Catalytic Activity of Pd(II) Complexes with Triphenylphosphito Ligands in the Sonogashira Reaction in Ionic Liquid Media

The reactivity of palladacycle dimeric complexes with substituted triarylphosphito ligands P(OR)₃ (R = Ph, m-MeC₆H₄, o-MeC₆H₄, C₆H₃-2,4-tBu₂) as well as their non-orthometallated analogues PdCl₂[P(OR)₃]₂ was tested in a copper-free Sonogashira reaction with iodobenzene and phenylacetylene as substrates and imidazolium ionic liquids as the reaction medium. The ionic liquids [bmim][PF₆], [bmim][BF₄] and [emim][SO₄Et] were chosen. The palladium complexes studied showed high activity, and the yield of diphenylacetylene ranged from 31 to 98% in 1 h. The best results were obtained in [bmim][PF₆] for PdCl₂[P(O-m-MeC₆H₄)₃]₂ (84%) and for orthopalladated dimer with the same phosphite (98%).     

Generating orally active galanin analogues with analgesic activities

The endogenous neuropeptide galanin has anticonvulsant and analgesic properties mediated by galanin receptors expressed in the central and peripheral nervous systems. Our previous work showed that by combining truncation of the galanin peptide with N- and C-terminal modifications afforded analogues that suppress seizures or pain upon intraperitoneal (i.p.) administration. To generate orally active galanin analogues, the previously reported lead compound Gal-B2 (NAX 5055) was redesigned by 1) central truncation, (2) introduction of D-amino acids, and 3) addition of backbone spacers. Analogue D-Gal(7-Ahp)-B2, containing 7-aminoheptanoic acid as a backbone spacer and an oligo-D-lysine motif at the C terminus, exhibits anticonvulsant and analgesic activity post-i.p. administration. Oral administration of D-Gal(7-Ahp)-B2 demonstrates analgesic activity with decreases in both acute and inflammatory pain in the mouse formalin model of pain at doses as low as 8 mg kg(-1) .     

Elastic and Dielectric Behavior of Highly Disordered Pb(Sc1/2Ta1/2)O3 Single Crystal

The room temperature sound velocity v_[111] = 4742 m/s and the elastic constant c_[111] = (c₁₁+2c₁₂+4c₄₄) = 203 GPa was determined from the Brillouin shift of the longitudinal acoustic mode in highly disordered Pb(Sc_1/2Ta_1/2)O₃ single crystal. The degree of order S = 0.13 of the crystal was determined both from the occupation factor of the Sc and Ta atoms obtained for the full structure refinement at room temperature and 440 K from the ratios of the intensities of the superstructure and fundamental reflections. The dielectric response of the crystal is characterized by a dispersive maximum at T_{ε * max} ≈ 250 K and the Vogel-Fulcher temperature T_VF = 209 K.     

Asymmetrical dicationic ionic liquids based on both imidazolium and aliphatic ammonium as potential electrolyte additives applied to lithium secondary batteries

Asymmetrical dicationic ionic liquids based on the combination of imidazolium and aliphatic ammonium cations with TFSI anion, MIC_nN₁₁₁-TFSI₂, have been synthesized for the first time, wherein MI represents imidazolium cation, N₁₁₁ represents trimethylammonium cation, and C_n represents spacer length. The physical and electrochemical properties of this family of ionic liquids were studied. 1-(3-Methylimidazolium-1-yl)ethane-(trimethylammonium) bi[bis(trifluoromethane-sulfonyl) imide] (MIC₂N₁₁₁-TFSI₂) shows solid-solid transition characteristics. 1-(3-Methylimidazolium-1-yl)pentane-(trimethylammonium) bi[bis(trifluoromethan-esulfonyl)imide] (MIC₅N₁₁₁-TFSI₂) has one of the lowest solid-liquid transformation temperatures among analogues, and belongs to the greatest thermal stable ionic liquids. Additionally, it has an order of conductivity of 10⁻¹ ms cm⁻¹, and electrochemical window of about 3.7 V at room temperature. To evaluate the potential of MIC₅N₁₁₁-TFSI₂ as an additive of electrolyte for lithium secondary batteries, cells composed of LiMn₂O₄ cathode/1 M LiPF₆ in EC:DMC (1:1, v/v) electrolytic solution containing 5 wt% of MIC₅N₁₁₁-TFSI₂/lithium metal anode have been prepared. The charge-discharge cycling test reveals that unlike the cases of Li/LiMn₂O₄ cells employing a conventional electrolyte with a monocationic ionic liquid, such as 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl) imide (EtMeImTFSI) as an additive, the performances of Li/LiMn₂O₄ cells do not drop with the addition of MIC₅N₁₁₁-TFSI₂ at 1C rate, moreover, the cell exhibits better discharge capacity and cycle durability compared with the cell using the conventional electrolyte.     

New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes

Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.     

Synthesis,crystal structure,and magnetic property of a stepped tetranuclear copper(II) complex of 3,5-diisopropylpyrazole-1-methoxide

Reaction of copper(II) chloride dihydrate in methanol with deprotonated 3,5-diisopropylpyrazole-1-methanol (dippmOH) led to the tetranuclear copper(II) complex [(dippmO)CuCl]₄ (1). The crystal structure of 1 indicates that two copper(II) ions connect via the oxygen atoms of dippmO⁻ ligands each other in which two dimeric units are formed. Furthermore, one of the coordinated oxygen atoms in a dimer is bonded to an adjacent copper(II) ion positioned other dimer, which gives rise to a stepped tetranuclear structure. 1 shows strong antiferromagnetic interactions through the oxo groups within the dimeric units (J₁ = − 239 cm^− 1) and weak antiferromagnetic couplings between the dimers (J₂ = − 15 cm^− 1).     

A ¹⁸F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma₁ receptors

In this study, we synthesized and evaluated a new spirocyclic piperidine derivative 3 , containing a 4‐fluorobutyl side chain, as a PET radioligand for neuroimaging of σ₁ receptors. In vitro, compound 3 displayed high affinity for σ₁ receptors (K_i=1.2 nM ) as well as high selectivity. [¹⁸F] 3 radiosynthesis was performed from the corresponding tosylate precursor, with high radiochemical yield (45–51 %), purity (>98 %), and specific activity (>201 GBq μmol^?1). Metabolic stability of [¹⁸F] 3 in the brain of CD‐1 mice was verified, and no penetration of peripheral radiometabolites into the cerebral tissue was observed. Results of ex vivo autoradiography revealed that the distribution of [¹⁸F] 3 in the brain corresponded to regions with high σ₁ receptor density. The highest region‐specific total‐to‐nonspecific ratio was determined in the facial nucleus (4.00). Biodistribution studies indicated rapid and high levels in brain uptake of [¹⁸F] 3 (2.2 % ID per gram at 5 min p.i.). Pre‐administration of haloperidol significantly inhibited [¹⁸F] 3 uptake into the brain and σ₁ receptor‐expressing organs, further confirming in vivo target specificity.     

Engineered humanized diabodies for microPET imaging of prostate stem cell antigen-expressing tumors

We have previously demonstrated preclinical in vivo targeting of prostate stem cell antigen (PSCA) using a humanized anti-PSCA 2B3 monoclonal antibody (mAb). However, humanization resulted in 5-fold loss of apparent affinity relative to the parental mAb (1 nM). In this study, diabodies (scFv dimers of 55 kDa) were generated from 2B3 including variants with different linker lengths as well as back-mutations to original murine residues to improve affinity. Parental 2B3 (p2B3) and back-mutated 2B3 (bm2B3) diabodies (Dbs) with five- or eight-amino acid linkers (p2B3-Db5, p2B3-Db8, bm2B3-Db5 and bm2B3-Db8) were evaluated for binding to PSCA by flow cytometry and affinities were determined by surface plasmon resonance. Back-mutation restored the affinity from 5.4 to 1.9 nM. Stability, evaluated by size exclusion, revealed that diabodies with eight-residue linkers existed as a mixture of dimeric and monomeric species at low concentrations (相似文献   

Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 2 Caused by CYS59TYR BOLA3 Mutation

Multiple mitochondrial dysfunctions syndrome (MMDS) is a rare neurodegenerative disorder associated with mutations in genes with a vital role in the biogenesis of mitochondrial [4Fe–4S] proteins. Mutations in one of these genes encoding for BOLA3 protein lead to MMDS type 2 (MMDS2). Recently, a novel phenotype for MMDS2 with complete clinical recovery was observed in a patient containing a novel variant (c.176G > A, p.Cys59Tyr) in compound heterozygosity. In this work, we aimed to rationalize this unique phenotype observed in MMDS2. To do so, we first investigated the structural impact of the Cys59Tyr mutation on BOLA3 by NMR, and then we analyzed how the mutation affects both the formation of a hetero-complex between BOLA3 and its protein partner GLRX5 and the iron–sulfur cluster-binding properties of the hetero-complex by various spectroscopic techniques and by experimentally driven molecular docking. We show that (1) the mutation structurally perturbed the iron–sulfur cluster-binding region of BOLA3, but without abolishing [2Fe–2S]²⁺ cluster-binding on the hetero-complex; (2) tyrosine 59 did not replace cysteine 59 as iron–sulfur cluster ligand; and (3) the mutation promoted the formation of an aberrant apo C59Y BOLA3–GLRX5 complex. All these aspects allowed us to rationalize the unique phenotype observed in MMDS2 caused by Cys59Tyr mutation.     

A Parallel Semisynthetic Approach for Structure–Activity Relationship Studies of Peptide YY

The gut hormone peptide YY (PYY) is postprandially secreted from enteroendocrine L cells and is involved in the regulation of energy homeostasis. The N‐terminal truncated version PYY(3–36) decreases food intake and has potential as an anti‐obesity agent. The anorectic effect of PYY(3–36) is mediated through Y₂ receptors in the hypothalamus, vagus, and brainstem regions, and it is well known that the C‐terminal tetrapeptide sequence of PYY(3–36) is crucial for Y₂ receptor activation. The aim of this work was to develop a semisynthetic methodology for the generation of a library of C‐terminally modified PYY(3–36) analogues. By using an intein‐based expression system, PYY(3–29) was generated as a C‐terminal peptide α‐thioester. Heptapeptides bearing an N‐terminal cysteine and modifications at one of the four C‐terminal positions were synthesized in a 96‐well plate by parallel solid‐phase synthesis. In the plate format, an array of [Ala30]PYY(3–36) analogues were generated by ligation, desulfurization, and subsequent solid‐phase extraction. The generated analogues, in which either Arg33, Gln34, Arg35, or Tyr36 had been substituted with proteinogenic or non‐proteinogenic amino acids, were tested in a functional Y₂ receptor assay. Generally, substitutions of Tyr36 were better tolerated than modifications of Arg33, Gln34, and Arg35. Two analogues showed significantly improved Y₂ receptor selectivity; therefore, these results could be used to design new drug candidates for the treatment of obesity.     

Synthesis and Characterization of A-B-A-Type Nonionic Dimeric Dispersants for Pigment Dispersion

An acid-catalyzed esterification method was employed to synthesize five A-B-A-type nonionic dimeric surfactants (XOP-3, XOP-4, XOP-6, XOP-9, and XOP-10) comprising of octyl phenyl ether (OP-10) and a homologous series of α, ω-dicarboxylic acids (C_3, C_4, C_6, C_9, and C₁₀) as the spacer molecules. The various surfactants produced were characterized based on Fourier transform infrared (FT-IR) spectroscopy, mass spectra (MS), and ¹H NMR spectra. The newly synthesized series of surfactants were used for the dispersion of Hostaperm Pink E (Pigment Red 122) in an ultrasonic disruptor. Based on the selected pigment, the interfacial, colloidal, and rheological properties of the pigment dispersion were examined. The dispersion performances and properties of the surfactants produced differed based on the number of carbon atoms in hydrocarbon chains of the various spacer molecules. Due to this, surfactants created with short to moderate hydrocarbon chain spacer molecules exhibited a better dispersion performance than that of surfactants created with long hydrocarbon chain spacer molecules. The calculated cross-sectional area values of the various surfactants synthesized confirmed their differences in dispersion performance and properties.     

A novel quasi-dimeric oxidation product of (+)-catechin from lipid peroxidation

A novel quasi-dimeric oxidation product of (+)-catechin, formed during the radical-scavenging reaction that prevents lipid peroxidation, was isolated by chromatography, and its structure was elucidated by infrared, ultraviolet and¹H and¹³C nuclear magnetic resonance spectra and mass spectrometry. It was 5′-[3-[3,4-(3′,5′-dihydroxy) benzo-8-oxo-2,7-dioxabicyclo [4.4.0] deca-3,9-dien-10-yl]acryloyl]-(+)-catechin. It is an unusual type of dimer of flavan-3-ol derivatives, which is different from the naturally formed dimer, procyanidin.     

Temperature–Time Texture Transition of Pb(Zr1−xTix)O3 Thin Films: I, Role of Pb-rich Intermediate Phases

Lead-rich intermediate phases, in particular Pt_5–7Pb and PbO, are found to form on Pt(111) atop Ti–buffered Si substrates prior to formation of Pb(Zr_{1− x} Ti _x )O₃ (PZT) thin films. Pt_5–7Pb is a [111] textured transient intermetallic phase that nucleates PZT[111] texture. PbO is a [001] textured layer compound that nucleates PZT[100] texture. The formation conditions and lattice matching of these intermediate phases have been examined. The presence of other possible intermediate phases, such as pyrochlore and Zr and Ti-rich phases, has also been investigated but found unrelated to the texture selection of perovskite PZT.     

Attachment chemistry of organic molecules on Si(111)-7 x 7

Molecular attachment chemistry is emerging as an important approach to tailor the chemical, physical, and mechanical properties of silicon surfaces, as well as to incorporate organic functions into silicon-based devices for various technological needs. The chemical bonding and reactivity of various organic molecules on Si(111)-7 x 7 were systematically studied using XPS, HREELS, TPD, UPS, STM, and DFT calculations. The spatial arrangements and unique electronic properties of reactive adatoms and rest atoms on the surface offer rich attachment chemistry for organic functionalities. Investigations demonstrated that organic molecules can be chemically bound to Si(111)-7 x 7 through several reaction pathways, including [4 + 2]- and [2 + 2]-like additions, dative bonding, and dissociative reaction. This Account reviews the recent progress and current understanding of reactivity, selectivity, and mechanisms of organic molecules on Si(111)-7 x 7.     

Microstructure of Lanthanum Magnesium Niobate at Elevated Temperature

Microstructural studies of the complex perovskite compound La(Mg_2/3Nb_1/3)O₃ (LMN) were conducted using transmission electron microscopy (TEM) and X-ray diffractometry (XRD) at elevated temperatures. 1:1 chemical ordering of B-site cations and tilting of oxygen octahedra were observed in LMN. Three types of superlattice reflections, [1—2]{111}, [1—2]{110}, and [1—2]{100} were observed at room temperature and at 800°C in electron diffraction patterns. In the XRD experiments, the [1—2]{210} and [1—2]{300} extra peaks disappeared at temperatures >1200°C. However, the intensity of the superlattice [1—2]{111} peak did not change with increased temperature up to 1400°C. These results strongly indicated that the origin of superlattice reflection [1—2]{111} was different from that of the other superlattice reflections. It was mainly caused by the 1:1 chemical ordering of magnesium and niobium atoms. The TEM image observed at 800°C showed the ordered domain structures separated by the antiphase boundaries.     

A predesigned 1D chain of alternating di-μ1,1-azido bridged dinuclear Ni(II) and pyrazine: Synthesis,structure and magnetic properties

A new Ni(II) complex, [Ni₂(L)₂(μ_1,1-N₃)₂(pyz)]_n (1) (where pyz = pyrazine) has been synthesized using a dinuclear di-μ_1,1-azido bridged Ni₂ molecular building block derived from a tridentate NNO donor Schiff base ligand, HL (2-[(3-methylamino-propylimino)-methyl]-phenol) along with pyrazine as spacer. Single crystal X-ray analysis shows that complex 1 is a 1D chain in which dimeric Ni₂ units [Ni₂L₂(N₃)₂] are linked to each other by the bridging pyrazine ligand. Variable-temperature magnetic susceptibility studies indicate the presence of moderate ferromagnetic exchange coupling in complex 1 with J value of 53.54 cm^− 1.     

Asymmetric synthesis and conformational analysis by NMR spectroscopy and MD of Aba- and α-MeAba-containing dermorphin analogues

Dermorphin analogues, containing a (S)‐ and (R)‐4‐amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐one scaffold (Aba) and the α‐methylated analogues as conformationally constrained phenylalanines, were prepared. Asymmetric phase‐transfer catalysis was unable to provide the (S)‐α‐Me‐o‐cyanophenylalanine precursor for (S)‐α‐MeAba in acceptable enantiomeric purity. However, by using a Schöllkopf chiral auxiliary, this intermediate was obtained in 88 % ee. [(S)‐Aba 3‐Gly 4]dermorphin retained μ‐opioid affinity but displayed an increased δ‐affinity. The corresponding R epimer was considerably less potent. In contrast, the [(R)‐α‐MeAba 3‐Gly 4]dermorphin isomer was more potent than its S epimer. Tar‐MD simulations of both non‐methylated [Aba 3‐Gly 4]dermorphin analogues showed a degree of folding at the C‐terminal residues toward the N terminus of the peptide, without however, adopting a stabilized β‐turn conformation. The α‐methylated analogues, on the other hand, exhibited a type I/I′ β‐turn conformation over the α‐MeAba 3 and Gly 4 residues, which was stabilized by a hydrogen bond involving Tyr 5‐H_N and D ‐Ala 2‐CO.     

Interaction of nitrogen with iron surfaces: II. Fe(110)

Previous work on the interaction of N₂ with Fe(100) and (111) single-crystal planes was extended to the most densely packed (110) face. The dissociative chemisorption proceeds even slower than with the two other planes and is associated with an activation energy of about 7 kcal/mole at low coverages. At 683 K the initial rates of adsorption have a ratio of about 60:3:1 for Fe(111):(100):(110). The activation energy for desorption is estimated to be about 50 kcal/mole and is thus slightly smaller than on Fe(100)(58 kcal/mole), but higher than on Fe(111) (51 kcal/mole). The formation of two ordered surface structures (I and II) was observed. Their unit cell vectors b₁, b₂ are related with the (unreconstructed) substrate lattice vectors a₁, a₂ through: b₁ = 3a₁, b₁ = 2a₁ (I) (which may also be designated as 2 × 3 structure), and b₁ = 4a₁, b₁ = a₁ + 3a₂ (II). Both phases appear with two equivalent domain orientations with the mirror plane along the [001] direction. Structure I appears at lower surface concentrations than structure II; however their kinetics of formation is also influenced by the concentration of dissolved nitrogen. It is most probably that these large unit cells reflect the reconstruction of the topmost layer of Fe atoms [as in the case of the (111) plane]. For both surface structures quasihexagonal arrangements of Fe atoms may be constructed the nearest-neighbor distances for which agree to within ±3% with those in the (111) plane of fcc Fe₄N. Thus the concept of the formation of “surface nitrides” is further supported. Dissolution of nitrogen atoms in the bulk again interferes with the surface processes.