Aromatic A-ring analogues of orobanchol, new germination stimulants for seeds of parasitic weeds

Strigolactones are signaling compounds in plants of increasing importance. In this paper the focus is on their activity as germinating agents for seeds of parasitic weeds. The syntheses of aromatic A-ring analogues of the germination stimulant orobanchol have been described. Starting substrate is the ABC unit of the stimulant GR24. Oxidation at the C-4 position gives a 4-oxo derivative which on subsequent reduction produces two C-4 epimeric alcohols, syn and anti in a ratio of 82 : 3. For practical access of the C-4 anti alcohol, the predominant syn epimer is inverted by a Mitsunobu procedure. The anti C-4 alcohol is then coupled with the D-ring in a one-pot two-step process involving a formylation and a reaction with bromobutenolide to give a mixture of the diastereomeric aromatic A-ring analogues of orobanchol. In contrast, the syn C-4 alcohol cannot be coupled directly with the D-ring. Protection of the C-4 syn OH is a prequisite. The best protecting function is the SEM group as deprotection after coupling with the D-ring can then readily be achieved. The structures of these new analogues have been ascertained by X-ray analyses. Both diastereomers of the C-4 syn as well as the C-4 anti orobanchol analogues have been tested as germination agents of seeds of Striga hermonthica and Orobanche ramosa. In addition, the acetates of both epimeric C-4 alcohols have been prepared and tested. Both diastereomers of the 4-oxo derivative have been prepared and bioassayed as well. The bioassays reveal that the diastereomers having the natural relative configuration are most active. The data also suggest that hydrogen bonding is not an important factor in the binding of the stimulant molecules in the receptor.     

Cross-linking of CD4 induces cytoskeletal association of CD4 and p56lck

A membrane glycoprotein CD4 functions as a co-receptor of a T lymphocyte. The co-receptor function has been attributed to a protein tyrosine kinase, p56lck, which is activated upon CD4 binding to MHC molecule. In this study, we present evidences that one of the pathways through which CD4 transmits its signal is cytoskeleton association of p56lck tyrosine kinase as well as CD4 itself. Cytoskeletal association of both proteins is inhibited by a tyrosine kinase inhibitor, genistein, indicating that tyrosine protein kinase activation is important for cytoskeletal association of CD4 and p56lck. Cytoskeletal association of these proteins by CD4 cross-linking is not affected by inhibitors of protein kinase C nor PI3-kinase. Taken together, these results suggest that CD4 cross-linking activates a tyrosine kinase which then induces the simultaneous association of CD4 and p56lck with cytoskeleton.     

Metal-organic frameworks constructed from versatile [WS4Cu(x)](x-2) units: micropores in highly interpenetrated systems

Five metal-organic frameworks (MOFs) formed by [WS(4)Cu(x)](x-2) secondary building units (SBUs) and multi-pyridyl ligands are presented. The [WS(4)Cu(x)](x-2) SBUs function as network vertexes showing various geometries and connectivities. Compound 1 contains one-dimensional channels formed in fourfold interpenetrating diamondoid networks with a hexanuclear [WS(4)Cu(5)](3+) unit as SBU, which shows square-pyramidal geometry and acts as a tetrahedral node. Compound 2 contains brick-wall-like layer also with a hexanuclear [WS(4)Cu(5)](3+) unit as SBU. The [WS(4)Cu(5)](3+) unit in 2 is a new type of [WS(4)Cu(x)](x-2) cluster unit in which the five Cu(+) ions are in one plane with the W atom, forming a planar unit. Compound 3 shows a nanotubular structure with a pentanuclear [WS(4)Cu(4)](2+) unit as SBU, which is saddle-shaped and acts as a tetrahedral node. Compound 4 contains large cages formed between two interpenetrated (10,3)-a networks also with a pentanuclear [WS(4)Cu(4)](2+) unit acting as a triangular node. The [WS(4)Cu(4)](2+) unit in 4 is isomeric to that in 3 and first observed in a MOF. Compound 5 contains zigzag chains with a tetrahedral [WS(4)Cu(3)](+) unit as SBU, which acts as a V-shaped connector. The influence of synthesis conditions including temperature, ligand, anions of Cu(I) salts, and the ratio of [NH(4)](2)WS(4) to Cu(I) salt on the formation of these [WS(4)Cu(x)](x-2)-based MOFs were also studied. Porous MOF 3 is stable upon removal and exchange of the solvent guests, and when accommodating different solvent molecules, it exhibits specific colors depending on the polarity of incorporated solvent, that is, it shows a rare solvatochromic effect and has interesting prospects in sensing applications.     

Different Protonation Equilibria of 4‐Methylimidazole and Acetic Acid

Dynamic protonation equilibria in water of one 4‐methylimidazole molecule as well as for pairs and groups consisting of 4‐methylimidazole, acetic acid and bridging water molecules are studied using Q‐HOP molecular dynamics simulation. We find a qualitatively different protonation behavior of 4‐methylimidazole compared to that of acetic acid. On one hand, deprotonated, neutral 4‐methylimidazole cannot as easily attract a freely diffusing extra proton from solution. Once the proton is bound, however, it remains tightly bound on a time scale of tens of nanoseconds. In a linear chain composed of acetic acid, a separating water molecule and 4‐methylimidazole, an excess proton is equally shared between 4‐methylimidazole and water. When a water molecule is linearly placed between two acetic acid molecules, the excess proton is always found on the central water. On the other hand, an excess proton in a 4‐methylimidazole‐water‐4‐methylimidazole chain is always localized on one of the two 4‐methylimidazoles. These findings are of interest to the discussion of proton transfer along chains of amino acids and water molecules in biomolecules.     

Aminopyridines as acylation catalysts for tertiary alcohols

The acylation of unreactive alcohols with acid anhydrides is greatly facilitated by the addition of a catalytic (0.02–0.1 equivalent) amount of a 4-dialkylaminopyridine. The reaction is faster in nonpolar than in polar solvents and acetyl chloride is not as effective as acetic anhydride. Several pyridine, pyridazine, and quinoline derivatives have been examined as potential acylation catalysts. Of the systems examined, only a few of the 4-substituted pyridines were found to be acylation catalysts, the most effective being 4-pyrrolidinopyridine 4 and 1,1,3,3-tetramethyl-4-(4-pyridyl)guanidine 8. The reaction of t-butanol with an isocyanate is also accelerated by the presence of 4 but not as much as in the case of acylations. The cause of the pronounced effect of these pyridine species in catalyzing acylation reactions seems to be a combination of the increased donor ability of the 4-substituent and the stabilizing effect that this substituent has on an acyl pyridinium intermediate.     

基于蒽-苯并咪唑鎓的荧光传感器对H2PO4-的高选择性识别

设计合成了基于蒽-苯并咪唑鎓的受体分子1和2,通过荧光发射光谱研究了受体分子1和2对F^-、Cl^-、Br^-、I^-、AcO^-、HSO₄^-、H₂PO₄^-、NO₃^-、ClO₄^-等阴离子的识别性能。 研究发现,在受体分子1和2的乙腈溶液(5.0×10^-6 mol/L)中加入10倍化学计量的H₂PO₄^-时,受体分子1的荧光猝灭百分数为13%,受体分子2的荧光猝灭百分数高达94%,表明受体分子2在构型上与H₂PO₄^-更匹配,可作为H₂PO₄^-的荧光关闭型(turn-off)探针。 受体分子2与H₂PO₄^-的结合比为1:1,结合常数为(3.70±0.16)×10⁴ L/mol,检出限为3.77×10^-6 mol/L。     

Complexation behavior of a highly preorganized 7,7-diphenylnorbornane-derived macrocycle: towards the design of molecular clocks

The syntheses of two new cyclophane hosts, 4 and 6, are described. The main difference between them is the higher degree of preorganization of 4 as a consequence of the inclusion of the 7,7-diphenylnorbornane (DPN) subunit. The inner cavity of 4 adopts a belt-shaped structure, while 6 has a twisted geometry. In the solid state, the molecules of macrocycle 6 are stacked along an axis to form nanotubular structures. Compounds 4 and 6 form two of the strongest complexes between arene cyclophanes and Ag(+) reported up to date. The silver cation is located inside the cavity of the macrocycles. The stability of 4.Ag(+) is considerably higher than that of 6.Ag(+). The additional stabilization of 4.Ag(+) is attributed to higher preorganization of macrocycle 4. DNMR experiments as well as theoretical calculations carried out with 4.Ag(+) show evidence of Ag(+)-hopping between two different binding sites inside the macrocycle. This phenomenon could be the basis for the design of molecular clocks.     

Biological role of the PAK4 signaling pathway: A prospective therapeutic target for multivarious cancers

p21 activated kinase 4 (PAK4) along with PAK5 and PAK6 are members of the type II family of PAKs. From the type II family, PAK4 is being assessed as an expansively investigated area. PAK4 acts as a serine/threonine kinase in response to Rho GTPases, while interaction partners and substrates are rapidly extended, implying a diverse range of cellular functions regulated by PAK4, including cell cycle progression, proliferation, survival, cell adhesion, motility, neuronal development, and immune defense. Thus, altered expression and function of PAK4 imparts numerous pathological conditions. The overexpressed and, in some cases, amplified PAK4 gene is revealed to be associated with a diverse range of cancers. Ongoing findings explain how PAK4 is involved in cancer progression, promoting cancer cell growth, survival, and metastasis with the corresponding activation and signaling schemes. Meanwhile, upstream activating and downstream effector molecules are increasingly identified to elucidate the exact mode of action on the cancer progression role of PAK4. A plethora of approaches targeting PAK4 is continuing to assess the potentiality of inhibitors to eradicate the growth and metastasis of cancers overexpressing PAK4. Here, we summarize the findings on the role of PAK4 and its signaling pathways promoting cancers and examine PAK4 as a promising target for multitype cancers.     

The mechanism of C--X (X=F, Cl, Br, and I) bond activation in CX4 by a stabilized dialkylsilylene

The potential-energy surfaces for the abstraction and insertion reactions of dialkylsilylene with carbon tetrahalides (CX4) have been characterized in detail using density functional theory (B3LYP), including zero-point corrections. Four CX4 species, CF4, CCl(4), CBr4, and CI(4), were chosen as model reactants. The theoretical investigations described herein suggest that of the three possible reaction paths, the one-halogen-atom abstraction (X abstraction), the one-CX3-group abstraction (CX3 abstraction), and the insertion reaction, the X-abstraction reaction is the most favorable, with a very low activation energy. However, the insertion reaction can lead to the thermodynamically stable products. Moreover, for a given stable dialkylsilylene, the chemical reactivity has been found to increase in the order CF4相似文献   

A convenient route to 4-carboxy-4-anilidopiperidine esters and acids

The route selection and development of a convenient synthesis of 4-carboxy-4-anilidopiperidines is described. Previous routes were hampered by the low yield of the target esters as well as the inability to convert the esters to the required free acids. Considerations for large-scale production led to a modified synthesis that utilised a tert-butyl ester of 4-carboxy-4-anilidopiperidines which resulted in a dramatic increase in the overall yield of the target N-propionylated- 4-anilidopiperidine-4-carboxylic acids and their corresponding methyl esters. These compounds are now available for use as precursors and reference standards, of particular value for the production of 11C and 18F-labelled 4-carboxy-4-anilidopiperidine radiotracers.     

Mechanism regulating cell surface expression and activation of Toll-like receptor 4

The Toll family of receptors senses microbial invasion and activates defense responses. Toll-like receptor 4 (TLR4) is a member of the Toll family that senses lipopolysaccharide (LPS), a principal membrane component from Gram-negative bacteria. LPS is known as an endotoxin that strongly activates immune cells such as macrophages and dendritic cells. LPS recognition by TLR4 requires an additional accessory molecule, MD-2. MD-2 is associated with the extracellular portion of TLR4, directly binds to LPS, and regulates subsequent LPS-induced TLR4 clustering. LPS recognition occurs on the cell surface. The subcellular distribution of TLR was shown to influence TLR responses. An endoplasmic reticulum (ER) chaperone, glycoprotein 96, is required for the stability of TLR4 and the formation of a TLR4/MD-2 complex in ER. MD-2 facilitates TLR4 glycosylation and its trafficking to the cell surface. Recently, another molecule, a protein associated with Toll-like receptor 4 (PRAT4A), was shown to play a critical role in cell surface expression of TLR4. These molecules control LPS responsiveness by regulating the subcellular distribution of TLR4.     

Synthetic multivalent DNAzymes for enhanced hydrogen peroxide catalysis and sensitive colorimetric glucose detection

A peroxidase-mimic DNAzyme is a G-quadruplex (G₄) DNA–hemin complex, in which the G₄-DNA resembles an apoenzyme, and hemin is the cofactor for hydrogen peroxide (H₂O₂) catalysis. Twenty-one-mer CatG4 is a well-proven G₄-DNA as well as a hemin-binding aptamer for constituting a DNAzyme. This work studied if a multivalent DNAzyme with accelerated catalysis could be constructed using a multimeric CatG4 with hemin. We compared CatG4 monomer, dimer, trimer, and tetramer, which were prepared by custom oligo synthesis, for G₄ structure formation. According to circular dichroism (CD) analysis, we found that a CatG4 multimer exhibited more active G₄ conformation than the sum effect of equal-number CatG4 monomers. However, the DNAzyme kinetics was not improved monotonically along with the subunit number of a multimeric CatG4. It was the trivalent DNAzyme, trimeric CatG4:hemin, resulting in the rapidest H₂O₂ catalysis instead of a tetravalent one. We discovered that the trivalent DNAzyme’s highest catalytic rate was correlated to its most stable hemin-binding G₄ structure, evidenced by CD melting temperature analysis. Finally, a trivalent DNAzyme-based colorimetric glucose assay with a detection limit as low as 10 μM was demonstrated, and this assay did not need adenosine 5′-tri-phosphate disodium salt hydrate (ATP) as a DNAzyme boosting agent.     

Sb在Cu单晶电极上欠电位沉积的电化学和现场STM研究

应用循环伏安法和现场扫描隧道显微镜研究了在HClO4和H2SO4两种溶液中Sb于Cu(111)和Cu(100)电极上的欠电位沉积.结果表明,不同的表面原子排列和强吸附阴离子的存在将明显影响Sb的欠电位沉积行为.在结构较为开放的Cu(100)表面,Sb形成的欠电位沉积层结构也较为开放,并且伴随着表面合金的形成;而在密堆积的Cu(111)表面上,Sb形成了致密的单层结构.又当Cu(111)表面存在强吸附的SO42-时,Sb原子首先在SO42-吸附层与Cu表面交接的新台阶处成核,随后通过取代SO42-向上一层晶面发展,表现出独特的成核—生长行为;而在弱吸附的HClO4溶液中,Sb的欠电位沉积系以在晶面上随机形成一些单原子层高度的Sb岛为特征.在Cu(100)表面,通过SO42-的诱导共吸附,欠电位沉积的Sb原子形成了开放性更大的(4×4)结构,不同于在HClO4溶液中所形成的(22×22)R45°结构.     

Thermosetting resins from a tetra-functional vinylbenzene compound possessing cyclic siloxane cores

Cyclic siloxane is an attractive building block for incorporation of silicon-containing units as well as their distinguished properties to polymer materials. This work reports the synthesis and characterization of a tetra-functional vinylbenzene compound possessing cyclic siloxane cores (cD₄-4VB). Synthesis of cD₄-4VB is carried out using cD₄-4SiH as the reactive precursor and multiple-step reactions, including hydrosilylation, deacetylation, and S_N2 substitution. cD₄-4VB is an effective monomer for preparation of the corresponding cyclic silicon-based thermosetting resins (CR-cD₄-4VB). CR-cD₄-4VB shows attractive film formability and good thermo-mechanical properties, including a storage modulus of 2.0 GPa, a glass transition temperature of 282°C, a thermal stability above 400°C, a high char yield (at 800°C in nitrogen) of 55 wt%, and a dielectric constant of 3.12 at 10 GHz. This kind of resins have potential of application for halogen-free flame retardants and high-performance polymer films.     

Current Advances towards 4-Hydroxybutyrate Containing Polyhydroxyalkanoates Production for Biomedical Applications

Polyhydroxyalkanoates (PHA) are polyesters having high promise in biomedical applications. Among different types of PHA, poly-4-hydroxybutyrate (P4HB) is the only polymer that has received FDA approval for medical applications. However, most PHA producing microorganisms lack the ability to synthesize P4HB or PHA comprising 4-hydroxybutyrate (4HB) monomer due to their absence of a 4HB monomer supplying pathway. Thus, most microorganisms require supplementation of 4HB precursors to synthesize 4HB polymers. However, usage of 4HB precursors incurs additional production cost. Therefore, researchers have adopted strategies to reduce the cost, such as utilizing low-cost substrate as well as constructing 4HB monomer supplying pathways in microorganisms. We herein summarize the biomedical applications of P4HB, the natural producers of 4HB polymer, and the various strategies that have been applied in producing 4HB polymers in non-4HB producing microorganisms. It is expected that the readers would gain a vivid idea on the different strategic developments in the field of 4HB polymer production.     

Gas phase analogs of stable sodium-tin Zintl ions: anion photoelectron spectroscopy and electronic structure

Mass spectrometry and photoelectron spectroscopy together with first principles theoretical calculations have been used to study the electronic and geometric properties of the following sodium-tin, cluster anion/neutral cluster combinations, (Na(n)Sn(4))(-)/(Na(n)Sn(4)), n = 0-4 and (NaSn(m))(-)/(NaSn(m)), m = 4-7. These synergistic studies found that specific Zintl anions, which are known to occur in condensed Zintl phases, also exist as stable moieties within free clusters. In particular, the cluster anion, (Na(3)Sn(4))(-) is very stable and is characterized as (Na(+))(3)(Sn(4))(-4); its moiety, (Sn(4))(-4) is a classic example of a Zintl anion. In addition, the cluster anion, (NaSn(5))(-) was the most abundant species to be observed in our mass spectrum, and it is characterized as Na(+)(Sn(5))(2-). Its moiety, (Sn(5))(2-) is also known to be present as a Zintl anion in condensed phases.     

Ultrafast intramolecular charge transfer and internal conversion with tetrafluoro-aminobenzonitriles.

The five 2,3,5,6-tetrafluoro-4-aminobenzonitriles XABN4F with a dimethyl-amino (DMABN4F), diethyl-amino (DEABN4F), azetidinyl (AZABN4F), methyl-amino (MABN4F) or amino (ABN4F) group undergo ultrafast intramolecular charge transfer (ICT) at room temperature, in the polar solvent acetonitrile (MeCN) as well as in the nonpolar n-hexane. ICT also takes place with the corresponding non-fluorinated aminobenzonitriles DMABN, DEABN and AZABN in MeCN, whereas for these molecules in n-hexane only minor (DMABN, DEABN) or no (AZABN) ICT fluorescence is detected. For the secondary (MABN) and primary (ABN) amines, an ICT reaction does not occur, which makes ABN4F the first electron donor/acceptor molecule with an NH(2) group for which ICT is observed. The ICT state of the XABN4Fs has a dipole moment of around 14 D, clearly smaller than that of DMABN (17 D). This difference is attributed to the electron withdrawing from the CN group to the phenyl ring, exerted by the four F-substituents. The reaction from the initially prepared locally excited (LE) to the ICT state in n-hexane proceeds in the sub-picosecond time range: 0.35 ps (DMABN4F), 0.29 ps (DEABN4F) and 0.13 ps (AZABN4F), as determined from femtosecond transient absorption measurements. In the highly polar solvent MeCN, an ICT reaction time of around 90 fs is observed for all five XABN4Fs, irrespective of the nature of their amino group. This shows that with these molecules in MeCN the ICT reaction rate is limited by the solvent dielectric relaxation time of MeCN, for which a value of around 90 fs has been reported. It is therefore concluded that, during this ultrashort ICT reaction, a large-amplitude motion such as a full 90 degrees twist of the amino group is unlikely to occur in the XABN4Fs. The ICT state of the XABN4Fs is strongly quenched via internal conversion (IC), with a lifetime tau'(0) (ICT) down to 3 ps, possibly by a reaction passing through a conical intersection made accessible due to a deformation of the phenyl group by out-of-plane motions induced by vibronic coupling between low-lying pisigma* and pipi* states in the XABN4Fs.     

Accurate-mass identification of chlorinated and brominated products of 4-nonylphenol, nonylphenol dimers, and other endocrine disrupters

LC/ToF-MS was used to identify new chlorination and bromination products of 4-nonylphenol (4-NP), such as 4-NPBr2, 4-NPBrCl, 4-NP dimer (2 isomers), 4-NPCl dimer (2 isomers), 4-NPBr dimer, and a series of methoxy bromo and chloro 4-NPs from a laboratory study of nonylphenol chlorination. The identification procedure used the exact mass, exact mass of the isotope cluster, and their relative intensities, at an average mass accuracy of approximately 1 ppm. The products were produced by a simulated study of industrial cleaning procedures where 4-NP, nonylphenol ethoxylate (NPEO-1 and 2), and nonylphenol carboxylate (NPEC-1) were in contact with sodium hypochlorite solutions (with and without bromide) of various strengths (possible environmental scenarios) at neutral pH. The formation of the products was measured as a function of chlorine concentration, and it was found that 4-NP was the most reactive, producing 4-NPCl, 4-NPCl2, 4-NP (dimers), and the 4-NPCl (dimers). In the presence of bromide ions, a mixture results with products of 4-NPBr2, 4-NPCl, 4-NPCl2, 4-NPBrCl, 4-NPBr, and a 4-NPBr dimer. Less reactive to halogenation was NPEO, which formed only the monochloro and monobromo products, and the least reactive was NPEC. A simple stereochemical model is used to explain halogenation reactivity for the family of 4-NPs and NPEOs at neutral pH. The presence of halogenated 4-NP dimers (bromo and chloro diphenyl ethers) is discussed as a possible source of new endocrine disrupters.     

The unexpected desulfurization of 4-aminothiophenols

Thermolysis of 4-aminophenyl benzyl sulfide at 523 K in the hydrogen donor solvent (HDS), 9,10-dihydroanthracene (AnH2), gave 4-aminothiophenol and toluene as the predominant products of the homolytic S-C bond cleavage. Under these conditions, a portion of the 4-aminothiophenol was desulfurized to aniline with first-order kinetics and with a rate constant estimated by kinetic modeling to be 7.0x10(-6) s-1. Starting with 4-NH2C6H4SH at 523 K, it was found that sulfur loss was more efficient in the non-HDSs, anthracene and hexadecane, than in AnH2. Under similar (competitive) reaction conditions, YC6H4SHs with Y=H, 4-CN, and 3-CF3 were completely inert; with Y=4-CH3O, there was some very minor desulfurization, whereas with Y=4-N(CH3)2 and 4-N(CH3)(H), the sulfur extrusions were as fast as that for Y=4-NH2. We tentatively suggest that this apparently novel reaction is a chain process initiated by the bimolecular formation of diatomic sulfur, S2, followed by a reversible addition of ground state, triplet 3S2 to the thiol sulfur atom, 4-NH2C6H4S upward arrow(SS upward arrow)H, and insertion into the S-H bond, 4-NH2C6H4SSSH. In a cascade of reactions, aniline and S8 are formed with the chains being terminated by reaction of 4-NH2C6H4S upward arrow(SS upward arrow)H with 4-NH2C6H4SH. Such a reaction mechanism is consistent with the first-order kinetics. That this reaction is primarily observed with 4-YC6H4SH having Y=N(CH3)2, N(CH3)(H), and NH2 is attributed to the fact that these compounds can exist as zwitterions.     

Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) is believed to be responsible for the occurrence of RA by catalyzing citrullination of proteins. The citrullinated proteins act as autoantigens by stimulating an immune response. Citrullinated α-enolase has been identified as one of the autoantigens for RA. Hence, α-enolase serves as a suitable template for design of potential peptide inhibitors against PAD4. The binding affinity of α-enolase-derived peptides and PAD4 was virtually determined using PatchDock and HADDOCK docking programs. Synthesis of the designed peptides was performed using a solid phase peptide synthesis method. The inhibitory potential of each peptide was determined experimentally by PAD4 inhibition assay and IC₅₀ measurement. PAD4 assay data show that the N-P2 peptide is the most favourable substrate among all peptides. Further modification of N-P2 by changing the Arg residue to canavanine [P2 (Cav)] rendered it an inhibitor against PAD4 by reducing the PAD4 activity to 35 % with IC₅₀ 1.39 mM. We conclude that P2 (Cav) is a potential inhibitor against PAD4 and can serve as a starting point for the development of even more potent inhibitors.