Ring-closing metathesis: development of a cyclisation-cleavage strategy for the solid-phase synthesis of cyclic sulfonamides

A series of novel 7-membered cyclic sulfonamides have been synthesised using a solid-phase cyclisation-cleavage RCM strategy. Model solution studies indicated the sulfonamides were suitable substrates for RCM using the Grubbs' catalyst 2. Starting from either 2-carboxyethyl polystyrene (21) or Merrifield resin, various seven-membered sulfonamides were prepared in good to excellent yields at low catalyst loadings (2.5-5 mol%) using a flexible spacer between the polymer and the substrate. In addition, a novel double-armed linker was shown to allow efficient RCM cleavage of sulfonamides with as little as 1 mol% of the ruthenium alkylidene complex 2.     

A rapid multiresidue method for determination of pesticides in fruits and vegetables by using acetonitrile extraction/partitioning and solid-phase extraction column cleanup

A modification of a rapid and inexpensive multiresidue method for determination of pesticides in fruits and vegetables (QuEChERS method) is presented. Samples were extracted by shaking with acetic acid-acetonitrile (1 + 99). Water was removed by liquid-liquid partitioning with magnesium sulfate and sodium acetate. The extract was subjected to a single solid-phase extraction (SPE) column cleanup, which produced a cleaner extract than did the dispersive SPE cleanup used in the original QuEChERS method. Recovery data were obtained for 316 pesticide residues, at levels ranging from 20 ppb to 1.0 ppm. Data were provided by 3 different laboratories. The modified QuEChERS method resulted in a 65% reduction in solvent usage, when compared with the traditional multiresidue methods previously used in our laboratories.     

Synthesis of Polyoxygenated Tropolones and their Antiviral Activity against Hepatitis B Virus and Herpes Simplex Virus-1

Polyoxygenated tropolones possess a broad range of biological activity, and as a result are promising lead structures or fragments for drug development. However, structure–function studies and subsequent optimization have been challenging, in part due to the limited number of readily available tropolones and the obstacles to their synthesis. Oxidopyrylium [5+2] cycloaddition can effectively generate a diverse array of seven-membered ring carbocycles, and as a result can provide a highly general strategy for tropolone synthesis. Here, we describe the use of 3-hydroxy-4-pyrone-based oxidopyrylium cycloaddition chemistry in the synthesis of functionalized 3,7-dimethoxytropolones, 3,7-dihydroxytropolones, and isomeric 3-hydroxy-7-methoxytropolones through complementary benzyl alcohol-incorporating procedures. The antiviral activity of these molecules against herpes simplex virus-1 and hepatitis B virus is also described, highlighting the value of this approach and providing new structure–function insights relevant to their antiviral activity.     

A simple and rapid method for identifying and semi-quantifying peptide hormones in isolated pancreatic islets by direct-tissue matrix-assisted laser desorption ionization time-of-flight mass spectrometry

We describe a new, simple, robust and efficient method based on direct‐tissue matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry that enables consistent semi‐quantitation of peptide hormones in isolated pancreatic islets from normal and diabetic rodents. Prominent signals were measured that corresponded to all the main peptide hormones present in islet‐endocrine cells: (α‐cells) glucagon, glicentin‐related polypeptide/GRPP; (β‐cells) insulin I, insulin II, C‐peptide I, C‐peptide II, amylin; (δ‐cells) somatostatin‐14; and (PP‐cells), and pancreatic polypeptide. The signal ratios coincided with known relative hormone abundances. The method demonstrated that severe insulin deficiency is accompanied by elevated levels of all non‐β‐cell‐hormones in diabetic rat islets, consistent with alleviation of paracrine suppression of hormone production by non‐β‐cells. It was also effective in characterizing hormonal phenotype in hemizygous human‐amylin transgenic mice that express human and mouse amylin in approx. equimolar quantities. Finally, the method demonstrated utility in basic peptide‐hormone discovery by identifying a prominent new Gcg‐gene‐derived peptide (theoretical monoisotopic molecular weight 3263.5 Da), closely related to but distinct from GRPP, in diabetic islets. This peptide, whose sequence is HAPQDTEENARSFPASQTEPLEDPNQINE in Rattus norvegicus, could be a peptide hormone whose roles in physiology and metabolic disease warrant further investigation. This method provides a powerful new approach that could provide important new insights into the physiology and regulation of peptide hormones in islets and other endocrine tissues. It has potentially wide‐ranging applications that encompass endocrinology, pharmacology, phenotypic analysis in genetic models of metabolic disease, and hormone discovery, and could also effectively limit the numbers of animals required for such studies. Copyright © 2011 John Wiley & Sons, Ltd.     

On the equation , pseudoperfect numbers, and perfectly weighted graphs

We present all solutions to the equation with at most eight primes, improve the bound on the nonsolvability of the Erdös-Moser equation , and discuss the computational search techniques used to generate examples of perfectly weighted graphs.

     

Biogenic Sulfur-Based Chalcogenide Nanocrystals: Methods of Fabrication,Mechanistic Aspects,and Bio-Applications

Bio-nanotechnology has emerged as an efficient and competitive methodology for the production of added-value nanomaterials (NMs). This review article gathers knowledge gleaned from the literature regarding the biosynthesis of sulfur-based chalcogenide nanoparticles (S-NPs), such as CdS, ZnS and PbS NPs, using various biological resources, namely bacteria, fungi including yeast, algae, plant extracts, single biomolecules, and viruses. In addition, this work sheds light onto the hypothetical mechanistic aspects, and discusses the impact of varying the experimental parameters, such as the employed bio-entity, time, pH, and biomass concentration, on the obtained S-NPs and, consequently, on their properties. Furthermore, various bio-applications of these NMs are described. Finally, key elements regarding the whole process are summed up and some hints are provided to overcome encountered bottlenecks towards the improved and scalable production of biogenic S-NPs.     

Analysis of a Class of Frictional Contact Problems for the Bingham Fluid

We consider a mathematical model which describes the stationary flow of a Bingham fluid with friction. The frictional contact is modeled by a general velocity dependent dissipation functional. We derive a weak formulation of the model which consists in a variational inequality for the velocity field. We establish the existence and uniqueness of the weak solution as well as its continuous dependence with respect to the contact condition. Finally, we describe a number of concrete friction conditions which may be set in this general framework and for which our results apply.     

Urea as a protein destabilizing agent in electrospray ionisation

Urea is well known as a denaturant of proteins, but there is also evidence that millimolar amounts of urea may in fact stabilize protein complexes. Advances in mass spectrometric analysis have given us the opportunity to test the effect of urea on several noncovalent complexes in buffered solutions. We expected to see lower charge states if folded proteins were more compact (and therefore more stable), and higher charge states if the proteins were denatured. We have found that mM urea interferes with some noncovalent interactions, and that the extent of interference depends on the specific protein complex. The difference seems to be related to the type of interactions, with weak ones, such as H‐bonds, more sensitive to urea. Examples show that a quick check with urea may give some insights into protein stability in the mass spectrometer. Copyright © 2009 John Wiley & Sons, Ltd.