Microwave-Assisted Synthesis of Phenothiazine and Quinoline Derivatives

Application of a dynamic microwave power system in the chemical synthesis of some phenothiazine and quinoline derivatives is described. Heterocyclic ring formation, aromatic nucleophilic substitution and heterocyclic aldehydes/ketones condensation reactions were performed on solid support, or under solvent free reaction conditions. The microwave-assisted Duff formylation of phenothiazine was achieved. Comparison of microwave-assisted synthesis with the conventional synthetic methods demonstrates advantages related to shorter reaction times and in some cases better reaction yields.     

New WS9326A Derivatives and One New Annimycin Derivative with Antimalarial Activity are Produced by Streptomyces asterosporus DSM 41452 and Its Mutant

In this study, we report that Streptomyces asterosporus DSM 41452 is a producer of new molecules related to the nonribosomal cyclodepsipeptide WS9326A and the polyketide annimycin. S. asterosporus DSM 41452 is shown to produce six cyclodepsipeptides and peptides, WS9326A to G. Notably, the compounds WS9326F and WS9326G have not been described before. The genome of S. asterosporus DSM 41452 was sequenced, and a putative WS9326A gene cluster was identified. Gene‐deletion experiments confirmed that this cluster was responsible for the biosynthesis of WS9326A to G. Additionally, a gene‐deletion experiment demonstrated that sas16 encoding a cytochrome P450 monooxygenase was involved in the synthesis of the novel (E)‐2,3‐dehydrotyrosine residue found in WS9326A and its derivatives. An insertion mutation within the putative annimycin gene cluster led to the production of a new annimycin derivative, annimycin B, which exhibited modest inhibitory activity against Plasmodium falciparum.     

Cuticular Hydrocarbons as Sex Pheromone of the Bee <Emphasis Type="Italic">Colletes cunicularius</Emphasis> and the Key to its Mimicry by the Sexually Deceptive Orchid, <Emphasis Type="Italic">Ophrys exaltata</Emphasis>

Male Colletes cunicularius bees pollinate the orchid, Ophrys exaltata, after being sexually deceived by the orchid’s odor-mimicry of the female bee’s sex pheromone. We detected biologically active volatiles of C. cunicularius by using gas chromatographic–electroantennographic detection (GC-EAD) with simultaneous flame ionization detection. After identification of the target compounds by coupled gas chromatography–mass spectrometry (GC-MS), we performed behavioral tests using synthetic blends of the active components. We detected 22 EAD active compounds in cuticular extracts of C. cunicularius females. Blends of straight chain, odd-numbered alkanes and (Z)-7-alkenes with 21–29 carbon atoms constituted the major biologically active compounds. Alkenes were the key compounds releasing mating behavior, especially those with (Z)-7 unsaturation. Comparison of patterns of bee volatiles with those of O. exaltata subsp. archipelagi revealed that all EAD-active compounds were also found in extracts of orchid labella. Previous studies of the mating behavior in C. cunicularius showed linalool to be an important attractant for patrolling males. We confirmed this with synthetic linalool but found that it rarely elicited copulatory behavior, in accordance with previous studies. A blend of active cuticular compounds with linalool elicited both attraction and copulation behavior in patrolling males. Thus, linalool appears to function as a long-range attractant, whereas cuticular hydrocarbons are necessary for inducing short-range mating behavior.     

Thermal stability of polymers based on acrylamide and 2-acrylamido-2-methylpropane sulfonic acid in different temperature and salinity conditions

Partially hydrolyzed polyacrylamide (PHPA) is the most widely used polymer in enhanced oil recovery (EOR) applications. However, under conditions of high temperature and salinity, the PHPA molecules become hydrolyzed, causing a drastic reduction of the viscosity of the polymer solution due to the presence of negative charges, making the molecules more susceptible to interactions with cations. In this sense, in order to increase the stability of these polymers, an anionic monomer more resistant to cations such as 2-acrylamido-2-methylpropane sulfonic acid (AMPS) has been incorporated into the HPAM molecules. This work evaluated the thermal stability of a copolymer (acrylamide and AMPS - AN125) and a terpolymer (acrylamide, acrylate, and AMPS-FP5115) in the time course of 360 days. The tests were carried out in typical conditions of Brazilian offshore reservoirs, such as absence of oxygen, high temperature, and high salt concentration. The test method involved measurements of intrinsic viscosity in function of time and determination of the hydrolysis degree of the polymers by elemental analysis. The copolymer AN125 was more stable under the test conditions than the terpolymer FP 5115 due to the presence of a higher concentration of AMPS in the copolymer. The AMPS group was hydrolyzed to AA at a temperature of 100 °C, however, the increase in salt concentration delayed the onset of this degradation. The tests indicated that the presence of a higher AMPS content in the copolymer does not prevent the polymer from undergoing hydrolysis, but delays the polymer precipitation step in the solution.     

Habitat fragmentation has interactive effects on the population genetic diversity and individual behaviour of a freshwater salmonid fish

Sufficient genetic diversity can aid populations to persist in dynamic and fragmented environments. Understanding which mechanisms regulate genetic diversity of riverine fish can therefore advance current conservation strategies. The aim of this study was to investigate how habitat fragmentation interacted with population genetic diversity and individual behaviour of freshwater fish in large river systems. We studied a population of the long‐distance migratory, iteroparous freshwater salmonid European grayling (Thymallus thymallus) in south‐eastern Norway. Genotyping (n = 527) and radio‐tracking (n = 54) of adult fish throughout a 169‐km river section revealed three major migration barriers limiting gene flow and depleting genetic diversity upstream. Individuals from upstream areas that had dispersed downstream of barriers showed different movement behaviour than local genotypes. No natal philopatry was found in a large unfragmented river section, in contrast to strong fidelity to spawning tributaries known for individuals overwintering in lakes. We conclude that (a) upstream sub‐populations in fragmented rivers show less genetic variation, making it less likely for them to adapt to environmental changes; (b) fish with distinct genotypes in the same habitat can differ in their behaviour; (c) spawning site selection (natal philopatry) can differ between fish of the same species living in different habitats. Together this implies that habitat loss and fragmentation may differently affect individual fish of the same species if they live in different types or sections of habitat. Studying behaviour and genetic diversity of fish can unravel their complex ecology and help minimize human impact.     

Infrarotspektroskopischer (IR) Nachweis von gelöstem Wasser in abgeschreckten Schlacken (Modellsysteme Na2O · P2O5 und Na2O · 2 B2O3)

Inf rarotspektroskopie von Wasser in Schlacken. Chemischer Bindungszustand von Wasser in Schlacken, Abhängigkeit der integralen Extinktion der OH-Banden vom Wasserdampfpartialdruck. Wasserstoff beim ESU-Verfahren.     

Heterogeneous catalysts with programmable topologies generated by reticulation of organocatalysts into metal-organic frameworks: The case of squaramide

A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers containing organocatalytic centers.Here,we report that by combining this linker approach with reticular chemistry,and exploiting three-dimensioanl(3D)MOF-structural data from the Cambridge Structural Database,we have designed four heterogeneous MOF-based catalysts for standard organic transformations.These programmable MOFs are isoreticular versions of pcu IRMOF-16,feu UiO-68 and pillared-pcu SNU-8X,the three most common topologies of MOFs built from the organic linker p.p'-terphenyldicarboxylic acid(tpdc).To synthesize the four squaramide-based MOFs,we designed and synthesized a linker,4,4’-((3,4-dioxocyclobut-1-ene-1,2-diyl)bis(azanedyil))dibenzoic acid(Sq_tpdc),which is identical in directionality and length to tpdc but which contains organocatalytic squaramide centers.Squaramides were chosen because their immobilization into a framework enhances its reactivity and stability while avoiding any self-quenching phenomena.Therefore,the four MOFs share the same organocatalytic squaramide moiety,but confine it within distinct pore environments.We then evaluated these MOFs as heterogeneous H-bonding catalysts in organic transformations:a Friedel-Crafts alkylation and an epoxide ring-opening.Some of them exhibited good performance in both reactions but all showed distinct catalytic profiles that reflect their structural differences.     

Pediatric Brain Tumors: Signatures from the Intact Proteome

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.     

Efficiency of 4,4′‐bis(N,N‐diethylamino) benzophenone for the polymerization of dimethacrylate resins in thick sections

The efficiency of 4,4′‐bis(N,N‐diethylamino)benzophenone (DEABP) for the polymerization of dimethacrylate monomers in thick sections ( 1 – 2 mm) was studied. DEABP (λ_max = 365 nm) represents a complete initiating system as it contains both ketone and amine functional groups. During irradiation, DEABP photobleaches at a fast rate causing deeper penetration of light through the underlying layers, but the photoinitiation efficiency (rate of polymerization per photon absorption rate) is relatively poor. As a result, irradiation of methacrylate monomers at 365 nm results in a slow average polymerization rate and a reduced monomer conversion for thick sections due to the light attenuation caused by the high absorptivity of DEABP and photolysis products. These results highlight the inherent interlinking of light attenuation and photobleaching rate in polymerization of thick sections. Copyright © 2011 Society of Chemical Industry