Characterization of a peptide affinity support that binds selectively to staphylococcal enterotoxin B

The influences of mass transfer and adsorption-desorption kinetics on the binding of staphylococcal enterotoxin B (SEB) to an affinity resin with the peptide ligand, Tyr-Tyr-Trp-Leu-His-His (YYWLHH) have been studied. The bed and particle porosities, the axial dispersion coefficient and the pore diffusivity were measured using pulse experiments under unretained conditions. Adsorption isotherms for SEB on YYWLHH resins with peptide densities in the range from 6 to 220 micromol/g were measured and fitted to a bi-Langmuir equation. At peptide densities below 9 micromol/g and above 50 micromol/g, dissociation constants were lower (2 x 10(-3) to 7 x 10(-3) mol/m3), and binding capacities were larger (43-47 mg SEB/g). In the range from 9 to 50 micromol/g dissociation constants were larger (13 x 10(-3) to 24 x 10(-3) mol/m3) and capacities were lower (33-37 mg SEB/g). These observations are consistent with a transition from single point attachment of the protein to the ligand at low peptide densities to multipoint attachment at high peptide densities. The general rate (GR) model of chromatography was used to fit experimental breakthrough curves under retained conditions to determine the intrinsic rate constants for adsorption, which varied from 0.13 to 0.50 m3 mol(-1) s(-1), and exhibited no clear trend with increasing peptide density. An analysis of the number of transfer units for the various mass transfer steps in the column indicated that film mass transfer, pore diffusion (POR) and the kinetics of adsorption can all play an important role in the overall rate of adsorption, with the intrinsic adsorption step apparently being the rate determining step at peptide densities below 50 micromol/g.     

Polystyrene/decahydronaphthalene/propane phase equilibria and polymer conformation properties from intrinsic viscosities

The influence of dissolved propane (up to 31.2 wt %) on the phase equilibria of 5 wt % polystyrene (PS) dissolved in 66/34 wt % trans/cis‐decahydronaphthalene (DHN) was measured over the temperature range of 323–423 K. A suitable temperature, pressure, and propane composition operating space was defined to measure intrinsic viscosities of a single fluid phase. Intrinsic viscosities of PS in cosolvent mixtures of propane and trans/cis‐DHN were measured between 323 and 423 K and between 70 and 208 bar. The addition of propane to the isomeric mixture of DHN resulted in a decreased solvent quality for PS, causing a contraction of the PS coil. The most dramatic decrease in solvent quality with the addition of propane occurred at 323 K and 70 bar with approximately a 36% reduction in the viscometric radius with the addition of 45 mol % propane to DHN. At 423 K, the solvent quality was less sensitive to the addition of propane and only a 13% reduction in the viscometric radius was observed at 70 bar and 45 mol % propane in DHN. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Electroactive thiazole derivatives capped with ferrocenyl units showing charge-transfer transition and selective ion-sensing properties: a combined experimental and theoretical study

The synthesis, optical and electrochemical properties, and X-ray characterization of two thiazole derivatives capped by ferrocenyl groups (5 and 7) and their model compounds with one ferrocenyl, either at 2 or 5 position of the mono- or bis-thiazolyl rings (3, 9, 11, and 14), are presented. Bisferrocenyl thiazole 5 forms the mixed-valence species 5*+ by partial oxidation which, interestingly, shows an intramolecular electron-transfer phenomenon. Moreover, the reported heteroaromatic compounds show selective ion-sensing properties. Thus, ferrocenylthiazoles linked across the 5 position of the heteroaromatic ring are selective chemosensors for Hg2+ and Pb2+ metal ions; 5-ferrocenylthiazole 3 operates through two channels, optical and redox, for Hg2+ and only optical for Pb2+, whereas 1,1'-bis(thiazolyl)ferrocene 14 is only an optical sensor for both metal ions. Moreover, complex 3 behaves as an electrochemically induced switchable chemosensor because of the low metal-ion affinity of the oxidized 3*+ species. On the other hand, ferrocenylthiazole 9, in which the heterocyclic ring and the ferrocene group are linked across the 2 position, is a selective redox sensor for Hg2+ metal ions, and it responds optically, as does bis(thiazolyl)ferrocene 11, to a narrow range of cations (Zn2+, Cd2+, Hg2+, Ni2+, and Pb2+). Finally, bis(ferrocenyl)thiazole 5 is a dual optical and redox sensor for Zn2+, Cd2+, Hg2+, Ni2+, and Pb2+, whereas bis(ferrocenyl) compound 7, bearing a bis(thiazole) unit as a bridge, is only a chromogenic sensor for Zn2+, Cd2+, Hg2+, Ni2+, and Pb2+. The experimental data and conclusions about both the electronic and ion-sensing properties are supported by DFT calculations which show, in addition, an unprecedented intramolecular electron-transfer reorganization after the first one-electron oxidation of compound 5.     

Advantages of the Ns group in the reactions of N-SO2R inosines with benzylamine and with NH3

The reactivity of N¹-alkylsulfonyl- and N¹-arylsulfonyl-2′,3′,5′-tri-O-acetylinosine with benzylamine and with ¹⁵NH₃, regarding the attack on C2, has been shown to be in the order CF₃SO₂ (Tf) > 2,4-(NO₂)₂C₆H₃SO₂ (DNs) ? 4-NO₂C₆H₄SO₂ (pNs) ≈ C₆F₅SO₂ (PFBs) > 2-NO₂C₆H₄SO₂ (Ns) ? CH₃SO₂ (Ms) > 4-CH₃C₆H₄SO₂ (Ts) > 2,4,6-(CH₃)₃C₆H₂SO₂ (Mts). In spite of its intermediate reactivity, the Ns group is the most appropriate, since in this case the formation of by-products is minimised during the ring-opening and ring-closing steps of the process. Another advantage of the Ns group is thus disclosed.     

High-Yielding Enantioselective Synthesis of the Macrolactam Aglycon of Sch 38516 from Two Units of (2R)-2-Ethyl-4-penten-1-ol

The same precursor —namely, (2R)-2-ethyl-4-penten-1-ol—was used to obtain fragments C9–C13 and C1–C8 of 1 , the aglycon of Sch 38516 (which is active against Candida sp.) and fluvirucin B₁ (which is active against influenza A virus). The key steps of the synthesis were the aldol-like reaction between the two fragments and the macrolactamization of a 13-azidotridecanoic acid derivative (see scheme). MOM=methoxymethyl, Py=2-pyridyl.     

Mixed fluoroamine complexes of chromium(III)

Summary Mixed difluoro(diamine)(diamme)chromium(III) complexes have been synthesized with ethylenediamine (en), 1,3 propanediamine(tn) and 1,2-cyclohexanediamine(chxn):trans-[CrF₂(aa)(bb)]Br (aa=en, bb=tn; aa=tn, bb= chxn) andcis-[CrF₂(aa)(bb)]Br (aa=en, bb=chxn). The corresponding fluoroaqua(diamine) (diamine)chromium(III) complexes have been prepared by acid hydrolysis as perchlorate or iodide salts. All have been characterized by chemical analysis, electronic and i.r. spectra and conductivity measurements.     

Design,Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors

Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM-15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC₅₀ values of 0.23 and 1.29 µM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC₅₀ values of 14.0, 13.7 and 13.0 µM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM-15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention.     

New synthetic “tricks” using old reagents. A mild method for the conversion of RCONHR′ to RCONHR″

N-Alkyl-N-nitrosoamides, RCON(NO)R′, react with primary aliphatic amines (NH₂R″), in refluxing dichloromethane or at room temperature, to give RCONHR″ in 65–98% yields.