Synthesis and reactivity of molybdenum and tungsten bis(dinitrogen) complexes supported by diphosphine chelates containing pendant amines.

Molybdenum and tungsten bis(dinitrogen) complexes of the formula M(N(2))(2)(PNP)(2) (M = Mo and W) and W(N(2))(2)(dppe)(PNP), supported by diphosphine ligands containing a pendant amine of the formula (CH(2)PR(2))(2)NR' = P(R)N(R')P(R) (R = Et, Ph; R' = Me, Bn), have been prepared by Mg reduction of metal halides under an N(2) atmosphere. The complexes have been characterized by NMR and IR spectroscopy, X-ray crystallography, and cyclic voltammetry. Reactivity of the target Mo and W bis(dinitrogen) compounds with CO results in the formation of dicarbonyl complexes.

Scaling in the diffusion limited aggregation model.

We present a self-consistent picture of diffusion limited aggregation (DLA) growth based on the assumption that the probability density P(r,N) for the next particle to be attached within the distance r to the center of the cluster is expressible in the scale-invariant form P[r/R{dep}(N)]. It follows from this assumption that there is no multiscaling issue in DLA and there is only a single fractal dimension D for all length scales. We check our assumption self-consistently by calculating the particle-density distribution with a measured P(r/R{dep}) function on an ensemble with 1000 clusters of 5×10{7} particles each.

Treating menopausal symptoms with a complex remedy or placebo: a randomized controlled trial.

Objective: To evaluate the efficacy and safety of a complex remedy compared with placebo to treat menopausal symptoms.

Methods: A total of 102 peri- and postmenopausal women requiring treatment for menopausal symptoms were randomized to receive a complex anthroposophic remedy prepared in the homeopathic manner (Apis regina tota GL D4, Argentum metallicum D5, Ovaria bovis GL D4), 3 × 10 globuli daily (2 × 12 weeks) and placebo (12 weeks) in different orders of remedy (R) and placebo (P) (1: R/R/P, 2: P/R/R, 3: R/P/R). The primary endpoint was change in climacteric symptoms assessed by the Menopause Rating Scale II (MRS II) after 12 weeks.

Synthesis, conformational stability, and asymmetric transformation of atropisomeric 1,8-bisphenolnaphthalenes.

Highly congested, axially chiral 1,8-bisphenolnaphthalenes have been synthesized in 75% overall yield by palladium-catalyzed Suzuki coupling of 1,8-diiodonaphthalene and 4-methoxy-2-methylphenylboronic acid followed by regioselective formylation and deprotection. The C(2)-symmetric anti-stereoisomers of 1,8-bis(2'-methyl-4'-hydroxy-5'-formylphenyl)naphthalene, 5, and its diimine analogues 9 and 10 were found to be significantly more stable than the corresponding syn-isomer. Crystallographic analysis revealed that this stereochemical preference results from a unique intramolecular hydrogen bonding motif and concomitant minimization of steric repulsion.

Possible origin of efficient navigation in small worlds.

The small-world phenomenon is one of the most important properties found in social networks. It includes both short path lengths and efficient navigation between two individuals. It is found by Kleinberg that navigation is efficient only if the probability density distribution of an individual to have a friend at distance r scales as P(r) ∼ r(-1).

Effective multidimensional crossover behavior in a one-dimensional voter model with long-range probabilistic interactions.

A variant of the standard voter model, where a randomly selected site of a one-dimensional lattice (d=1) adopts the state of another site placed at a distance r from the previous one, is proposed and studied by means of numerical simulations that are rationalized with the aid of dynamical and finite-size scaling arguments. The distance between the two sites is also selected randomly with a probability given by P(r)∝r(-(d+σ)), where σ is a control parameter. In this way one can study how the introduction of these long-range interactions influences the dynamic behavior of the standard voter model with nearest-neighbor interactions.

Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination.

Molecular data on a limited number of chromosomal loci have shown that the population of Neisseria meningitidis (Nm), a deadly human pathogen, is structured in distinct lineages. Given that the Nm population undergoes substantial recombination, the mechanisms resulting in the evolution of these lineages, their persistence in time, and the implications for the pathogenicity of the bacterium are not yet completely understood. Based on whole-genome sequencing, we show that Nm is structured in phylogenetic clades.

Determinants of agricultural pesticide concentrations in carpet dust.

Background: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes.

Objective: We identified determinants of concentrations of agricultural pesticides in dust.

Methods: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California.

Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines.

A unique multicomponent vaccine against serogroup B meningococci incorporates the novel genome-derived proteins fHbp, NHBA, and NadA that may vary in sequence and level of expression. Measuring the effectiveness of such vaccines, using the accepted correlate of protection against invasive meningococcal disease, could require performing the serum bactericidal assay (SBA) against many diverse strains for each geographic region. This approach is impractical, especially for infants, where serum volumes are very limited.

Reactions of tertiary phosphines with alcohols in aqueous media.

The phosphines R(2)R'P [R = R' = Me, Et, (n)Pr, (i)Pr, (CH(2))(3)OH; Me(2)PhP and MePh(2)P] react with 2- or 4-hydroxybenzyl alcohols, including "lignin-type" vanillyl, syringyl, and alpha-methylvanillyl alcohols, in a 1:1 ratio in aqueous media, to give zwitterionic phosphobetaine products; these on treatment with aq HCl form the corresponding phosphonium chlorides in good to excellent yields. The syringyl derivative [3,5-(OMe)(2)-4-OH-C(6)H(2)CH(2)PEt(3)]Cl was structurally characterized by X-ray analysis. Kinetically, the reactivity of the benzyl alcohols, studied with the water-soluble [HO(CH(2))(3)](3)P, decreases with substituents in the order 2-hydroxy > 4-hydroxy > vanillyl > syringyl > alpha-methylvanillyl, while 3-hydroxybenzyl alcohol is unreactive; the trend is consistent with reactivity requiring the presence of an ortho- or para-OH substituent in the aromatic ring of the alcohol, and that the reactions proceed via a carbocation species stabilized as a quinone methide.

Interaction of tertiary phosphines with lignin-type, alpha,beta-unsaturated aldehydes in water.

To learn more about the bleaching action of pulps by (hydroxymethyl)phosphines, lignin chromophores, such as the alpha,beta-unsaturated aromatic aldehydes, sinapaldehyde, coniferylaldehyde, and coumaraldehyde, were reacted with the tertiary phosphines R2R'P [R = R' = Me, Et, (CH2)3OH, iPr, cyclo-C6H11, (CH2)2CN; R = Me or Et, R' = Ph; R = Ph, R' = Me, m-NaSO3-C6H4] in water at room temperature under argon. In all cases, initial nucleophilic attack of the phosphine occurs at the activated C=C bond to form a zwitterionic monophosphonium species. With the phosphines PR3 [R = Me, Et, (CH2)3OH] and with R2R'P (R = Me or Et, R' = Ph), the zwitterion undergoes self-condensation to give a bisphosphonium zwitterion that can react with aqueous HCl to form the corresponding dichloride salts (as a mixture of R,R- and S,S-enantiomers); X-ray structures are presented for the bisphosphonium chlorides synthesized from the Et3P and Me3P reactions with sinapaldehyde.

Formation of a phosphine-phosphinite ligand in RhCl(PRR'2)[P,P-R'(R)POCH2P(CH2OH)2] and R'H from cis-RhCl(PRR'2)2[P(CH2OH)3] via P-C bond cleavage.

Reaction of RhCl(1,5-cod)(THP), where THP = P(CH(2)OH)(3), with several PRR'2 phosphines (R = or not equal R') generates, concomitantly with R'H, the derivatives RhCl(PRR'(2))[P,P-R'(R)POCH(2)P(CH(2)OH)(2)] in two isomeric forms. The hydrogen of the hydrocarbon co-product derives from a THP hydroxyl group which becomes an 'alkoxy' group at the residual PRR' moiety, this resulting in the P,P-chelated R'(R)POCH(2)P(CH(2)OH)(2) ligand. One of the isomers of the PPh(3) system, cis-RhCl(PPh(3))[P,P-P(Ph)(2)OCH(2)P(CH(2)OH)(2)], was structurally characterized (cis refers to the disposition of the P atoms with Ph substituents).

Coordinatively unsaturated semisandwich complexes of ruthenium with phosphinoamine ligands and related species: a complex containing (R,R)-1,2-bis((diisopropylphosphino)amino)cyclohexane in a new coordination form kappa(3)P,P',N-eta(2)-P,N.

The syntheses of the chloro complexes [Ru(eta5-C5R5)Cl(L)] (R = H, Me; L = phosphinoamine ligand) (1a-d) have been carried out by reaction of [(eta5-C5H5)RuCl(PPh3)2] or {(eta5-C5Me5)RuCl}4 with the corresponding phosphinoamine (R,R)-1,2-bis((diisopropylphosphino)amino)cyclohexane), R,R-dippach, or 1,2-bis(((diisopropylphosphino)amino)ethane), dippae. The chloride abstraction reactions from these compounds lead to different products depending on the starting chlorocomplex and the reaction conditions. Under argon atmosphere, chloride abstraction from [(eta5-C5Me5)RuCl(R,R-dippach)] with NaBAr'4 yields the compound [(eta5-C5Me5)Ru(kappa3P,P'-(R,R)-dippach)][BAr'4] (2b) which exhibits a three-membered ring Ru-N-P by a new coordination form of this phosphinoamine.

Perylene bisimide atropisomers: synthesis, resolution, and stereochemical assignment.

The macrocyclization of the tetra-hydroxyphenoxy-substituted perylene bisimide 4 bearing two (R)-configured 2-octyl substituents in the imide positions by etherification with diethylene glycol ditosylate afforded both the diagonally bridged (1,7- and 6,12-linkage) and laterally bridged (1,12- and 6,7-linkage) regioisomers 6 and 7. The atropo-diastereomers of the diagonally bridged macrocycle 6 were separated by semipreparative HPLC on a chiral column, and their absolute configurations were determined by circular dichroism (CD) spectroscopy in combination with quantum chemical CD calculations. The isolated epimers (P,R,R)-6 and (M,R,R)-6 represent the first examples of diasteriomerically pure perylene bisimide atropisomers.

Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents.

The use of cholesterol-based cationic lipids and the ability of glucocorticoids to reduce local inflammatory response to lipoplexes motivated an investigation of structure-activity relationships for cationic steroids. A one-step synthetic scheme using iminothiolane was developed to link spermine to the 21-OH position of steroids via an amidine linkage. Five steroids (cortisol, dexamethasone, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone) with increasing hydrophobicity of the parent steroid (Log P(ster) from 1.

Embedding an allylmetal dimer in a chiral cavity: the unprecedented stereoselectivity of a twofold wittig [1,2]-rearrangement.

After alpha,alpha'-dimetalation, both 2,2'-diallyloxy-1,1'-binaphthyl and 2,2'-di-2-methylallyloxy-1,1'-binaphthyl undergo the Wittig rearrangement with perfect diastereoselectivity. When racemic 1,1'-binaphthyl-2,2'-diol ("BINOL") is used as the starting material, it gives rise to a 1:1 mixture of antipodal stereoisomers, whereas enantiomerically pure (M)-2,2'-diallyloxy-1,1'-binaphthyl affords (M)-(S,S)-1,1-(1,1'-binaphthyl-2,2'-diyl)bis(2-propen-1-ol) as the sole product. The (M)-(S,S)/(P)-(R,R) mixture resulting from the rearrangement of racemic 2,2'-diallyloxy-1,1'-binaphthyl can be effectively subjected to a kinetic racemate resolution by applying the Sharpless-Katsuki asymmetric epoxidation.

Modification of the trypsin-dependent cleavage activation site of the human metapneumovirus fusion protein to be trypsin independent does not increase replication or spread in rodents or nonhuman primates.

The contribution of cleavage activation of the fusion F protein of human metapneumovirus (HMPV) to replication and pathogenicity in rodents and nonhuman primates was investigated. Recombinant HMPVs were generated in which the naturally occurring trypsin-dependent cleavage sequence (R-Q-S-R downward arrow) was replaced by each of three sequences whose cleavage in vitro does not depend upon added trypsin. Two of these were multibasic sequences derived from avian metapneumovirus type A (R-R-R-R) or type C (R-K-A-R), with the former containing the consensus furin protease cleavage motif (R-X-R/K-R downward arrow).

Lewis base catalyzed, enantioselective aldol addition of methyl trichlorosilyl ketene acetal to ketones.

The catalytic enantioselective addition of an acetate enolate equivalent to ketones is described. Methyl trichlorosilyl ketene acetal reacts with a wide range of ketones in the presence of pyridine N-oxide to afford the aldol addition products in excellent yields. Chiral 2,2'-pyridyl bis-N-oxides bearing various substituents at the 3,3'- and 6,6'-positions also provide excellent yields of the aldol products with variable enantioselectivities ranging from 94/6 er for aromatic ketones to nearly racemic for aliphatic ketones.

Chiral trialkanolamine-based hemicryptophanes: synthesis and oxovanadium complex.

[reaction: see text] A novel class of chiral hemicryptophane hosts has been synthesized in diastereoisomerically pure form, namely, M-(R,R,R)-1a/P-(S,S,S)-1a and M-(S,S,S)-1b/P-(R,R,R)-1b. The C3-symmetrical precursor 9 was prepared, using either (R)- or (S)-glycidyl nosylate, repectively, as the chiral pool reactant and subsequently cyclized (trimerized) in the presence of Sc(OTf)3. The four stereoisomers were fully characterized and displayed two pairs of mirror-image CD spectra, which were used to determine their absolute configuration.

Sequential arrangement of gamma-valerolactone enantiomers enclathrated in cholic acid channels as studied by 13C solid-state NMR: elucidation of the optical resolution mechanism.

The mechanism of the optical resolution of gamma-valerolactone (VAL) enantiomers by enclathration in cholic acid (CA) channels was investigated. 13C cross-polarization magic-angle spinning spectra of CA/VAL inclusion compounds show four methyl 13C peaks of VAL with different intensities depending on the enantiomeric ratios. The four peaks were assigned to the inner and end (S)-(-)-enantiomers (S) in the S domain and the inner and end (R)-(+)-enantiomers (R).

Monochromatic path crossing exponents and graph connectivity in two-dimensional percolation.

We consider the fractal dimensions d(k) of the k-connected part of percolation clusters in two dimensions, generalizing the cluster (k=1) and backbone (k=2) dimensions. The codimensions x(k)=2-d(k) describe the asymptotic decay of the probabilities P(r,R) approximately (r/R)(x(k)) that an annulus of radii r<<1 and R>>1 is traversed by k disjoint paths, all living on the percolation clusters. Using a transfer matrix approach, we obtain numerical results for x(k), k View Article and Find Full Text PDF

Metabolic and cardiorespiratory responses to "the lactate clamp".

To evaluate the hypothesis that precursor supply limits gluconeogenesis (GNG) during exercise, we examined training-induced changes in glucose kinetics [rates of appearance (R(a)) and disappearance (R(d))], oxidation (R(ox)), and recycling (R(r)) with an exogenous lactate infusion to 3.5-4.0 mM during rest and to pretraining 65% peak O(2) consumption (VO(2 peak)) levels during exercise.

Structural aspects of the interaction between heterogeneic human papillomavirus type 1 E4-specific T cell receptors and the same peptide/HLA-DQ8 complex.

TCR usage has been studied in a panel of Th cell clones specific for the same peptide epitope (P N S Q D R G R P R R S D), derived from the human papillomavirus type 1 (HPV1) E4 protein, and restricted through HLA-DQ8. After identifying the V, D, and J genes used by the TCRs and sequencing across the V(D)J junctions, five different alpha-chain sequences and five different beta-chain sequences, comprising six independent clones, were identified. A structural model of our E4 peptide/HLA-DQ8 complex predicted that the guanidinyl side chain on the arginine residue at position 6 of the peptide could exist in different orientations.

Purification and characterization of DNA polymerase alpha-associated replication protein A-dependent yeast DNA helicase A.

A novel, eukaryotic, hexameric DNA helicase that was earlier identified as a component of the multiprotein polymerase alpha complex [Biswas et al. (1993) Biochemistry 32, 13393-13398] has been purified to homogeneity and characterized. Thus far, our studies demonstrated that helicase A shares certain unique features of two other hexameric DNA helicases: the DnaB helicase of Escherichia coli and the T-antigen helicase of the SV40 virus.