Preparation of trimethylsilyl alkyne complexes of bis(pentamethylcyclopentadienyl)zirconium, (η-C5Me5)2Zr(RC≡CSiMe3), and their regioselective reactions with nitrous oxide

Benzene solutions of Cp^*₂ZrCl₂ (1) (Cp^* = η⁵-C₅Me₅) react with the alkynes Me₃SiC≡CPh, Me₃SiC≡C(c-C₅H₉) and Me₃SiC≡CCMe₃ in the presence of Na/Hg amalgam to afford high yields of the respective alkyne complexes Cp^*₂Zr(Me₃SiC≡CPh) (2), Cp^*₂Zr{Me₃SiC≡C(c-C₅H₉)} (3) and Cp^*₂Zr(Me₃SiC≡CCMe₃) (4) as crystalline compounds. Complex 2 crystallizes in the triclinic space group with a = 9.791(6), b = 10.466(6), c = 15.756(12) Å, = 86.09 (5), β = 72.09(5), γ = 72.06(4)° and Z = 2. The least-squares refinement converged to R(F) = 0.0604 and R(wF) = 0.0628 for the 3655 unique data with F_o > 4σ (F_o). Salient metrical parameters of the bound alkyne include the following: C(30)-C(31) = 1.340(9) Å; Zr-C(30) = 2.178(6) Å; Zr-C(31) = 2.219(5) Å; C(30)-C(31)-Si = 141.0(5)°; C(31)-C(30)-C(26) = 135.5(5)°. Nitrous oxide reacts with 2 or 3 to afford ((5) R = Ph; (6) R = c-C₅H₉) and 1 equiv. of N₂ via an intermediate, , which is unstable with respect to loss of dinitrogen to give the oxametallacyclobutene derivatives 5 and 6. The oxygen-atom insertion is regiospecific for the Zr-C bond that is attached to the carbyl (Ph or c-C₅H₉) substituent. Under similar conditions, complex 4, in which the alkyne is particularly labile, gives a myriad of products in its reaction with N₂O.     

Molybdenum balance in healthy young Japanese women

The absorption and balance of molybdenum (Mo) were examined in 43 healthy young Japanese women in four metabolic studies performed once a year from 2001 to 2004. In each year, an 18-d metabolic study, including two successive balance study sessions of 4 d, was designed and four kinds of dietary menus were supplied to the subjects periodically. Since the protein sources of the menus were specified in 2001–2003, and soybean products were poor in 2001 and 2002 and rich in the 2003, Mo intake in 2001 and 2002 was about 150 μg/d while that in 2003 reached 318 μg/d. In 2004, the protein sources were not specified and Mo intake was 217 μg/d. This range of Mo intake overlapped that in the Japanese population. When the results of the four studies were pooled, Mo balance was calculated as 0.09±0.37 μg/d/kg (mean±SD), and no significant relationship (r=0.142) was observed between the intake and balance. Between the apparent absorption (Y) and the intake (X), a significant (r=0.988, p<0.001) positive linear regression (Y=0.927X-0.523) was observed. Similarly, a significant (r=0.960, p<0.001) positive linear regression was observed between Mo intake and urinary excretion. These results indicate that more than 90% of Mo contained in a routine dietary menu is absorbed, most of Mo absorbed is excreted in urine, and Mo balance is in equilibrium in the general Japanese population.     

A randomized, double-blind, placebo-controlled, clinical dose–response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold

The aim of this study was to verify the efficacy and safety of an herbal medication containing an extract of a mixture of Baptisiae tinctoriae radix, Echinaceae pallidae/purpureae radix and Thujae occidentalis herba (SB-TOX) in the treatment of upper respiratory tract infections (URIs), and to test whether SB-TOX's clinical efficacy is dose dependent. A total of 91 adults (mean age 42.1±13.0 years) were randomised to receive 19.2 mg of SB-TOX (n=31), 9.6 mg SB-TOX (n=29) or placebo (n=31) three times daily for 3–12 days. Since a “running nose” is the main symptom of a common cold, the total number of facial tissues used throughout the clinical duration of their cold was the primary efficacy parameter. In the intention-to-treat analysis, this total number of tissues decreased with increasing extract dose. The slope across groups according to the Jonckheere test was significant (p=0.0259). In the high-dose group, the standardised effect size Δ/SD was 0.46 compared with placebo. Time to relevant improvement in cold symptoms (measured as the time until less than 30 tissues per day were used) was 1.1 days (95% CI 0.52; 1.67), 0.76 days (95% CI 0.28; 1.24) and 0.52 days (95% CI 0.22; 0.82) in the placebo, low-dose and high-dose groups, respectively (p_LogRank=0.0175). No adverse events were reported. This study demonstrates the efficacy and safety of SB-TOX in the treatment of URIs, and that its efficacy is dose dependent.     

Atorvastatin, a potent HMG-CoA reductase inhibitor, is not antipyretic in rats

1. We investigated whether atorvastatin, a plasma cholesterol lowering and anti-inflammatory drug, attenuates lipopolysaccharide-induced fever in rats.

2. Sprague–Dawley rats, implanted with abdominal temperature-sensitive telemeters, were administered either lipopolysaccharide and placebo (n=7), lipopolysaccharide and atorvastatin (n=6), saline and placebo (n=8), or saline and atorvastatin (n=7).

3. Atorvastatin (100 mg kg⁻¹) was administered orally, as a suspension in a flavoured gelatine cube (placebo cubes contained no drug), 90 min before intraperitoneal injection of pyrogen (Salmonella typhosa lipopolysaccharide, 75 μg kg⁻¹) or sterile saline.

4. Atorvastatin did not disrupt normal thermoregulation. Atorvastatin also did not attenuate lipopolysaccharide-induced changes in body temperature and cage activity.

Crystal structure and catalytic activity of a copper(II) complex based on a tetradentate bis-benzimidazole diamide ligand

A dimeric copper(II) complex bridged via a new tetra dentate bis benzimidazole diamide ligand [N,N′-bis(benzimidazolyl-2-yl)(methyl)pentane diamide](GBGA) with the composition [Cu₂(GBGA)₂(NO₃)₂](NO₃)₂ has been isolated and characterized. The X-ray structure of the above complex reveals that the unit cell consists of two centrosymmetric, crystallographically independent molecules, but differing in the coordination mode of ion. In one case ion is symmetric bidentate while in the other case it is monodentate. The coordination around Cu(II) is either a trigonally distorted octahedron (where the N2–O2 equatorial plane is formed by two benzimidazole N atoms and two carbonyl O atoms) or a distorted square pyramidal. The copper(II) complex carries out the selective oxidation of cinnamyl alcohol (allylic), geraniol (aliphatic-allylic) and 3-pyridyl carbinol (hetero aryl alcohol) to their respective aldehydes in the presence of tertiary butyl hydroperoxide as an alternative source of oxygen. The catalytic efficiency has been found to be much higher for the analogous copper(II) complex formed with the corresponding N-octylated ligand (O-GBGA). The percentage yield of the products viz geranial, cinnamyl aldehyde and 3-pyridyl carbinal varies between 34% and 57%. While the respective turnovers are 13-, 19- and 32-fold with respect to the copper(II) catalyst. A higher turnover in the case of 3-pyridyl carbinol is due to the transformation of the parent Cu(II) catalyst (having a N2–O2 type equatorial plane) to a more active Cu(II) species which have been shown to have a 4N donor equatorial plane as identified by low temperature EPR spectroscopy. Such a switch from a carbonyl O donor to an amine N donor of the peptidic link in the ligand may be important for the redox functioning of copper(II) bound to small peptides.     

Chemomodulatory effects of Terminalia chebula against nickel chloride induced oxidative stress and tumor promotion response in male Wistar rats

Nickel, a major environmental pollutant is a known potent nephrotoxic agent. In this communication we report the chemopreventive effect of Terminalia chebula on nickel chloride (NiCl₂) induced renal oxidative stress, toxicity and cell proliferation response in male Wistar rats. Administration of NiCl₂ (250 μmoL Ni/kg body weight) to male Wistar rats resulted in an increase in the reduced renal glutathione content (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H₂O₂ generation, blood urea nitrogen (BUN) and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (p<0.001). Nickel chloride (NiCl₂) treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [³H] incorporation into renal DNA (p<0.001). Prophylactic treatment of rats with T. chebula (25 mg/kg body weight and 50 mg/kg body weight) daily for one week resulted in the diminution of NiCl₂ mediated damage as evident from the down regulation of glutathione content, GST, GR, LPO, H₂O₂ generation, BUN, serum creatinine, DNA synthesis (p<0.001) and ODC activity (p<0.01) with concomitant restoration of GPx activity. Thus, the present investigation suggests that T. chebula extract could be used as therapeutic agent for cancer prevention as evident from this study where it blocks or suppresses the events associated with chemical carcinogenesis.     

Heritability of dominant–aggressive behaviour in English Cocker Spaniels

A total of 51 seven-week-old English Cocker Spaniel puppies were measured for dominant–aggressive behaviour using the Campbell Test. The dogs consisted of a F₁ full sibs and half sibs from matings of 4 sires with 10 dams. The purpose of this study was to determine if the variability observed in this behavioural characteristic has an additive genetic component and if so, to estimate heritability (h²). Coat colour and sex were examined as fixed effects.

According to the results of the study: (1) there are highly significant differences between sexes; with males being more dominant than females, regardless of coat colour; (2) there are highly significant differences in aggressive behaviour depending on coat colour with greater to lesser dominance found in golden, black and particolour coats in that order; (3) there is no interaction between sex and colour when exhibiting greater or lesser dominance; (4) heritability, estimated on sire components, is , indicating that the variability observed in dominant–aggressive behaviour is in part due to genetic factors; and (5) heritability estimated on dam components is , which implies that the maternal effect (genetic and environmental) is an important factor in this type of behaviour.

It is concluded that there is an additive genetic, and therefore, hereditary factor for dominant–aggressive behaviour in the English Cocker Spaniel. Some of the fixed factors include: sex (males are dominant over females), coat colour (golden-coated are the more dominant dogs followed by the black-coated and finally by the particolour coat dogs) and the common environmental effect due to litter.     

Evaluation of the environmental stress index (ESI) for the southern hemisphere

The environmental stress index (ESI), constructed from ambient temperature, relative humidity, and solar radiation, was further evaluated from databases collected in Israel and New Zealand. High correlations were found between ESI and WBGT (R²=0.959 and R²=0.973 for Israel and New Zealand, respectively). However, for the New Zealand database, residuals were not distributed symmetrically around the zero line, which might be due to the difference in the global radiation spectrum. The ultraviolet radiation measurements were significantly higher in New Zealand than in Israel. As a consequence, a correction factor might be needed for ESI to be used in the southern hemisphere.     

1D copper(II) and zinc(II) coordination polymers containing an unusual twisted oxalate bridge

Two new copper(II) complexes, Cu(L1)(ClO₄)₂ (1), {[(μ-oxalate)Cu(L1)] · 5H₂O}_n (2), and a zinc(II) complex, {[(μ-oxalate)Zn(L2)] · 3H₂O · 0.5DMF}_n (3) (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,0^1.18,0^7.12]docosane), have been synthesized and characterized by X-ray crystallography. In 1, the ligand conformation is planar, and the octahedral coordination about the copper(II) ion is completed by weakly interacting ions. In 2 and 3, bridging oxalate ligands coordinate to copper(II) or zinc(II) ions in an unusually twisted bis-monodentate (trans-1,1′-bicoordination) mode.

The rigidity and steric hindrance of macrocycles L1 and L2 by the introduction of two cyclohexane rings and methyl groups on a cyclam (1,4,8,11-tetraazacyclotetradecane) skeleton cause the bridging oxalate ligands to adopt such unusual geometries in 2 and 3.     

Possible sequence of pyrogenic afferent processing in the POA

(1) It is generally considered that fever is modulated in the preoptic-anterior hypothalamic area (POA) in response to signaling by pyrogenic cytokines elaborated in the periphery by mononuclear phagocytes and the consequent induction of prostaglandin (PG)E₂ in the POA. The mechanism of the centripetal transmission of this pyrogenic signal, however, is controversial. One hypothesis suggests that it is conveyed via the vagus to the nucleus tractus solitarius and from there to the POA via the ventral noradrenergic bundle, causing the intraPOA release of norepinephrine (NE) which then stimulates the production of PGE₂. (2) In this article, we review recent data from our laboratory showing that NE microdialyzed into the POA of conscious guinea pigs or injected intracerebroventricularly into conscious mice indeed evokes two distinct core temperature (T_c) rises, viz., one ₁-adrenoceptor (AR)-mediated, rapid in onset and PGE₂-independent, and the other ₂-AR-mediated, delayed and COX-2/PGE₂-dependent. (3) We further present new data suggesting that the febrile response of conscious guinea pigs to intraperitoneally injected lipopolysaccharide (LPS) is mediated by intraPOA NE in accord with the above sequence, i.e., via ₁-AR to initiate the first, PGE₂-independent elevation of T_c, and via ₂-AR to induce the delayed production of COX-2-dependent PGE₂ and the continued rise of T_c. (4) These results thus validate the presumptive involvement of NE in LPS fever induction in guinea pigs.     

Olefin versus sulfur coordination of benzo[b]thiophene (BT) in Cp(CO)2Re(η:η-μ2-BT)Cr(CO)3

Reactions of Cr(CO)₃(η⁶-BT), in which the Cr is π-coordinated to the benzene ring of benzo[b]thiophene (BT), with Cp′(CO)₂Re(THF), where Cp′ = η⁵-C₅H₅ or η⁵-C₅Me₅, give the products Cp′(CO)₂Re(η²:η⁶-μ₂-BT)Cr(CO)₃ in which the Cr remains coordinated to the benzene ring and Re is bound to the C(2)=C(3) double bond. An X-ray diffraction study of Cp(CO)₂Re(η²:η⁶-μ₂-BT)Cr(CO)₃ (3) provides details of the geometry. This structure contrasts with that of the Cp′(CO)₂Re(BT) complexes that exist as mixtures of isomers in which the BT is coordinated to the Re through either the double bond (2,3-η²) or the sulfur (η¹(S)). Thus, the electron-withdrawing Cr(CO)₃ group in 3 stabilizes the 2,3-η² mode of BT coordination to the Cp′(CO)₂Re fragment. Implications of these results for catalytic hydrodesulfurization of BT are discussed. Crystal data for 3: triclinic, space group

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.     

Effects of CO2-bath immersion (100 ppm) on thermoregulatory responses in humans

The effects of CO₂ (100 ppm) bathing were investigated. It was found that the chest blood flow, chest sweat rate and tympanic temperature were significantly greater during the immersion in CO₂ bathing than in freshwater bathing (P<0.05). Thus, CO₂ bathing at 100 ppm could produce cutaneous vasodilatation in the immersed skin, affecting thermoregulation.     

Spatial fiber type distribution in normal human muscle: Histochemical and tensiomyographical evaluation

The variability of fiber type distribution in nine limb muscles was examined with histochemical and tensiomyographical (TMG) methods in two groups of 15 men aged between 17 and 40 years. The aim of this study was to determine the extent to which the relative occurrence of different fiber types and subtypes varies within human limb muscles in function to depth and to predict fiber type proportions with a non-invasive TMG method.

The distribution of different fiber types varied within the muscles, as a function of depth, with a predominance of type 2b fibers at the surface and type 1 fibers in deeper regions of the muscle. For all the analyzed muscles the contraction times measured at stimulus intensity 10% of supramaximal stimulus (10% MS) were significantly (p<0.05) shorter than the contraction times measured at 50% of supramaximal stimulus intensity (50% MS). The Pearson's correlation coefficient between percentage of type 1 muscle fibers measured at the surface of the muscle and contraction time at 10% MS, obtained by TMG was statistically significant (r=0.76,P<0.01). Also the Pearson's correlation coefficient between percentage of type 1 muscle fibers measured in the deep region of the muscle and contraction time at 50% MS obtained by TMG was also statistically significant (r=0.90,P<0.001).

These findings suggest that the contraction time obtained by TMG may be useful for non-invasive examining of muscle fiber types spatial distribution in humans.     

Syntheses, structures and properties of novel 3D lanthanide metal-organic frameworks with paddle-wheel building blocks

Three new complexes Ln(BDC)_1.5(DEF) [Ln = La(1), Ce(2), Nd(3); H₂BDC = 1,4-benzenedicarboxylic acid; DEF = N,N-diethylformamide] have been solvothermally synthesized and characterized by single-crystal X-ray diffraction. Complexes 1–3 are isostructural and crystallize in triclinic space group . They display three-dimensional frameworks and 18.7986 Å × 11.3230 Å rhombic channels along the a axis without interpenetration. Two eight-coordinated metal centers are connected with two dimonodentate BDC groups and two chelating/bridging bidentate BDC groups to give a paddle-wheel building block. The building blocks are connected through two carboxyl groups to lead to a one-dimensional infinite inorganic chain (–M–O–C–O–M–) along the [1 0 0] direction. Thermogravimetric analyses (TGA) and X-ray powder diffraction (XPRD) were determined for the three complexes. An observed intense blue luminescence with an emission band peaking at 372 nm for them may result from ligand-to-metal charge transfer (LMCT). Variable-temperature magnetic susceptibility of 2 and 3 was investigated and found deviated from the Curie–Weiss law.     

Methylene bridged binuclear bis(imino)pyridyl iron(II) complexes and their use as catalysts together with Al(i-Bu)3 for ethylene polymerization

Three novel methylene bridged binuclear iron(II) complexes: (R,R′ = i-C₃H₇ (6); R = i-C₃H₇, R′ = CH₃ (7); R,R′ = CH₃ (8))} have been synthesized. Activated by Al(i-Bu)₃, complex 6 shows very poor activity for the polymerization of ethylene at one bar ethylene pressure, whereas, 7 and 8 exhibit much higher activity than mononuclear iron catalysts {[ArNC(Me)C₅H₃N(Me)CNAr′]FeCl₂ (Ar,Ar′ = 2,6-C₆H₃-i-Pr (9); Ar = 2,6-C₆H₃-i-Pr₂, Ar′ = 2,6-C₆H₃–Me₂ (10); Ar,Ar′ = 2,6-C₆H₃–Me₂ (11))}. The molecular weight (M_w) of PE produced by 7 and 8 are in the range 13.2–46.0 × 10⁴ and much higher than those produced by mononuclear iron catalysts 9 and 10. GPC results demonstrate that 7 and 8 yield PE with a broad/bimodal molecular weight distribution (MWD). In contrast, 9 and 10 yield PE with relatively narrow and unimodal MWD (4.26 and 3.55). Elevating the temperature and Al/Fe molar ratio will narrow the MWD of PE.     

Mixed-ligand complexes of technetium XIII. A new and facile synthesis, structure and electrochemical behaviour of trans-[Tc(dppe)2(buNC)2](PF6)· ethanol (dppe = bis(diphenylphosphino)ethane, buNC= tert-butylisocyanide)

The Tc(I) mixed-ligand complex, trans-[Tc(dppe)₂(bu^tNC)₂](PF₆) (dppe=bis(diphenylphosphino)ethane, bu^tNC=tert-butyl-isocyanide) has been prepared from [Tc(tu−S)₆³⁺ (tu-S=thiourea) and a mixture of both ligands. The compound crystallizes triclinic in the space group

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). The technetium atom has a slightly distorted octahedral coordination sphere with the isocyanide ligands in trans-position to each other. By cyclic voltammetry, at a Pt electrode, trans-[Tc(dppe)₂(bu^tNC)₂](PF₆) undergoes a single electron reversible oxidation at E_1/2^ox=0.91 V versus SCE.     

Three Ni/Co(II) complexes with 4,4′-bipyridine and benzoic acid derivatives as mixed coligands: Hydrothermal syntheses, structures, and magnetisms

The hydrothermal reactions of 3,5-dinitrobenzoic acid, or p-toluic acid, 4,4′-bipyridine, with transition metal chlorides in basified solvent gave rise to three coordination polymers, [Ni₂(3,5-DNBC)₄(4,4′-bpy)₂(H₂O)] (1), [Co(3,5-DNBC)₂(4,4′-bpy)₂] (2), [Co₃(4,4′-bpy)(p-ToC)₆] (3), and characterized by elemental analysis, IR, single-crystal X-ray diffraction and variable-temperature magnetic measurements. Compound 1 crystallizes in the monoclinic system, P2₁/c space group, the structure determination reveals that 1 has a 2D network based on lozenge grids, where each Ni^II is in 4O + 2N coordination mode. Compound 2 is also monoclinic system, P2/c space group, and the X-ray structural analysis shows that 2 also has a 2D network but based on rectangular grids with the Co^II atom in a CoN₂O₄ environment. Compound 3 crystallizes in the triclinic system, space group, and polymerizes through nitrogen and oxygen atoms giving 1D chains with the Co^II(1) atom in a CoO₆ environment and Co^II(2) is in N + 4O coordination mode. In good agreement with the expected behavior, magnetic susceptibility measurements show weak ferromagnetic interactions for 1 and 3, whereas compound 2 exhibits moderate antiferromagnetic coupling.     

Efficacy of a Comfrey root extract ointment in comparison to a Diclo-fenac gel in the treatment of ankle distortions: Results of an observer-blind, randomized, multicenter study

In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the “chemical-synthetical” and the “phytotherapeutical” approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe^® f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7±1 days, four times a day.

Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling, figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of “neutral-zero”, consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively.

It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01–103.09 h*N/cm² and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.     

The rhodium(III) trisacetonitrile complexes: a re-investigation of the synthesis of fac- and mer- [RhCl3(CH3CN)3], their characterization by 2D NMR spectroscopy and the X-ray crystal structure of mer-[RhCl3(CH3CN)3] · CH3CN

It is shown that the reaction of RhCl₃·3H₂O with acetonitrile normally produces mixtures of mer- and fac-[RhCl₃(CH₃CN)₃] (1a and 1b, respectively). The IR and ¹H NMR spectra of these isomers were re-investigated. Their two-dimensional (¹⁰³Rh,¹H) NMR spectra were also recorded. Equilibrium and exchange studies of 1a and 1b in CD₃C were performed. It was found that in 1a the exchange rate of the nitrile molecule trans to Cl is much faster than those of mutually trans nitriles. Also the nitrile molecules in 1b underwent fast exchange in CD₃CN; however, their rate was slightly faster than that of the more labile CH₃CN in 1a. The X-ray crystal structure of mer-[RhCl₃(CH₃CN)₃]·CH₃CN (1c) was determined. Crystal data: triclinic space group

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