Preparation of Sec-Alkyl Isouronium Salts

Eight examples of sec-alkyl isouronium salts were readily prepared from sec-alcohols, cynamide, and methanesulfonic acid (or CF₃SO₃H or HBF₄).     

Infrared spectra of two sexithiophenes in neutral and doped states: a theoretical and spectroscopic study

The FT-infrared spectra of two sexithiophenes having their end ,′-positions substituted by n-hexyl or -thiohexyl groups, in neutral and doped states, are studied with the main aim of deriving information about the π-electrons delocalization and about the electronic structure of the charged defects created upon doping with iodine. The analysis of the experimental data is aided by Density Functional Theory calculations. The modifications in the electronic structure of the sexithiophene backbone induced by the n-thiohexyl encapsulation are discussed from the point of view of single molecule interactions in thiol-terminated π-conjugated oligomers bound to metallic or cluster electrodes.     

Star-shaped azo-based dipolar chromophores: design, synthesis, matrix compatibility, and electro-optic activity

Three new azo-benzene-based push-pull chromophores with dendritic architecture were synthesized as active materials for electro-optic applications. These chromophores were synthesized in six or seven synthetic steps with an overall yield of around 80% per step and high purity. UV-vis spectroscopy showed significant influence of the transient dipole moment on the observed r(33) values. The chromophores were stable to photochemical oxidation in ambient light and air. The electrical poling conditions were optimized for each chromophore as the T(g) of the composite material varied significantly. The highest EO coefficient achieved was 22-25 pm/V at 1550 nm wavelength. STEM analysis of the blends enabled the correlation of the activity of these large chromophores with the blend morphology. An amorphous polycarbonate host effectively disperses the chromophores in 2-20 nm aggregates in the active materials. However, macrophase separation into 200-500 nm aggregates was observed in a methacrylate host matrix.     

Quantitative analysis of imazamox herbicide in environmental water samples by capillary electrophoresis electrospray ionization mass spectrometry

Capillary electrophoresis-mass spectrometry (CE-MS) with an electrospray ionization interface was applied for the quantitative analysis of imazamox pesticide in well water, potable water, and pond water. The detector response for imazamox was determined to be linear over the concentration range of 50-1 ng/ml. The limits of quantitation and detection of the method were determined to be 200 and 20 ng/l for imazamox compound in each type of water sample, respectively. The total sample preparation and CE-MS analysis time was under 2 h.     

Synthesis of 2,6-disubstituted dihydropyrans via an efficient BiBr3-initiated three component, one-pot cascade

The rapid synthesis of cis-2,6-disubstituted dihydropyrans is achieved in a three-component, one-pot cascade reaction. BiBr₃-mediated addition of ketene silyl acetals or silyl enol ethers to β,γ-unsaturated cis-4-trimethylsilyl-3-butenal provides a Mukaiyama aldol adduct containing a vinylsilane moiety tethered to a silyl ether. Addition of a second aldehyde initiates a domino sequence involving intermolecular addition followed by an intramolecular silyl-modified Sakurai (ISMS) reaction. Isolated yields of this one-pot reaction vary from 44 to 80% and all compounds were isolated as the cis-diastereomers (10 examples).     

A biofuel cell with electrochemically switchable and tunable power output

An electroswitchable and tunable biofuel cell based on the biocatalyzed oxidation of glucose is described. The anode consists of a Cu(2+)-poly(acrylic acid) film on which the redox-relay pyrroloquinoline quinone (PQQ) and the flavin adenine dinucleotide (FAD) cofactor are covalently linked. Apo-glucose oxidase is reconstituted on the FAD sites to yield the glucose oxidase (GOx)-functionalized electrode. The cathode consists of a Cu(2+)-poly(acrylic acid) film that provides the functional interface for the covalent linkage of cytochrome c (Cyt c) that is further linked to cytochrome oxidase (COx). Electrochemical reduction of the Cu(2+)-poly(acrylic acid) films (applied potential -0.5 V vs SCE) associated with the anode and cathode yields the conductive Cu(0)-poly(acrylic acid) matrixes that electrically contact the GOx-electrode and the COx/Cyt c-electrode, respectively. The short-circuit current and open-circuit voltage of the biofuel cell correspond to 105 microA (current density ca. 550 microA cm(-2)) and 120 mV, respectively, and the maximum extracted power from the cell is 4.3 microW at an external loading resistance of 1 kOmega. The electrochemical oxidation of the polymer films associated with the electrodes (applied potential 0.5 V) yields the nonconductive Cu(2+)-poly(acrylic acid) films that completely block the biofuel cell operation. By the cyclic electrochemical reduction and oxidation of the polymer films associated with the anode and cathode between the Cu(0)-poly(acrylic acid) and Cu(2+)-poly(acrylic acid) states, the biofuel cell performance is reversibly switched between "ON" and "OFF" states, respectively. The electrochemical reduction of the Cu(2+)-polymer film to the Cu(0)-polymer film is a slow process (ca. 1000 s) because the formation and aggregation of the Cu(0)-clusters requires the migration of Cu(2+) ions in the polymer film and their reduction at conductive sites. The slow reduction of the Cu(2+)-polymer films allows for the controlling of the content of conductive domains in the films and the tuning of the output power of the biofuel cell. The electron-transfer resistances of the cathodic and anodic processes were characterized by impedance spectroscopy. Also, the overall resistances of the biofuel cell generated by the time-dependent electrochemical reduction process were followed by impedance spectroscopy and correlated with the internal resistances of the cell upon its operation.     

Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator

BACKGROUND: Urokinase-type plasminogen activator (uPA) is a protease associated with tumor metastasis and invasion. Inhibitors of uPA may have potential as drugs for prostate, breast and other cancers. Therapeutically useful inhibitors must be selective for uPA and not appreciably inhibit the related, and structurally and functionally similar enzyme, tissue-type plasminogen activator (tPA), involved in the vital blood-clotting cascade. RESULTS: We produced mutagenically deglycosylated low molecular weight uPA and determined the crystal structure of its complex with 4-iodobenzo[b]thiophene 2-carboxamidine (K(i) = 0.21 +/- 0.02 microM). To probe the structural determinants of the affinity and selectivity of this inhibitor for uPA we also determined the structures of its trypsin and thrombin complexes, of apo-trypsin, apo-thrombin and apo-factor Xa, and of uPA, trypsin and thrombin bound by compounds that are less effective uPA inhibitors, benzo[b]thiophene-2-carboxamidine, thieno[2,3-b]-pyridine-2-carboxamidine and benzamidine. The K(i) values of each inhibitor toward uPA, tPA, trypsin, tryptase, thrombin and factor Xa were determined and compared. One selectivity determinant of the benzo[b]thiophene-2-carboxamidines for uPA involves a hydrogen bond at the S1 site to Ogamma(Ser190) that is absent in the Ala190 proteases, tPA, thrombin and factor Xa. Other subtle differences in the architecture of the S1 site also influence inhibitor affinity and enzyme-bound structure. CONCLUSIONS: Subtle structural differences in the S1 site of uPA compared with that of related proteases, which result in part from the presence of a serine residue at position 190, account for the selectivity of small thiophene-2-carboxamidines for uPA, and afford a framework for structure-based design of small, potent, selective uPA inhibitors.     

Production of hybrid 16-membered macrolides by expressing combinations of polyketide synthase genes in engineered Streptomyces fradiae hosts

Combinations of the five polyketide synthase (PKS) genes for biosynthesis of tylosin in Streptomyces fradiae (tylG), spiramycin in Streptomyces ambofaciens (srmG), or chalcomycin in Streptomyces bikiniensis (chmG) were expressed in engineered hosts derived from a tylosin-producing strain of S. fradiae. Surprisingly efficient synthesis of compounds predicted from the expressed hybrid PKS was obtained. The post-PKS tailoring enzymes of tylosin biosynthesis acted efficiently on the hybrid intermediates with the exception of TylH-catalyzed hydroxylation of the methyl group at C14, which was efficient if C4 bore a methyl group, but inefficient if a methoxyl was present. Moreover, for some compounds, oxidation of the C6 ethyl side chain to an unprecedented carboxylic acid was observed. By also expressing chmH, a homolog of tylH from the chalcomycin gene cluster, efficient hydroxylation of the 14-methyl group was restored.