Studies on the Regioselectivity of Horner-Wadsworth-Emmons (Hwe) Reactions on 3,4-Enuloses. Further Evidence of Phosphonate-Phosphate Rearrangements Through Five Membered Cyclic Intermediates.

ABSTRACT

The Horner-Wadsworth-Emmons (HWE) reaction was performed on methyl 3,6-di-O-benzoyl-2-deoxy-α-D-glycero-hex-2-enopyranosid-4-ulose (1) with the potassium enolates of dimethyl [(methoxycarbonyl)methyl]phosphonate (2) or diethyl [(ethoxycarbonyl) methyl]phosphonate (3) under different conditions (metallic cation and solvent) in order to study regio- and stereochemical aspects of the reaction. In the presence of lithium ions, no reaction took place. When sodium enolates were employed, 1,2-addition was the main reaction in chelating solvents, whereas the 1,4-adduct is favoured in the less polar, non chelating toluene. Only 1,2-addition was observed with potassium enolates. Evidence of phosphonate-phosphate rearrangements through five membered cyclic intermediates is described.     

Dunaliella tertiolecta (Chlorophyta) Avoids Cell Death Under Ultraviolet Radiation By Triggering Alternative Photoprotective Mechanisms

The effect of different ultraviolet radiation (UVR) treatments combining PAR (P), UVA (A) and UVB (B) on the molecular physiology of Dunaliella tertiolecta was studied during 6 days to assess the response to chronic UVR exposure. UVR reduced cell growth but did not cause cell death, as shown by the absence of SYTOX Green labeling and cellular morphology. However, caspase‐like enzymatic activities (CLs), (regarded as cell death proteases), were active even though the cells were not dying. Maximal quantum yield of fluorescence (F_v/F_m) and photosynthetic electron transport rate (ETR) dropped. Decreased nonphotochemical quenching (NPQ) paralleled a drop in xanthophyll cycle de‐epoxidation under UVB. Reactive oxygen species (ROS) and D1 protein accumulation were inversely correlated. PAB exhibited elevated ROS production at earlier times. Once ROS decayed, D1 protein recovered two‐fold compared with P and PA at later stages. Therefore, PsbA gene was still transcribed, suggesting ROS involvement in D1 recovery by its direct effect on mRNA‐translation. We add evidence of an UVB‐induced positive effect on the cells when P is present, providing photoprotection and resilience, by means of D1 repair. This allowed cells to survive. The photoprotective mechanisms described here (which are counterintuitive in principle) conform to an important ecophysiological response regarding light stress acclimation.     

Properties of nucleic acid staining dyes used in gel electrophoresis

Nucleic acid staining dyes are used for detecting nucleic acids in electrophoresis gels. Historically, the most common dye used for gel staining is ethidium bromide, however due to its toxicity and mutagenicity other dyes that are safer to the user and the environment are preferred. This Short Communication details the properties of dyes now available and their sensitivity for detection of DNA and their ability to permeate the cell membrane. It was found that GelRed? was the most sensitive and safest dye to use with UV light excitation, and both GelGreen? and Diamond? Nucleic Acid Dye were sensitive and the safer dyes using blue light excitation.     

New Features in the Lipid A Structure of <Emphasis Type="Italic">Brucella suis</Emphasis> and <Emphasis Type="Italic">Brucella abortus</Emphasis> Lipopolysaccharide

Brucellaceae are Gram-negative bacteria that cause brucellosis, one of the most distributed worldwide zoonosis, transmitted to humans by contact with either infected animals or their products. The lipopolysaccharide exposed on the cell surface has been intensively studied and is considered a major virulence factor of Brucella. In the last years, structural studies allowed the determination of new structures in the core oligosaccharide and the O-antigen of this lipopolysaccharide. In this work, we have reinvestigated the lipid A structure isolated from B. suis and B. abortus lipopolysaccharides. A detailed study by MALDI-TOF mass spectrometry in the positive and negative ion modes of the lipid A moieties purified from both species was performed. Interestingly, a new feature was detected: the presence of a pyrophosphorylethanolamine residue substituting the backbone. LID-MS/MS analysis of some of the detected ions allowed assurance that the Lipid A structure composed by the diGlcN3N disaccharide, mainly hexa-acylated and penta-acylated, bearing one phosphate and one pyrophosphorylethanolamine residue.

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Integration of microchip electrophoresis with electrochemical detection using an epoxy-based molding method to embed multiple electrode materials

This paper describes the use of epoxy-encapsulated electrodes to integrate microchip-based electrophoresis with electrochemical detection. Devices with various electrode combinations can easily be developed. This includes a palladium decoupler with a downstream working electrode material of either gold, mercury/gold, platinum, glassy carbon, or a carbon fiber bundle. Additional device components such as the platinum wires for the electrophoresis separation and the counter electrode for detection can also be integrated into the epoxy base. The effect of the decoupler configuration was studied in terms of the separation performance, detector noise, and the ability to analyze samples of a high ionic strength. The ability of both glassy carbon and carbon fiber bundle electrodes to analyze a complex mixture was demonstrated. It was also shown that a PDMS-based valving microchip can be used along with the epoxy-embedded electrodes to integrate microdialysis sampling with microchip electrophoresis and electrochemical detection, with the microdialysis tubing also being embedded in the epoxy substrate. This approach enables one to vary the detection electrode material as desired in a manner where the electrodes can be polished and modified as is done with electrochemical flow cells used in liquid chromatography.     

Full enzymatic hydrolysis of commercial sucrose laurate by immobilized-stabilized derivatives of lipase from Thermomyces lanuginosa

Sucrose laurate is a detergent that is useful for various biochemical applications because it is a green compound and is easily degradable after hydrolysis with a lipase or esterase. One problem observed in the process of sucrose laurate degradation is that most commercial detergent preparations are impure, necessitating the hydrolysis of all of the sucrose esters present in the preparation, all of them with detergent properties. In this article, a highly active catalyst, which is able to perform the hydrolysis of commercial sucrose laurate, is presented. The use of glyoxyl agarose preparations of a previously aminated Thermomyces lanuginosa lipase (TLL) enabled complete hydrolysis, in less than 30 min, of all of the compounds that comprise the mixture. In addition, this derivative is stable in the presence of 20% ethanol, which is necessary to prevent microbial contamination.     

Theranostic Applications of Nanomaterials in Cancer: Drug Delivery, Image-Guided Therapy, and Multifunctional Platforms

Successful cancer management depends on accurate diagnostics along with specific treatment protocols. Current diagnostic techniques need to be improved to provide earlier detection capabilities, and traditional chemotherapy approaches to cancer treatment are limited by lack of specificity and systemic toxicity. This review highlights advances in nanotechnology that have allowed the development of multifunctional platforms for cancer detection, therapy, and monitoring. Nanomaterials can be used as MRI, optical imaging, and photoacoustic imaging contrast agents. When used as drug carriers, nanoformulations can increase tumor exposure to therapeutic agents and result in improved treatment effects by prolonging circulation times, protecting entrapped drugs from degradation, and enhancing tumor uptake through the enhanced permeability and retention effect as well as receptor-mediated endocytosis. Multiple therapeutic agents such as chemotherapy, antiangiogenic, or gene therapy agents can be simultaneously delivered by nanocarriers to tumor sites to enhance the effectiveness of therapy. Additionally, imaging and therapy agents can be co-delivered to provide seamless integration of diagnostics, therapy, and follow-up, and different therapeutic modalities such as chemotherapy and hyperthermia can be co-administered to take advantage of synergistic effects. Liposomes, metallic nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes, and quantum dots are examples of nanoformulations that can be used as multifunctional platforms for cancer theranostics. Nanomedicine approaches in cancer have great potential for clinically translatable advances that can positively impact the overall diagnostic and therapeutic process and result in enhanced quality of life for cancer patients. However, a concerted scientific effort is still necessary to fully explore long-term risks, effects, and precautions for safe human use.     

Observation and mechanistic study of facile C-O bond formation between a well-defined aryl-copper(III) complex and oxygen nucleophiles

A well-defined macrocyclic aryl–Cu(III) complex (2) reacts readily with a variety of oxygen nucleophiles, including carboxylic acids, phenols and alcohols, under mild conditions to form the corresponding aryl esters, biaryl ethers and alkyl aryl ethers. The relationship between these reactions and catalytic C-O coupling methods is demonstrated by the reaction of the macrocyclic aryl–Br species with acetic acid and p-fluorophenol in the presence of 10 mol% Cu(I). An aryl-Cu(III)-Br species 2(Br) was observed as an intermediate in the catalytic reaction. Investigation of the stoichiometric C-O bond-forming reactions revealed nucleophile-dependent changes in the mechanism. The reaction of 2 with carboxylic acids revealed a positive correlation between the log(k(obs)) and the pK(a) of the nucleophile (less-acidic nucleophiles react more rapidly), whereas a negative correlation was observed with most phenols (more-acidic phenols react more rapidly). The latter trend resembles previous observations with nitrogen nucleophiles. With carboxylic acids and acidic phenols, UV-visible spectroscopic data support the formation of a ground-state adduct between 2 and the oxygen nucleophile. Collectively, kinetic and spectroscopic data support a unified mechanism for aryl-O coupling from the Cu(III) complex, consisting of nucleophile coordination to the Cu(III) center, deprotonation of the coordinated nucleophile, and C-O (or C-N) reductive elimination from Cu(III).