Restrained expression of canine glucocorticoid receptor splice variants α and P prognosticates fatal disease outcome in SIRS

Glucocorticoids play a central role in the inflammatory response and alleviate the symptoms in critically ill patients. The glucocorticoid action relies on the glucocorticoid receptor (GR) which translocates into the nucleus upon ligand-binding and regulates transcription of a battery of genes. Although the GR is encoded by a single gene, dozens of its splice variants have been described in diverse species. The GRα isoform encodes the full, functionally active protein that is composed of a transactivation, a DNA-binding, and a C-terminal ligand-binding domain. The second most highly expressed receptor variant, the GR-P, is formed by an intron retention that introduces an early stop codon and results in a probably dysfunctional protein with truncated ligand-binding domain. We described the canine ortholog of GR-P and showed that this splice variant is highly abundant in the peripheral blood of dogs. The level of cGRα and cGR-P transcripts are elevated in patients of SIRS and the survival rate is increased with elevated cGRα and cGR-P expression. The ratio of cGRα and cGR-P mRNA did not differ between the survivor and non-survivor patients; thus, the total GR expression is more pertinent than the relative expression of GR isoforms in assessment of the disease outcome.

Crystal structures of 9-[bis(benzylsulfanyl)methyl]anthracene and of cyclo-dodecakis(μ2-phenylmethanethiolato-κ2 S:S)hexapalladium(6 Pd—Pd)–anthracene-9,10-dione (1/1)

The first title compound, C29H24S2, L1, represents an example of an anthracene-based functionalized dithioether, which may be useful as a potential chelating or terminal ligand for coordination chemistry. This dithioacetal L1 crystallizes in the monoclinic space group P21/c. The phenyl rings of the benzyl groups and that of the anthracene unit form dihedral angles of 49.21 (4) and 58.79 (5)° and the crystal structure displays short C–H...π contacts. Surprisingly, when attempting to coordinate L1 to [PdCl2(PhCN)2], instead of the targeted chelate complex [PdCl2(κ2-L1)], a cleavage reaction leads to the formation of the centrosymmetric hexanuclear cyclic cluster of composition [Pd6(μ2-SCH2Ph)12] Pd6, or [Pd6(C7H7S)12]·C14H8O2. This tiara-shaped hexamer crystallizing in the triclinic space group P\overline{1} consists of six approximately square planar Pd(II)S4 centers, which are interconnected through twelve μ2-bridging benzyl thiolate groups. The Pd...Pd contacts range from 3.0892 (2) to 3.1609 (2) Å and can be considered as weakly bonding. The unit cell of Pd6 contains also a co-crystallized anthracene-9,10-dione molecule.

Structure and NMR properties of the dinuclear complex di-μ-azido-κ4 N 1:N 1-bis[(azido-κN)(pyridine-2-carboxamide-κ2 N 1,O)zinc(II)]

The new diamagnetic complex, [Zn2(N3)4(C6H6N2O)2] or [Zn2(pca)2(μ1,1-N3)2(N3)2] was synthesized using pyridine-2-carboxamide (pca) and azido ligands, and characterized using various techniques: IR spectroscopy and single-crystal X-ray diffraction in the solid state, and nuclear magnetic resonance (NMR) in solution. The molecule is placed on an inversion centre in space group P\overline{1}. The pca ligand chelates the metal centre via the pyridine N atom and the carbonyl O atom. One azido ligand bridges the two symmetry-related Zn2+ cations in the end-on coordination mode, while the other independent azido anion occupies the fifth coordination site, as a terminal ligand. The resulting five-coordinate Zn centres have a coordination geometry intermediate between trigonal bipyramidal and square pyramidal. The behaviour of the title complex in DMSO solution suggests that it is a suitable NMR probe for similar or isostructural complexes including other transition-metal ions. The diamagnetic nature of the complex is reflected in similar 1H and 13C NMR chemical shifts for the free ligand pca as for the Zn complex.

Nitride-incorporated W–Fe–S double cubane clusters: terminal ligand substitutions and redox behaviors

Five nitride-incorporated W–Fe–S double cubanes with different terminal ligands have been synthesized and their redox behaviors were studied.

Self-assembly and supramolecular isomerism in 1D metal-organometallic networks based on transition-metal assemblies from 1,1’-ferrocene-dicarboxylic acid and ancillary nitrogen heterocycle ligands

A series of eight novel 1D metal-organometallic networks of Cu(II)/Co(II)/Cd(II) and Zn(II) bearing bidentate ligands 1,10’-phenanthroline (1,10’-phen), 5,5’-dimethyl-2,2’-bipyridine (5,5’-diMe-2,2’-bipy) and terminal ligand 4-stilbazole (4-Stb) were prepared by hydrothermal synthesis and...

STRUCTURE OF THE ZINC COMPLEX WITH CYCLOHEXYL AСETOACETATE

Binuclear complex of Zn(II) with cyclohexyl acetoacetate was obtained and structurally characterized for the first time. According to structural data, the crystal system is triclinic, space group P-1; a = 7.6530(4), b = 12.2412(8), c = 12.9102(9) Å; α = 90.198(5), β = 101.071(5), γ = 96.937(5) deg. The molecular structure corresponds to the formula [Zn2(C10H15O3)4(C2H5OH)2]. The complex is located in a special position to the symmetry center of the unit cell. The coordination polyhedrons of the Zn atoms are the same distorted octahedrons formed by six oxygen atoms. Each formed by 4 oxygen atoms in the equatorial position, which belong to three ligand molecules: terminal ligand (2 oxygen atoms) and bridged ligand (1 oxygen atom) which chelate the zinc atom of the named polyhedron and 1 oxygen atom belong to a bridged ligand that chelates the other nucleus and monodentantly coordinated to mentioned one. Two oxygen atoms occupy an axial position, one of which belongs to the terminal ligand, mentioned above and the other to the coordinated ethanol molecule. The bond between the complex nuclei is stabilized by two hydrogen bonds formed by the hydrogen atoms from hydroxyl groups of ethanol molecules and the enol oxygen atoms of the terminal ligands of the other nucleus. The compound was also characterized by IR-spectroscopy, characteristic bands (сm-1) are: ν(C–H) - 2936, 2860, ν(C=O) & ν(C=C) – 1612, ν(C=O) + δ(C–H) – 1532, ν(C=C) & ν(C-CH3)– 1252, δ(C–H) – 1172, π(C–H) – 784, ν(M–O) – 456, 416. IR spectroscopy data confirm the bidentate coordination of cyclohexyl acetoacetate to zinc atoms in deprotonated form with the formation of chelated metallocycles. The structure of the complex is similar to the structures of cobalt and nickel complexes with cyclohexyl acetoacetate. Analysis of XRD-data (which are supplemented with this work) for Co(II), Ni(II) and Zn(II) complexes with acetoacetic acid esters shows that their structure, in particular the number of metal centers in the structures, regardless of the nature of the central atom or the alcohol fragment, but determined the presence of components capable of complementing the coordination sphere of the metal in reaction media.

The effects of terminal tagging on homomeric interactions of the sigma 1 receptor

The sigma 1 receptor (σ1R) has been implicated in cancers, neurological disorders, and substance use disorders. Yet, its molecular and cellular functions have not been well-understood. Recent crystal structures of σ1R reveal a single N-terminal transmembrane segment and C-terminal ligand-binding domain, and a trimeric organization. Nevertheless, outstanding issues surrounding the functional or pharmacological relevance of σ1R oligomerization remain, such as the minimal protomeric unit and the differentially altered oligomerization states by different classes of ligands. Western blot (WB) assays have been widely used to investigate protein oligomerizations. However, the unique topology of σ1R renders several intertwined challenges in WB. Here we describe a WB protocol without temperature denaturization to study the ligand binding effects on the oligomerization state of σ1R. Using this approach, we observed unexpected ladder-like incremental migration pattern of σ1R, demonstrating preserved homomeric interactions in the detergent environment. We compared the migration patterns of intact σ1R construct and the C-terminally tagged σ1R constructs, and found similar trends in response to drug treatments. In contrast, N-terminally tagged σ1R constructs show opposite trends to that of the intact construct, suggesting distorted elicitation of the ligand binding effects on oligomerization. Together, our findings indicate that the N-terminus plays an important role in eliciting the impacts of bound ligands, whereas the C-terminus is amenable for modifications for biochemical studies.

Terminal coordination of diatomic boron monofluoride to iron

Boron monofluoride (BF) is a diatomic molecule with 10 valence electrons, isoelectronic to carbon monoxide (CO). Unlike CO, which is a stable molecule at room temperature and readily serves as both a bridging and terminal ligand to transition metals, BF is unstable below 1800°C in the gas phase, and its coordination chemistry is substantially limited. Here, we report the isolation of the iron complex Fe(BF)(CO)2(CNArTripp2)2 [ArTripp2, 2,6-(2,4,6-(i-Pr)3C6H2]2C6H3; i-Pr, iso-propyl], featuring a terminal BF ligand. Single-crystal x-ray diffraction as well as nuclear magnetic resonance, infrared, and Mössbauer spectroscopic studies on Fe(BF)(CO)2(CNArTripp2)2 and the isoelectronic dinitrogen (N2) and CO complexes Fe(N2)(CO)2(CNArTripp2)2 and Fe(CO)3(CNArTripp2)2 demonstrate that the terminal BF ligand possesses particularly strong σ-donor and π-acceptor properties. Density functional theory and electron-density topology calculations support this conclusion.