A simple and robust preparation of N-acetylindoxyls: precursors for indigogenic substrates.

A generalised, simple and efficient synthesis of N-acetyl-5-bromo-4-chloroindoxyl and related analogues required for the synthesis of indigogenic substrates to probe for biological activities is reported. The method is both synthetically and operationally simple and represents a significant improvement on existing methods.

Stable triazolylphosphonate analogues of phosphohistidine.

Histidine-phosphorylated proteins and the corresponding kinases are important components of bacterial and eukaryotic cell-signalling pathways, and are therefore potential drug targets. The study of these biomolecules has been hampered by the lability of the phosphoramidate functional group in the phosphohistidines and the lack of generic antibodies. Herein, the design and concise synthesis of stable triazolylphosphonate analogues of N1- and N3-phosphohistidine, and derivatives suitable for bioconjugation, are described.

Discovery of tetrasubstituted pyrazines as semiochemicals in a sexually deceptive orchid.

Sexually deceptive orchids employ mimicry of insect sex pheromones to exploit a diverse group of pollinators. The chemical structures of five semiochemicals (1-3, 7, 8) produced by populations of the warty hammer orchid, Drakaea livida, pollinated by a thynnine wasp in the genus Catocheilus were elucidated. With the exception of (2,5-dimethylpyrazin-3-yl)methyl 3-methylbutanoate (7), all active compounds were tetrasubstituted pyrazines, including hydroxymethyl (1) and ester (2 and 3) trimethylpyrazine derivatives. Male Catocheilus wasps were responsive to all of these compounds in GC-EAD experiments.

Selective binding of imidazolium cations in building multi-component layers.

Addition of 1-alkyl-3-methylimidazolium (C(n)-mim) cations 3-5 to a mixture of bis-phosphonium cation 2 and sodium p-sulfonatocalix[4]arene (1) in the presence of lanthanide ions results in the selective binding of an imidazolium cation into the cavity of the calixarene. The result is a multi-layered solid material with an inherently flexible interplay of the components. Incorporating ethyl-, n-butyl- or n-hexyl-mim cations into the multi-layers results in significant perturbation of the structure, the most striking effect is the tilting of the plane of the bowl-shaped calixarene relative to the plane of the multi-layer, with tilt angles of 7.2, 28.9 and 65.5 degrees , respectively. The lanthanide ions facilitate complexation, but are not incorporated into the structures and, in all cases, the calixarene takes on a 5- charge, with one of the lower-rim phenolic groups deprotonated. ROESY NMR experiments and other (1)H NMR spectroscopy studies establish the formation of 1:1 supermolecules of C(n)-mim and calixarene, regardless of the ratio of the two components, and indicate that the supermolecules undergo rapid exchange on the NMR spectroscopy timescale.

Octapi interactions: self-assembly of a Pd-based [2]catenane driven by eightfold pi interactions.

An unprecedented 2.5 nm array of pi interactions between eight aromatic rings drives the formation of a [2]catenane. Disruption of this array through the use of longer ligands results in the formation of only single, uncatenated rings. The catenated complex is shown to persist in solution alongside its constituent metallomacrocycles.

Enhancing the efficacy of cation-independent mannose 6-phosphate receptor inhibitors by intracellular delivery.

Intracellular delivery of M6P/IGFII receptor inhibitors exhibits better efficacy than extracellular inhibitors to regulate TGFß1 mediated upregulation of profibrotic marker, collagen I.

Enhanced bi-stability in a ruthenium alkynyl spiropyran complex.

The inclusion of a ligated ruthenium moiety to ethynyl spiropyran, 5'-ethynyl-1',3',3'-trimethyl-6-nitrospiro[chromene-2,2'-indoline], has been shown to increase the lifetime of the ring-opened merocyanine form twentyfold. Calculations suggest that the higher barrier to thermal reversion of the merocyanine form of the metal alkynyl complex arises from the capacity for greater delocalisation of charge consequent of the presence of the ruthenium moiety. The complex may provide a different switching mechanism to the 5,5'-dithienylperfluorocyclopentene electrode decoupling seen previously.

Rhizobium leguminosarum bv. viciae produces a novel cyclic trihydroxamate siderophore, vicibactin.

Trihydroxamate siderophores were isolated from iron-deficient cultures of three strains of Rhizobium leguminosarum biovar viciae, two from Japan (WSM709, WSM710) and one from the Mediterranean (WU235), and from a Tn5-induced mutant of WSM710 (MNF7101). The first three all produced the same compound (vicibactin), which was uncharged and could be purified by solvent extraction into benzyl alcohol. The gallium and ferric complexes of vicibactin were extractable into benzyl alcohol at pH 5.0, while metal-free vicibactin could be extracted with good yield at pH 8.0. The trihydroxamate from MNF7101 (vicibactin 7101) could not be extracted into benzyl alcohol, but its cationic nature permitted purification by chromatography on Sephadex CM-25 (NH+ 4 form). Relative molecular masses and empirical formulae were obtained from fast-atom-bombardment MS. The structures were derived from one- and two-dimensional 1H and 13C NMR spectroscopy, using DQF-COSY, NOESY, HMQC and HMBC techniques on the compounds dissolved in methanol-d 4 and DMSO-d 6. Vicibactin proves to be a cyclic molecule containing three residues each of (R)-2,5-diamino-N 2-acetyl-N 5-hydroxypentanoic acid (N 2-acetyl-N 5-hydroxy-D-ornithine) and (R)-3-hydroxybutanoic acid, arranged alternately, with alternating ester and peptide bonds. Vicibactin 7101 differed only in lacking the acetyl substitution on the N2 of the N 5-hydroxyornithine, resulting in net positive charge; it was still functional as a siderophore and promoted 55Fe uptake by iron-starved cells of WSM710 in the presence of an excess of phosphate. The rate of vicibactin biosynthesis by iron-deficient cells of WSM710 was essentially constant between pH 5.5 and 7.0, but much decreased at pH 5.0. When iron-starved cultures were supplemented with potential precursors for vicibactin, the rates of its synthesis were consistent with both ß-hydroxybutyrate and ornithine being precursors. At least three genes seem likely to be involved in synthesis of vicibactin from ornithine and ß-hydroxybutyrate: a hydroxylase adding the -OH group to the N5 of ornithine, an acetylase adding the acetyl group to the N2 of ornithine, and a peptide synthetase system.

Azolium-linked cyclophanes: a comprehensive examination of conformations by 1H NMR spectroscopy and structural studies.

The synthesis and characterization of a series of azolium-linked cyclophanes are reported. The cyclophanes consist of two azolium groups (17 examples) or three imidazolium groups (1 example) linked to two benzenoid units (benzene, naphthalene, p-xylene, mesitylene, 1,2,3,4- and 1,2,4,5-tetramethylbenzene, 2,6-pyridine, and p-tert-butylphenol) via methylene groups. Cyclophanes containing ortho-, meta-, and para-substitution patterns in the benzenoid units were examined. The conformations of the cyclophanes were examined in solution by variable-temperature NMR studies and in the solid state by crystallographic studies. The p-cyclophanes and mesitylene-based m- and o/m-cyclophanes are rigid on the NMR time scale, as indicated by sharp (1)H NMR spectra at all accessible temperatures. The non-mesitylene-based m-cyclophanes and the o-cyclophanes are fluxional on the NMR time scale at high temperatures, but in most cases, specific conformations can be "frozen out" at low temperatures. Many structures deduced from solution studies were consistent with those in the solid state.