Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design,synthesis and biological evaluation

A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain.     

Ultrafine molybdenum carbide nanoparticles supported on nitrogen doped carbon nanosheets for hydrogen evolution reaction

Nitrogen doped carbon nanosheets supported molybdenum carbides nanoparticles (Mo_xC/NCS) have been synthesized by tuning the mass ratio of melamine and ammonia molybdate. The Mo₂C/NCS-10 exhibits superior electrocatalytic performance and stability for HER, which was attributed to N-doped carbon nanosheets, small particle size, mesoporous structure, and large electrochemical active surface area.     

Simultaneous extraction of organotin, organolead and organomercury species from soils and litter

Extracting organotin compounds (OTC) from soils is difficult due to the high cation exchange and complexation capacity of soils, and little information about OTC in soils is available. In this study, a new extraction method, combining 1 M CaCl₂, 0.1% tropolone, and glacial acetic acid was developed. Recoveries of mono-substituted OTC from spiked plant litter, and soil samples were improved substantially to 40% compared to classical glacial acetic acid extraction commonly used in sedimentology, yielding <10% recovery in C-rich soil samples. Simultaneously, the recovery of other OTC, trimethyllead and monomethylmercury was satisfactory. The recoveries of most species from the spiked litter, upland and wetland soils exceeded 70%. The new method extracted much more organometallics from unspiked organic soils and litter than microwave- and ultrasound-assisted extraction and accelerated solvent extraction, most likely due to exchange of organometallics from the solid phase by Ca²⁺. The method is simple, highly efficient and with low contamination. Together with GC-ICP-mass spectrometry, the method allows the detection of these organometallics in the pg g⁻¹ range and it is particularly suitable for soil and plant materials with low organometallics contents.     

A highly enantioselective hetero-Diels-Alder reaction of aldehydes with Danishefsky's diene catalyzed by chiral titanium(IV) 5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol complexes

The catalytic effect of chiral Lewis acids on the hetero-Diels-Alder reaction between aldehydes and Danishefsky's diene (1) has been investigated. A variety of combinations of different ligands and Lewis acids have been examined as catalysts for the hetero-Diels-Alder reaction between benzaldehyde and 1, and it has been found that the readily accessible Ti(IV)-H(8)-BINOL (TiHBOL) complex is a very effective catalyst for the reaction, leading to products with very high enantioselectivity (up to 99% ee) and yield (92%). The hetero-Diels-Alder reaction of other aldehydes with 1 under the catalysis of TiHBOL is a general reaction which proceeds well with very high enantioselectivity and isolated yield for various aldehydes at 0 degrees C to room temperature. Based on the experimental results, the proposed mechanism of the hetero-Diels-Alder reaction and the dihedral angle effects of ligands are discussed.     

Flow constant-current stripping analysis for antimony(III) and antimony(V) with gold fibre working electrodes : Application to Natural Waters

Antimony(III) is determined by means of electrolysis at ?0.40 V vs. Ag/AgCl on a gold-coated gold fibre electrode for 0.5–10 min in a redox buffer containing 0.01 M iron(II) in 0.10 M hydrochloric acid, and subsequent stripping with a constant current of 0.50μA either in 2 M hydrochloric acid or in 4 M hydrochloric acid/4 M calcium chloride. Antimony(V) is determined by the same procedure in 4 M hydrochloric acid medium. Bismuth(III) is masked by the addition of iodide to the sample prior to electrolysis. Antimony(III) and antimony(V) are determined by standard addition methods; the whole procedure including digital and graphical evaluation of the results is fully automated. The antimony(V) concentrations in the river water reference sample SLRS-1 and the seawater reference sample NASS-1 were found to be 0.63 and 0.31 μg l^?1 with standard deviations of 0.046 and 0.051 μg l^?1, respectively (n=15). The certified value for SLRS- 1 is 0.63±0.05 μg l^?1; no certified value is available for NASS-1.     

Determination of tin in canned foods by UV/visible spectrophotometric technique using mixed surfactants

The complex of tin(IV) with bromopyrogallol red (BPR) in the presence of nonyl phenoxy polyethoxyethanol (OP) and cetyltrimethylammonium bromide (CTAB) has a sensitive absorption peak at 304 nm. Under the optimal conditions, Beer's law is obeyed over the range 0.1-2.5 mug ml(-1) Sn(IV) with molar absorptivity being 8.2 x 10(4) l mol(-1) cm(-1) and detection limit 0.018 mug ml(-1). As compared with the visible method which also uses BPR as chromogenic reagent (lambda(max) = 550 nm), our method is sensitive and selective because of the complex's high, sharp absorption peak. In addition, the present method is simple and rapid, no heating or standing is needed. By means of the mixed surfactants the precipitation caused by the ion association of cetyltrimethylammonium cation and I(-)(3) anion is avoided if iodide is used for separating micro amounts of tin(IV) from a sample matrix. An application of the proposed method to the determination of Sn(IV) in a canned food was made with satisfactory results.     

Metal-betaine interactions—X. Preparation and crystal structures of bis(triethyl betaine)bis(nitrato)disilver(I) and catena-bis(triethyl betaine)disilver(I) diperchlorate

Two silver(I) complexes of triethyl betaine (Et₃N⁺CH₂COO⁻, Et₃BET) have been prepared and characterized by X-ray crystallography. Both complexes, [Ag₂(Et₃BET)₂ (NO₃)₂] (1) and [Ag₂(Et₃BET)₂]_n (ClO₄)_2n (2), contain centrosymmetric bis-carboxylato-bridged Ag₂(carboxylato-O,O′)₂ dimers (Ag---O = 2.16–2.23 Å). The dimeric unit in 1 is bound to a chelating nitrato group [Ag---O = 2.524(3), 2.619(3) Å] at each axial site, resulting in a discrete molecule. In 2 the dimers are extended into a stair-like cationic chain via the coordination of each metal centre by a carboxylato oxygen atom [Ag---O =2.565(5) Å] from an adjacent unit. The intra-dimer Ag… Ag distance is 2.928(1) Å for 1 and 2.856(2) Å for 2.     

Homolysis of the Ln-N (Ln = Yb, Eu) bond. Synthesis, structural characterization and catalytic activity of ytterbium(II) and europium(II) complexes with methoxyethyl functionalized indenyl ligands

The interaction of methoxyethyl functionalized indene compounds (C(9)H(6)-1-R-3-CH(2)CH(2)OMe, R =t-BuNHSiMe(2)(1), Me(3)Si (2), H (3)) with [(Me(3)Si)(2)N](3)Ln(mu-Cl)Li(THF)(3)(Ln=Yb (4), Eu (5)) produced a series of new ytterbium(II) and europium(II) complexes via tandem silylamine elimination/homolysis of the Ln-N (Ln=Yb, Eu) bond. Treatment of the lanthanide(III) amides [(Me(3)Si)(2)N](3)Ln(mu-Cl)Li(THF)(3)(Ln=Yb (4), Eu (5) with 2 equiv. of, 1,2 and 3, respectively, produced, after workup, the ytterbium(II) complexes [eta5:eta1-Me(2)Si(MeOCH(2)CH(2)C(9)H(5))(NHBu-t)](2)Yb(II) (6), (eta5:eta1-MeOCH(2)CH(2)C(9)H(5)SiMe(3))(2)Yb(II) (7), (eta5:eta1-MeOCH(2)CH(2)C(9)H(6))(2)Yb(II)(8) and the corresponding europium(II) complexes [eta5:eta1-Me(2)Si(MeOCH(2)CH(2)C(9)H(5))(NHBu-t)](2)Eu(II)(9), (eta5:eta1-MeOCH(2)CH(2)C(9)H(5)SiMe(3))(2)Eu(II)(10) and (eta5:eta1-MeOCH(2)CH(2)C(9)H(6))(2)Eu(II)(11) in moderate to good yield. In contrast, interaction of the corresponding indene compounds 1, 2 or 3 with the lanthanide amides [(Me(3)Si)(2)N](3)Ln (Ln = Yb, Eu) was not observed, while addition of 0.5 equiv. of anhydrous LiCl to the corresponding reaction mixture produced, after workup, the corresponding ytterbium(II) or europium(II) complexes. All the new compounds were fully characterized by spectroscopic and elemental analyses. The structures of complexes, and were determined by single-crystal X-ray analyses. The catalytic activity of all the ytterbium(II) and europium(II) complexes on MMA polymerization was examined. It was found that all the ytterbium(II) and europium(II) complexes can function as single-component MMA polymerization catalysts. The temperature, solvent and ligand effects on the catalytic activity were studied.     

The migrastatin family: discovery of potent cell migration inhibitors by chemical synthesis

The first asymmetric total synthesis of (+)-migrastatin (1), a macrolide natural product with anti-metastatic properties, has been accomplished. Our concise and flexible approach utilized a Lewis acid-catalyzed diene aldehyde condensation (LACDAC) to install the three contiguous stereocenters and the trisubstituted (Z)-alkene of migrastatin (2 + 3 --> 21). Construction of the two remaining stereocenters and incorporation of the glutarimide-containing side chain was achieved by an anti-selective aldol addition of propionyl oxazolidinone 28 to angelic aldehyde 27, followed by a Horner-Wadsworth-Emmons (HWE) coupling of 32 with glutarimide aldehyde 5. Finally, the assembly of the macrocycle was realized by a highly (E)-selective ring-closing metathesis (35 --> 37). Utilizing the power of diverted total synthesis (DTS), a series of otherwise inaccessible analogues was prepared and evaluated for their potential as tumor cell migration inhibitors in several in vitro assays. These studies revealed a dramatic increase in activity when the natural motif was considerably simplified, presenting macrolactones 45 and 48, as well as macrolactam 55, macroketone 60, and CF(3)-alcohol 71 as promising anti-metastatic agents.     

Studies on the Binding Mode of Pinacyanol Chloride to Nucleic Acids

The interaction of pinacyanol chloride(PC) with nucleic acids has been investigated by a series of experiments.Extensive hypochromism,appreciable peak shifts,isosbestic points and new peaks of the product of binding to nucleic acids in the spectra were observed.They showed that the interaction between PC and nucleic acids occurred.The results from absorption spectra of DNA,DNA melting,electrophoresis and fluorescence polarization studies have indicated that PC binds to DNA in nonintercalative way.Consistent with the nonintercalation,the studies of fluorescence titration and absorption titration specified that the binding of PC to nucleic acids occurred by an outside stacking binding,in which nucleic acids served for acting templates,The fact that the new absorption peaks of bound PC at ca,485nm are just close to the absorption bands of Haggregate of PC at high concentrations without DNA further supports the outside stacking binding mode,In addition,other evidence indicated that the interaction between PC and nucleic acids is not purely electrostatic.