Degraded and oxetane-bearing limonoids from the roots of Melia azedarach

Brine shrimp lethality test (BST)-guided fractionation of a methanol extract of the roots of Melia azedarach resulted in the isolation of two new limonoids, 9alpha-hydroxy-12alpha-acetoxyfraxinellone (1) and 7,14-epoxy-azedarachin B (2), together with the known compounds, 12alpha-hydroxyfraxinellone (4), 9alpha-hydroxyfraxinellone (5), azedarachin B (6), and neoazedarachin B (7). The structures of 1 and 2 were elucidated by analysis of spectroscopic data and comparison of their NMR data with those of the known compounds. Compounds 1, 2 and 4-7 exhibited significant activity in the BST, in particular, azedarachin B (6) showed remarkable BST activity with an LC(50) value of 0.0098 microM.     

Nuclear relaxation of H2 and H2@C60 in organic solvents

The 1H nuclear spin-lattice relaxation time (T1) of H2 and H2@C60 in organic solvents varies with solvent, and it varies proportionally for H2 and for H2@C60. Since intermolecular magnetic interactions are ruled out, the solvent must influence the modulating processes of the relaxation mechanisms of H2 both in the solvent cage and inside C60. The temperature dependence of T1 also is very similar for H2 and H2@C60, T1 going through a maximum by varying the temperature in solvents which allow a wide range of temperatures to be explored. This behavior is attributed to the presence of dipolar and spin-rotation mechanisms which have an opposite dependence on temperature.     

Synthesis of peptidoglycan fragments and evaluation of their biological activity

The peptidoglycan (PG) bacterial cell wall glycoconjugate has been well known as a strong immunopotentiator. Partial structures of PG were chemically synthesized for elucidation of precise biological activities. Effective construction of distinct repeating glycans of PG was accomplished by the coupling of a key disaccharide glucosaminyl-beta(1-4)-muramic acid unit. Stereoselective glycosylation of disaccharide units was achieved by neighboring group participation of the N-Troc (Troc = 2,2,2-trichloroethoxycarbonyl) group and appropriate reactivity of N-Troc-glucosaminyl trichloroacetimidate. By using an efficient synthetic strategy, mono-, di-, tetra- and octasaccharide fragments of PG were synthesized in high yields. The biological activity of synthetic fragments of PG was evaluated by induction of tumor necrosis factor-alpha (TNF-alpha) from human monocytes, and toll-like receptor 2 (TLR2) and Nod2 dependencies by using transfected HEK293 cells, respectively. Here we reveal that TLR2 was not stimulated by the series of synthetic PG partial structures, whereas Nod2 recognizes the partial structures containing the MDP moiety.     

Theoretical study of the photodesorption mechanism of nitric oxide on a Ag(111) surface: a nonequilibrium Green's function approach to hot-electron tunneling

The photoinduced desorption of NO molecules on a Ag surface was studied theoretically using a recently developed method based on the nonequilibrium Green's function approach combined with the density functional theory. Geometry optimizations for the stable NO dimer phase were carried out, and two structures of adsorbed dimers were identified. We calculated the reaction probabilities as a function of incident photon energy for each of the dimers and compared them with experimental action spectra. The two main features of the action spectra, (i) a long tail to the long wavelength (approximately 600 nm) and (ii) a rapid increase at approximately 350 nm, were well reproduced. By theoretical analysis, we found the importance of quantum interference for the interfacial charge transfer between the metal substrate and the adsorbate, as well as the contribution of secondary electrons. Our calculations suggest that the photoactive species is dimeric and that the resonant level is single for the photodesorption of NO.     

Infrared photodissociation spectroscopy of protonated ammonia cluster ions, NH4+(NH3)n (n=5-8), by using infrared free electron laser

Infrared photodissociation action spectra of protonated ammonia cluster ions, NH(4) (+)(NH(3))(n) (n=5-8), were measured in the range of 1020-1210 cm(-1) by using a tunable infrared free electron laser. Analyses by the density functional theory (DFT) show that the spectral features observed can be assigned to the nu(2) vibrational mode of the NH(3) molecules in NH(4) (+)(NH(3))(n). Size dependence of the spectra supports structural models obtained by the DFT calculations, in which the NH(4) (+) ion is solvated by the four nearest-neighbor NH(3) molecules. For NH(4) (+)(NH(3))(5), the spectrum between 1000 and 1700 cm(-1) was measured. The nu(4) bands of the NH(3) molecules and the NH(4) (+) ion were found in the range of 1420-1700 cm(-1).     

Liquid chromatography/tandem mass spectrometry characterization of oxidized amyloid beta peptides as potential biomarkers of Alzheimer's disease

Alzheimer's disease is characterized by the deposition of senile plaques that consist primarily of amyloid beta peptides. There is substantial evidence that amyloid beta is oxidized in vivo, which has led to the suggestion that oxidative stress is an important mediator of Alzheimer's disease. Metal-catalyzed oxidation can mimic in vivo oxidation of amyloid beta because the metal ion binds to the amino acid residues at the site of oxidation, which then deliver reactive oxygen species to that site. Based on electrospray mass spectrometry, it has been suggested that metal-catalyzed oxidation occurs on histidines-13 and -14. Unfortunately, the amyloid beta peptides provide complex spectra, so it is difficult to definitively characterize the sites of oxidation. Trypsin digestion of both native and oxidized amyloid beta1-16 and amyloid beta1-40 resulted in the formation of tryptic peptides corresponding to amyloid beta6-16, which could be separated by liquid chromatography (LC). Sites of oxidation were then unequivocally characterized as histidine-13 and histidine-14 by LC/tandem mass spectrometric (MS/MS) analysis of the tryptic peptides. The ability to analyze the specific amyloid beta6-16 tryptic fragments derived from full-length amyloid beta peptides will make it possible to determine whether oxidation in vivo occurs at specific histidine residues and/or at other amino acid residues such as methionine-35. Using methodology based on LC/MS/MS it will also be possible to analyze the relative amounts of oxidized peptides and native peptide in cerebrospinal fluid from patients with Alzheimer's disease as biomarkers of oxidative stress.     

Regioselectively N-methylated azacalix[8]arene octamethyl ether prepared by catalytic aryl amination reaction using a temporal N-silylation protocol

[Structure: see text] A temporal N-silylation protocol in the catalytic aryl amination reaction has been devised to prepare nitrogen-bridged calixarene analogues. The protocol involves a smooth in situ N-silylation before aryl amination reaction, followed by spontaneous cleavage of the N-Si bond in the usual workup process, to furnish secondary aromatic amines as the cross-coupled product with no silyl group on the nitrogen atom. A successful application to the preparation of regioselectively N-methylated azacalix[8]arene is described, together with the crystallographic analysis.     

Radical trifluoromethylation of ketone silyl enol ethers by activation with dialkylzinc

[reaction: see text] The radical trifluoromethylation of ketone silyl enol ethers gave alpha-CF(3) ketones in good yields with wide scope of the ketonic substrates including acyclic ketones and cyclopentanone. The use of dialkylzinc to activate the silyl enol ethers is the key to the efficient radical trifluoromethylation.