Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part VI: Synthesis and incorporation of the novel polyhydroxylated 5-aminocyclopent-1-enecarboxylic acids into peptides

The first total synthesis of enantiopure methyl (3aR,4S,5S,6R,6aS)-4-benzyloxycarbonylamino-6-hydroxy-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-5-carboxylate has been carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines. This approach is based on an intramolecular cyclization that leads to 2-oxabicyclo[2.2.1]heptane derivatives. E1cb elimination of the methoxy substituent was observed when attempting to incorporate these β-amino acid into peptides. As a result, the synthesis and incorporation of the first polyhydroxylated 5-aminocyclopent-1-enecarboxylic acid into peptides were developed.     

(Liquid + liquid) equilibria for ternary mixtures of (alkane + benzene + [EMpy] [ESO4]) at several temperatures and atmospheric pressure

In this work, the separation of benzene from aliphatic hydrocarbons (hexane, or heptane) is investigated by extraction with 1-ethyl-3-methylpyridinium ethylsulphate ionic liquid, [EMpy][ESO₄]. (Liquid + liquid) equilibria (LLE) data are determined for the ternary systems: {hexane (1) + benzene (2) + [EMpy][ESO₄] (3)} at T = (283.15, 293.15, 298.15, and 303.15) K and {heptane (1) + benzene (2) + [EMpy][ESO₄] (3)} at T = (283.15 and 298.15) K and atmospheric pressure. The selectivity and distribution coefficient, derived from the tie line data, were used to determine whether the ionic liquid is a good solvent for the extraction of aromatic from aliphatic compounds. The consistency of the tie line data was ascertained by applying the Othmer–Tobias and Hand equations. The experimental results for the ternary systems were well correlated with the NRTL equation. A study of the temperature effect and the influence of the chain length of the alkanes were realized. The results obtained were compared with other ionic liquids. There are no literature data for the mixtures discussed in this paper.     

Mechanism and stereoselectivity of the aza-Wittig reaction between phosphazenes and aldehydes

The mechanism of the aza-Wittig reaction between phosphazenes and aldehydes has been studied computationally, using DFT methods (B3LYP/6-31G level), and experimentally. It has been found that the reaction consists of a tandem [2+2] cycloaddition-cycloreversion sequence in which pi and sigma orbitals as well as lone pairs are involved. Both [2+2] processes take place via thermally allowed supra-supra mechanisms. P-trimethyl-lambda(5)-phosphazenes are predicted to be more reactive than their P-triphenyl analogues. The stereochemical outcome of the whole reaction depends only on the second step, because conformational changes in the intermediate 1,3,2-lambda(5)-oxazaphosphazetidines have a much lower activation energy than the second [2+2] cycloreversion reaction. Preferential or exclusive formation of the corresponding (E)-imines is predicted.     

Rearrangement of 4,5-epoxy-9-trimethylsilyldecalines. Application to the synthesis of the natural eremophilane (-)-aristolochene

Several 4,5-epoxy-9-trimethylsilyl-eudesmanes and 15-nor-eudesmanes, having different relative stereochemistry and substitution at the oxirane ring, have been prepared starting from (-)-carvone and subjected to acid-promoted rearrangement. The presence of the silicon at C9 favors two different main reaction pathways involving C14-methyl or C1-methylene migration through the stabilization of a C10 carbocation intermediate. Selective 1,2-migration of the bridgehead methyl group takes place with trisubstituted beta-epoxide and tetrasubstituted alpha-epoxide, yielding 4-hydroxy-eremophilane and 15-nor-eremophilane compounds, while the trisubstituted alpha-epoxide suffers successive rearrangements to give a 1-hydroxy-15-nor-eremophilane through a pathway involving the initial migration of the C1 methylene. The synthetic utility of these rearrangements is shown by the synthesis of natural (-)-aristolochene.     

Amperometric determination of sulfite using screen-printed electrodes modified with metallic nanoparticles

We report on the amperometric determination of sulfite using screen-printed carbon electrodes (SPCEs) modified with gold and silver nanoparticles that were deposited on the electrode to improve the capabilities of detection. The electrode is fairly selective and responds to sulfite with an oxidation current (at 300 mV and pH 6) in the 9.80 to 83.33 μM concentration range. The precision in terms of repeatability and reproducibility is 14.4 % and 10.7 % in the case of SPCEs modified by gold nanoparticles. The method was applied to the determination of sulfite in drinking water, pickle juice and vinegar. Recoveries ranged from 96 % to 104 %.

Manganese(II) complexes of scorpiand-like azamacrocycles as MnSOD mimics

Mn(II) complexes of scorpiand-type azamacrocycles constituted by a tretrazapyridinophane core appended with an ethylamino tail including 2- or 4-quinoline functionalities show very appealing in vitro SOD activity. The observed behaviour is related to structural and electrochemical parameters.     

ACMA (9-amino-6-chloro-2-methoxy acridine) forms three complexes in the presence of DNA

The interaction of ACMA (9-amino-6-chloro-2-methoxy acridine) (D) with DNA (P) has been studied by absorbance, fluorescence, circular dichroism, spectrophotometry, viscometry and unwinding electrophoresis. A T-jump kinetic study has also been undertaken. The experimental data show that, totally unlike other drugs, ACMA is able to form with DNA three complexes (PD(I), PD(II), PD(III)) that differ from each other by the characteristics and extent of the binding process. The main features of PD(I) fulfil the classical intercalation pattern and the formation/dissociation kinetics have been elucidated by T-jump techniques. PD(II) and PD(III) are also intercalated species but, in addition to the dye units lodged between base pairs, they also bear dye molecules externally bound, more in PD(III) relative to PD(II). A reaction mechanism is put forward here. Comparison between absorbance, fluorescence and kinetic experiments has enabled us to determine the binding constants of the three complexes, namely (6.5 ± 1.1) × 10(4) M(-1) (PD(I)), (5.5 ± 1.5) × 10(4) M(-1) (PD(II)) and (5.7 ± 0.03) × 10(4) M(-1) (PD(III)). The Comet assay reveals that the ACMA binding to DNA brings about genotoxic properties. The mutagenic potential studied by the Ames test reveals that ACMA can produce frameshift and transversion/transition mutations. ACMA also is able to produce base-pair substitution in the presence of S9 mix. Moreover, the MTT assays have revealed cytotoxicity. The biological effects observed have been rationalized in light of these features.     

Distribution of lipids in human brain

The enormous abundance of lipid molecules in the central nervous system (CNS) suggests that their role is not limited to be structural and energetic components of cells. Over the last decades, some lipids in the CNS have been identified as intracellular signalers, while others are known to act as neuromodulators of neurotransmission through binding to specific receptors. Neurotransmitters of lipidic nature, currently known as neurolipids, are synthesized during the metabolism of phospholipid precursors present in cell membranes. Therefore, the anatomical identification of each of the different lipid species in human CNS by imaging mass spectrometry (IMS), in association with other biochemical techniques with spatial resolution, can increase our knowledge on the precise metabolic routes that synthesize these neurolipids and their localization. The present study shows the lipid distribution obtained by MALDI-TOF IMS in human frontal cortex, hippocampus, and striatal area, together with functional autoradiography of cannabinoid and LPA receptors. The combined application of these methods to postmortem human brain samples may be envisioned as critical to further understand neurological diseases, in general, and particularly, the neurodegeneration that accompanies Alzheimer’s disease.     

A multi-criteria optimization model for humanitarian aid distribution

Natural disasters are phenomenons which strike countries all around the world. Sometimes, either by the intensity of the phenomenon or the vulnerability of the country, help is requested from the rest of the world and relief organizations respond by delivering basic aid to those in need. Humanitarian logistics is a critical factor in managing relief operations and, in general, there is a lack of attention on the development of mathematical models and solution algorithms for strategic and tactical decisions in this area. We acknowledge that in humanitarian logistics traditional cost minimizing measures are not central, and postulate that other performance measures such as time of response, equity of the distribution or reliability and security of the operation routes become more relevant. In this paper several criteria for an aid distribution problem are proposed and a multi-criteria optimization model dealing with all these aspects is developed. This model is the core of a decision support system under development to assist organizations in charge of the distribution of humanitarian aid. Once the proposed criteria and the model are described, an illustrative case study based on the 2010 Haiti catastrophic earthquake is presented, showing the usefulness of the proposal.     

Tailoring Covalent Organic Frameworks To Capture Water Contaminants

Covalent organic frameworks (COFs) are attractive materials receiving increasing interest in the literature due to their crystallinity, large surface area, and pore uniformity. Their properties can be tailored towards specific applications by judicious design of COF building blocks, giving access to tailor-made pore sizes and surfaces. In this Concept article, developments in the field of COFs that have allowed these materials to be explored for contaminant adsorption are discussed. Strategies to obtain water-stable materials with highly ordered structures and large surface areas are reviewed. Post-synthetic modification approaches, by which pore surfaces can be tuned to target specific contaminants, are described. Recent advances in COF formulations, crucial for future implementation in adsorption devices, are highlighted. At the end, future challenges which need to be addressed to allow for the deployment of COFs for the capture of water contaminants will be discussed.