A Design Strategy for Single‐Stranded Helicates using Pyridine‐Hydrazone Ligands and PbII

The reactions of py‐hz ligands ( L1–L5 ) with Pb(CF₃SO₃)₂?H₂O resulted in some rare examples of discrete single‐stranded helical Pb^II complexes. L1 and L2 formed non‐helical mononuclear complexes [Pb L1 (CF₃SO₃)₂]?CHCl₃ and Pb L2 (CF₃SO₃)₂][Pb L2 CF₃SO₃]CF₃SO₃?CH₃CN, which reflected the high coordination number and effective saturation of Pb^II by the ligands. The reaction of L3 with Pb^II resulted in a dinuclear meso‐helicate [Pb₂ L3 (CF₃SO₃)₂Br]CF₃SO₃?CH₃CN with a stereochemically‐active lone pair on Pb^II. L4 directed single‐stranded helicates with Pb^II, including [Pb₂ L4 (CF₃SO₃)₃]CF₃SO₃?CH₃CN and [Pb₂ L4 CF₃SO₃(CH₃OH)₂](CF₃SO₃)₃?2 CH₃OH?2 H₂O. The acryloyl‐modified py‐hz ligand L5 formed helical and non‐helical complexes with Pb^II, including a trinuclear Pb^II complex [Pb₃ L5 (CF₃SO₃)₅]CF₃SO₃?3CH₃CN?Et₂O. The high denticity of the long‐stranded py‐hz ligands L4 and L5 was essential to the formation of single‐stranded helicates with Pb^II.     

“Everything flows?”: elastic effects on startup flows of yield-stress fluids

It is now 30 years since Barnes and Walters published a provocative paper in which they asserted that the yield stress is an experimental artifact. We now know that the situation is far more complicated than understood at the time, and that the mechanics of the solid material prior to yielding must be considered carefully. In this paper, we examine the response of a well-studied “simple” yield-stress material, namely a Carbopol gel that exhibits no thixotropy, and demonstrate the significance of the pre-yielding behavior through a number of elementary measurements.     

Development and validation of a LC-MS/MS assay for quantitation of plasma citrulline for application to animal models of the acute radiation syndrome across multiple species

The potential risk of a radiological catastrophe highlights the need for identifying and validating potential biomarkers that accurately predict radiation-induced organ damage. A key target organ that is acutely sensitive to the effects of irradiation is the gastrointestinal (GI) tract, referred to as the GI acute radiation syndrome (GI-ARS). Recently, citrulline has been identified as a potential circulating biomarker for radiation-induced GI damage. Prior to biologically validating citrulline as a biomarker for radiation-induced GI injury, there is the important task of developing and validating a quantitation assay for citrulline detection within the radiation animal models used for biomarker validation. Herein, we describe the analytical development and validation of citrulline detection using a liquid chromatography tandem mass spectrometry assay that incorporates stable-label isotope internal standards. Analytical validation for specificity, linearity, lower limit of quantitation, accuracy, intra- and interday precision, extraction recovery, matrix effects, and stability was performed under sample collection and storage conditions according to the Guidance for Industry, Bioanalytical Methods Validation issued by the US Food and Drug Administration. In addition, the method was biologically validated using plasma from well-characterized mouse, minipig, and nonhuman primate GI-ARS models. The results demonstrated that circulating citrulline can be confidently quantified from plasma. Additionally, circulating citrulline displayed a time-dependent response for radiological doses covering GI-ARS across multiple species.     

Effects of the standardization of quantitative fluorometry on the automated evaluation of platelet antibodies

An automated fluorescence invertoscope featuring a computer-controlled scanning stage with plate inserts for multiple samples, a photomultiplier tube and software controlling every function of the microscope were used to collect the fluorescence data after analog-to-digital conversion. Principal differences between this method and qualitative platelet tests include the standardization of all test reagents and the quantitative evaluation of possible autofluorescence. The automated data acquisition permitted the separate evaluation of the fluorescence intensities of all materials to ensure low background fluorescence and optimal fluorochrome concentrations. EDTA-anticoagulated platelets of 100 donors were incubated with serum, subsequently with fluorescein- or rhodamine-treated IgG, washed, counted in PBS-glycerol, and mounted on thin glass plates. Each plate contained 5000 cells per test and negative and positive controls.     

φ meson production fromp\bar p collisions at\sqrt s = 1.8 TeV

Fermilab experiment E735 located at the CO intersection region of the $\sqrt s = 1.8$ TeV $p\bar p$ collider analysed over 900 Φ→K ⁺ K ^? events. Measured were the transverse momentum spectrum, the correlation between the average transverse momentum <pt> and the charged particle multiphcityN _c , as well as the probability of Φ production per charged track,N _Φ /N _c , versusN _c . We have also made an estinate of the total inclusive cross section for Φ mesons, $\sigma (p\bar p \to \phi X) = 7.3 \pm 2.2 mb$ .     

Synthesis of 3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin

The synthesis of an isomeric mixture of 4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl analogues 6 of the C-glycosylpyranonaphthoquinone antibiotic medermycin is described. The key 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-5-methoxy-1,4-naphthoquinone 8 was prepared via Stille coupling of 6-(3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)-3-bromo-1,4- naphthoquinone 17 with (alpha-ethoxyvinyl)tributyl-stannane followed by hydrolysis and oxidation of the resultant hydroquinone 18. Bromonaphthoquinone 17 in turn was afforded by oxidative demethylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)-3- bromo-1,4,5-trimethoxynaphthalene 16 formed by regioselective bromination of 6-(4-acetyl-3-azido-2,3,6-trideoxy- beta-D-arabino-hexopyranosyl)-1,4,5-trimethoxynaphthalene 10. This latter naphthalene 10 was prepared via direct C-glycosylation of naphthol 12 with glycosyl donor 11 using BF3.Et2O in acetonitrile. The regioselectivity of the bromination of naphthalene 10 was independently determined by reductive monomethylation of the 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-5-methoxy-1,4-naphthoquinone 22 to naphthol 23 followed by selective ortho bromination to bromide 24 and methylation to 16. Attempts to effect acetylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-3-bromo-1,4,5-trimethoxynaphthalene 16 and 3-bromo-6-(3-dimethylamino-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-1,4,5-trimethoxynaphthalene 26 via Stille coupling with (alpha-ethoxyvinyl)tributylstannane were low yielding thereby establishing the necessity to use an azido group as a latent dimethylamino group and a more electrophilic bromonaphthoquinone as the coupling partner for the Stille reaction. Addition of 2-trimethylsilyloxyfuran 9 to 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)- 5-methoxy-1,4-naphthoquinone 8 afforded the furofuran adducts 7 and 19 as an inseparable mixture of diastereomers. Oxidative rearrangement of this diastereomeric mixture using ceric ammonium nitrate afforded the inseparable diastereomeric furonaphthopyrans 6 and 20.     

XAFS spectral analysis of the cadmium coordination geometry in cadmium thiolate clusters in metallothionein

We report the combination of measurement and prediction of X-ray absorption fine structure (XAFS) data, where the term XAFS refers to the overall spectrum that encompasses both the X-ray Absorption Near Edge Structure (XANES) region as well as the Extended X-ray Absorption Fine Structure (EXAFS) region, to evaluate the cadmium thiolate cluster structures in the metalloprotein metallothionein. XAFS spectra were simulated using coordinates from molecular models of the protein calculated by molecular mechanics/molecular dynamics (MM3/MD), from NMR analyses, and from analysis of X-ray diffraction data. XAFS spectra were also simulated using the coordinates from X-ray crystallographic data for [Cd(SPh)4]2-, CdS, [Cd2(mu-SPh)2(SPh)4]2-, and [Cd4(mu-SPh)6(SPh)4]2-. The simulated XAFS data that were calculated using the FEFF8 program closely resemble the experimental data reported for [Cd(SPh)4]2-, CdS, [Cd2(mu-SPh)2(SPh)4]2-, [Cd4(mu-SPh)6(SPh)4]2-, rabbit liver metallothionein cadmium alpha-domain (Cd4-alpha MT), and cadmium rabbit liver betaalpha metallothionein (Cd7-betaalpha MT). MM3 force field parameters were modified to include cadmium-sulfur bonding and were initially set to values derived from published X-ray diffraction and EXAFS experimental data. The force field was further calibrated and adjusted through comparison between experimental spectra taken from the literature and simulated XAFS spectra calculated using the FEFF8 program in combination with atomic coordinates from MM3/MD energy minimization. MM3/MD techniques were used with the calibrated force field to predict the high-resolution structure of the metal clusters in rabbit liver Cd7-MT. Structures for Cd3S9 (beta) MT and Cd4S11 (alpha) MT domains from MM3/MD calculations and those previously reported for Cd7-MT on the basis of 1H and 113Cd NMR data were compared. Structural differences between the different models for these cadmium thiolate clusters were evident. Combining the measurement and simulation of XAFS data provides an excellent method of assessing, modeling, and predicting metal-binding sites in metalloproteins when X-ray absorption spectroscopy (XAS) data are available.