coupled atmosphere–ocean chemistry general circulation model SOCOL-MPIOM (modeling tools for studies of SOlar Climate Ozone Links-Max Planck Institute Ocean Model) covering the time period 1780 to 1840 AD. We carried out several sensitivity ensemble experiments to separate the effects of (i) reduced solar ultra-violet (UV) irradiance, (ii) reduced solar visible and near infrared irradiance, (iii) enhanced galactic cosmic ray intensity as well as less intensive solar energetic proton events and auroral electron precipitation, and (iv) volcanic aerosols. The introduced changes of UV irradiance and volcanic aerosols significantly influence stratospheric dynamics in the early 19th century, whereas changes in the visible part of the spectrum and energetic particles have smaller effects. A reduction of UV irradiance by 15%, which represents the presently discussed highest estimate of UV irradiance change caused by solar activity changes, causes global ozone decrease below the stratopause reaching as much as 8% in the midlatitudes at 5 hPa and a significant stratospheric cooling of up to 2 °C in the mid-stratosphere and to 6 °C in the lower mesosphere. Changes in energetic particle precipitation lead only to minor changes in the yearly averaged temperature fields in the stratosphere. Volcanic aerosols heat the tropical lower stratosphere, allowing more water vapour to enter the tropical stratosphere, which, via HOx reactions, decreases upper stratospheric and mesospheric ozone by roughly 4%. Conversely, heterogeneous chemistry on aerosols reduces stratospheric NOx, leading to a 12% ozone increase in the tropics, whereas a decrease in ozone of up to 5% is found over Antarctica in boreal winter. The linear superposition of the different contributions is not equivalent to the response obtained in a simulation when all forcing factors are applied during the Dalton Minimum (DM) – this effect is especially well visible for NOx/NOy. Thus, this study also shows the non-linear behaviour of the coupled chemistry-climate system. Finally, we conclude that especially UV and volcanic eruptions dominate the changes in the ozone, temperature and dynamics while the NOx field is dominated by the energetic particle precipitation. Visible radiation changes have only very minor effects on both stratospheric dynamics and chemistry.

Climate and chemistry effects of a regional scale nuclear conflict

Previous studies have highlighted the severity of detrimental effects for life on earth after an assumed regionally limited nuclear war. These effects are caused by climatic, chemical and radiative changes persisting for up to one decade. However, so far only a very limited number of climate model simulations have been performed, giving rise to the question how realistic previous computations have been. This study uses the coupled chemistry climate model (CCM) SOCOL, which belongs to a different family of CCMs than previously used, to investigate the consequences of such a hypothetical nuclear conflict. In accordance with previous studies, the present work assumes a scenario of a nuclear conflict between India and Pakistan, each applying 50 warheads with an individual blasting power of 15 kt ("Hiroshima size") against the major population centers, resulting in the emission of tiny soot particles, which are generated in the firestorms expected in the aftermath of the detonations. Substantial uncertainties related to the calculation of likely soot emissions, particularly concerning assumptions of target fuel loading and targeting of weapons, have been addressed by simulating several scenarios, with soot emissions ranging from 1 to 12 Tg. Their high absorptivity with respect to solar radiation leads to a rapid self-lofting of the soot particles into the strato- and mesosphere within a few days after emission, where they remain for several years. Consequently, the model suggests earth's surface temperatures to drop by several degrees Celsius due to the shielding of solar irradiance by the soot, indicating a major global cooling. In addition, there is a substantial reduction of precipitation lasting 5 to 10 yr after the conflict, depending on the magnitude of the initial soot release. Extreme cold spells associated with an increase in sea ice formation are found during Northern Hemisphere winter, which expose the continental land masses of North America and Eurasia to a cooling of several degrees. In the stratosphere, the strong heating leads to an acceleration of catalytic ozone loss and, consequently, to enhancements of UV radiation at the ground. In contrast to surface temperature and precipitation changes, which show a linear dependence to the soot burden, there is a saturation effect with respect to stratospheric ozone chemistry. Soot emissions of 5 Tg lead to an ozone column reduction of almost 50% in northern high latitudes, while emitting 12 Tg only increases ozone loss by a further 10%. In summary, this study, though using a different chemistry climate model, corroborates the previous investigations with respect to the atmospheric impacts. In addition to these persistent effects, the present study draws attention to episodically cold phases, which would likely add to the severity of human harm worldwide. The best insurance against such a catastrophic development would be the delegitimization of nuclear weapons.

Probing the Electrocatalytic Oxygen Reduction Reaction Reactivity of Immobilized Multicopper Oxidase CueO

The bioelectrocatalytic (oxygen reduction reaction, ORR) properties of the multicopper oxidase CueO immobilized on gold electrodes were investigated. Macroscopic electrochemical techniques were combined with in situ scanning tunneling microscopy (STM) and surface-enhanced Raman spectroscopy at the ensemble and at the single-molecule level. Self-assembled monolayer of mercaptopropionic acid, cysteamine, and p-aminothiophenol were chosen as redox mediators. The highest ORR activity was observed for the protein attached to amino-terminated adlayers. In situ STM experiments revealed that the presence of oxygen causes distinct structure and electronic changes in the metallic centers of the enzyme, which determine the rate of intramolecular electron transfer and, consequently, affect the rate of electron tunneling through the protein. Complementary Raman spectroscopy experiments provided access for monitoring structural changes in the redox state of the type 1 copper center of the immobilized enzyme during the CueO-catalyzed oxygen reduction cycle. These results unequivocally demonstrate the existence of a direct electronic communication between the electrode substrate and the type 1 copper center.