Synthetic, structural, and stability studies of metal complexes of cross -bridged tetraamine macrocycles

Cross-bridging of tetraazamacrocyclic ligands with an ethylene unit forms a family of bicyclic tetraamine ligands originally designed and synthesized by the Weisman-Wong research group to selectively complex small metal ions such as Li+ in a cis-folded configuration. Cu(II), Ga(III), and In(III) complexes of these cross-bridged ligands have potential radiometal-based pharmaceutical applications due to their high kinetic stabilities. Cu(II) complexes of eight cross-bridged tetraazamacrocyclic ligands have been synthesized and structurally characterized. Their relative kinetic stabilities were evaluated by monitoring acid-promoted dissociation processes using UV-Vis spectroscopy. The copper complex of a dicarboxylate pendant-armed cross-bridged cyclam was the most inert, consistent with its superior in vivo stability. This is also in accord with the fact that copper fits best in this ligand as indicated by the largest Nax-Cu-N ax bond angle of this complex compared to other six-coordinate Cu(II) complexes of cross-bridged ligands. Ga(III) and In(III) complexes of three of the ligands have been prepared and characterized. The indium complex of cross-bridged cyclen with the poorest fit in the solid-state showed the lowest inertness as indicated by its partial decomplexation in water. By contrast, gallium complexes of cross-bridged cyclam (ligand 1) and a dicarboxylate pendant-armed cross-bridged cyclen have been found to be stable in acidic D2O (pD = 1.07) for more than seven months. Thus we were able to investigate the possible solution structures of the Ga(III) complex of ligand 1 in acidic D2O using NMR techniques. Zn(II), Cd(II) and Hg(II) complexes of the eight cross-bridged ligands have been synthesized and whenever appropriate, structurally characterized. Comparison of their solid-state structures suggested the selectivity of this family of cross-bridged ligands for Zn(II) ion based on its best fit inside the cleft formed by the cross-bridged ligands. In addition, the kinetic stabilities of selected Zn(II), Cd(II) and Hg(II) complexes were studied. As with copper and indium complexes, the Zn(II) complex of cross-bridged cyclam is more inert than that of cross-bridged cyclen. These results indicate that cross-bridged cyclam and its derivatives have more potential for radiopharmaceutical applications than related cross-bridged cyclen and its derivatives

Distinct slab interfaces imaged within the mantle transition zone

Oceanic lithosphere descends into Earth’s mantle at subduction zones and drives material exchange between Earth’s surface and its deep interior. The subduction process creates chemical and thermal heterogeneities in the mantle, with the strongest gradients located at the interfaces between subducted slabs and the surrounding mantle. Seismic imaging of slab interfaces is key to understanding slab compositional layering, deep-water cycling and melting, yet the existence of slab interfaces below 200 km remains unconfirmed. Here, we observe two sharp and slightly dipping seismic discontinuities within the mantle transition zone beneath the western Pacific subduction zone that coincide spatially with the upper and lower bounds of the high-velocity slab. Based on a multi-frequency receiver function waveform modelling, we found the upper discontinuity to be consistent with the Mohorovičić discontinuity of the subducted oceanic lithosphere in the mantle transition zone. The lower discontinuity could be caused by partial melting of sub-slab asthenosphere under hydrous conditions in the seaward portion of the slab. Our observations show distinct slab–mantle boundaries at depths between 410 and 660 km, deeper than previously observed, suggesting a compositionally layered slab and high water contents beneath the slab

The expression and antigenicity of a truncated spike-nucleocapsid fusion protein of severe acute respiratory syndrome-associated coronavirus

<p>Abstract</p> <p>Background</p> <p>In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities.</p> <p>Results</p> <p>Genes encoding truncated nucleocapsid (N) and spike (S) proteins of <it>SARSCoV </it>were cloned into the expression vector <it>pQE30 </it>and fusionally expressed in <it>Escherichia coli </it>M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses <it>HCoV </it>229E and <it>HCoV </it>OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with <it>SARSCoV </it>at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to <it>SRASCoV </it>appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit <it>SARSCoV</it>. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with <it>SARSCoV </it>at day 33 post injection were completely protected from virus replication.</p> <p>Conclusion</p> <p>The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.</p

Plasma metabonomics of classical swine fever virus-infected pigs

Classical swine fever (CSF) is an infectious disease caused by Classical swine fever virus (CSFV), which is characterized by depression, high fever, extensive skin bleeding, leukopenia, anorexia, alternating constipation, and diarrhea. Hemorrhagic infarction of the spleen is the main characteristic pathological change following CSFV infection. Large-scale outbreaks of CSF are rare in China and are mainly distributed regionally. The clinical symptoms of CSF are not obvious, and show variation from typical to atypical symptoms, which makes diagnosis based on clinical symptoms and pathology challenging. In recent years, the incidence of CSF-immunized pig farms in China has increased and new CSFV gene subtypes have appeared, posing new challenges to the prevention and control of CSF in China. Changes in metabolites caused by viral infection reflect the pathogenic process. Metabonomics can reveal the trace metabolites of organisms; however, plasma metabonomics of CSFV-infected pigs have rarely been investigated. Therefore, we used an established pig CSFV infection model to study changes in plasma metabolites. The results showed significant differences in forty-five plasma metabolites at different time periods after CSFV infection in pigs, with an increase in twenty-five metabolites and a decrease in twenty metabolites. These changed metabolites were mainly attributed to the tricarboxylic acid cycle, amino acid cycle, sugar metabolism, and fat metabolism. Thirteen metabolic pathways changed significantly in CSFV-infected pigs, including tricarboxylic acid cycle, inositol phosphate metabolism, glycine, serine and threonine metabolism,lysine degradation, alanine, aspartate and glutamic acid metabolism, pantothenate and CoA biosynthesis, β-alanine metabolism, lysine degradation, arginine and proline metabolism, glycerolipid metabolism, phenylalanine metabolism, arachidonic acid metabolism, linoleic acid metabolism. Among these, changes in fatty acid biosynthesis and metabolism occurred at all time periods post-infection. These results indicate that CSFV infection in pigs could seriously alter metabolic pathways

Effects of Molecular Structure and Packing Order on the Stretchability of Semicrystalline Conjugated Poly(Tetrathienoacene-diketopyrrolopyrrole) Polymers

The design of polymer semiconductors possessing high charge transport performance, coupled with good ductility, remains a challenge. Understanding the distribution and behavior of both crystalline domains and amorphous regions in conjugated polymer films, upon an applied stress, shall provide general guiding principles to design stretchable organic semiconductors. Structure–property relationships (especially in both side chain and backbone engineering) are investigated for a series of poly(tetrathienoacene-diketopyrrolopyrrole) polymers. It is observed that the fused thiophene diketopyrrolopyrrole-based polymer, when incorporated with branched side chains and an additional thiophene spacer in the backbone, exhibits improved mechanical endurance and, in addition, does not show crack propagation until 40% strain. Furthermore, this polymer exhibits a hole mobility of 0.1 cm2 V−1 s−1 even at 100% strain or after recovered from strain, which reveals prominent continuity and viscoelasticity of the polymer thin film. It is also observed that the molecular packing orientations (either edge-on or face-on) significantly affect the mechanical compliance of the polymer films. The improved stretchability of the polymers is attributed to both the presence of soft amorphous regions and the intrinsic packing arrangement of its crystalline domains