Copper-assisted oxidation of catechols into quinone derivatives

Catechols are ubiquitous substances often acting as antioxidants, thus of importance in a variety of biological processes. The Fenton and Haber–Weiss processes are thought to transform these molecules into aggressive reactive oxygen species (ROS), a source of oxidative stress and possibly inducing degenerative diseases. Here, using model conditions (ultrahigh vacuum and single crystals), we unveil another process capable of converting catechols into ROSs, namely an intramolecular redox reaction catalysed by a Cu surface. We focus on a tri-catechol, the hexahydroxytriphenylene molecule, and show that this antioxidant is thereby transformed into a semiquinone, as an intermediate product, and then into an even stronger oxidant, a quinone, as final product. We argue that the transformations occur via two intramolecular redox reactions: since the Cu surface cannot oxidise the molecules, the starting catechol and the semiquinone forms each are, at the same time, self-oxidised and self-reduced. Thanks to these reactions, the quinone and semiquinone are able to interact with the substrate by readily accepting electrons donated by the substrate. Our combined experimental surface science and ab initio analysis highlights the key role played by metal nanoparticles in the development of degenerative diseases.

An antioxidant catechol transforms following intramolecular redox reactions into highly reactive oxygen species, a semiquinone and a quinone, on copper.     

A simple and fast micromethod for the analysis of polychlorinated biphenyls in air by sorbent enrichment and ultrasound-assisted solvent extraction

A combination of sorbent enrichment and ultrasound-assisted solvent extraction has been used to determine polychlorinated biphenyls in air. Analytes were sampled by pumping a known volume of air through a porous polymer (Tenax TA). The enriched adsorbent was transferred into a glass vial, and ultrasound-assisted extraction of the analytes was then performed in n-hexane. Quantification was carried out by using gas chromatography coupled to tandem mass spectrometry. Breakthrough volume of the sampling step was studied, indicating that 10 m³ of air could be processed without losses of the most volatile compounds. Good recoveries (75–96%) were obtained, and limits of detection at the sub ng m^–3 were achieved for all the analytes. The proposed method is very simple and fast, avoiding the use of large solvent volumes and time-consuming preconcentration steps.     

As, Bi, Sb and Sn determination in atmospheric particulate matter by direct solid sampling-hydride generation-electrothermal atomic absorption spectrometry

A novel, rapid and simple method by hydride generation-electrothermal atomic absorption spectrometry (HG-ETAAS) after direct As, Bi, Sb and Sn hydrides generation from untreated filters of atmospheric particulate matter (PM₁₀ and PM_2.5) was optimised. PM₁₀ and PM_2.5 were not subjected to any pre-treatment: circular portions between 0.28 and 6.28 cm² were directly placed into the reaction vessel of a batch mode generation system. A 2⁸ × 3/64 Plackett–Burman design was used as a multivariate strategy for the evaluation of the effects of several variables affecting the hydride generation, trapping and atomisation efficiencies. Trapping temperature was the most statistically significant variable for As, Bi and Sn. Atomisation temperature was also statistically significant for Sb determination. Optimum values of significant variables were selected by using univariate optimisation approaches. An aqueous calibration method was used throughout. The developed method has been found to be precise with relative standard deviations of 6.2, 5.3, 9.1 and 7.5% for 11 determinations in a filter sample containing 0.7, 1.0, 1.4 and 1.7 μg l⁻¹ for As, Bi, Sb and Sn, respectively. Results obtained by direct solid sampling-HG-ETAAS have been found statistically comparable with those obtained after conventional method based on an acid digestion followed to ICP-MS. Absolute detection limits were 37, 15, 30, and 41 ng l⁻¹ for As, Bi, Sb and Sn, respectively. Detection limits referred to the air volume sampled (in the range of 0.020–0.050 ng m⁻³) were low enough for the determination of several hydride-forming elements from PM₁₀ and PM_2.5 samples collected in a non-polluted suburban area of A Coruña (NW Spain).     

On the generation of novel anticancer drugs by recombinant DNA technology: the use of combinatorial biosynthesis to produce novel drugs

Chemotherapeutic drugs for cancer treatment have been traditionally originated by the isolation of natural products from different environmental niches, by chemical synthesis or by a combination of both approaches thus generating semisynthetic drugs. In the last years, a number of gene clusters from several antitumor biosynthetic pathways, mainly produced by actinomycetes and belonging to the polyketides family, are being characterized. Genetic manipulation of these antitumor biosynthetic pathways will offer in the near future an alternative for the generation of novel antitumor derivatives and thus complementing current methods for obtaining novel anticancer drugs. Novel antitumor derivatives have been produced by targetted gene disruption and heterologous expression of single (or a few) gene(s) in another hosts or by combining genes from different, but structurally related, biosynthetic pathways ("combinatorial biosynthesis"). These strategies take advantage from the "relaxed substrate specificity" that characterize secondary metabolism enzymes.     

Effect of ionic interactions on the oxidation of Fe(II) with H2O2 in aqueous solutions

The oxidation of Fe(II) with H₂O₂ has been measured in NaCl and NaClO₄ solutions as a function of pH, temperature T (K) and ionic strength (M, mol-L^–1). The rate constants, k (M^–1-sec^–1), d[Fe(II)]/DT=-k[Fe(II)][₂O₂]at pH=6.5 have been fitted to equations of the formlog k = log k₀+ AI ^1/2+BI+CI ^1/2/T Where log k₀=15.53-3425/T in water; A=–2.3, –1.35; B=0.334, 0.180; and C=391, 235, respectively, for NaCl (=0.09) and NaClO₄ ( =0.08). Measurements made in NaCl solutions with added anions yield rates in the order B(OH) ₄ ^– >HCO ₃ ^– >ClO ₄ ^– >Cl^–>NO ₃ ^– >SO ₄ ^2– and are attributed to the relative strength of the interactions of Fe²⁺ or FeOH⁺ with these anions. The FeB(OH) ₄ ⁺ species is more reactive while the FeCO ₃ ⁰ , FeCl⁺, FeNO ₃ ⁺ and FeSO ₄ ⁰ species are less reactive than the FeOH⁺ ion pair. The general trend is similar to our earlier studies of the oxidation of Fe(II) with O₂ except for B(OH) ₄ ^– . The effect of pH on the logk was found to be a quadratic function of the concentration of H⁺ or OH^– from pH=4 to 8. These results have been attributed to the different rate constants for Fe²⁺ (k₀) and FeOH⁺ (k₁) which are related to the measured k by, k=k_0Fe + k_1FeOH, where _i is the molar fraction of species i. The rates increase due to the greater reactivity of FeOH⁺ compared to Fe²⁺. k₀ is independent of composition and ionic strength but k₁ is a function of ionic strength and composition due to the interactions of FeOH⁺ with various anions.     

New oxamidato-bridged Cu(II)-Ni(II) complexes: supramolecular structures with thiocyanate ligands and hydrogen bonds. Magnetostructural studies: DFT calculations

Four new supramolecular compounds of Cu(II)-Ni(II) have been synthesized and characterized: [Cu(Me(2)oxpn)Ni(mu-NCS)(H(2)O)(tmen)](2)(ClO(4))(2) (1), [Cu(Me(2)oxpn)Ni(mu-NCS)(H(2)O)(tmen)](2)(PF(6))(2) (2), [Cu(oxpn)Ni(mu-NCS)(NCS) (tmen)](n) (3), and [Cu(Me(2)oxpn)Ni(mu-NCS)(NCS)(tmen)](n) (4), where oxpn = N,N'-bis(3-aminopropyl)oxamidate, Me(2)oxpn = N,N'-bis(3-amino-2,2'-dimethylpropyl)oxamidate, and tmen = N,N,N',N'-tetramethylethylenediamine. Their crystal structures were solved. Complexes 1 and 2 have the same tetranuclear cationic part but a different counteranion. The cationic part consists of two [Cu(Me(2)oxpn)Ni] moieties linked by SCN(-) bridged ligands and intra-tetranuclear hydrogen bonds. In the case of complex 3, a two-dimensional system was built, the thiocyanate ligand linking the dinuclear units gives a chain, and the chains are linked together by hydrogen bonds; intrachain hydrogen bonds are also present. For complex 4, the thiocyanate ligands produce intermolecular linkages between the dinuclear entities, giving a one-dimensional system; intrachain hydrogen bonds are also present. The magnetic properties of the four complexes were studied by susceptibility measurements vs temperature. DFT calculations were made to study the contribution of the SCN(-) and hydrogen bond bridges in the magnetic coupling.     

First enantioselective total synthesis of (-)-Centrolobine

[structure: see text] The first enantioselective total synthesis of (-)-Centrolobine is described. The key reaction is the synthesis of the cis-disubstituted tetrahydropyran framework by intramolecular cyclization of the enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute configuration of (-)-Centrolobine is proposed.     

Design and Application of a Set of Vitreous Standards for EDS-SEM Microanalysis of Melting Shop Slags

Non-metallic inclusions in steel are formed due to interactions between liquid steel and its environment in the melting shop (refractories and slags). Particles not trapped in the slag remain in the cast steel, impairing steel properties in service. Inclusion composition varies and certified standards covering the whole compositional range are unavailable.The present study describes the preparation of a set of homogeneous, glassy and crystalline standards with a wide compositional range for use in analysing non-metallic steel inclusions. For this, materials were designed based on knowledge of the compositional range of interest in the Al₂O₃–SiO₂–CaO–MgO–CaF₂ system, which is the matrix of the most frequent steel inclusions. The composition and microstructural homogeneity of the reference materials was verified.     

Energetic and topological analyses of the oxidation reaction between Mo(n) (n = 1, 2) and N2O

The interaction between molybdenum, atom, and dimer, with nitrous oxide has been investigated using density functional theory. The analysis of the potential energy surfaces for both reactions has revealed that a single molybdenum atom can activate the N--O bond of N2O requiring a small activation energy. However, the presence of several intersystem crossings between three different spin states, namely, septet, quintet and triplet states, seems to be the major constraint to the Mo + N2O reaction. Contrarily, the low-lying excited states (triplet and quintet) do not participate in the reaction between the molybdenum dimer and N2O. The latter reaction fully evolves on the singlet spin surface. Three different regions have been distinguished along the pathway: formation of an adduct complex, formation of an inserted compound, and the N2 detachment. The connection between the two first regions has been characterized by the formation of a special complex in which the N--O bond is so weakened that it could be considered as a first step in the insertion process. It has been shown that the topological changes along the pathways provide a clear explanation for the geometrical changes that occur along the reaction pathway. In summary, the detachment of the N2 molecule is found to be kinetically an effective process for both reactions, owing to the high exothermicity and consequently to the high internal energy of the insertion intermediates. However, in the case of Mo atom, the reaction should be a slow process due to the presence of spin-forbidden transitions. These results fully agree with previous experimental works.     

Development of a liquid chromatography/tandem mass spectrometry assay for the quantification of PM00104, a novel antineoplastic agent, in mouse, rat, dog, and human plasma

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay was developed and validated to quantify a novel antineoplastic agent, PM00104, in mouse, rat, dog, and human plasma. The method was validated to demonstrate the specificity, limit of quantification (LOQ), accuracy, and precision of measurements. The calibration range for PM00104 was established using PM00104 standards from 0.01-5.0 ng/mL in blank plasma. The selected reaction monitoring (SRM), based on the m/z 692.2 --> 218.2 transition, was specific for PM00104, and that based on the m/z 697.2 --> 218.2 transition was specific for PM00104 ((13)C(2),(2)H(3)) (the internal standard, IS); no endogenous materials interfered with the analysis of PM00104 and IS from blank plasma. The assay was linear over the concentration range 0.01-5.0 ng/mL. The correlation coefficients for the calibration curves ranged from 0.9981-0.9999. The mean intra-day and inter-day accuracies for all calibration standards (n = 8) ranged from 97-105% (< or =5% bias) in human plasma, and the mean inter-day precision for all calibration standards was less than 8.5%. The mean intra- and inter-day assay accuracy for all quality control (QC) replicates in human plasma (n = 9), determined at each QC level throughout the validated runs, ranged from 96-112% (< or =12% bias) and from 102-105% (< or =5% bias), respectively. The mean intra- and inter-day assay precision was less than 15.0 and 11.8% for all QC levels, respectively. For the QC samples prepared in animal species plasma, the %CV values of the assays ranged from 1.8-8.8% in mouse plasma, from 3.7-13.8% in rat plasma, and from 3.0-7.2% in dog plasma. The assay accuracies ranged from 92-102% (< or =8% bias) for all QC levels prepared in mouse plasma; ranged from 93-106% (< or =7% bias) in rat plasma; and ranged from 95-114% (< or =14% bias) in dog plasma. The assay has been used to support preclinical pharmacokinetic and toxicokinetic studies and is currently used to measure PM00104 plasma concentrations to support clinical trials.