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Deuterated isohumulones can be prepared directly from humulones by an acyloin ring contraction under either magnesium-catalyzed basic conditions or by photochemical-induced reactions in deuterated solvents. Reactions of humulones with biphasic methylene chloride/aqueous NaOD and MgSO4 in D2 O leads to stereoselective formation of cis - d3-isohumulones (cis / trans ratio of 82:18) as the magnesium salts in yields of 71–83%. Greater than 95% incorporation of three deuterons is observed at the C5 position of the pentenone ring and the methylene position of the C4 acyl group. Photochemical isomerization with a 400 nm blue LED source enables stereospecific formation of deuterated trans -isohumulones in 36–82% yield with greater than 95% incorporation of deuterium at the C5 ring position. Oxidation of humulones with cumene hydroperoxide in basic D2 O gives isohumulinones with partial 55–73% incorporation of deuterium due to keto–enol isomerization of the methylene substituent of the C4 acyl group. The structural identities of the deuterated products are determined by a combination of negative-mode electrospray mass spectrometry (MS-ESI–) and 2D heteronuclear proton–carbon HMQC NMR analysis. [ABSTRACT FROM AUTHOR]

An experimental procedure for synthesis of diapocynin, a metabolite of apocynin which has anti-oxidative and anti-inflammatory properties is described. The procedure can be used to demonstrate to students the ability of apocyanin to blocks the activity of NADPH oxidase, a cell membrane enzyme known to protect against reactive oxygen species.

Dietary supplements containing plant materials of Annonaceae species (Annona muricata L., A. squamosa L., A. mucosa JACQ., A. squamosa × cherimola Mabb.) were extracted by hot, pressurized ethyl acetate and analyzed for their effect in vitro on Lund human mesencephalic neurons. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell death was determined by lactate dehydrogenase levels. Three supplements strongly decreased the cell viability at extract concentrations of 1 µg/mL, of which 1 decreased cell viability at 0.1 µg/µL. Also, strong neuronal toxicities of these supplements were found. Cell death was observed at concentrations of 10 µg/mL. The degree of toxicity was comparable to the ones found in Annonaceous fruit extracts. Two fruit pulps of Annonaceae (A. muricata and A. squamosa) showed a reduction in cell viability at lower concentrations. The fruit pulp extract of A. muricata revealed the strongest neurotoxic effect, with 67% cell death at a concentration of 1 µg/mL. A high reduction in cell viability coupled with pronounced cell death was found at 0.1 µg/mL for an Annonaceous seed extract. These results demonstrate that the intake of dietary supplements containing plant material from Annonaceae may be hazardous to health in terms of neurotoxicity. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (pneumococcus) remains a significant health threat worldwide, especially to the young and old. While some of the biomolecules involved in pneumococcal pathogenesis are known and understood in mechanistic terms, little is known about the molecular details of bacterium/host interactions. We report here the solution structure of the‘repeated’adhesion domains (domains R1 and R2) of the principal pneumococcal adhesin, choline binding protein A (CbpA). Further, we provide insights into the mechanism by which CbpA binds its human receptor, polymeric immunoglobulin receptor (pIgR). The R domains, comprised of 12 imperfect copies of the leucine zipper heptad motif, adopt a unique 3-a-helix, raft-like structure. Each pair ofa-helices is antiparallel and conserved residues in the loop between Helices 1 and 2 exhibit a novel‘tyrosine fork’structure that is involved in binding pIgR. This and other structural features that we show are conserved in most pneumococcal strains appear to generally play an important role in bacterial adhesion to pIgR. Interestingly, pneumococcus is the only bacterium known to adhere to and invade human cells by binding to pIgR. [ABSTRACT FROM AUTHOR]

Procedures based on high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection and liquid chromatography-mass spectrometry (LC-MS) are described for analyzing diapocynin. Diapocynin was synthesized by oxidative coupling of two apocynin monomers, through the in situ generation of sulfate radicals. It was purified by washing 3 times each with boiling water, followed by boiling methanol. HPLC was used to determine the concentration of unreacted apocynin and other impurities and the purity of the diapocynin that had been synthesized. Negative-ion, atmospheric pressure chemical ionization (APCI) LC-MS was used to determine the molecular weights of impurities. The method using HPLC with UV detection provided a calibration curve that was linear from 0.16 to 24 microg/mL. The LC-MS method was linear from 0.005 to 2 microg/mL. It was found that diapocynin has low solubility in deionized water and corn oil but is soluble in dimethylsulfoxide (DMSO) and alkaline aqueous solutions. Also, diapocynin is 13 times more lipophilic than apocynin, even though both compounds have the same p K a of 7.4. The log of the octanol/water partition coefficient (log P) was 1.01 for apocynin and 1.82 for diapocynin. A solution of 5.5 mg/mL (16.7 mM) diapocynin in DMSO was found to be stable for at least 30 days when stored at room temperature.

The complex [7,10-mu-H-7-CO-7,7-(PPh3)2-isonido-7,8,9-ReC2B7H9] has been synthesized by treatment of the complex salt [NHMe3][3,3-Cl2-3,3-(CO)2-closo-3,1,2-ReC2B9H11] with PPh3 in refluxing THF (tetrahydrofuran) and isolated as intensely colored orange-red microcrystals. Spectroscopic NMR and IR data have suggested that the product has a highly asymmetric structure with two inequivalent PPh3 ligands and a single CO ligand. Measurement of 11B NMR spectra in particular have indicated seven distinct boron vertexes, although the resulting cage degradation by removal of two BH vertexes was confirmed only following X-ray crystallographic analysis, which revealed the pentadecahedral isonido-7,8,9-ReC2B7 architecture. The 11B NMR resonances span an enormous chemical shift range (Deltadelta = 113), and this appears to be a direct consequence of the deshielding of the boron vertex directly opposite the quadrilateral |ReCCB| aperture. The new complex has been shown by electrochemical measurements to undergo a reversible one-electron oxidation. Digitally simulated cyclic voltammograms support a proposed square scheme (E(1/2) = 0.58, 0.69 V vs ferrocene) involving a reversible isonido-closo transition of the metallacarborane cage. Most unusually for a metallacarborane complex, ambient temperature solutions in CH2Cl2 and DMF have been shown to be intensely turquoise-blue fluorescent (lambda(em) = 442 nm, Phi = 0.012). Fluorescence spectroscopy measurements in MeTHF (2-methyltetrahydrofuran) glass at 77 K have indicated that the likely cause of such a broad emission is dual fluorescence (lambda(em) = 404, 505 nm), with both emissions displaying vibronic structure. Following excited-state lifetime decay analysis, the emissive behavior has been accredited to metal-perturbed 1IL states, with the lower energy emission arising from a slight geometric distortion of the initially excited complex.