Design and parallel solid-phase synthesis of ring-fused 2-pyridinones that target pilus biogenesis in pathogenic bacteria

A new method for the solid-phase synthesis of enantiomerically enriched highly substituted ring-fused 2-pyridinones 13 has been developed. The synthesis mediates introduction of substituents at two positions in the 2-pyridinone ring in a diverse manner and is suitable for parallel synthesis. (19)F NMR spectroscopy was used as a tool to monitor each of the five steps in the reaction sequence. The optimized conditions thus obtained were then used to prepare a library of 20 2-pyridinones with high yields. The library members were chosen from a statistical multivariate design to ensure diversity and reliable data for structure-activity relationships. Screening of the library against the bacterial periplasmic chaperone PapD was performed using surface plasmon resonance. Three new 2-pyridinones with a higher affinity for the chaperone PapD than the previous best 13[10,1] were found, and important structural features could be deduced.     

Chloroheptakis(dimethyl sulfoxide)­uranium(IV) trichloride

In the title complex, [UCl(C₂H₆OS)₇]Cl₃, the uranium metal center is coordinated in a distorted bicapped trigonal prism geometry by seven O atoms from di­methyl sulfoxide ligands and by a terminal chloride ligand. Charge balance is maintained by three outer‐sphere chloride ions per uranium(IV) metal center. Principle bond lengths include U—O 2.391 (2)–2.315 (2) Å, U—Cl 2.7207 (9) Å, and average S—O 1.540 (5) Å.     

Deep desulfurization by selective adsorption of dibenzothiophenes on Ag+/SBA-15 and Ag+/SiO2

Silver (Ag+) salts adsorbed on amorphous silica or mesoporous SBA-15 extract dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-Me2DBT) from simulated, hydrotreated petroleum feedstocks.     

EFFICACY OF PHOTODYNAMIC THERAPY ON ORIGINAL AND RECURRENT RAT MAMMARY TUMORS

Abstract— Photodynamic therapy has demonstrated efficacy toward primary, metastatic and recurrent human tumors. Here, we investigated the ability of photodynamic therapy, using Photofrin, to inhibit growth of R3230AC mammary adenocarcinomas when tumors were treated as original implants and again as lesions recurring at the initial treatment site. The results demonstrate that both initial implants and lesions recurring after the first photodynamic treatment respond similarly to the same photodynamic therapy protocol, with mean tumor volume doubling times of ˜ 11 days in both cases. Cells cultured from original tumor implants or tumors that recurred after photodynamic treatment accumulate equivalent amounts of [¹⁴C]polyhematoporphyrin. Single cell suspensions prepared from either original or recurrent tumors from animals administered 5 mg/kg Photofrin and exposed to light in vitro displayed comparable phototoxicity. Additionally, examination of tumors by light microscopy revealed no morphological differences between the original tumor implants and the recurrent lesions. Taken together, these data indicate that lesions which recurred at the site of the initial photodynamic treatment were not resistant to a second identical course of photodynamic therapy.     

Effect of some additives on the photoxidation of rigid PVC

The photoxidative degradation of PVC was studied by i.r. and u.v. spectroscopy and gel permeation chromatography. It was found that the photoxidative degradation of unprocessed PVC is an auto-accelerating chain scission process. Carboxylic groups were found to be the main product formed during degradation. The molecular weights $\text{M}{}_{\mathrm{n}}$ and $\text{M}{}_{\mathrm{w}}$ both decreased, but the molecular weight distribution widened with increasing length of exposure. Single additives, such as calcium stearate. Wax E and a solid organotin stabilizer, altered the rate but not the mode of the degradation. Combination of the three additives changed the mode of the photoxidation from auto-accelerating to constant rate of degradation. Processing at 170° with the combined additives increased the rate constants.     

Targeting cell surface receptors with ligand-conjugated nanocrystals

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.     

New methodologies for the preparation of porphodimethenes and their conversion to trans-porphyrins with functionalized naphthyl spacers

The MacDonald [2 + 2]-type condensation of readily available 5-aryl-substituted dipyrromethanes with acenaphthenequinone leads to the trans-syn- and anti-porphodimethenes, which in turn can be converted to the alpha,alpha- and alpha,beta-porphyrin atropisomers, respectively. Treatment of the metalated or unmetalated porphodimethenes with KOH or NaOMe in THF followed by protonation with HCl results in a ring opening of the acenaphthenone and formation of the trans-8-carboxynaphthylporphyrins or their esters (NaOMe) after oxidation. Alternatively, the porphyrin formation can be accomplished by reaction of the porphodimethenes with acids in the presence of water or methanol. Reaction with NaBH(4) in a THF--methanol mixture yields the corresponding dialcohols in nearly quantitative yields. Sixteen different building blocks were prepared in order to evaluate the generality of this new synthetic approach, with Ar = 2,4,6-Me(3)C(6)H(2); 2,6-Cl(2)C(6)H(3); 2,6-F(2)C(6)H(3); 3,4-tBu(2)C(6)H(3); 3,4,5-(MeO)(3)C(6)H(2); 4-BrC(6)H(4); 4-MeC(6)H(4); and 4-MeOOCC(6)H(4) at the meso positions. The synthesized porphodimethenes and porphyrins have been fully characterized, and the X-ray structure analyses of three representative derivatives are presented.     

Routine determination of major anions in atmospheric aerosols by capillary electrophoresis

Capillary electrophoresis (CE) with indirect UV detection utilizing a pyromellitate-based electrolyte was used for the routine analysis of major anions in atmospheric aerosols collected on filters with high-volume (Hi-Vol) samplers. The long-term reliability of the CE system was checked over an 8-month period during which over 2900 samples were analyzed. In addition, approximately 1100 samples were analyzed in parallel by ion chromatography (IC). It has been shown that acceptable analytical performance can be routinely obtained. The agreement between the CE and IC results is good, generally better than 20% at concentrations larger than 1 mg l⁻¹.     

Low Reynolds Number Interactions between Colloidal Particles near the Entrance to a Cylindrical Pore

The interaction between stable colloidal particles arriving at a pore entrance was studied using a numerical method for the case where the particle size is smaller than but of the same order as the pore size. The numerical method was adapted from a front-tracking technique developed for studying incompressible, multifluid flow by S. O. Unverdi and G. Tryggvason (J. Comp. Phys. 100, 25, 1992). The method is based on the finite difference solution of Navier-Stokes equation on a stationary, structured, Cartesian grid and the explicit representation of the particle-liquid interface using an unstructured grid that moves through the stationary grid. The simulations are in two dimensions, considering both deformable and nondeformable particles, and include interparticle colloidal interactions. The interparticle and particle-pore hydrodynamic interactions, which are very difficult to determine using existing analytical and semi-numerical, semi-analytical techniques in microhydrodynamics, are naturally accounted for in our numerical method and need not be explicity determined. Two- and three-particle motion toward a pore has been considered in our simulations. The simulations demonstrate how the competition between hydrodynamic forces and colloidal forces acting on particles dictate their flow behavior near the pore entrance. The predicted dependence of the particle flow behavior on the flow velocity and the ratio of pore size to particle size are qualitatively consistent with the experimental observations of V. Ramachandran and H. S. Fogler (J. Fluid Mech. 385, 129, 1999). Copyright 2000 Academic Press.     

Mechanisms of antioxidant action: Stabilisation of nitrile rubber by interpenetrating networks based on thiol adducts

Nitrile rubbers containing three thiol antioxidants ((I) to (III)) in bound form have been evaluated as masterbatch concentrates by dilution in unstabilised nitrile rubber both at the latex stage and in the polymer melt. Both procedures give effective substantive systems in the case of the hindered phenol (I) and the aromatic thiol amide (II). Both show a high level of antioxidant retention under very severe technological conditions (oil/air oven cyclical test at 150°C). Antioxidant (III), which has only a minor structural difference from (II), is very much less effective as a substantive antioxidant.