Highly efficient synthesis of linear pyrrole oligomers by twofold Heck reactions

The twofold Heck reaction of the vinylpyrroles 3a and 3b with the iodobenzenes 4a-c led to the linear pyrrole oligomers 5, 6, and 7. The synthesis of both symmetrical and unsymmetrical oligomers, such as 10a and 10b, was also accomplished by a Heck reaction of 8 and 9 and by a Heck reaction of 3a and 11 followed by a Wittig reaction and a second Heck reaction with 8. The pentacyclic oligomers 14 and 19 were prepared by a twofold Heck reaction of 13 with 4 and by a twofold Heck reaction of 15 with 16 followed by a Wittig reaction and a twofold Heck reaction with 8.     

Influence of preparative conditions on molecular weight and stereoregularity distributions of polypropylene

The influence of preparative conditions on the molecular weight and stereoregularity distributions of polypropylene was investigated. The stereoregularity distribution is narrowed by using a highly stereospecific catalyst, by decreasing the polymerization temperature, and for the three-component catalyst by keeping the mole proportion of the electron-donating third component at 0.5. The molecular weight distribution can be narrowed by using a highly stereospecific catalyst, a high monomer concentration, and a high polymerization temperature, and by having a lower conversion, particularly at low monomer concentration. The possibility of long-chain branching in polypropylene was indicated by data from the fractionation of tritium-labeled polymers.     

Back-electron transfer suppresses the periodic length dependence of DNA-mediated charge transport across adenine tracts

DNA-mediated charge transport (CT) is exquisitely sensitive to the integrity of the bridging pi-stack and is characterized by a shallow distance dependence. These properties are obscured by poor coupling between the donor/acceptor pair and the DNA bridge, or by convolution with other processes. Previously, we found a surprising periodic length dependence for the rate of DNA-mediated CT across adenine tracts monitored by 2-aminopurine fluorescence. Here we report a similar periodicity by monitoring N 2-cyclopropylguanosine decomposition by rhodium and anthraquinone photooxidants. Furthermore, we find that this periodicity is attenuated by consequent back-electron transfer (BET), as observed by direct comparison between sequences that allow and suppress BET. Thus, the periodicity can be controlled by engineering the extent of BET across the bridge. The periodic length dependence is not consistent with a periodicity predicted by molecular wire theory but is consistent with a model where multiples of four to five base pairs form an ideal CT-active length of a bridging adenine domain.     

A nanocatalyst-based assay for proteins: DNA-free ultrasensitive electrochemical detection using catalytic reduction of p-nitrophenol by gold-nanoparticle labels

This communication reports a nanocatalyst-based electrochemical assay for proteins. Ultrasensitive detection has been achieved by signal amplification combined with noise reduction: the signal is amplified both by the catalytic reduction of p-nitrophenol to p-aminophenol by gold-nanocatalyst labels and by the chemical reduction of p-quinone imine to p-aminophenol by NaBH4; the noise is reduced by employing an indium tin oxide electrode modified with a ferrocenyl-tethered dendrimer and a hydrophilic immunosensing layer.     

Enantiomer systems of carnitinamide inorganic salts: introductory studies to a successful entrainment resolution

The ready availability of (R)-carnitinamide, an immediate synthetic precursor of (R)-carnitine, is an ambitious goal and resolutions, due to the very low cost of racemic carnitinamide, can be the most convenient technology to achieve it. Before developing a new advantageous resolution of carnitinamide chloride by entrainment, we characterized the enantiomer systems formed by the chloride, nitrate and sulfate of carnitinamide, mainly by DSC and IR analyses, proving that a different type of racemate is produced by each of these salts: a conglomerate by the chloride, a racemic compound by the nitrate and a solid solution, a very rare type of enantiomer system, by the sulfate.     

Direct Combination of a High Performance Liquid Chromatograph and a Circular Dichroism Spectrometer for Separation and Structural Analysis of Proteins

Abstract

Basic studies of the combined system of a high performance liquid chromatograph (HPLC) and a circular dichroism (CD) spectrometer for separation and analysis of proteins are described. The HPLC-CD measurement of standard protein mixture was easily carried out by using a micro flow-cell device with a beam condenser and with a thin cell of a 1 mm-optical path. The effluent was firstly monitored at 280 nm by using an UV detector and subsequently monitored at 220 nm by using a CD spectrometer. The CD spectrum at each chromatographic peak by CD was measured in the wavelength region of 250–195 nm by a stopped flow method.     

Models for Oscillating Polymerization: Activation by Product in a System with Flow

In this work, four polymerization mechanisms with flow are proposed where sustained oscillation can be present: (1) Polyaddition initiated by radicals produced by initiator decomposition, which is catalyzed by the polymer, first‐order termination, a polymer disappears by a reaction with a third substance and by leaving the system in the exit flow. (2) Polycondensation where the polymer has catalytic activity upon H to produce a monomer, first‐order termination and a monomer disappears by a reaction with a third substance, and there is exit flow for all the species. (3) Polycondensation with catalytic activity of the polymer upon A to produce a monomer, first‐order termination, conformational transitions of the polymers, one of the polymer conformations disappears by a reaction with a monomer and exit flow for all the species. (4) Polycondensation combined with polyaddition where the polycondensation polymer product has catalytic activity on the monomer, first‐order termination and exit flow of all the species.     

Microphase separation during the concurrent formation of two polymer networks

As a rule, interpenetrating polymer networks (IPNs) are multiphase systems, and the degree of microphase separation is determined by the competition between the chemical kinetics of reaction and the physical kinetics of phase separation. For semi-IPNs of crosslinked polyurethane and linear polystyrene obtained by a one-step process, the development of the morphology has been followed by light transmission measurements and by optical microscopy, and finally examined by scanning electron microscopy. When phase separation takes place after gelation, the rather short elastic chains of polyurethane limit the growth of the styrenic phase at a submicroscopic level and the materials thus formed are transparent. On the contrary, when the reaction medium can phase-separate before gelation of polyurethane, the final morphology results from a superposition of two levels of phase separation: i) a fine dispersion of the components and ii) a gross phase separation of polystyrene noduli surrounded by a polyurethane-rich shell.     

The use of radioactive bacteriophage proteins as X-Y markers for silver stained two-dimensional electrophoresis gels and quantification of the patterns.

We have demonstrated the feasibility of using bacteriophage ghost proteins, tritiated by metabolic labeling, as a set of standard markers for two-dimensional gels in which the proteins are to be detected by silver staining. The results indicate that a 2.5 microgram load of phage proteins yields a reproducible silver pattern of 48 spots. The spots can also be readily identified by radioautography and radiofluorography, establishing their value as a standard constellation of markers. Quantification of these patterns by computerized densitometry indicates a general agreement between detection by silver staining and detection by radiofluorography.     

Unidirectional redox-stimulated movement around a C-C single bond

A remarkable challenge for the design of molecular machines is the realization of a synchronized and unidirectional movement caused by an external stimulus. Such a movement can be achieved by a unidirectionally controlled change of the conformation or the configuration. Biphenol derivatives are one possibility to realize a redox-driven unidirectional molecular switch. For this reason, a 4,4'-biphenol derivative was fixed to a chiral cyclopeptidic scaffold and stimulated by chemical oxidants and reduction agents. The conformation of the switch was determined by DFT calculations by using B3LYP and the 6-31G* basis set. The switching process was observed by UV and circular dichroism (CD) spectroscopic measurements. Several oxidation agents and various conditions were tested, among which (diacetoxy)iodobenzene (DAIB) in methanol proved to be the best. In this way it was possible to synthesize a redox-stimulated molecular switch with a movement that is part of a rotation around a biaryl binding axis.     

Photochemical micropatterning of carbohydrates on a surface

In this report, we demonstrate a versatile method for the immobilization and patterning of unmodified carbohydrates onto glass substrates. The method employs a novel self-assembled monolayer to present photoactive phthalimide chromophores at the air-monolayer interface. Upon exposure to UV radiation, the phthalimide end-groups graft to surface-adsorbed carbohydrates, presumably by a hydrogen abstraction mechanism followed by radical recombination to form a covalent bond. Immobilized carbohydrate thin films are evidenced by fluorescence, ellipsometry and contact-angle measurements. Surface micropatterns of mono-, oligo-, and polysaccharides are generated by exposure through a contact photomask and are visualized by condensing water onto the surface. The efficiency of covalent coupling is dependent on the thermodynamic state of the surface. The amount of surface-grafted carbohydrate is enhanced when carbohydrate surface interactions are increased by the incorporation of amine-terminated molecules into the monolayer. Glass substrates modified with mixed monolayers of this nature are used to construct carbohydrate microarrays by spotting the carbohydrates with a robot and subsequently illuminating them with UV light to covalently link the carbohydrates. Surface-immobilized polysaccharides display well-defined antigenic determinants for antibody recognition. We demonstrate, therefore, that this novel technology combines the ability to create carbohydrate microarrays using the current state-of-the-art technology of robotic microspotting and the ability to control the shape of immobilized carbohydrate patterns with a spatial resolution defined by the UV wavelength and a shape defined by a photomask.     

Reaction of aminodihydropentalenes with HB(C6F5)2: the crucial role of dihydrogen elimination

The aminodihydropentalene derivative 1a reacts with the Lewis acidic RB(C(6)F(5))(2) boranes (2a-c) by C-C bond cleavage to yield the formal borylene insertion products 3. In contrast, 1a,b react with HB(C(6)F(5))(2) at 55 °C by elimination of dihydrogen to yield the iminium-stabilized zwitterionic heterofulvenes 10a,b. The reaction pathways were studied by preparation of the kinetically controlled intermediates 7a,b and the thermodynamically controlled products 9a,b, monitored by variable-temperature NMR experiments, and supported by DFT calculations. The trapping reactions of 9a with HCl and PhCHO, respectively, led to the addition products 13 and 14. Compounds 3c, 7a,b, 10a,b, 11, 13, and 14 were characterized by X-ray diffraction.     

Patterning biomolecules with a water-soluble release and protection interlayer

We report on a general lithography method for high-resolution biomolecule patterning with a bilayer resist system. Biomolecules are first immobilized on the surface of a substrate and covered by a release-and-protection interlayer of water-soluble polymer. Patterns can then be obtained by lithography with a spin-coated resist layer in a conventional way and transferred onto the substrate by reactive ion etching. Afterward, the resist layer is removed by dissolution in water. To demonstrate a high-resolution patterning, soft UV nanoimprint lithography has been used to produce high-density dot arrays of poly-(L-lysine) molecules on a glass substrate. Both fluorescence images and cell proliferation behaviors on such a patterned substrate have shown evidence of improved stability of biomolecule immobilization comparing to that obtained by microcontact printing techniques.     

Synthesis of cationic porphyrin modified amino acids

Derivatives of amino acids bearing a porphyrin moiety on a side chain were synthesized by coupling a porphyrin to a glutamic acid side chain; the utility of these compounds was demonstrated by their use in solid-phase synthesis of a peptide bearing a cationic porphyrin and by studying its DNA-binding properties.     

A Total Synthesis of FK-506(1)

A total synthesis of FK-506 (1) is presented. The synthesis features a highly convergent approach utilizing a block coupling strategy. Top and bottom half sections of the molecule are coupled by addition of a vinyl cuprate with a spiroenone. The alpha-allyl aldol functionality is revealed by a reductive opening of the spiroenone system. The labile alpha,beta-diketoamide hemiketal portion of the molecule is prepared by a late stage generation and oxidation of a masked enediol. Top and bottom half segments are themselves derived by coupling of smaller subunits, resulting in a very convergent route.     

Scavenger-receptor targeted photodynamic therapy

Covalent conjugation of a photosensitizer to a ligand that specifically recognized and internalized by a cell-surface receptor may be a way of improving the selectivity of photodynamic therapy (PDT). The class A Type-I scavenger receptor of macrophages, which among other ligands recognizes maleylated serum albumin and has a high capacity is a good candidate for testing this approach. Chlorin(e6) was covalently attached to bovine serum albumin to give conjugates with molar substitution ratios of 1:1 and 3:1 (dye to protein), and these conjugates could then be further modified by maleylation. A novel way of purifying the conjugates by acetone precipitation was developed in order to remove traces of unbound dye that could not be accomplished by size-exclusion chromatography. Conjugates were characterized by polyacrylamide gel electrophoresis and thin-layer chromatography. Photosensitizer uptake was measured by target J774 murine macrophage-like cells and nontarget OVCAR-5 human ovarian cancer cells, and phototoxicity was examined after illumination by a 660 nm diode laser by a tetrazolium assay. All of the purified conjugates were taken up by and after illumination killed J774 cells while there was only small uptake and no phototoxicity toward OVCAR-5 cells. The higher dye:protein ratio and maleylation of the conjugates both produced higher uptakes and lower survival ratios in J774 cells. The uptake and phototoxicity by J774 cells were decreased after incubation at 4 degrees C demonstrating internalization, and confocal microscopy with organelle-specific green fluorescent probes showed largely lysosomal localization. Uptake and phototoxicity by J774 cells could both be competed by addition of the scavenger receptor ligand maleylated albumin. These data show that scavenger receptor-targeted PDT gives a high degree of specificity toward macrophages and may have applications in the treatment of tumors and atherosclerosis.     

Conditions for the onset of current oscillations at the limiting current of the iron electrodissolution in sulfuric acid solutions

The experimental conditions and parameters that control the transition from a steady to an nonsteady limiting current and vice versa in the anodic Fe dissolution are studied in sulfuric acid solutions by using a downward-facing Fe electrode. Periodic and chaotic current oscillations are observed at the beginning of the limiting current region within a fixed potential region by decreasing the sulfuric acid concentration, by increasing the Fe-disk rotation rate and by increasing a series external resistance. It is found that current oscillations emerge when theIR drop exceeds a critical value (IR)_crit. The latter depends on the hydrodynamic conditions pertaining to the system. This is realized by the differences appeared in the value of (IR)_crit on using a stationary or a rotating Fe electrode. The effect of hydrodynamic conditions is shown by additional experimental results obtained by using an upward-facing Fe electrode, by increasing the density and viscosity of the solution on addition of glycerol, and by altering the solution properties near the Fe surface on addition of halide ions. Dedicated to the ninetieth anniversary of Ya.M. Kolotyrkin’s birth. This article was submitted by the authors in English.     

功能性CdSe纳米晶的合成及自组装膜光致发光

以巯基丙酸(RSH)为稳定剂,采用湿化学法合成了功能性CdSe纳米晶,用XRD、TEM表征其粒度和形貌,用UV-Vis监测成核及成膜过程。结果表明：制得的CdSe近似呈球形,平均粒径为48 nm。利用静电自组装法层层组装成CdSe-PDDA复合膜,荧光测试表明：所得CdSe纳米晶自组装复合膜(CdSe-PDDA)的荧光强度随着组装层数的增加而呈线性增强,该复合膜在582 nm附近有黄绿色荧光发射。     

Magnetic targeting and cellular uptake of polymer microcapsules simultaneously functionalized with magnetic and luminescent nanocrystals

By using a flow channel system for modeling the bloodstream in the circulatory system and by locally creating a magnetic field gradient caused by a permanent magnet, we demonstrate specific trapping of polymer capsules simultaneously functionalized with two types of nanoparticles--magnetic and luminescent nanocrystals. In the regions where the capsules were trapped by the magnetic field, drastically increased uptake of capsules by cells has been observed. The uptake of capsules by cells could be conveniently monitored with a fluorescence microscope by the luminescence of CdTe nanocrystals that had been embedded into the shells of the capsules. Our experiments envisage the feasibility of magnetic targeting of polymer capsules loaded by pharmaceutical agents to pathogenic parts of a tissue.     

High-performance liquid chromatography of sulphadimethoxine and its N1-glucuronide, N4-acetyl and N4-acetyl-N1-glucuronide metabolites in human plasma and urine

Sulphadimethoxine is metabolized in humans by N1-glucuronidation and by N4-acetylation. Sulphadimethoxine-N1-glucuronide can be measured by the direct high-performance liquid chromatographic analysis and without enzymic deglucuronidation. The N1-glucuronide can be measured by an isocratic as well as by a gradient mobile phase. The group contribution of the N1-glucuronide moiety to the capacity factor is a reduction of 0.24 in the isocratic system and 0.55 in the gradient system. N4-Acetylation increases the capacity factor by a factor 1.4 in the isocratic system and by 1.06 in the gradient system.