Structure-activity relationship study of leucinostatin A,a modulator of tumor−stroma interaction

Structure-activity relationship study of leucinostatin A, a natural nonapeptide, was performed to gain insight into the structural requirements for leucinostatin A to exhibit antiproliferative activity against DU-145 prostate cancer cells under cocultured conditions with the corresponding stromal cells. Twenty truncated peptide analogs of leucinostatin A revealed that the nonapeptide structure as a whole is essential for the biological activity. Alanine scanning demonstrated the importance of some of the amino acid components, including hydroxyleucine and the second leucine from the N-terminus. Two of the three aminoisobutyric acids could be substituted with one of the enantiomers of alanine, clearly demonstrating that each methyl group in these portions has a distinct influence on the growth-inhibitory activity.     

Effect of nitrogen doping on the properties of AlSiO film for wide bandgap semiconductors

A gate insulator film with a wide bandgap and a high dielectric constant is required to achieve high-power field effect transistors (FET) using wide bandgap semiconductors such as SiC, GaN, and diamond. It is observed that an aluminum silicon oxide (AlSiO) film containing 11% nitrogen has a high resistivity of 5 × 10¹⁵ Ω cm, and the leakage current of a nitrogen-doped aluminum silicon oxide (AlSiON) film is also suppressed at high temperature, as compared to the AlSiO film. For example, the leakage current at 240 °C is four orders of magnitude smaller than that of the AlSiO film, suggesting that the AlSiON film is applicable to high temperature operation of wide bandgap semiconductor devices.     

Differentiation of the Stereochemistry and Anomeric Configuration for 1-3 Linked Disaccharides Via Tandem Mass Spectrometry and <Superscript>18</Superscript>O-labeling

Collision-induced dissociation (CID) of deprotonated hexose-containing disaccharides (m/z 341) with 1–2, 1–4, and 1–6 linkages yields product ions at m/z 221, which have been identified as glycosyl-glycolaldehyde anions. From disaccharides with these linkages, CID of m/z 221 ions produces distinct fragmentation patterns that enable the stereochemistries and anomeric configurations of the non-reducing sugar units to be determined. However, only trace quantities of m/z 221 ions can be generated for 1–3 linkages in Paul or linear ion traps, preventing further CID analysis. Here we demonstrate that high intensities of m/z 221 ions can be built up in the linear ion trap (Q3) from beam-type CID of a series of 1–3 linked disaccharides conducted on a triple quadrupole/linear ion trap mass spectrometer. ¹⁸O-labeling at the carbonyl position of the reducing sugar allowed mass-discrimination of the “sidedness” of dissociation events to either side of the glycosidic linkage. Under relatively low energy beam-type CID and ion trap CID, an m/z 223 product ion containing ¹⁸O predominated. It was a structural isomer that fragmented quite differently than the glycosyl-glycolaldehydes and did not provide structural information about the non-reducing sugar. Under higher collision energy beam-type CID conditions, the formation of m/z 221 ions, which have the glycosyl-glycolaldehyde structures, were favored. Characteristic fragmentation patterns were observed for each m/z 221 ion from higher energy beam-type CID of 1–3 linked disaccharides and the stereochemistry of the non-reducing sugar, together with the anomeric configuration, were successfully identified both with and without ¹⁸O-labeling of the reducing sugar carbonyl group.     

Assignment of the Stereochemistry and Anomeric Configuration of Sugars within Oligosaccharides Via Overlapping Disaccharide Ladders Using MSn

A systematic approach is described that can pinpoint the stereo-structures (sugar identity, anomeric configuration, and location) of individual sugar units within linear oligosaccharides. Using a highly modified mass spectrometer, dissociation of linear oligosaccharides in the gas phase was optimized along multiple-stage tandem dissociation pathways (MSⁿ, n = 4 or 5). The instrument was a hybrid triple quadrupole/linear ion trap mass spectrometer capable of high-efficiency bidirectional ion transfer between quadrupole arrays. Different types of collision-induced dissociation (CID), either on-resonance ion trap or beam-type CID could be utilized at any given stage of dissociation, enabling either glycosidic bond cleavages or cross-ring cleavages to be maximized when wanted. The approach first involves optimizing the isolation of disaccharide units as an ordered set of overlapping substructures via glycosidic bond cleavages during early stages of MSⁿ, with explicit intent to minimize cross-ring cleavages. Subsequently, cross-ring cleavages were optimized for individual disaccharides to yield key diagnostic product ions (m/z 221). Finally, fingerprint patterns that establish stereochemistry and anomeric configuration were obtained from the diagnostic ions via CID. Model linear oligosaccharides were derivatized at the reducing end, allowing overlapping ladders of disaccharides to be isolated from MSⁿ. High confidence stereo-structural determination was achieved by matching MSⁿ CID of the diagnostic ions to synthetic standards via a spectral matching algorithm. Using this MSⁿ (n = 4 or 5) approach, the stereo-structures, anomeric configurations, and locations of three individual sugar units within two pentasaccharides were successfully determined.

Efficient synthesis of neurotrophic honokiol using Suzuki–Miyaura reactions

Efficient synthesis of honokiol (1) was accomplished using two kinds of Suzuki–Miyaura reactions. The first Suzuki–Miyaura reaction was employed to couple 2-bromophenol (6) with 4-hydroxyphenylboronic acid (5), giving rise to biphenol 4, and the second coupling was used to introduce allyl groups at 5- and 3′-positions of honokiol. The total synthesis of 1 was completed in 74% yield over five steps from 6, or in 83% yield over four steps from biphenol 4.     

Total synthesis of (+)-eupomatilone 2 via asymmetric [2,3]-Wittig rearrangement of highly oxygenated biphenylmethyl ethers

We have achieved the total synthesis of (±)- and (+)-eupomatilone 2 isolated from the Australian shrub Eupomatia bennettii. The key reaction was an asymmetric [2,3]-Wittig rearrangement employing a bis(oxazoline) chiral ligand. Although the highly oxygenated biphenylmethyl ether exhibited considerably lowered enantioselectivity as compared with the non-substituted biphenylmethyl ether, the selectivity was improved to 89% ee by using n-BuLi and ether as the base and the co-solvent, respectively.     

Visualization of microvessels by angiography using inverse‐Compton scattering X‐rays in animal models

The fundamental performance of microangiography has been evaluated using the S‐band linac‐based inverse‐Compton scattering X‐ray (iCSX) method to determine how many photons would be required to apply iCSX to human microangiography. ICSX is characterized by its quasi‐monochromatic nature and small focus size which are fundamental requirements for microangiography. However, the current iCSX source does not have sufficient flux for microangiography in clinical settings. It was determined whether S‐band compact linac‐based iCSX can visualize small vessels of excised animal organs, and the amount of X‐ray photons required for real time microangiography in clinical settings was estimated. The iCSX coupled with a high‐gain avalanche rushing amorphous photoconductor camera could visualize a resolution chart with only a single iCSX pulse of ～3 ps duration; the resolution was estimated to be ～500 µm. The iCSX coupled with an X‐ray cooled charge‐coupled device image sensor camera visualized seventh‐order vascular branches (80 µm in diameter) of a rabbit ear by accumulating the images for 5 and 30 min, corresponding to irradiation of 3000 and 18000 iCSX pulses, respectively. The S‐band linac‐based iCSX visualized microvessels by accumulating the images. An iCSX source with a photon number of 3.6 × 10³–5.4 × 10⁴ times greater than that used in this study may enable visualizing microvessels of human fingertips even in clinical settings.     

Application of nano-scale zero-valent iron adsorbed on magnetite nanoparticles for removal of carbon tetrachloride: Products and degradation pathway

Nano-scale zero-valent iron (nZVI) attached to Fe₃O₄ nanoparticles (Fe⁰@Fe₃O₄), which has better dispersibility and a larger specific surface area than the nanoparticles alone, were prepared and applied to the reductive dechlorination of carbon tetrachloride (CT). CT removal efficiencies by Fe⁰@Fe₃O₄ composites with different ratios of the two components were compared. Under optimum conditions, when the Fe⁰/Fe₃O₄ ratio was 1:2, almost no CT was detected after 50 min and it took only about 30 min to reach a removal efficiency of 90%, compared with 120 min for an Fe⁰/Fe₃O₄ ratio of 1:4. An increase in the amount of nZVI in the catalyst effectively improved the removal of CT and accelerated the reaction rate. Chloroform was the main product. Compared with Fe₃O₄ alone, a significant increase in the solution concentrations of ferrous and ferric ions occurred in the Fe⁰@Fe₃O₄ system: both Fe²⁺ and Fe³⁺ reached their maximum concentrations at 60 min and then tended to decline over the next 60 min. The increase in Fe²⁺ concentration was attributed to the reaction between nZVI and CT, which produces ferrous ions when electrons transfer from Fe⁰ to organic chlorides. Synergistic effects between the composite constituents promoted the relative rates of mass transfer to reactive sites and Fe²⁺ generated in solution facilitated the reduction of chlorinated organic pollutants by magnetite. Thus, Fe⁰@Fe₃O₄ nanoparticles effectively achieved reductive dechlorination of CT and provide an improved nZVI catalyst for the remediation of chlorinated organic compounds.     

Raman spectra of biphenyl negative ion in tetrahydrofuran solution

Raman spectra of the mono-negative ion of biphenyl in tetrahydrofuran solution were obtained by Ar⁺, He–Ne and Kr⁺ laser exciting lines. The observed frequency shift from the neutral molecule and intensity enhancement by resonance Raman effect is discussed on the basis of MO considerations.