Highly efficient and versatile synthesis of libraries of constrained beta-strand mimetics

The general approach of using a bicyclic template to produce inhibitors of the protease superfamily of enzymes has been investigated. The Diels Alder cycloaddition reaction on solid support has been found to be highly efficient for the synthesis of libraries of compounds that mimic the beta-strand secondary structure of proteins. Several potent and selective inhibitors of proteases have been discovered.     

Facile synthesis and highly efficient selective adsorption properties of Y2Mo4O15 for methylene blue: Kinetics,thermodynamics and mechanical analyses

Y_2 Mo_4 O_(15) particles were prepared using a simple solution method(SSM) and used as a highly efficient selective adsorbent for methylene blue(MB) in aqueous solutions. The maximum adsorption capacity of the samples was determined based on the adsorption isotherms with different adsorbent doses at 298,318 and 338 K. The fittings of the temperature-dependent isotherms yield ΔrG_m~θ =-34.1 kJ/mol,Δ_rH_m~θ=-36.9 kJ/mol and Δ_rS_m~θ=-9.67 J/mol·K. The as-prepared Y_2 Mo_4 O_(15) has a very large maximum adsorption capacity(i.e., 198 mg/g) for MB at room temperature, and this value is only less than that of amorphous hardwood powder. Notably, 80 mg of adsorbent is able to completely decolorize 250 mL of30 mg/L MB aqueous solution. The kinetic parameters of the adsorption process were obtained from the temperature-dependent adsorption isotherm(i.e., E_1=26.9 kJ/mol and E_1 = 63.8 kJ/mol). The results of adsorption kinetics show that it is a pseudo-second-order reaction. The mechanism of the high selectivity and the large adsorption capacity is discussed based on competitive ion(CI) experiments and coordination theory.     

Dysprosium cerate nanostructures:facile synthesis,characterization,optical and photocatalytic properties

A facile approach was developed to prepare Dy_2Ce_2O_7 nanostructures. Dy_2Ce_2O_7 nanostructures were prepared by applying cerium(IV) ammonium nitrate and dysprosium nitrate as Ce and Dy precursors. It was found that the kind of connecting agent, space-filling template and chelating agent were significant factors for the control in shape and size. Transmission electron microscopy(TEM), X-ray diffraction(XRD), diffuse reflectance UV-vis spectroscopy(DR-UV-vis), field emission scanning electron microscopy(FESEM), photoluminescence spectroscopy(PL) and energy dispersive X-ray microanalysis(EDX) techniques were applied to characterize the Dy_2Ce_2O_7 nanostructures and investigate their optical characteristics. To examine the photocatalytic activity of as-produced Dy_2Ce_2O_7 nanostructures, the photocatalytic degradation of erythrosine dye as water pollutant was carried out. The results of the photocatalytic investigations suggest as-obtained nano-sized Dy_2Ce_2O_7 product as a new, proper and efficient candidate for photocatalytic usages under UV illumination.     

Highly regio- and stereoselective acylboration, acylsilation, and acylstannation of allenes catalyzed by phosphine-free palladium complexes: an efficient route to a new class of 2-acylallylmetal reagents

A new method for the synthesis of substituted 2-acylallylmetal reagents in a highly regio- and stereoselective fashion involving a three-component assembly of allenes, acyl chlorides, and bimetallic reagents (B-B, Si-Si, and Sn-Sn) catalyzed by phosphine-free palladium complexes is described. Treatment of various allenes (CR(2)R(3)=C=CH(2)) with acyl chlorides (R(1)COCl) and bispinacolatodiboron in the presence of PdCl(2)(CH(3)CN)(2) in toluene at 80 degrees C gave 2-acylallylboronates in moderate to good yields. The acylsilation of allenes with acid chlorides and hexamethyldisilane (5) proceeded successfully in the presence of Pd(dba)(2) in CH(3)CN affording the corresponding allylsilanes (CR(2)R(3)=C(COR(1))CH(2)SiMe(3)) in good to moderate yields. Several chloroformates (R(4)OCOCl) also react with 1,1-dimethylallene (2a) and 5 to afford allylsilanes (CR(2)R(3)=C(COOR(4))CH(2)SiMe(3)) in 66-70% yields. Acylstannation of allenes could also be achieved by slow addition of hexabutylditin (10) to the reaction mixture of acyl chloride (or chloroformate) and allene 2a in CH(3)CN in the presence of Pd(dba)(2) at 60 degrees C; the corresponding 2-substituted allylstannanes were isolated in moderate to good yields. The above catalytic reactions are completely regioselective and highly stereoselective. A mechanism is proposed to account for the catalytic reactions and the stereochemistry.     

Compomers and glass ionomers: bond strength to dentin and mechanical properties

Twenty-six patients with newly diagnosed ALL (age range 15-49 years, median 32 years) received treatment comprising: cycles 1 and 2: adriamycin 30 mg/m2 days 1-3, vincristine: 2 mg days 1, 8, and 15, with prednisolone 40 mg daily, given until complete remission (CR). L-asparaginase 10000 units/m2, days 1-14, was given only with the first cycle. Cycle 3 consisted of 100 mg/m2 etoposide orally, days 1-5, and 1 gm/m2 bd cytosine arabinoside (ara-C) days 1-5. Cycles 1-3 were then repeated. Intrathecal methotrexate (MTX) 12.5 mg was given on day 1 of each treatment cycle. The first 12 consecutive patients received this chemotherapy alone, the subsequent 14 received, in addition, 3 micrograms/kg GM-CSF subcutaneously, from day 4 of cycles 1,2,4 and 5 (and from day 6 of cycles 3 and 6) until the absolute neutrophil count had reached 0.5 x 10(9)/1. All patients in whom CR was achieved then received prophylactic cranial irradiation. With the exception of those with T-ALL, this was followed by oral maintenance therapy consisting of 6-mercaptopurine, MTX, and cyclophosphamide for 3 years. Patients receiving GM-CSF did not have shorter intercycle times or a lower incidence of documented infections than those who did not receive it. The CR rate was 89% overall-uninfluenced by GM-CSF, but higher than that achieved previously at St Bartholomew's Hospital in an equivalent age-group.     

An efficient synthesis of polyguanylic acid by a thermophilic polynucleotide phosphorylase

Polyguanylic acid (poly(G)) was synthesized from GDP in a yield of 60-75% by Thermus thermophilus polynucleotide phosphorylase (polyribonucleotide: orthophosphate nucleotidyltransferase, EC 2.7.7.8) at 70 degrees C, pH 8.5 in the presence of Mg2+. The yield was dependent on the ratio of GDP to Mg2+, but was independent of the concentrations of enzyme or substrate. The maximal rate of GDP polymerization was obtained when the ratio of GDP to Mg2+ was 3:1. However, by prolonged incubation, the higher initial ratio of over 4:1 was preferred because of the rapid consumption of GDP in the reaction mixture. Poly(G) prepared by 1 h incubation was heterogeneous in size from 5 S to over 23 S, but by prolonged incubation of 19 h the size of product converged to 9 S as judged by sucrose density gradient centrifugation. Its chain length was determined by terminal nucleoside analysis to be 200 nucleotides long.     

Respiratory rhythm generation in mammals: synaptic and membrane properties

Respiratory rhythm generation depends on a complex interaction between synaptic and membrane properties of functionally defined neurons. To gain a better understanding of how inhibitory and excitatory synaptic inputs lead to the generation of the respiratory rhythm we analyzed the depolarization pattern of respiratory neurons that were recorded in the transverse slice preparation of mice (P8-22) and the in vivo adult cat. Using voltage-calmp recordings from respiratory neurons and specific antagonists for inhibitory synaptic transmission we demonstrate under in vitro conditions, that inspiratory (n = 7) and post-inspiratory neurons (n = 13) received concurrent glycinergic and glutamatergic synaptic input during inspiration. A similar conclusion was gained with chloride injections into in vivo respiratory neurons. The inhibitory input was essential not only for generating the characteristic depolarization pattern of respiratory neurons, but also for switching the respiratory rhythm between inspiration and post-inspiration. The generation of the depolarization pattern depends also on intrinsic membrane properties. Negative current injections reveal that excitatory synaptic input was amplified by intrinsic bursting properties in some inspiratory neurons (n = 4) recorded in vitro. Although such properties have not been described under in vivo conditions our findings suggest that with respect to inspiratory, post-inspiratory and late-inspiratory neurons, the principle network organization is similar under both in vitro and in vivo conditions.     

Simple and efficient generation in vitro of nested deletions and inversions: Tn5 intramolecular transposition

We have exploited the intramolecular transposition preference of the Tn 5 in vitro transposition system to test its effectiveness as a tool for generation of nested families of deletions and inversions. A synthetic transposon was constructed containing an ori, an ampicillin resistance (Ampr) gene, a multi-cloning site (MCS) and two hyperactive end sequences. The donor DNA that adjoins the transposon contains a kanamycin resistance (Kanr) gene. Any Amprreplicating plasmid that has undergone a transposition event (Kans) will be targeted primarily to any insert in the MCS. Two different size targets were tested in the in vitro system. Synthetic transposon plasmids containing either target were incubated in the presence of purified transposase (Tnp) protein and transformed. Transposition frequencies (Ampr/Kans) for both targets were found to be 30-50%, of which >95% occur within the target sequence, in an apparently random manner. By a conservative estimate 10(5) or more deletions/inversions within a given segment of DNA can be expected from a single one-step 20 microl transposition reaction. These nested deletions can be used for structure-function analysis of proteins and for sequence analysis. The inversions provide nested sequencing templates of the opposite strand from the deletions.     

Design and synthesis of Fe-Ce-O@C with efficient photocatalytic activity

Fe-Ce-OH@AR14 was obtained via the adsorption of acid red 14(AR14) on Fe-Ce-OH prepared by the codeposition of cerium nitrate hexahydrate,ferric nitrate nonahydrate,and ammonia,and then Fe-Ce-O@C with high photocatalyic efficiency was synthesized by the calcination of Fe-Ce-OH@AR14 in N₂.For comparison,Fe-Ce-O was also prepared by the calcination of Fe-Ce-OH in N₂.The obtained materials were characte rized by X-ray diffraction(XRD),Raman,X-ray photoelectron spectroscopy(XPS...     

New orally active enkephalinase inhibitors: their synthesis, biological activity, and analgesic properties

A series of (4S)-4-[(2S)-benzyl-3-mercaptopropionylamino]-4-(N-phenylcarbamoyl )-butyric acids has been identified as potent systemically active enkephalinase inhibitors. Structure-activity relationships (SAR) are discussed. Further chemical modification of the inhibitors was carried out in order to identify the inhibitors which are orally active in an animal model. Compounds of particular interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic effects after oral administration were evaluated.     

High-pressure scheelite-type polymorph of SmCrO4: synthesis, structural characterization and magnetic properties

The new scheelite form of SmCrO4 oxide was obtained by heating the zircon-type SmCrO4 oxide at 4 GPa and 803 K.X-ray diffraction revealed that this scheelite SmCrO4 phase crystallized with tetragonal symmetry,S.G.141/a and lattice parameters:a=0.50776(3)nm and c=1.15606(2)nm.This structural phase transition from zircon to scheelite involved a decreasing of around 10% in the unit cell volume.Although the Cr-O and Sm-O distances did not change very much in both zircon and scheelite polymorphs,the changes occurred in the bond angles were remarkable that appear to support the proposed reconstructive model to explain this structural zircon-scheelite phase transition.Magnetic susceptibility and magnetization measurements revealed that the scheelite SmCrO4 oxide behaved an antiferromagnetic material,where the Sm3+and Cr5+were simultaneously ordered.The estimated Neel temperature,TN,was 16 K and the critical field at 12 K associated with the memmagnetic transition was 3.2 T.     

Phototoxicity associated with diclofenac: a photophysical, photochemical, and photobiological study on the drug and its photoproducts

Diclofenac (1) is a photosensitizing nonsteroidal antiinflammatory drug. Its photodecomposition gives rise to chlorocarbazole 2a. This product undergoes photodehalogenation to 3a in a subsequent step. When the photobiological activities of 1, 2a, and 3a are compared by means of the photohemolysis test, it is clearly observed that chlorocarbazole 2a causes cell lysis with a markedly higher efficiency than the parent drug or the secondary photoproduct 3a. Laser flash photolysis studies suggest that photodehalogenation of 2a occurs from its excited triplet state via quenching by ground-state 2a and formation of an excimer. As a consequence, an aryl radical plus an N-centered carbazolyl radical are formed. These radical intermediates appear to be responsible for the observed photobiological effects of diclofenac, via hydrogen abstraction from the target biomolecules, which initiates a type-I photodynamic effect. The efficient peroxidation of model lipids, such as linoleic acid, photosensitized by 2a are in favor of this proposal. Thus, the photosensitizing properties of diclofenac appear to be associated with the photochemical and photobiological activity of its major photoproduct.     

A series of 3D lanthanide complexes based on H bond and halogen-halogen interactions:Synthesis,structure, spectroscopic and thermal properties

Four lanthanide coordination complexes, namely, [Ln(2,3-DClBA)_3(5,5'-dmebipy)(H_2O)]_2(Ln=Sm(1), Eu(2), Dy(3), Ho(4)); 2,3-DClBA=2,3-dichlorobenzoate; 5,5'-dmebipy=5,5'-dmethylbipyridine) were synthesized and characterized by elemental analysis, infrared spectroscopy and single crystal X-ray diffraction. Findings indicated that complex 3 was a dinuclear molecule, and the center Dy~(3+) was eight-coordinated. Each dinuclear units could be connected by H bond and halogen-halogen interactions. Luminescent property of complex 2 suggested the typical intense emissions of Eu~(3+) ions. Thermal analysis showed that the complexes decomposed in three steps: the coordination water was lost firstly then the neutral ligand 5,5'dmebipy was lost and lastly the 2,3-DClBA ligand was lost.     

Monophthalocyanine complexes of samarium and terbium with axial ligands:synthesis,structure and optoelectronic properties

The monophthalocyanine complexes of samarium and terbium containing axial 2-mercaptobenzothiazole(Pc Sm(MBT)(1)), 2-(2-benzoxazol-2-yl) phenolate(Pc Tb(OON)(2)) or 2-(2-benzothiazol-2-yl)phenolate(Pc Tb(SON)(3)) ligands were synthesized and identified by elemental, LDI-TOF and X-ray(for 1) analysis.Photoluminescence(PL) and electroluminescence(EL) spectra of the compounds contained only emission bands of phthalocyanine and axial ligands but did not contain the bands of f-f transitions.It was found that among the complexes 1, 2, 3 the latter had highest photoconductivity(~10–7 S/cm) and photovoltaic properties.An organic photovoltaic device(OPV) of configuration of ITO/3/C60/Alq3/Al revealed open-circuit voltage(VOC) of 0.24 V and short current density(ISC) of 0.3 μA/cm2 under illumination by a xenon lamp at 17 m W/cm2.