Acetate Acetylacetonate Ampy Ruthenium(II) Complexes as Efficient Catalysts for Ketone Transfer Hydrogenation

The mixed acetate acetylacetonate (acac) ruthenium(II) phosphine complexes Ru(OAc)(acac)P2 [P2=(PPh3)2, Ph2P(CH2)4PPh2 (dppb)] were prepared by protonation of Ru(OAc)2(PPh3)2 with acetylacetone in dichloromethane. Reaction of the dppb derivative with 2-(aminomethyl)pyridine (ampy) affords the complex Ru(OAc)(acac)(ampy)(dppb), which converts to [Ru(acac)(ampy)(dppb)](OAc) in toluene at 90 \ub0C. In the former derivative the ampy ligand is monodentate and coordinates through the NH2-moiety. The isolated acac complexes are active catalysts for the transfer hydrogenation of ketones with loadings as low as 0.01 mol%, the ampy having a strong accelerating effect. Several aromatic and aliphatic ketone substrates are converted to their corresponding alcohols, and different electronic influences through substituents on acetophenone are tolerated

Preparation of Neutral trans - Cis [Ru(O2CR)2P2(NN)], Cationic [Ru(O2CR)P2(NN)](O2CR) and Pincer [Ru(O2CR)(CNN)P2] (P = PPh3, P2= diphosphine) Carboxylate Complexes and their Application in the Catalytic Carbonyl Compounds Reduction

The diacetate complexes trans-[Ru(\u3ba1-OAc)2(PPh3)2(NN)] (NN = ethylenediamine (en) (1), 2-(aminomethyl)pyridine (ampy) (2), 2-(aminomethyl)pyrimidine (ampyrim) (3)) have been isolated in 76-88% yield by reaction of [Ru(\u3ba2-OAc)2(PPh3)2] with the corresponding nitrogen ligands. The ampy-type derivatives 2 and 3 undergo isomerization to the thermodynamically most stable cationic complexes [Ru(\u3ba1-OAc)(PPh3)2(NN)]OAc (2a and 3a) and cis-[Ru(\u3ba1-OAc)2(PPh3)2(NN)] (2b and 3b) in methanol at RT. The trans-[Ru(\u3ba1-OAc)2(P2)2] (P2 = dppm (4), dppe (5)) compounds have been synthesized from [Ru(\u3ba2-OAc)2(PPh3)2] by reaction with the suitable diphosphine in toluene at 95 \ub0C. The complex cis-[Ru(\u3ba1-OAc)2(dppm)(ampy)](6) has been obtained from [Ru(\u3ba2-OAc)2(PPh3)2] and dppm in toluene at reflux and reaction with ampy. The derivatives trans-[Ru(\u3ba1-OAc)2P2(NN)] (7-16; NN = en, ampy, ampyrim, 8-aminoquinoline; P2 = dppp, dppb, dppf, (R)-BINAP) can be easily synthesized from [Ru(\u3ba2-OAc)2(PPh3)2] with a diphosphine and treatment with the NN ligands at RT. Alternatively these compounds have been prepared from trans-[Ru(OAc)2(PPh3)2(NN)] by reaction with the diphosphine in MEK at 50 \ub0C. The use of (R)-BINAP affords trans-[Ru(\u3ba1-OAc)2((R)-BINAP)(NN)] (NN = ampy (11), ampyrim (15)) isolated as single stereoisomers. Treatment of the ampy-type complexes 8-15 with methanol at RT leads to isomerization to the cationic derivatives [Ru(\u3ba2-OAc)P2(NN)]OAc (8a-15a; NN = ampy, ampyrim; P2 = dppp, dppb, dppf, (R)-BINAP). Similarly to 2, the dipivalate trans-[Ru(\u3ba1-OPiv)2(PPh3)2(ampy)] (18) is prepared from [Ru(\u3ba2-OPiv)2(PPh3)2] (17) and ampy in CHCl3. The pincer acetate [Ru(\u3ba1-OAc)(CNNOMe)(PPh3)2] (19) has been synthesized from [Ru(\u3ba2-OAc)2(PPh3)2] and HCNNOMe ligand in 2-propanol with NEt3 at reflux. In addition, the dppb pincer complexes [Ru(\u3ba1-OAc)(CNN)(dppb)] (CNN = AMTP (20), AMBQPh (21)) have been obtained from [Ru(\u3ba2-OAc)2(PPh3)2], dppb, and HAMTP or HAMBQPh with NEt3, respectively. The acetate NN and pincer complexes are active in transfer hydrogenation with 2-propanol and hydrogenation with H2 of carbonyl compounds at S/C values of up to 10000 and with TOF values of up to 160000 h-1

One Hundred Years of Observations of the Be Star HDE 245770 (the X-ray Binary A0535+26/V725 Tau): The End of an Active Phase

UBV observations of the X-ray binary system A0535+26/V725 Tau at the Crimean Station of the Sternberg Astronomical Institute in 1980-1998 are presented. Based on our and published data, we analyze the photometric history of the star from 1898.Comment: Translated from Pis'ma Astronomicheskii Zhurnal, Vol. 26, No. 1, 2000, pp. 13-2

Jack superpolynomials with negative fractional parameter: clustering properties and super-Virasoro ideals

The Jack polynomials P_\lambda^{(\alpha)} at \alpha=-(k+1)/(r-1) indexed by certain (k,r,N)-admissible partitions are known to span an ideal I^{(k,r)}_N of the space of symmetric functions in N variables. The ideal I^{(k,r)}_N is invariant under the action of certain differential operators which include half the Virasoro algebra. Moreover, the Jack polynomials in I^{(k,r)}_N admit clusters of size at most k: they vanish when k+1 of their variables are identified, and they do not vanish when only k of them are identified. We generalize most of these properties to superspace using orthogonal eigenfunctions of the supersymmetric extension of the trigonometric Calogero-Moser-Sutherland model known as Jack superpolynomials. In particular, we show that the Jack superpolynomials P_{\Lambda}^{(\alpha)} at \alpha=-(k+1)/(r-1) indexed by certain (k,r,N)-admissible superpartitions span an ideal {\mathcal I}^{(k,r)}_N of the space of symmetric polynomials in N commuting variables and N anticommuting variables. We prove that the ideal {\mathcal I}^{(k,r)}_N is stable with respect to the action of the negative-half of the super-Virasoro algebra. In addition, we show that the Jack superpolynomials in {\mathcal I}^{(k,r)}_N vanish when k+1 of their commuting variables are equal, and conjecture that they do not vanish when only k of them are identified. This allows us to conclude that the standard Jack polynomials with prescribed symmetry should satisfy similar clustering properties. Finally, we conjecture that the elements of {\mathcal I}^{(k,2)}_N provide a basis for the subspace of symmetric superpolynomials in N variables that vanish when k+1 commuting variables are set equal to each other.Comment: 36 pages; the main changes in v2 are : 1) in the introduction, we present exceptions to an often made statement concerning the clustering property of the ordinary Jack polynomials for (k,r,N)-admissible partitions (see Footnote 2); 2) Conjecture 14 is substantiated with the extensive computational evidence presented in the new appendix C; 3) the various tests supporting Conjecture 16 are reporte

Kondo Effect in Systems with Spin Disorder

We consider the role of static disorder in the spin sector of the one- and two-channel Kondo models. The distribution functions of the disorder-induced effective energy splitting between the two levels of the Kondo impurity are derived to the lowest order in the concentration of static scatterers. It is demonstrated that the distribution functions are strongly asymmetric, with the typical splitting being parametrically smaller than the average rms value. We employ the derived distribution function of splittings to study the temperature dependence of the low-temperature conductance of a sample containing an ensemble of two-channel Kondo impurities. The results are used to analyze the consistency of the two-channel Kondo interpretation of the zero-bias anomalies observed in Cu/(Si:N)/Cu nanoconstrictions.Comment: 16 pages, 5 figures, REVTe

Selective small molecule induced degradation of the BET bromodomain protein BRD4

The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1. However, the lack of intra-BET selectivity limits the scope of current inhibitors as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We designed Proteolysis Targeted Chimeras (PROTACs) that tether JQ1 to a ligand for the E3 ubiquitin ligase VHL, aimed at triggering the intracellular destruction of BET proteins. Compound MZ1 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 over BRD2 and BRD3. The activity of MZ1 is dependent on binding to VHL but is achieved at a sufficiently low concentration not to induce stabilization of HIF-1α. Gene expression profiles of selected cancer-related genes responsive to JQ1 reveal distinct and more limited transcriptional responses induced by MZ1, consistent with selective suppression of BRD4. Our discovery opens up new opportunities to elucidate the cellular phenotypes and therapeutic implications associated with selective targeting of BRD4

Relationships between serum adiponectin and soluble TNF-α receptors and glucose and lipid oxidation in lean and obese subjects

Insulin resistance might be associated with an impaired ability of insulin to stimulate glucose oxidation and inhibit lipid oxidation. Insulin action is also inversely associated with TNF-α system and positively related to adiponectin. The aim of the present study was to analyze the associations between serum adiponectin, soluble TNF-α receptors concentrations and the whole-body insulin sensitivity, lipid and glucose oxidation, non-oxidative glucose metabolism (NOGM) and metabolic flexibility in lean and obese subjects. We examined 53 subjects: 25 lean (BMI < 25 kg × m−2) and 28 with overweight or obesity (BMI > 25 kg × m−2) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese subjects had lower insulin sensitivity, adiponectin and higher sTNFR1 (all P < 0.001) and sTNFR2 (P = 0.001). Insulin sensitivity was positively related to adiponectin (r = 0.49, P < 0.001) and negatively related to sTNFR1 (r = −0.40, P = 0.004) and sTNFR2 (r = −0.52, P < 0.001). Adiponectin was related to the rate of glucose (r = 0.47, P < 0.001) and lipid (r = −0.40, P = 0.003) oxidation during the clamp, NOGM (r = 0.41, P = 0.002) and metabolic flexibility (r = 0.36, P = 0.007). Serum sTNFR1 and sTNFR2 were associated with the rate of glucose (r = −0.45, P = 0.001; r = −0.51, P < 0.001, respectively) and lipid (r = 0.52, P < 0.001; r = 0.46, P = 0.001, respectively) oxidation during hyperinsulinemia, NOGM (r = −0.31, P = 0.02; r = −0.43, P = 0.002, respectively) and metabolic flexibility (r = −0.47 and r = −0.51, respectively, both P < 0.001) in an opposite manner than adiponectin. Our data suggest that soluble TNF-α receptors and adiponectin have multiple effects on glucose and lipid metabolism in obesity

Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity

INTRODUCTION: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. METHODS: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. RESULTS: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). DISCUSSION: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. HIGHLIGHTS: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone