Catalytic Oxidation of Iron(II) Aqua Complex by Oxygen in the Presence of Palladium(II) Tetraaqua Complex

The catalytic oxidation of iron(II) with oxygen occurs along with an autocatalytic reaction between palladium(II) tetraaqua complex and iron(II) aqua complex in an oxygen atmosphere. The reaction is catalyzed by a compound of palladium in an intermediate oxidation state, presumably by a small palladium cluster formed in the course of the reduction of palladium(II) tetraaqua complex with iron(II) aqua complex.     

DpgC is a metal- and cofactor-free 3,5-dihydroxyphenylacetyl-CoA 1,2-dioxygenase in the vancomycin biosynthetic pathway

3,5-Dihydroxyphenylglycine is a crucial amino acid monomer in the nonribosomal glycopeptide antibiotic vancomycin. This nonproteinogenic amino acid is constructed from malonyl-CoA by a set of four enzymes, DpgA-D, in the biosynthetic cluster. DpgC is an unusual metal-free, cofactor-free enzyme that consumes O(2) during the conversion of 3,5-dihydroxyphenylacetyl-CoA (DPA-CoA) to the penultimate intermediate 3,5-dihydroxyphenylglyoxylate (DPGx). We show that in anaerobic incubations, DpgC catalyzes the exchange of the C(2)-methylene hydrogens of DPA-CoA at unequal rates, consistent with enzyme-mediated formation of the substrate-derived C(2)-carbanion as an early intermediate. Incubations with (18)O(2) reveal that DpgC transfers both atoms of an O(2) molecule to DPGx product. This establishes DpgC as a 1,2-dioxygenase that mediates thioester cleavage by the oxygen transfer process. These results are consistent with a DPA-CoA C(2)-peroxy intermediate, followed by enzyme-directed alpha-peroxylactone formation and collapse by O-O bond cleavage.     

Reaction mechanism and kinetics of the traceless Staudinger ligation

The traceless Staudinger ligation enables the formation of an amide bond between a phosphinothioester (or phosphinoester) and an azide without the incorporation of residual atoms. Here, the coupling of peptides by this reaction was characterized in detail. Experiments with [(18)O]H(2)O indicated that the reaction mediated by (diphenylphosphino)methanethiol proceeded by S-->N acyl transfer of the iminophosphorane intermediate to form an amidophosphonium salt, rather than by an aza-Wittig reaction and subsequent hydrolysis of the resulting thioimidate. A continuous (13)C NMR-based assay revealed that the rate-determining step in the Staudinger ligation of glycyl residues mediated by (diphenylphosphino)methanethiol was the formation of the initial phosphazide intermediate. Less efficacious coupling reagents and reaction conditions led to the accumulation of an amine byproduct (which resulted from a Staudinger reduction) or phosphonamide byproduct (which resulted from an aza-Wittig reaction). The Staudinger ligation mediated by (diphenylphosphino)methanethiol proceeded with a second-order rate constant (7.7 x 10(-3) M(-1) s(-1)) and yield (95%) that was unchanged by the addition of exogenous nucleophiles. Ligations mediated by phosphinoalcohols had lower rate constants or less chemoselectivity. Accordingly, (diphenylphosphino)methanethiol was judged to be the most efficacious known reagent for effecting the traceless Staudinger ligation.     

Using hierarchical self-assembly to form three-dimensional lattices of spheres

This paper describes an approach to the fabrication of three-dimensional (3-D) structures of millimeter-scale spherical beads having a range of lattices-tetragonal, cubic, and hexagonal-using hierarchical self-assembly. The process has five steps: (i) metal-coated beads are packed in a rod-shaped cavity in an elastomeric polymer (poly(dimethylsiloxane), PDMS); (ii) the beads are embedded in a second polymer (PDMS or polyurethane, PU) using a procedure that leaves the parts of the beads in contact with the PDMS exposed; (iii) the exposed areas of the beads are coated with a solder having a low melting point; (iv) the polymer rods-with embedded beads and exposed solder drops-are suspended in an approximately isodense medium (an aqueous solution of KBr) and allowed to self-assemble by capillary interactions between the drops of molten solder; and (v) the assembly is finished by several procedures, including removing the beads from the polymer matrix by dissolution, filling the voids left with another material, and dissolving the matrix. The confinement of the beads in regular structures in polymer rods makes it possible to generate self-assembled structures with a variety of 3-D lattices; the type of the lattice formed can be controlled by varying the size of the beads, and the size and shape of the cross-section of the rods.     

Design, synthesis, evaluation, and structure of vitamin D analogues with furan side chains

Based on the crystal structures of human vitamin D receptor (hVDR) bound to 1α,25-dihydroxy-vitamin D(3) (1,25 D) and superagonist ligands, we previously designed new superagonist ligands with a tetrahydrofuran ring at the side chain that optimize the aliphatic side-chain conformation through an entropy benefit. Following a similar strategy, four novel vitamin D analogues with aromatic furan side chains (3a, 3b, 4a, 4b) have now been developed. The triene system has been constructed by an efficient stereoselective intramolecular cyclization of an enol triflate (A-ring precursor) followed by a Suzuki-Miyaura coupling of the resulting intermediate with an alkenyl boronic ester (CD-side chain, upper fragment). The furan side chains have been constructed by gold chemistry. These analogues exhibit significant pro-differentiation effects and transactivation potency. The crystal structure of 3a in a complex with the ligand-binding domain of hVDR revealed that the side-chain furanic ring adopts two conformations.     

A sialylation study of mouse brain gangliosides by MALDI a-TOF and o-TOF mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) process of sialoglycoconjugates is generally accompanied by different levels of cleavage of sialic acid residues and/or by dehydration, and decarboxylation reactions. Quantitative densitometry of the mouse brain ganglioside (MBG) components separated by high-performance thin layer chromatography (HPTLC) and evidenced by orcinol staining was a basis to verify the ganglioside composition pattern with respect to the relative abundances of individual components in the mixture. A systematic mass spectrometry (MS) sialylation analysis has been carried out to evaluate the feasibility of an axial time-of-flight (a-TOF) MS, equipped with a vacuum MALDI source and an orthogonal-TOF (o-TOF) instrument with an ion source operated at about 1 mbar of N(2). Besides, the esterification by one methyl group of the carboxyl group in sialic acid to increase the stability of the ganglioside species for MALDI MS analysis has been tested and the yield of intact ganglioside species and of the neutral loss of water and carbon dioxide estimated. For the sialylation analysis of native ganglioside mixtures the MALDI o-TOF analysis with 6-azo-2-thiothymine/diammonium citrate (ATT/DAC) as a matrix appears as an optimal approach for ganglioside profiling.     

Fluorescent nanoparticle adhesion assay: a novel method for surface pKa determination of self-assembled monolayers on silicon surfaces

Since the computer industry enables us to generate smaller and smaller structures, silicon surface chemistry is becoming increasingly important for (bio-)analytical and biological applications. For controlling the binding of charged biomacromolecules such as DNA and proteins on modified silicon surfaces, the surface pK(a) is an important factor. Here we present a fluorescent nanoparticle adhesion assay as a novel method to determine the surface pK(a) of silicon surfaces modified with weak acids or bases. This method is based upon electrostatic interactions between the modified silicon surface and fluorescent nanoparticles with an opposite charge. Silicon slides were modified with 3-aminopropyltriethoxysilane (APTES) and were further derivatized with succinic anhydride. Layer thickness of these surfaces was determined by ellipsometry. After incubating the surfaces with an amine-reactive fluorescent dye, fluorescence microscopy revealed that the silicon surfaces were successfully modified with amine- and carboxyl-groups. Two surface pK(a) values were found for APTES surfaces by the fluorescent nanoparticle adhesion assay. The first surface pK(a) (6.55 ± 0.73) was comparable with the surface pK(a) obtained by contact angle titration (7.3 ± 0.8), and the second surface pK(a) (9.94 ± 0.19) was only found by using the fluorescent nanoparticle adhesion assay. The surface pK(a) of the carboxyl-modified surface by the fluorescent nanoparticle adhesion assay (4.37 ± 0.59) did not significantly differ from that found by contact angle titration (5.7 ± 1.4). In conclusion, we have developed a novel method to determine the surface pK(a) of modified silicon surfaces: the fluorescent nanoparticle adhesion assay. This method may provide a useful tool for designing pH-dependent electrostatic protein and particle binding/release and to design surfaces with a pH-dependent surface charge for (bio-)analytical lab-on-a-chip devices or drug delivery purposes.     

Hammett correlations in the photosensitized oxidation of 4-substituted thioanisoles

Singlet oxygen is quenched by a series of 4-substituted thioanisoles (methoxy to nitro), with rate constant k(t) = 7 x 10(4) to 7 x 10(6) M(-)(1) s(-)(1), close to the value observed for the myoglobin-catalyzed sulfoxidation of the same sulfides. Correlations with sigma (rho = -1.97) and with E(ox) (slope -3.9 V(-)(1)) are evidence for an electrophilic mechanism. In methanol sulfoxides are formed (85%) via an intermediate quenched by diphenyl sulfoxide; competing minor paths lead to arylthiols, arylsulfenic acid, and aryl sulfoxides. In aprotic solvents, the sulfoxidation is quite sluggish, but carboxylic acids (mostly 100. The protonated persulfoxide is formed in this case and acts as an electrophile with sulfides, again with a rate constant correlating with sigma (rho = -1.78).     

Development of a decarboxylative palladation reaction and its use in a Heck-type olefination of arene carboxylates

The development of a palladium-catalyzed decarboxylative coupling reaction of arene carboxylates with olefinic substrates is described. The optimized procedure for decarboxylative palladation employs Pd(O2CCF3)2 as catalyst (0.2 equiv) in the presence of Ag2CO3 (3 equiv) in the solvent 5% DMSO-DMF and proceeds at temperatures of 80-120 degrees C with a wide range of arene carboxylates and alkenes as substrates. The process is proposed to proceed by an initial Ar-SE reaction involving ipso attack of an electrophilic Pd(II) intermediate on an arene carboxylate to form an arylpalladium(II) species with loss of carbon dioxide. This intermediate is then proposed to react with an olefinic substrate by steps common to the Heck coupling process. Reoxidation of the liberated Pd(0) in situ is proposed to establish the catalytic cycle.     

Synthesis of polyaspartate macromonomer having a vinyl end group and application to dispersion copolymerization of styrene

Sodium polyaspartate (PAspNa) macromonomer with an acryloyl end group was synthesized for dispersion polymerization. At first, a poly(succinimide) (PSI) derivative with a hydroxyphthalimide end group was synthesized by polycondensation of l-aspartic acid and 4-hydroxyphthalic acid. Then, the PSI derivative was end-capped with an acryloyl group by a reaction with acrlyloyl chloride. Finally, a PAspNa derivative with a vinyl end group was synthesized by a hydrolysis of succinimide units by sodium hydroxide. The synthesized macromonomer was applied as a polymerizable stabilizer in dispersion copolymerization of styrene in a mixture of ethanol and water. The PAspNa macromonomer acted as an effective stabilizer and gave sub-micron-sized polymeric particles in dispersion polymerization in polar medium.     

Crystal structures of triazine-3-thione derivatives by reaction with copper and cobalt salts

The reaction of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione L1H2OCH3 with copper(II) chloride leads to the formation of an organic molecule L2 containing two triazine rings linked by a new S-S bond. A binuclear copper(II) complex, 1, containing L1 is also isolated. The reaction of L1H2OCH3 with copper(I) chloride yields a hexanuclear cluster of copper(I), 2, in which the copper atoms form a distorted octahedron with the ligand L1 acting as an NS chelate and sulfur bridge, giving to the copper ion a trigonal geometry by one N and two S atoms. In any reaction of the disulfide L2 with metal salts, complexes containing this molecule are isolated. Reactions with copper(I) and copper(II) chloride and nickel(II) and cadmium(II) nitrate produce the S-S bond cleavage, giving complexes containing the triazine L1 behaving as the NS anion, which show spectroscopic characteristics identical with those formed by reaction with L1H2OCH3. However, the reaction with cobalt(II) nitrate gives a low-spin octahedral cobalt(III) complex, in which an asymmetric rupture of the disulfide L2 has been produced, giving an unexpected complex with a new ligand and keeping the S-S bond.     

Synthesis of a dimeric Lewis antigen and the evaluation of the epitope specificity of antibodies elicited in mice

The Lewis(y)-Lewis(x) heptasaccharide, modified by an artificial aminopropyl spacer, was synthesized by an approach that employed two orthogonally protected lactosamine building blocks. A p-(benzoyl)-benzyl glycoside was used as a novel anomeric protecting group, which could be selectively removed at a late stage in the synthesis, thus offering the benefit of enhanced flexibility. The artificial aminopropyl moiety was modified by a thioacetyl group, which allowed an efficient conjugation to keyhole limpet hemocyanin (KLH) that had been activated with electrophilic 3-(bromoacetamido)-propionyl groups. Mice were immunized with the Le(y)Le(x)-BrAc-KLH antigen. Analysis of the sera by ELISA established that a strong helper T-cell immune response was raised against the Le(y)Le(x) saccharide. Further ELISA analysis showed that the titer for monomeric Le(y) tetrasaccharide was tenfold lower whereas recognition of the Le(x) trisaccharide was negligible.     

Characterization of the switch in the mechanism of an intramolecular Diels-Alder reaction

Changing the dienophile moiety of an intramolecular Diels-Alder (IMDA) cycloaddition from an allyl ether to an allenyl ether can dramatically change the regioselectivity. We hereby show by density functional theory computations that such unprecedented divergence is produced by an underlying change in the mechanism of the reaction. The allyl ether yields a fused tetrahydrofuran through a classical Diels-Alder reaction, whereas the allenyl ether yields a (methylidene)tetrahydropyran through a stepwise process. The latter reaction involves an extreme asynchronism in the bond-forming events with a diradicaloid intermediate that is stabilized by conjugation and synergistic (captodative) effects. Comparison with intermolecular model D-A reactions, which are concerted processes with various degrees of asynchrony, helps explain the change in regioselectivity for the IMDA reaction of allyl systems and the shift in mechanism for the IMDA reaction of the allenyl derivatives studied.     

QUENCHING OF PHOTOEXCITED 4,4'-DICARBOXY-2,2'-BIPYRIDINEBIS(2,2'-BIPYRIDINE)RUTHENIUM(II) BY OXYGEN IN AQUEOUS SOLUTION AND IN SILK FIBROIN MEMBRANE

Abstract— Photoluminescence and quenching of 4,4'-dicarboxy-2,2'-bipyridinebis(2,2'-bipyridine)-ruthenium(II) complex (Ru(DCbpy)(bpy)²₂⁺) in an aqueous solution as well as in a silk fibroin membrane were studied. Emission quenching by oxygen in an aqueous solution showed a linear relationship with respect to oxygen concentration. When the complex was incorporated into a silk fibroin membrane by adsorption from an aqueous solution into a preformed membrane, the photoexcited state of the complex was not quenched by oxygen in an aqueous phase. However, when the complex was incorporated into a silk fibroin membrane by casting a mixture of the complex and silk fibroin, the photoexcited complex was quenched by oxygen in an aqueous phase. In this case the Stern-Volmer plots showed a downward-deviating curve indicating heterogeneity of the probe site. Emission intensity decreased with an increase of the water content in the silk fibroin membrane.     

HPLC study of tyrosinase inhibition by thiopronine

Thiopronine (N-2-mercaptopropionyl-glycine, NMPG) inhibits the o-dihydroxy-phenolase activities of mushroom tyrosinase. When d,l-3-4-dihydroxyphenylalanine (DOPA) is employed as substrate, the inhibition was found to be a competitive-type with K(i) of 0.95 micro m. We found in addition that thiopronine interacts with the enzymatic generated product (o-quinone) to form a colourless conjugate compound causing an apparent inhibition. These data suggest that thiopronine inhibits mushroom tyrosinase activity in two ways: (1) by forming an adduct with dopaquinone; and (2) by direct interaction with the enzyme probably towards the copper (II) present in the active site or cysteine-rich domains. This finding was indicated by the presence of a lag period prior to the attainment of an inhibited steady-state rate. Both lag period and steady-state rate were dependent on thiopronine and substrate concentrations. An increase of thiopronine concentration causes longer lag periods as well as a concomitant decrease in the tyrosinase activity. The presence of an excess of copper (II) reverses the inhibition exerted by thiopronine.     

Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by beta-bromo alcohols. The resulting esters undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a beta-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 --> 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the cyclization product.     

Highly efficient and selective epoxidation of alkenes by photochemical oxygenation sensitized by a ruthenium(II) porphyrin with water as both electron and oxygen donor

Visible light irradiation of a reaction mixture of carbonyl-coordinated tetra(2,4,6-trimethyl)phenylporphyrinatoruthenium(II) (Ru(II)TMP(CO)) as a photosensitizer, hexachloroplatinate(IV) as an electron acceptor, and an alkene in alkaline aqueous acetonitrile induces selective epoxidation of the alkene with high quantum yield (Phi = 0.6, selectivity = 94.4% for cyclohexene and Phi = 0.4, selectivity = 99.7% for norbornene) under degassed conditions. The oxygen atom of the epoxide was confirmed to come from a water molecule by an experiment with H(2)(18)O. cis-Stilbene was converted into its epoxide, cis-stilbeneoxide, without forming trans-stilbeneoxide. trans-Stilbene, however, did not exhibit any reactivity. Under neutral conditions, an efficient buildup of the cation radical of Ru(II)TMP(CO) was observed at the early stage of the photoreaction, while an addition of hydroxide ion caused a rapid reaction with the cation radical to promote the reaction with reversion to the starting Ru(II)TMP(CO). A possible involvement of a higher oxidized state of Ru such as Ru(IV), Ru(V), Ru(VI) through a dismutation of the Ru(III) species was excluded by an experiment with Ru(VI)TMP(O)(2). Decarbonylation of the Ru complex was also proven to be invalid. A reaction mechanism involving an electron transfer from the excited triplet state of Ru(II)TMP(CO) to hexachloroplatinate(IV) and subsequent formation of OH(-)-coordinated Ru(III) species, leading to an oxo-ruthenium complex as the key intermediate of the photochemical epoxidation, was postulated.     

Rapid preparation of multifunctional surfaces for orthogonal ligation by microcontact chemistry

Microcontact chemistry has been applied to patterned glass and silicon substrates by successive reaction of unprotected and monoprotected heterobifunctional linkers with alkene-terminated self-assembled monolayers (SAMs) to produce bi-, tri-, and tetrafunctional surfaces. Photochemical microcontact printing of an azide thiol linker followed by immobilization of an acid thiol linker on an undecenyl-terminated SAM results in a well-defined, micropatterned surface with terminal azide, acid, and alkene groups. Biologically relevant molecules (biotin, carbohydrates) have been selectively attached to the surface by means of orthogonal ligation chemistry, and the resulting microarrays display selective binding to fluorescently labeled proteins. An orthogonally addressable, tetrafunctional surface (azide, acid, alkene, and amine) can be prepared by an additional printing step of a tert-butyloxycarbonyl (Boc)-protected alkyne amine linker on the azide structures by using the copper(I)-catalyzed azide-alkyne Huisgen cycloaddition and subsequent removal of the protective group.     

Electrochemical antioxidant detection technique based on guanine-bonded graphene and magnetic nanoparticles composite materials

An antioxidant (AO) amperometric technique based on guanine attached to graphene and Fe(3)O(4) nanoparticles (NPs) magnetic materials was developed. Guanine molecules acted as an antioxidant competitor were bonded with graphene nanosheets, onto which magnetic Fe(3)O(4) NPs were attached and the as-prepared magnetic composite can be attracted to the electrode surface by an external magnetic field. When applied with negative potentials, the dissolved oxygen was reduced to H(2)O(2) at the electrode surface, and then reacted with the EDTA-Fe(ii) complex via a Fenton-like reaction to produce OH radicals. After oxidation damage by OH radicals, the electrochemical oxidation of guanine gave a decreased current. In the presence of AOs, the reactive oxygen species (ROS, e.g. OH radicals and H(2)O(2)) were scavenged by AOs and fewer guanine probe molecules were oxidized, thus inducing a higher electrochemical oxidation current of guanine. So AOs competed with the guanine probe molecules toward oxidation by ROS. The current signals of the guanine probe molecules were proportional to the concentrations of AOs. A kinetic model was proposed to quantify the ROS scavenging capacities of the AOs. Using guanine as an oxidizable probe and OH radicals and H(2)O(2) as endogenous ROS, this kind of AO detection technique mimicks the antioxidant protection mechanism by small AO molecules in the human body.     

Synthesis and characterization of phthalocyanines with direct Si-Si linkages

Several cofacial phthalocyanines (Pcs) with an Si-Si linkage were obtained by one-step condensation of 1H-isoindole-1,3(2H)-diimine with hexachlorodisilane as template in quinoline. They were characterized by gel-permeation chromatography, IR, NMR spectroscopy, and mass spectrometry, and cyclic voltammetry. The results strongly suggest that we indeed obtained Pc dimers directly linked by an Si-Si bond using this novel concept of utilizing a compound/salt with an element-element bond as a template. The cofacial dimer structures are reasonably supported by X-ray absorption near-edge structure (XANES), electronic absorption and magnetic circular dichroism (MCD) spectra, and molecular orbital (MO) calculations. Interestingly, they show an electronic absorption spectrum very similar to that of silicon tetrabenztriazacorrole (SiTBC).