An investigation of the chemical stability of arsenosugars in basic environments using IC-ICP-MS and IC-ESI-MS/MS

This paper evaluates the chemical stability of four arsenosugars using tetramethylammonium hydroxide (TMAOH) as an extraction solvent. This solvent was chosen because of the near quantitative removal of these arsenicals from difficult to extract seafood (oysters and shellfish). Four arsenosugars (3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropylene glycol--As(328), 3-5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropanesulfonic acid--As(392), 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl hydrogen sulfate--As(408), and 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl-2,3-hydroxypropyl phosphate--As(482)) were evaluated. The stability of these four arsenosugars were studied independently in a solution of 2.5% TMAOH at 60 degrees C over a period of up to 8 h. Two arsenosugars, As(328) and As(392), were found to be relatively stable in this solution for up to 8 h. However, As(408) and As(482) formed detectable quantities of dimethylarsinic acid (DMAA) and As(328) within 0.5 and 2 h, respectively. It was found that 97% of As(408) degrades after 8 h of treatment producing 3.4 times as much DMAA as As(328). This is contrary to As(482), which produces 13 times as much As(328) as DMAA and only 37% of the As(482) was converted by the 8 h treatment at 60 degrees C. These degradation products led to the investigation of weaker TMAOH extraction solvents. Three different concentrations (2.5%, 0.83% and 0.25%) were used to determine the effect of TMAOH concentration on the degradation rate of As(408). By reducing the TMAOH concentration to 0.83%, the conversion of the arsenosugar to As(328) and DMAA is nearly eliminated (less than 5% loss). Arsenosugars, As(408) and As(482), were also studied in 253 mM NaOH to verify the degradation products. The NaOH experiments were conducted to investigate a possible hydroxide based reaction mechanism. Similar degradation plots were found for each arsenosugar when compared to the 2.5% TMAOH data. A mechanism has been proposed for the formation of As(328) from As(408) and As(482) in base via an SN2 reaction (hydroxide attack) at the side chain carbon adjacent to the inorganic ester. The formation of DMAA is observed in all arsenosugars after prolonged exposure. This probably occurs via an SN2 attack at the arsenic atom.     

Global and local electrophilicity patterns of diazonium ions and their reactivity toward pi-nucleophiles

The global and local electrophilicity patterns of a series of 15 diazonium ions have been evaluated using the absolute scale of electrophilicity proposed by Parr et al. (J. Am. Chem. Soc. 1999, 121, 1922). The predicted global electrophilicity pattern of the whole series of diazonium ions correctly compares with the experimental electrophilicity recently determined for these charged electrophiles. The global electrophilicity is then projected into the different potential active sites of the molecular ions using the electrophilic Fukui function. The highest regional electrophilicity power is found at the terminal nitrogen atom of the arenediazonium ions, yet the highest positive charge is located on the nitrogen atom directly attached to the aromatic ring. This result is consistent with the observed reactivity displayed by diazonium ions toward substituted alkenes, thereby suggesting that the formation of the azocarbocation intermediate is mostly orbital rather than charge controlled.     

Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design

The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.     

Electrochemical synthesis and characterization of conducting polymers in supercritical carbon dioxide

This contribution reports the first synthesis of conducting polymers (CPs), specifically, polyaniline (PAn) and polypyrrole (PPy), in supercritical carbon dioxide (scCO2). CPs synthesized electrochemically in scCO2 were characterized with cyclic voltammetry (CV), four-point probe conductivity, scanning electron microscopy (SEM), and UV-vis spectroscopy. Preliminary data indicate that CPs synthesized by this method exhibit novel morphology and high conductivity comparable to that synthesized by traditional methods.     

Zerovalent Rhodium and Iridium Silatranes Featuring Two‐Center,Three‐Electron Polar σ Bonds

Species with 2‐center, 3‐electron (2c/3e^?) σ bonds are of interest owing to their fascinating electronic structures and potential for interesting reactivity patterns. Report here is the synthesis and characterization of a pair of zerovalent (d⁹) trigonal pyramidal Rh and Ir complexes that feature 2c/3e^? σ bonds to the Si atom of a tripodal tris(phosphine)silatrane ligand. X‐ray diffraction, continuous wave and pulse electron paramagnetic resonance, density‐functional theory calculations, and reactivity studies have been used to characterize these electronically distinctive compounds. The data available highlight a 2c/3e^? bonding framework with a σ*‐SOMO of metal 4‐ or 5d_z² parentage that is partially stabilized by significant mixing with Si (3p_z) and metal (5‐ or 6p_z) orbitals. Metal‐ligand covalency thus buffers the expected destabilization of transition‐metal (TM)‐silyl σ*‐orbitals by d–p mixing, affording well‐characterized examples of TM–main group, and hence polar, 2c/3e^? σ “half‐bonds”.     

Direct and simultaneous spectrofluorometric determination of naproxen and salicylate in human serum assisted by chemometric analysis

A direct method for the simultaneous determination of naproxen and salicylate in human serum is reported, based on a combination of spectrofluorometric measurements with two multivariate calibration techniques: partial least-squares (PLS-1) and the novel net analyte preprocessing (NAP). The method is rapid, selective and sensitive, and is based on the measurement of the fluorescence spectra of NH₃ alkalinized whole human sera at the excitation wavelength of 315 nm. It can be applied within the ranges of concentrations 50-200 ng ml⁻¹ for naproxen and 100-300 ng ml⁻¹ for salicylate. The employed chemometric techniques have been compared on the basis of the statistical indicators for calibration and validation. Reproducibility and interference studies in abnormal sera have also been carried out.     

Simulation of aerated lagoon using artificial neural networks and multivariate regression techniques

The aim of this study was to develop an empirical model that provides accurate predictions of the biochemical oxygen demand of the output stream from the aerated lagoon at International Paper of Brazil, one of the major pulp and paper plants in Brazil. Predictive models were calculated from functional link neural networks (FLNNs), multiple linear regression, principal components regression, and partial least-squares regression (PLSR). Improvement in FLNN modeling capability was observed when the data were preprocessed using the PLSR technique. PLSR also proved to be a powerful linear regression technique for this problem, which presents operational data limitations.     

Preliminary characterization of anhydrous ethanol used in Brazil as automotive fuel

This work reports preliminary studies on the characterisation of anhydrous ethanol (AEA) used as an automotive fuel mixed with gasoline in Porto Alegre (South Brazil). Pre-concentration of the impurities contained in 1000 ml of AEA was carried on through solid-phase extraction using XAD4 resin. The main compounds in the extract were identified by means of spectral data from the library of the equipment. The concentrate was then fractionated using a preparative liquid chromatographic column filled with activated silica gel and the elution procedure was carried out with, n-hexane, n-hexane-benzene (1:1, v/v) and dichloromethane. Prior to analysis by GC-MS, each fraction was reduced to 1 ml with a gentle stream of nitrogen. Saturated linear hydrocarbons and aromatic hydrocarbons eluted in the first fraction and oxygenated compounds such as aldehydes. ketones and alcohols, eluted in the second one. were the main compounds detected in the sample.     

Formation of a cyclobutylidene ring: intramolecular [2 + 2] cycloaddition of allyl and vinylidene C=C bonds under mild conditions

Intramolecular [2 + 2] cycloaddition of two C=C bonds in vinylidene complexes [Ru(eta5-C9H7){=C=C(R)H}(PPh3){kappa1-(P)-PPh2(C3H5)][BF4] affords cyclobutylidene complexes [Ru(eta5-C9H7){kappa2-(P,C)-(=CC(R)HCH2CHCH2PPh2)}(PPh3)][BF4], which can be also obtained by reaction of terminal alkynes with [Ru(eta5-C9H7)(PPh3){kappa3-(P,C,C)-PPh2(C3H5)}][PF6]. The reaction proceeds under mild conditions via vinylidene complexes, and the activation parameters were determined by kinetic studies.