Antitumour polycyclic acridines. Palladium(0) mediated syntheses of quino[4,3,2-kl]acridines bearing peripheral substituents as potential telomere maintenance inhibitors

Pd(0) mediated couplings between substituted 2-(pivaloylamino)benzeneboronic acids and 3,6-disubstituted-10-methylacridones 13 bearing a bromo or trifluoromethylsulfonyloxy substituent in the 1-position yield intermediate 1-arylacridones 16 which can be can be cyclised to new 8-methylquino[4,3,2-kl]acridines 17 with phosphorus oxychloride or 6 M HCI in EtOH. Heck reactions between triflate-substituted substrates 17 and acrylic acid derivatives afforded quinoacridines with unsaturated side-chains in the 6-position. Alkylboranes, prepared by interaction of 9-borabicyclo[3,3,1]nonane (9-BBN) and allyl acetate or N-allyltrifluoroacetamide, participated in Suzuki-Miyaura reactions with chloro-substituted 8-methylquinoacridines to form derivatives bearing functionalised propyl groups in the 6- and 10-positions. Representative 8-methylquinoacridines were methylated with methyl iodide to yield telomerase-inhibitory 8,13-dimethylquinoacridinium iodides 24.     

Modulating artificial membrane morphology: pH-induced chromatic transition and nanostructural transformation of a bolaamphiphilic conjugated polymer from blue helical ribbons to red nanofibers.

Design and characterization of helical ribbon assemblies of a bolaamphiphilic conjugated polymer and their color-coded transformation into nanofibers are described. An L-glutamic acid modified bolaamphiphilic diacetylene lipid was synthesized and self-assembled into right-handed helical ribbons with micron scale length and nano scale thickness under mild conditions. The ribbon structures were further stabilized by polymerizing well-aligned diacetylene units to form bisfunctional polydiacetylenes (PDAs). Transitions from flat sheets to helical ribbons and tubes were observed by transmission electron microscopy. The helical ribbons appear to originate from the rupture of flat sheets along domain edges and the peeling off between stacked lipid layers. These results point to the applicability of chiral packing theory in bolaamphiphilic supramolecular assemblies. Contact mode atomic force microscopy observations revealed that high order existed in the surface packing arrangement. Hexagonal and pseudorectangular packings were observed in flat and twisted regions of the ribbons, respectively, suggesting a correlation between microscopic morphologies and nanoscopic packing arrangements. The tricarboxylate functionalities of the bolaamphiphilic lipid provide a handle for the manipulation of the bisfunctional PDAs' morphology. Increasing solution pH caused the fraying of helical ribbons into nanofibers accompanied by a sharp blue-to-red chromatic transition. A dramatic change in circular dichroism spectra was observed during this process, suggesting the loss of chirality in packing. A model is proposed to account for the pH-induced morphological change and chromatic transition. The color-coded transition between two distinct microstructures would be useful in the design of sensors and other "smart" nanomaterials requiring defined molecular templates.     

Toward an understanding of the furoxan-dinitrosoethylene equilibrium

The tautomerism of furoxan (1,2,5-oxadiazole-2-oxide) has been investigated by different computational methods comprising modern density functionals as well as single-reference and multi-reference ab initio methods. The ring-opening process to 1,2-dinitrosoethylene is the most critical step of the reaction and cannot be treated reliably by low-level computations. The existence of cis-cis-trans-1,2-dinitrosoethylene as a stable intermediate is advocated by perturbational methods, but high-level coupled-cluster calculations identify this as an artifact. In contrast to the analogous reaction in benzofuroxans, cis-cis-cis-1,2-dinitrosoethylene was found to be a transition state rather than a local minimum. Model potentials were used to explain the occurrence and the disappearing of transition states and local minima relative to the reaction of benzofuroxan. Low-lying triplet states that can be accessed due to spin-orbit coupling were investigated as taking part in alternative routes to a proposed singlet pathway. Barriers for rotations of the nitroso groups on the S(0) and T(1) surfaces are reported.     

Aqueous solution speciation of Fe(III) complexes with dihydroxamate siderophores alcaligin and rhodotorulic acid and synthetic analogues using electrospray ionization mass spectrometry

Aqueous solutions of Fe3+ complexes of cyclic (alcaligin) and linear (rhodotorulic acid) dihydroxamate siderophores and synthetic linear eight-carbon-chain and two-carbon-chain dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln; n = 2 and 8) were investigated by electrospray ionization mass spectrometry (ESI-MS). Information was obtained relevant to the structure and the speciation of various Fe(III)-dihydroxamate complexes present in aqueous solution by (1) comparing different ionization techniques (ESI and FAB), (2) altering the experimental parameters (Fe3+/ligand ratio, pH, cone voltage), (3) using high-stability hexacoordinated Fe(III) siderophore complex mixtures (ferrioxamine B/ferrioxamine E) as a calibrant to quantify intrinsically neutral (H+ clustered or protonated) and intrinsically charged complexes, and (4) using mixed-metal complexes containing Fe3+, Ga3+, and Al3+. These results illustrate that for all dihydroxamic acid ligands investigated multiple tris- and bis-chelated mono- and di-Fe(III) species are present in relative concentrations that depend on the pH and Fe/L ratio.     

Highly sensitive non‐isotopic restriction endonuclease fingerprinting of nucleotide variability in the gp60 gene within Cryptosporidium species,genotypes and subgenotypes infective to humans,and its implications

The high‐resolution analysis of genetic variation has major implications for the identification of parasites and micro‐organisms to species and subspecies as well as for population genetic and epidemiological studies. In this study, we critically assessed the effectiveness of a PCR‐based restriction endonuclease fingerprinting (REF) method for the detection of mutations in the 60 kDa glycoprotein gene (gp60) of Cryptosporidium, a genus of parasitic protists of major human and animal health importance globally. This gene displays substantial intraspecific variability in sequence, particularly in a TCA (perfect and imperfect) microsatellite region, is present as a single copy in the nuclear genome and is used widely as a marker in molecular epidemiological studies of Cryptosporidium hominis and C. parvum, the two predominant species that infect humans. The results of this study demonstrated an exquisite capacity of REF to detect nucleotide variability in the gp60 gene within each of the two species. The differentiation of genotypes/subgenotypes based on REF analysis was supported by targeted sequencing, allowing the detection of levels of variation as low as a single‐nucleotide transversion for amplicons of ∼1 kb in size. The high‐throughput potential and relatively low‐cost of REF make it a particularly useful tool for large‐scale genetic analyses of C. hominis and C. parvum. REF could also be utilized for comparative surveys of genetic variability across large nuclear genomic regions. Such analyses of Cryptosporidium in clinical and environmental samples by REF have important implications for identifying sources of infection, modes of transmission and/or possible infectivity to humans, thus assisting in the surveillance and control of cryptosporidiosis. Given its excellent mutation detection capacity, REF should find broad applicability to various single‐copy genes as well as a wide range of other protozoan and metazoan parasites. (The nucleotide sequences reported in this article are available in the GenBank database under accession numbers GU214343–GU214371).     

Der sog. „unlösliche“ Bestandteil des Kautschuks und sein Einfluß auf die Qualität desselben

Ohne ZusammenfassungUebersetzt von Hans Brehm (Dresden).     

Der Einfluß der stickstoffhaltigen und harzigen Bestandteile auf die Vulkanisierungsfähigkeit von Kautschuk

Ohne Zusammenfassung Uebersetzt von H. Brehm (Dresden).     

Universal abelian covers of superisolated singularities

We give explicit examples of Gorenstein surface singularities with integral homology sphere link, which are not complete intersections. Their existence was shown by Luengo–Velasco, Melle–Hernández and Némethi, thereby providing counterexamples to the universal abelian covering conjecture of Neumann and Wahl (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)