Metabolism and excretion of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]-pyrimidin-4-one (SK3530) in rats

The in vitro and in vivo metabolism of a novel PDE 5 inhibitor, SK3530, was investigated in rats. Bile, plasma, feces, urine and liver samples were collected and analyzed using a high-performance liquid chromatography (HPLC) system equipped with ultraviolet (UV), mass spectrometric and radioactivity detectors. After a single oral administration, the mean radiocarbon recovery was 92.32+/-6.26%, with 91.25+/-6.25 and 1.07+/-0.21% in the feces and urine, respectively. The biliary excretion of radioactivity for the first 24 h period was approximately 38.82%, suggesting that SK3530 is cleared by hepatobiliary excretion. In vitro incubation of SK3530 with rat and human liver microsomes resulted in the formation of twelve and ten metabolites, respectively. SK3530 was extensively metabolized to twenty different metabolites, including three glucuronide and three sulfate conjugates in rats. The structures of these metabolites were elucidated based on MSn spectral analyses. Six major metabolic pathways were identified in the rat: N-dealkylation and oxidation of the hydroxyethyl moiety; N,N-deethylation and hydroxylation of the piperazine ring; hydroxylation of the propyl group and sulfate conjugation. An additional metabolite due to aromatic hydroxylation was also identified in hepatic microsomes.     

1-Phenyl-1-propyne on Cu(111): TOFMS TPD, XPS, UPS, and 2PPE Studies

The bonding properties of 1-phenyl-1-propyne (PP, C6H5CCCH3) on Cu(111) at 100 K have been studied using temperature-programmed desorption (TPD), and X-ray, ultraviolet, and two-photon photoemission spectroscopies (XPS, UPS, and 2PPE). In TPD, there is no evidence for dissociation. Multilayer desorption occurs at 187 K, and monolayer desorption occurs at 320 (83.5 kJ/mol) and 390 K (102.4 kJ/mol), with the latter dominating. Based on the calibrated C(1s) XPS, the saturation monolayer coverage is one PP per four surface Cu atoms. The broad and asymmetric C(1s) intensity profile of the monolayer can be resolved into three symmetric components, with peaks at 283.6, 284.5, and 285.2 eV and intensities of 2:6:1, respectively. These are attributed, respectively, to acetylenic carbons bound to Cu, phenyl, and methyl carbons. The monolayer valence band ultraviolet photoemission spectrum profile contains four resonances attributable to PP perturbed by interactions with the Cu(111) substrate. With the exception of the highest occupied molecular orbital (HOMO) that is shifted by 0.4 eV, these are uniformly shifted by 1 eV further from the Fermi level for the multilayer. Calculated electron density plots of the occupied orbitals coupled with UPS profiles suggest a spectator role for the phenyl group and bonding to Cu via the acetylenic carbons. The adsorption of 1.0 monolayer (ML) of PP on Cu(111) lowers the work function by 0.85 eV. Using 2PPE, two unoccupied orbitals were identified at 1.0 (U1*-LUMO) and 0.6 eV (U2*-image state) below the vacuum level. A chemisorption model consistent with these spectroscopic results and the major chemisorption peak in TPD involve di-sigma-bonding of the acetylenic carbons to a pair of second-nearest neighbor surface Cu atoms (cross-bridge).     

Syntheses and biological activities of α-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil and its polymers

The new monomer, α-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil (METFU), was synthesized by the reaction of 5-fluorouracil (5-FU) and exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride (ETA) in order to prepare polymers containing 5-FU moiety. Poly(α-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(METFU)], poly(α-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouraci-co-acrylic acid) [poly(METFU-co-AA)], and poly(α-methoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil-co-vinyl acetate) [poly(METFU-co- VAc)] were synthesized by photopolymerizations using 2,2-dimethoxy-2-phenylacetophenone (DMP) as an initiator. The synthesized METFU and the polymers were identified by FTIR and ¹H-NMR spectroscopies. The contents of METFU in poly(METFU-co-AA) and poly(METFU-co-VAc) determined by elemental analysis were 52 and 60 mol %, respectively. The average molecular weights and polydispersity indices determined with GPC were as follows: M n = 9,400, M w = 11,400 M w/M n = 1.21 for poly(METFU), M n = 14,400, M w = 26,800, M w/M n = 1.86 for poly(METFU-co-AA), and M n = 23,100, M w = 33,000, M w/M n = 1.43 for poly(METFU-co-VAc). The in vitro cytotoxicities of samples were evaluated with mouse mammary carcinoma (FM3A), mouse leukemia (P388), and human histiocytic lymphoma (U937) as cancer cell lines, and mouse liver cells (AC2F) as a normal cell line. The in vivo antitumor activities of synthesized polymers against mice bearing the sarcoma 180 tumor cell line were greater than those of 5-FU at concentrations of 0.8 and 80 mg/kg. © 1998 John Wiley & Sons, Inc. J. Polym. Sci. A Polym. Chem. 36: 2177–2184, 1998     

Copper-catalyzed aerobic oxidative dehydrogenation for conversion of 2-(alkylthio)-1,4-dihydropyrimidines to 2-(alkylthio)pyrimidines

A simple and efficient aerobic oxidative dehydrogenation reaction method for the conversion of 2-(alkylthio)-1,4-dihydropyrimidines to 2-(alkylthio)pyrimidines using copper catalyst with no additives, such as an oxidant, acid, or base, has been developed. The reaction was successful with a wide range of 2-(alkylthio)-1,4-dihydropyrimidine substrates.     

Solid-state ion-selective electrodes for the potentiometric determination of hexacyanoferrate (II)

Hexacyanoferrate(II)-sensing electrodes were prepared by mixing Ag₂S and Ag₄Fe (CN)₆. The 6:1 Ag₂S/Ag₄Fe (CN)₆ provided the best potentiometric response and speed of response. The log concentration vs. potential curves were linear with Nernstian slope (14.8 mV/decade) over the range 10^?1-10^?6 M hexacyanoferrate (II) at pH 7.00 with constant ionic strength. Interferences included iodide, sulfide and bromide. This electrode was used as indicator in potentiometric titrations of hexacyanoferrate (II).     

Pore formation in in situ processed MgB2 superconductors

MgB₂ bulks were prepared by an in situ process which utilizes the reaction between boron and magnesium powder. The reaction time was fixed at 0.5 h and the temperature was changed from 600 °C to 1000 °C. The density decrease due to pore formation and mass (mainly magnesium) loss during the formation reaction of MgB₂ was observed in all samples. In addition to the pore formation, a pellet expansion which can be explained by the outgrowth of MgB₂ grains was also observed. Two different mechanisms were adopted to explain the pore formation; Kirkendall pores formed at a temperature below the melting point (m.p.) of magnesium by a difference in the diffusivity between magnesium and boron, and the pores formed at a temperature above the m.p. by melting of magnesium and a capillary movement. The density, T_c and J_c results suggest that the current carrying capacity can be improved by a careful control of the process parameters regarding a pore evolution.     

Anti-biofouling properties of comblike block copolymers with amphiphilic side chains

Surfaces of novel block copolymers with amphiphilic side chains were studied for their ability to influence the adhesion of marine organisms. The surface-active polymer, obtained by grafting fluorinated molecules with hydrophobic and hydrophilic blocks to a block copolymer precursor, showed interesting bioadhesion properties. Two different algal species, one of which adhered strongly to hydrophobic surfaces, and the other, to hydrophilic surfaces, showed notably weak adhesion to the amphiphilic surfaces. Both organisms are known to secrete adhesive macromolecules, with apparently different wetting characteristics, to attach to underwater surfaces. The ability of the amphiphilic surface to undergo an environment-dependent transformation in surface chemistry when in contact with the extracellular polymeric substances is a possible reason for its antifouling nature. Near-edge X-ray absorption fine structure spectroscopy (NEXAFS) was used, in a new approach based on angle-resolved X-ray photoelectron spectroscopy (XPS), to determine the variation in chemical composition within the top few nanometers of the surface and also to study the surface segregation of the amphiphilic block. A mathematical model to extract depth-profile information from the normalized NEXAFS partial electron yield is developed.     

Constructing connected bicritical graphs with edge-connectivity 2

A graph $G$ is said to be bicritical if the removal of any pair of vertices decreases the domination number of $G$. For a bicritical graph $G$ with the domination number $t$, we say that $G$ is $t$-bicritical. Let $\lambda \left(G\right)$ denote the edge-connectivity of $G$. In [2], Brigham et al. (2005) posed the following question: If $G$ is a connected bicritical graph, is it true that $\lambda \left(G\right)\ge 3?$In this paper, we give a negative answer toward this question; namely, we give a construction of infinitely many connected $t$-bicritical graphs with edge-connectivity $2$ for every integer $t\ge 5$. Furthermore, we give some sufficient conditions for a connected $5$-bicritical graph to have $\lambda \left(G\right)\ge 3$.