Tree ring microanalysis by LA–ICP–MS for environmental monitoring: validation or refutation? Two case histories

An empirical approach is presented for validating trace metal profiles in tree rings for use as environmental archives. Concentration profiles of Zn, Cd, Cu, Pb and U in tree rings and lake sediments are compared for assessing the reliability of the former as an environmental proxy. Laser ablation sampling in conjunction with inductively coupled plasma mass spectrometry (LA–ICP–MS) is used for the direct analysis of tree rings. An optimised analytical protocol is devised with particular emphasis on sample preparation and quantification strategy. Significant correlations in the two environmental archives were found for zinc, copper and uranium, while cadmium and lead temporal trends, although showing enrichment in recent years, do not agree with the concentration profiles in lacustrine sediment cores. A chemical model based on metal affinity for hard type ligands present in wood is proposed to explain these results. Moreover, spring and winter wood are analysed separately thanks to the high spatial resolution of laser ablation sampling. As a result, enhanced metal loadings are shown to lead to intraring differences in trace metal concentrations.     

Synthesis and Biophysical Studies on 35‐Deoxy Amphotericin B Methyl Ester

The use of molecular editing in the elucidation of the mechanism of action of amphotericin B is presented. A modular strategy for the synthesis of amphotericin B and its designed analogues is developed, which relies on an efficient gram‐scale synthesis of various subunits of amphotericin B. A novel method for the coupling of the mycosamine to the aglycone was identified. The implementation of the approach has enabled the preparation of 35‐deoxy amphotericin B methyl ester. Investigation of the antifungal activity and efflux‐inducing ability of this amphotericin B congener provided new clues to the role of the 35‐hydroxy group and is consistent with the involvement of double barrel ion channels in causing electrolyte efflux.     

Standard Model without elementary scalars and high energy Lorentz violation

If Lorentz symmetry is violated at high energies, interactions that are usually non-renormalizable can become renormalizable by weighted power counting. Recently, a CPT invariant, Lorentz violating extension of the Standard Model containing two scalar-two fermion interactions (which can explain neutrino masses) and four fermion interactions (which can explain proton decay) was proposed. In this paper we consider a variant of this model, obtained suppressing the elementary scalar fields, and argue that it can reproduce the known low-energy physics. In the Nambu–Jona-Lasinio spirit, we show, using a large N _c expansion, that a dynamical symmetry breaking takes place. The effective potential has a Lorentz invariant minimum and the Lorentz violation does not reverberate down to low energies. The mechanism generates fermion masses, gauge-boson masses and scalar bound states, to be identified with composite Higgs bosons. Our approach is not plagued by the ambiguities of approaches based on non-renormalizable vertices. The low-energy effective action is uniquely determined and predicts relations among parameters of the Standard Model.     

Fostering and Understanding Iron Detection at the Ultratrace Level by Adsorptive Stripping Voltammetry with Catalytic Enhancement

Iron detection at the ultratrace level in seawater is at the forefront in chemical oceanography research and analytical methodologies for its determination are actively sought. Voltammetric methods and specifically cathodic stripping voltammetry (CSV) with catalytic enhancement, are particularly fit for this purpose as they avoid any separation and pretreatment step, showing high sensitivity and robustness towards the saline matrix. Here we introduce a simplification in the instrumentation for iron detection by CSV using 2,3‐dihydroxynaphthalene (DHN) as the ligand, atmospheric oxygen as the catalytic enhancer and a small 0.5 mL cell. The simplification involves the use of a standard, non‐specialized voltammetric cup as a holder for the small cell and the introduction of a simple silver wire as a pseudoreference electrode. The latter reduces the risk of sample contamination and is perfectly suited for employment with the small, 0.5 mL volume cell. Extensive optimization was performed in both ultrapure and seawater: a square wave frequency of 10 Hz was adopted, whereas the ligand concentration did not significantly influence the limit of detection (around 10 and 40 pM for ultrapure and seawater, respectively). The latter difference in signal to noise ratio was explained by the kinetics of iron complex reduction. The method was successfully validated by the analysis of a seawater sample with consensus value.     

The Microalga Skeletonema marinoi Induces Apoptosis and DNA Damage in K562 Cell Line by Modulating NADPH Oxidase

Chronic myeloid leukemia (CML) is a myeloproliferative disease that activates multiple signaling pathways, causing cells to produce higher levels of reactive oxygen species (ROS). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are a major generator of ROS in leukemia, and marine natural products have shown promising activities for the treatment of hematopoietic malignancies. In the present study, we investigated the effect of the marine microalga Skeletonema marinoi (S.M.), a ubiquitous diatom that forms massive blooms in the oceans, on the human leukemia cell line K562. The effects of S.M. extract on cell viability, production of ROS, nitric oxide (NO), and apoptosis were examined. In this preliminary work, S.M. was able to decrease cell viability (p < 0.05) and increase apoptosis levels (p < 0.05) in K562 cells after 48 h of treatment. In addition, the levels of NOX, NO, and malondialdehyde (MDA) were reduced in K562-treated cells (p < 0.05), whereas the levels of SOD, CAT, and GPx increased during treatment (p < 0.05). Finally, analyzing Bax and Bcl-2 expression, we found a significant increase in the proapoptotic protein Bax and a sustained decrease in the antiapoptotic protein Bcl-2 (p < 0.05) in the K562-treated cells.     

A formal total synthesis of eleutherobin using the ring-closing metathesis (RCM) reaction of a densely functionalized diene as the key step: investigation of the unusual kinetically controlled RCM stereochemistry

Asymmetric oxyallylation reactions and ring-closing metathesis have been used to synthesize compound 3, a key advanced intermediate used in the total synthesis of eleutherobin reported by Danishefsky and co-workers. The aldehyde 6, which is readily prepared from commercially available R-(-)-carvone in six steps in 30 % overall yield on multigram quantities, was converted into the diene 5 utilizing two stereoselective titanium-mediated Hafner-Duthaler oxyallylation reactions. The reactions gave the desired products (8 and 12) in high yields (73 and 83 %, respectively) as single diastereoisomers, with the allylic alcohol already protected as the p-methoxyphenyl (PMP) ether, which previous work has demonstrated actually aids ring-closing metathesis compared to other protective groups and the corresponding free alcohol. Cyclization under forcing conditions, using Grubbs' second-generation catalyst 13, gave the ten-membered carbocycle (E)-14 in 64 % yield. This result is in sharp contrast to similar, but less functionalized, dienes, which have all undergone cyclization to give the Z stereoisomers exclusively. A detailed investigation of this unusual cyclization stereochemistry by computational methods has shown that the E isomer of the ten-membered carbocycle is indeed less thermodynamically stable than the corresponding Z isomer. In fact, the selectivity is believed to be due to the dense functionality around the ruthenacyclobutane intermediate that favors the trans-ruthenacycle, which ultimately leads to the less stable E isomer of the ten-membered carbocycle under kinetic control. During the final synthetic manipulations the double bond of enedione (E)-16 isomerized to the more thermodynamically stable enedione (Z)-4, giving access to the advanced key-intermediate 3, which was spectroscopically and analytically identical to the data reported by Danishefsky and co-workers, and thereby completing the formal synthesis of eleutherobin.