Structure and magnetic properties of LnIII[Ru2(CO3)4] · 8H2O

Ln^III[Ru₂(CO₃)₄] · 8H₂O (Ln = Gd, Nd, Ho, Yb) is formed from the reaction of Ln^III and [Ru₂(CO₃)₄]^3? in water. These Ln^III materials have a 3D network structure composed of linked chains and μ_n-CO₃ linkages to both Ru and Ln^III sites, and are best described as Ln^III(OH₂)₄[Ru₂(CO₃)₄]_1/2[Ru₂(CO₃)₄(OH₂)₂]_1/2 · 3H₂O. Complete characterization of the Gd^III species is presented, as the other Ln^III are isostructural and exhibit large spin–orbit coupling leading to complex magnetic behavior. Magnetic ordering is not observed above 2 K.     

First example of photomagnetic effects in ionic pairs [Ni(bipy)3]2[Mo(CN)8] · 12H2O

Ionic triads formed by [Ni^II(bipy)₃]²⁺ (bipy = 2,2′-bipyridyl) and diamagnetic [M^IV(CN)₈]^4? (M = Mo and W) were prepared and structurally characterized. The two compounds are isostructural and their structure consists of a three-dimensional hydrogen-bonded framework where cation–anion interactions occur through short contacts M–CN?H–C(bipy). Before irradiation, the Mo analogue behaves as paramagnet with small intermolecular interactions between the [Ni^II(bipy)₃]²⁺ cations. Upon irradiation with visible light, it exhibits a reversible photomagnetic effect, which is interpreted in terms of the formation of paramagnetic [Mo^V(CN)₈]^3? and [Ni^II(bipy)₂(bipy^?)]⁺ due to the outer-sphere electron transfer.     

[RuIII(medtra)(H2O)] (medtra = N-methylethylenediaminetriacetate) complex – A highly efficient NO inhibitor with low toxicity

Stopped-flow kinetic measurements were used to compare the reactivities of [Ru(medtra)(H₂O)] (medtra³⁻ = N-methylethylenediaminetriacetate) (1) and [Ru(hedtra)(H₂O)] (2) (hedtra³⁻ = N-hydroxyethylethylenediaminetriacetate) with NO in aqueous solution at 15 °C, pH 7.2 (phosphate buffer). The measured second-order rate constants (3 × 10³ and 6 × 10⁴ M⁻¹ s⁻¹ for 1 and 2, respectively) are three to four order of magnitudes lower than that for the reaction between [Ru^III(edta)(H₂O)]⁻ (3) with NO. However, NO scavenging studies of complexes 1–3, conducted by measuring the difference in nitrite production between treated and untreated murine macrophage cells, revealed that despite being less kinetically reactive toward NO, the [Ru(medtra)(H₂O)] complex exhibited the highest NO scavenging ability and lowest toxicity of compounds 1–3.     

New coordination polymers based on a novel polynitrile ligand: Synthesis,structure and magnetic properties of the series [M(tcnoetOH)2(4,4′-bpy)(H2O)2] (tcnoetOH− = [(NC)2CC(OCH2CH2OH)C(CN)2]−; M = Fe,Co and Ni)

A novel polynitrile anionic ligand, tcnoetOH^?(=[(NC)₂CC(OCH₂CH₂OH)C(CN)₂]^?), has been synthesized by a one-pot reaction from a cyclic acetal and malononitrile. This ligand has been successfully used to prepare, with 4,4′-bpy as co-ligand, a novel series of coordination polymers formulated as [M(tcnoetOH)₂(4,4′-bpy)(H₂O)₂] with M(II) = Fe (1), Co (2) and Ni (3). These isostructural compounds present a linear chain structure consisting of octahedrally coordinated metal ions bridged by trans 4,4′-bpy ligands. The coordination sphere of the metal ions is completed with two terminal tcnoetOH^? ligand and two water molecules. The magnetic properties indicate that the three compounds are paramagnetic, as expected from the long 4,4′-bpy bridge connecting the metal atoms. Their magnetic properties have been fitted with a model of isolated ions including a zero field splitting for the Fe(II) and Ni(II) derivatives.     

Neumark-Nord 2 – A multiphase Middle Palaeolithic open-air site in the Geisel Valley (Central Germany)

The lake basin Neumark-Nord 2 (NN 2) is located in the Geisel Valley in Saxony-Anhalt (Germany). It was scientifically investigated between 2003 and 2008. The sediment sequence, which is about 10 to 11 m thick, consists of limnic deposits, mostly silts mixed with clays and sands. Sedimentological as well as palynological, malacological and palaeomagnetic investigations, supported by absolute datings, date the entire sequence into the Eemian and Early Weichselian. Within the deposits several archaeological find horizons were discovered. Neumark-Nord 2/2 (NN 2/2) at the beginning of the Eemian and Neumark-Nord 2/0 (NN 2/0) with an early Weichselian were the most important archaeological horizons. Both find horizons represent former lake shore sites, where numerous crushed animal bones and other faunal debris were found, which can be regarded as remains of hunted game. With regard to the rich lithic material, both find horizons differ remarkably. In NN2/2, a simple artefact spectrum with a certain Levallois component and a dominance of denticulated, notched and laterally retouched specimens. In NN 2/0, on the other hand, bifacial tools such as backed knives and sometimes finely retouched scrapers are dominant, while the Levallois component fades completely into the background. Thus, NN 2 is one of the few open-air sites in archaeological landscape of Central German where several middle Palaeolithic find horizons occur in superposition.     

Microsolvation and hydration enthalpies of CaC2O4(H2O) n (n = 0-16) and C2O4 2-(H2O) n (n = 0-14): an ab initio study

We studied hydrated calcium oxalate and its ions at the restricted Hartree–Fock RHF/6-31G* level of theory. Performing a configurational search seems to improve the fit of the HF/6-31G* level to experimental data. The first solvation shell of calcium oxalate contains 13 water molecules, while the first solvation shell of oxalate ion is formed by 14 water molecules. The first solvation shell of Ca(II) is formed by six water molecules, while the second shell contains five. At 298.15 K, we estimate the asymptotic limits (infinite dilution) of the total standard enthalpies of hydration for Ca(II), oxalate ion and calcium oxalate as ?480.78, –302.78 and –312.73 kcal mol^?1, resp. The dissociation of hydrated calcium oxalate is an endothermic process with an asymptotic limit of +470.84 kcal mol^?1.

Influence of ligands on the fac⇌Δhνmer isomerization in [RuCl3(NO)(P–P)] complexes, [P–P = R2P(CH2)nPR2 (n = 1–3) and R2P(CH2)POR2, PR2–CHCH–PR2, R = Ph and (C6H11)2P-(CH2)2-P(C6H11)2]

[RuCl₃(NO)(P–P)], [P–P = R₂P(CH₂)_nPR₂ (n = 1–3) and R₂P(CH₂)POR₂, PR₂–CHCH–PR₂, R = Ph and (C₆H₁₁)₂P-(CH₂)₂-P(C₆H₁₁)₂] were obtained and characterized by ³¹P {¹H} NMR, IR spectroscopies and cyclic voltammetry. The structures of fac-[RuCl₃(NO)(P–P)], P–P = dppm (1), dppe (2), c-dppen (3) and dppp (4), mer-[RuCl₃(NO)(dcpe)] (6a) and mer-[RuCl₃(NO)(dppmO)] (7) have been determined by X-ray diffraction. Photochemical isomerization of fac- to mer-[RuCl₃(NO)(P–P)] was observed under white light in a CH₂Cl₂ solution and in solid state. The isomerization processes were followed by IR and ³¹P {¹H} spectra. The mer-[RuCl₃(¹⁵NO)(dppb)] isomer was used for the definition of the phosphorus atoms in the structure of the complex in solution. The electrochemical study shows that the oxidation/reduction processes observed in these complexes are dependent on both the isomer (fac or mer) and the solvent. In CH₂Cl₂, the NO⁺ reduction potentials are less negative for the mer-isomers than for the fac ones, while in CH₃CN solvent these potentials are, in general, very close for both isomers.     

Metabolomics – an overview. From basic principles to potential biomarkers (part 2)

The metabolome, which represents the complete set of molecules (metabolites) of a biological sample (cell, tissue, organ, organism), is the final downstream product of the metabolic cell process that involves the genome and exogenous sources. The metabolome is characterized by a large number of small molecules with a huge diversity of chemical structures and abundances. Exploring the metabolome requires complementary analytical platforms to reach its extensive coverage. The metabolome is continually evolving, reflecting the continuous flux of metabolic and signaling pathways. Metabolomic research aims to study the biochemical processes by detecting and quantifying metabolites to obtain a metabolic picture able to give a functional readout of the physiological state. Recent advances in mass spectrometry (one of the mostly used technologies for metabolomics studies) have given the opportunity to determine the spatial distribution of metabolites in tissues. In a two-part article, we describe the usual metabolomics technologies, workflows and strategies leading to the implementation of new clinical biomarkers. In this second part, we first develop the steps of a metabolomic analysis from sample collection to biomarker validation. Then with two examples, autism spectrum disorders and Alzheimer's disease, we illustrate the contributions of metabolomics to clinical practice. Finally, we discuss the complementarity of in vivo (positron emission tomography) and in vitro (metabolomics) molecular explorations for biomarker research.     

A novel vanadium(V) homocitrate complex: synthesis,structure, and biological relevance of [K2(H2O)5][(VO2)2(R,S-homocitrate)2]·H2O

Initial investigations into the possible roles of homocitric acid in the biosynthesis and function of the active site cofactor of nitrogenase resulted in the isolation and characterization of the dinuclear vanadium(V) species [K₂(H₂O)₅][(VO₂)₂(R,S-C₇H₈O₇)₂]·H₂O ( 1). Complex 1 represents the first synthetic structurally characterized transition metal homocitrate complex and may represent an early mobilized precursor in the biosynthesis of VFeco. Compound 1 was characterized by a variety of physical methods, including X-ray crystallography. Crystal data: space group P?* (#2), with a?=?10.292 (3)?Å, b?=?16.663 (3)?Å, c?=?8.343 (1)?Å, α?=?95.93 (1)°, β?=?105.74 (2)°, γ?=?90.86 (2)°, V?=?1386 (1)?ų, and Z?=?2. The homocitrate ligand is coordinated to the vanadium(V) atoms in a bidentate fashion via the deprotonated bridging hydroxyl group and a carboxylate donor. This unique coordination mode accurately mimics the coordination of homocitrate to the cofactor of nitrogenase.     

sHER-2 : un nouveau marqueur ?

The extracellular domain of the HER-2 (ERBB2) oncoprotein (p105^HER-2, ECD HER-2) is shed in the serum and can be detected by immunoassay. The currently approved cutoff for an elevated HER-2 ECD is greater than 15 ng/mL. HER-2 ECD is attractive as a potentially useful serum biomarker. In metastatic breast cancer, serum assay of HER-2 ECD is recommended to assess HER-2 status when unknown in primary tumor or metastatic biopsy is not feasible. In that case, it has been recommended to consider a 50 ng/mL serum HER-2 ECD cutoff as criteria to select patients for HER-2 targeted therapy. It might offer additional prognostic or predictive value compared with HER-2 tumor tissue testing. In addition, it can be measured serially and might be able to monitor treatment response, predict relapse or provide a real-time assessment of HER-2 status at metastatic disease.     

Catalytic effect of (H2O)n (n = 1–3) clusters on the reaction of HNO2 + HO → H2O + NO2 under tropospheric conditions

ABSTRACT

The effect of (H₂O)_n (n?=?1–3) on the HNO₂?+?HO → H₂O?+?NO₂ reaction has been investigated theoretically at the CCSD(T)/CBS//B3LYP/6-311?+?G(3df,2pd) level of theory, coupled with rate constant calculations by using variational transition state theory. Our results show that, when (H₂O)_n (n?=?1–3) was introduced into HNO₂?+?HO → H₂O?+?NO₂ reaction, the product of the reaction did not change, but the potential energy surface became quite complex, yielding two kinds of reactions, namely HNO₂···(H₂O)_n (n?=?1–3)?+?HO and HO···(H₂O)_n (n?=?1–3)?+?HNO₂. In all catalysed reactions with (H₂O)_n (n?=?1–3), the former reaction type is favourable than the latter one with its effective rate constant respectively larger by 6–1 orders of magnitude than that of latter one. Within the temperature range of 240–320?K, the relative impacts on water monomer are much more obvious than dimer and trimer. However, the effective rate constant with water is larger by 658%–17% times of magnitude, showing that the positive water effect is obvious under atmospheric conditions.     

Linear homobimetallic 4-thioacetyl-substituted NCN pincer palladium(II) and platinum(II) complexes with N-bidentate connecting units (NCN = [C6H2(CH2NMe2)2-2,6-R-4]−)

The synthesis and characterization of homobimetallic palladium and platinum complexes of type [(Me(O)CS-4-NCN–M ← N^∩N → M–NCN-4-SC(O)Me](OTf)₂ (Me(O)CS-4-NCN = [C₆H₂(CH₂NMe₂)₂-2,6-SC(O)Me-4]^?; N^∩N = 4,4′-bipyridine (bipy); M = Pd, 12; M = Pt, 13) is reported. The required bifunctional thio-acetyl NCN pincer starting compound NC(Br)N-4-SC(O)Me (2) has been synthesized by the consecutive reactions of NC(Br)N–I (I-1-C₆H₂(CH₂NMe₂)₂-3,5-Br-4) (1) with ^tBuLi, S₈ and Me(O)CCl, respectively. Chemoselective metallation at the C_aryl–Br bond was achieved by the reaction of 2 with the palladium(0) source [Pd₂(dba)₃] (3) (dba = dibenzylidene acetone). Treatment of thus formed [Pd(NCN-4-SC(O)Me)(Br)] (4) with [AgOTf] (8) (OTf = triflate, OSO₂CF₃) gave [Pd(NCN-4-SC(O)Me)(H₂O)][OTf] (9) which was further reacted with 0.5 equiv. of 4,4′-bipyridine (11a) to afford rigid-rod structured 12. When [Pt(tol)₂(SEt₂)]₂ (5) (tol = 4-tolyl) was used instead of 3, then 13 was produced via the in situ formation of [PtBr(NCN-4-SC(O)Me)] (7) and [Pt(NCN-4-SC(O)Me)(H₂O)][OTf] (10). Another possibility to synthesize 7 relied upon the subsequent reaction of 1 with 0.5 equiv. of 5 to give [PtBr(NCN-4-I)] (6) which further reacted with ^tBuLi, 1/8 S₈ and Me(O)CCl to afford 7. The cyclic voltammograms of 2, 7, and 13 are discussed.Complex 7 was structurally characterized by single crystal X-ray crystallography. Organometallic 7 crystallizes with three independent molecules in the asymmetric unit and displays a monomeric structure as commonly encountered in d⁸-metal pincer chemistry.     

TMC8 (EVER2) attenuates intracellular signaling by Zn2 + and Ca2 + and suppresses activation of Cl− currents

Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca^2 + activated Cl⁻ channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and 8 (EVER1, EVER2) cause epidermodysplasia verruciformis. This rare skin disease is characterized by abnormal susceptibility to HPV infection and cancer. We found that in contrast to Ano1 the common paralogues TMC4–TMC8 did not produce Ca^2 + activated Cl⁻ currents when expressed in HEK293 cells. On the contrary, TMC8 was found to be localized in the endoplasmic reticulum (ER), where it inhibited receptor mediated Ca^2 + release, activation of Ano1 and volume regulated LRRC8-related Cl⁻ currents. Zn^2 + is co-released from the ER together with Ca^2 + and thereby further augments Ca^2 + store release. Because TMC8 is required to lower cytosolic Zn^2 + concentrations by the Zn^2 + transporter ZnT-1, we hypothesize that HPV infections and cancer caused by mutations in TMC8 are related to upregulated Zn^2 +/Ca^2 + signaling and activation of Ano1.     

Genomic instability induced by mutant succinate dehydrogenase subunit D (SDHD) is mediated by O2(-•) and H2O2

SDHD mutations are associated with human cancers but the mechanisms that may contribute to transformation are unknown. The hypothesis that mutations in SDHD increase levels of superoxide leading to genomic instability was tested using site-directed mutagenesis to generate a truncated SDHD cDNA that was expressed in Chinese hamster fibroblasts. Stable expression of mutant SDHD resulted in 2-fold increases in steady-state levels of superoxide that were accompanied by a significantly increased mutation rate as well as a 70-fold increase in mutation frequency at the hprt locus. Overexpression of MnSOD or treatment with polyethylene glycol conjugated (PEG)-catalase suppressed mutation frequency in SDHD mutant cells by 50% (P<0.05). Simultaneous treatment with PEG-catalase and PEG-SOD suppressed mutation frequency in SDHD mutant cells by 90% (P<0.0005). Finally, 95% depletion of glutathione using l-buthionine-[S,R]-sulfoximine (BSO) in SDHD mutant cells caused a 4-fold increase in mutation frequency (P<0.05). These results demonstrate that mutations in SDHD cause increased steady-state levels of superoxide which significantly contributed to increases in mutation rates and frequency mediated by superoxide and hydrogen peroxide. These results support the hypothesis that mutations in SDHD may contribute to carcinogenesis by increasing genomic instability mediated by increased steady-state levels of reactive oxygen species.     

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm². A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm². The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm². The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm². Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm² were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm² and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.     

A new Pennsylvanian (Late Carboniferous) – Permian foraminiferal genus (Lateenoglobivalvulina nov. gen., Biseriamminoidea) and its paleobiogeographic distribution

Lateenoglobivalvulina nov. gen. (Biseriamminoidea, Foraminifera) is introduced for biserial tests with a coiled initial part and a rectilinear evolute terminal part. The test has globular chambers progressively increasing in dimension. The shape of the test in axial section is isosceles triangle with a vertex angle of 90–100° or higher. The genus includes three species: Lateenoglobivalvulina spiralis (Morozova, 1949), L. pergrata (Konovalova, 1962) and L. arguta (Konovalova, 1962). The new genus belongs to the subfamily Globivalvulininae Reitlinger, 1950 emend. herein and to the family Globivalvulinidae Reitlinger, 1950, superfamily Biseriamminoidea Chernysheva, 1941. Lateenoglobivalvulina evolved from Globivalvulina Schubert, 1921 during the Pennsylvanian, it inhabited the Boreal Realm during the Pennsylvanian-Kungurian and it migrated to the southwest Paleotethys Ocean during the Sakmarian-Kubergandian.