Evolution of Fe-based intermetallic phases during homogenization of Al–Fe hypoeutectic alloy

Journal of Thermal Analysis and Calorimetry - Homogenization heat treatment is the first step in the processing of aluminium alloys, which for most alloys is carried out before any deformation...     

Chalice-Type Tridentate Silicon Lewis Acids of C3 Symmetry in a Single Step Starting from Hexadehydrotribenzo[12]annulene

Tridentate Lewis acids with aligned functions were synthesized based on the rigid framework hexadehydrotribenzo[12]annulene. The backbone and its fluorinated analogue were synthesised in one-pot syntheses, with alkyne deprotection and Sonogashira cross coupling reaction being carried out in one step. Hydrosilylation of the annulene with chlorohydrosilanes proceeded highly selectively and afforded rigid poly-Lewis acids with three SiCl₃ or SiCl₂Me substituents perfectly oriented to one side of the molecule in a single step. The progress of hydrosilylation was investigated by time-correlated NMR spectroscopic studies. The crystal structures show that the framework is symmetrically functionalised and the silyl substituents are aligned in one direction. To increase the acidity of the Lewis acids the chlorosilyl substituents were fluorinated with SbF₃. Further investigation of hydrometallation reactions (M=B, Al, Ga, Sn) did not lead to corresponding structures.     

Ventral and dorsal streams processing visual motion perception (FDG-PET study)

Background

Cullin ubiquitin ligases are activated via the covalent modification of Cullins by the small ubiquitin-like protein nedd8 in a process called neddylation. Genetic mutations of cullin-4b (cul4b) cause a prevalent type of X-linked intellectual disability (XLID) in males, but the physiological function of Cul4B in neuronal cells remains unclear.

Results

There are three major isoforms of Cul4B (1, 2, and 3) in human and rodent tissues. By examining the endogenous Cul4B isoforms in the brain, this study demonstrates that Cul4B-1 and Cul4B-2 isoforms are unneddylated and more abundant in the brain whereas the lesser species Cul4B-3 that misses the N-terminus present in the other two isoforms is neddylated. The data suggest that the N-terminus of Cul4B inhibits neddylation in the larger isoforms. Immunostaining of human NT-2 cells also shows that most Cul4B is unneddylated, especially when it is localized in the process in G0-synchronized cells. This study demonstrates that Cul4B accumulates during mitosis and downregulation of Cul4B arrests NPCs and NT-2 cells in the G2/M phase of the cell cycle. In both human and rodent brain tissues, Cul4B-positive cells accumulate ??-catenin in the dentate subgranular zone and the subventricular zone. These Cul4B-positive cells also co-express the MPM-2 mitotic epitope, suggesting that Cul4B is also necessary for mitosis progression in vivo.

Conclusions

This study provides first evidence that unneddylated Cul4B isoforms exist in the brain and are necessary for mitosis progression in NPCs. The data suggest that unneddylated Cul4B isoforms specifically inhibits ??-catenin degradation during mitosis. Furthermore, unneddylated Cul4B may play a role in addition to cell cycle since it is exclusively localized to the processes in starved NT-2 cells. Further analyses of the different isoforms of Cul4B will help understand the cognitive deficits in Cul4B-linked XLID and give insights into drug and biomarker discoveries.     

Effect of oxalate test dose size on absolute and percent oxalate absorption

The purpose of this pilot study was to establish the dependence or independence of oxalate absorption on the quantity of the test dose of sodium oxalate over a range of test doses corresponding to physiological dietary oxalate intake values. Gastrointestinal oxalate absorption was measured with the [¹³C₂]oxalate absorption test. Six healthy volunteers were always tested under standardized dietary conditions with 63 mg dietary oxalate and 800 mg dietary calcium per day. The volunteers were tested thrice each with sodium oxalate test doses of 25, 50, 200, and 600 mg. Additionally, 1000 mg sodium oxalate was applied once to three of these volunteers. The oxalate absorption of the six volunteers tested under the standardized conditions with 50 mg sodium [¹³C₂]oxalate was 7.2 ± 2.62 % (mean ± SD), similar to the 120 volunteers tested previously: 8.0 ± 4.4 % (mean ± SD). The tests with sodium [¹³C₂]oxalate doses in the range 25–1000 mg revealed similar percent oxalate absorption values. In conclusion, in healthy volunteers, the amount of oxalate absorbed in the gastrointestinal tract increased proportionally with the higher test doses of oxalate. However, percent oxalate absorption remained unchanged with test doses in the dose range of physiological dietary oxalate intakes.     

Time resolved simultaneous detection of 14NO and 15NO via mid-infrared cavity leak-out spectroscopy

We present a ring-down absorption spectrometer based on a continuous-wave CO laser in the mid-infrared spectral region near λ?=?5 μm. Using a linear ring-down cavity (length: 0.5 m) with high reflective mirrors (R?=?99.988 %), we observed a noise-equivalent absorption coefficient of 3?×?10^?10 cm^?1Hz^?1/2. This corresponds to a noise-equivalent concentration of 800 parts per trillion (ppt) for ¹⁴NO and 40 ppt for ¹⁵NO in 1 s averaging time. We achieve a time resolution of 1 s which allows time resolved simultaneous detection of the two N isotopes. The δ¹⁵N value was obtained with a precision of ±1.2‰ in a sample with a NO fraction of 11 ppm. The simultaneous detection enables the use of ¹⁵NO as a tracer molecule for endogenous biomedical processes.     

Labelling Studies for Structure Elucidation of a New Hydroxymetabolite of Tramadol

Abstract

Tramadol, racemic 1-(3-methoxyphenyl)-2-(dimethylaminomethyl)cyclohexane-1-ol, is an effective analgesic drug. Metabolites of tramadol described so far originate from O- and N-demethylation and are excreted in urine directly or after conjugation. A further metabolite was found in human liver microsome incubations and in the urine of volunteers after ingestion of tramadol. To elucidate the structure of the new metabolite, seven deuterated isotopomers of tramadol have been synthesized and ingested by volunteers. The mass spectra of the metabolites derived showed (i) that it was a hydroxy metabolite, (ii) that the hydroxy group was not located on the aromatic ring, the side chain, or the positions 2 and 6 of the cyclohexane ring, (iii) that the hydroxy-group was introduced to one of the the positions 3, 4 or 5 of the cyclohexane ring. The hydroxy metabolite was formed preferentially from the (-)-enantiomer, (1S,2S)-tramadol.     

Charged, but Found "Not Guilty": Innocence of the Suspect Bridging Ligands [RO(O)CNNC(O)OR](2-) = L(2-) in [(acac)(2)Ru(μ-L)Ru(acac)(2)](n), n = +,0,-,2-

Neutral diastereoisomeric diruthenium(III) complexes, meso- and rac-[(acac)(2)Ru(μ-adc-OR)Ru(acac)(2)] (acac(-) = 2,4-pentanedionato and adc-OR(2-) = dialkylazodicarboxylato = [RO(O)CNNC(O)OR](2-), R = tert-butyl or isopropyl), were obtained from electron transfer reactions between Ru(acac)(2)(CH(3)CN)(2) and azodicarboxylic acid dialkyl esters (adc-OR). The meso isomer 3 with R = isopropyl was structurally characterized, revealing two deprotonated and N-N coupled carbamate functions in a reduced dianionic bridge with d(N-N) = 1.440(5) ?. A rather short distance of 4.764 ? has been determined between the two oxidized, antiferromagnetically coupled Ru(III) centers. The rac isomer 4 with R = isopropyl exhibited stronger antiferromagnetic coupling. While the oxidation of the neutral compounds was fully reversible only for 3 and 4, two well-separated (10(8) < K(c) < 10(10)) reversible one-electron reduction steps produced monoanionic intermediates 1(-)-4(-) with intense (ε ≈ 3000 M(-1) cm(-1)), broad (Δν(1/2) ≈ 3000 cm(-1)) absorptions in the near-infrared (NIR) region around 2000 nm. The absence of electron paramagnetic resonance (EPR) signals even at 4 K favors the mixed-valent formulation Ru(II)(adc-OR(2-))Ru(III) with innocently behaving bridging ligands over the radical-bridged alternative Ru(II)(adc-OR(?-))Ru(II), a view which is supported by the metal-centered spin as calculated by density functional theory (DFT) for the methyl ester model system. The second reduction of the complexes causes the NIR absorption to disappear completely, the EPR silent oxidized forms 3(+) and 4(+), calculated with asymmetrical spin distribution, do not exhibit near infrared (NIR) activity. The series of azo-bridged diruthenium complex redox systems [(acac)(2)Ru(μ-adc-R)Ru(acac)(2)](n) (n = +,0,-,2-), [(bpy)(2)Ru(μ-adc-R)Ru(bpy)(2)](k) (k = 4+,3+,2+,0,2-), and [(acac)(2)Ru(μ-dih-R)Ru(acac)(2)](m) (m = 2+,+,0,-,2-; dih-R(2-) = 1,2-diiminoacylhydrazido(2-)) is being compared in terms of electronic structure and identity of the odd-electron intermediates, revealing the dichotomy of innocent vs noninnocent behavior.     

Silylation products of cyclic tri-aminal carbanions and their lithiation

The structure of 1,3,5-trimethyl-1,3,5-triaza-cyclohexane (TMTAC) was determined by single crystal X-ray diffraction and compared with earlier gas-phase data. It shows a preference for an aee-conformation in all phases. Lithiated TMTAC, [(RLi)(2)·(RH)] (1) (R = 2,4,6-trimethyl-2,4,6-triaza-cyclohex-1-yl), was reacted with Et(3)SiCl, Ph(3)SiCl and PhMe(2)SiCl to afford the substituted silanes Et(3)SiR (1), Ph(3)SiR (2) and PhMe(2)SiR (3) in moderate yields. They were characterised by NMR spectroscopy ((1)H, (13)C, (29)Si). 1 reacts with Me(2)SiCl(2) and Ph(2)SiCl(2) to give Me(2)SiR(2) (5) and Ph(2)SiR(2) (6) which were characterised by NMR spectroscopy. 5 was also identified by crystal structure determination. Analogous triple substitution could not be observed by employing trichlorosilanes. Quantumchemical calculations explain this by sterical overcrowding of the silicon atom. The reaction of 1 with SiCl(4) did not yield fourfold substitution but a formal insertion product of SiCl(2) into a C-N bond of the TMTAC ring (2,4,6-trimethyl-2,4,6-triaza-1,1-dichloro-1-sila-cycloheptane, 7) in very small quantities. It was identified by X-ray crystallography and shows an intramolecular Si···N dative bond. The reactions of (3) and (5) with n-butyl lithium afforded lithiation of the silicon bound methyl groups in both cases. The products, 8 and 9, were characterised by NMR spectroscopy ((1)H, (13)C, (29)Si), 8 was also characterised by X-ray crystallography.