One-pot synthesis of 2,4-benzodiazepin-1-ones using benzotriazole methodology

2, 4-Benzodiazepin-1-ones were prepared in moderate to good yields by reaction of bis(benzotriazolylmethyl)amines with ortho-metalated N-substituted benzamides.     

Normal,abnormal and pseudo-abnormal reaction pathways for the imine-peroxyacid reaction

Steric and mesomeric effects have a marked influence upon the formation of oxaziridine (normal pathway) or nitrone (abnormal pathway) products from the imine-peroxyacid reaction; n.m.r. studies of the thermal isomerization of oxaziridines to nitrones provide evidence of a pseudo-abnormal oxidation pathway.     

Copper hydroxydiphosphate with a one-dimensional arrangement of copper polyhedra: Cu3[P2O6OH]2

A new copper hydroxydiphosphate Cu3(P2O6OH)2 was synthesized, by soft chemistry. The crystal structure was solved ab initio from X-ray powder diffraction data in the triclinic space group P. The structure is built up from [Cu3O10]infinity zigzag chains linked by P2O6(OH) groups to form a tridimensional framework. The [Cu3O10]infinity chains consist of edge-sharing polyhedra. The structure contains two sorts of copper polyhedra: one CuO6 octahedron and two CuO5 pyramids. Magnetization measurements confirm the presence of divalent copper and suggest antiferromagnetic interactions at low temperature.     

Activation of the stress-activated JNK and p38 MAP kinases in human cells by Photofrin-mediated photodynamic therapy

We have examined the possible role of the stress-activated JNK and p38 protein kinases in cellular sensitivity following Photofrin-mediated photodynamic therapy (PDT). Previously we reported that immortalized Li-Fraumeni syndrome (LFS) cells are more resistant to Photofrin-mediated PDT compared to normal human fibroblasts (NHF) at equivalent cellular Photofrin levels. In the current work we report that Photofrin-mediated PDT increased the activity of JNK1 and p38 within 30 min in both cell types. However, the increased activity of JNK1 and p38 was transient in the sensitive NHF cells and returned back to near basal levels by 3 h after PDT. In contrast, the resistant LFS cells exhibited a more prolonged activation of JNK and p38, which lasted for at least 11 h and 7 h after PDT, respectively. Blocking of the p38 pathway in LFS cells by transient infection with a recombinant adenovirus expressing a dominant negative mutant of p38 or in HeLa cells by stable transfection with a dominant negative mutant of p38 had no effect on cell survival following PDT. These data suggest that although Photofrin-mediated PDT is able to induce JNK1 and p38 in human cells, the p38 pathway alone does not play a major role in the sensitivity of LFS cells to Photofrin-mediated PDT.     

Peering into the self-assembly of surfactant templated thin-film silica mesophases

It is now recognized that self-assembly is a powerful synthetic approach to the fabrication of nanostructures with feature sizes smaller than achievable with state of the art lithography and with a complexity approaching that of biological systems. For example, recent research has shown that silica/surfactant self-assembly combined with evaporation (so-called evaporation induced self-assembly EISA) can direct the formation of porous and composite thin-film mesostructures characterized by precise periodic arrangements of inorganic and organic constituents on the 1-50-nm scale. Despite the potential utility of these films for a diverse range of applications such as sensors, membranes, catalysts, waveguides, lasers, nano-fluidic systems, and low dielectric constant (so-called low k) insulators, the mechanism of EISA is not yet completely understood. Here, using time-resolved grazing incidence small-angle X-ray scattering (GISAXS) combined with gravimetric analysis and infrared spectroscopy, we structurally and compositionally characterize in situ the evaporation induced self-assembly of a homogeneous silica/surfactant/solvent solution into a highly ordered surfactant-templated mesostructure. Using CTAB (cetyltrimethylammonium bromide) as the structure-directing surfactant, a two-dimensional (2-D) hexagonal thin-film mesophase (p6mm) with cylinder axes oriented parallel to the substrate surface forms from an incipient lamellar mesophase through a correlated micellar intermediate. Comparison with the corresponding CTAB/water/alcohol system (prepared without silica) shows that, for acidic conditions in which the siloxane condensation rate is minimized, the hydrophilic and nonvolatile silicic acid components replace water maintaining a fluidlike state that avoids kinetic barriers to self-assembly.     

Proton transfer to nickel-thiolate complexes. 1. Protonation of [Ni(SC(6)H(4)R-4)(2)(Ph(2)PCH(2)CH(2)PPh(2))] (R = Me, MeO, H, Cl, or NO(2))

The kinetics of the equilibrium reaction between [Ni(SC(6)H(4)R-4)(2)(dppe)] (R= MeO, Me, H, Cl, or NO(2); dppe = Ph(2)PCH(2)CH(2)PPh(2)) and mixtures of [lutH](+) and lut (lut = 2,6-dimethylpyridine) in MeCN to form [Ni(SHC(6)H(4)R-4)(SC(6)H(4)R-4)(dppe)](+) have been studied using stopped-flow spectrophotometry. The kinetics for the reactions with R = MeO, Me, H, or Cl are consistent with a single-step equilibrium reaction. Investigation of the temperature dependence of the reactions shows that DeltaG = 13.6 +/- 0.3 kcal mol(-)(1) for all the derivatives but the values of DeltaH and DeltaS vary with R (R = MeO, DeltaH() = 8.5 kcal mol(-)(1), DeltaS = -16 cal K(-)(1) mol(-)(1); R = Me, DeltaH() = 10.8 kcal mol(-)(1), DeltaS = -9.5 cal K(-)(1) mol(-)(1); R = Cl, DeltaH = 23.7 kcal mol(-)(1), DeltaS = +33 cal K(-)(1) mol(-)(1)). With [Ni(SC(6)H(4)NO(2)-4)(2)(dppe)] a more complicated rate law is observed consistent with a mechanism in which initial hydrogen-bonding of [lutH](+) to the complex precedes intramolecular proton transfer. It seems likely that all the derivatives operate by this mechanism, but only with R = NO(2) (the most electron-withdrawing substituent) does the intramolecular proton transfer step become sufficiently slow to result in the change in kinetics. Studies with [lutD](+) show that the rates of proton transfer to [Ni(SC(6)H(4)R-4)(2)(dppe)] (R = Me or Cl) are associated with negligible kinetic isotope effect. The possible reasons for this are discussed. The rates of proton transfer to [Ni(SC(6)H(4)R-4)(2)(dppe)] vary with the 4-R-substituent, and the Hammett plot is markedly nonlinear. This unusual behavior is attributable to the electronic influence of R which affects the electron density at the sulfur.     

Single wall carbon nanotube amplification: en route to a type-specific growth mechanism

With the desire to mass produce any specific n,m type of single wall carbon nanotube (SWNT) from a small sample of the same material, we disclose here the preliminary work directed toward that goal. The ultimate protocol would involve taking a single n,m-type nanotube sample, cutting the nanotubes in that sample into many short nanotubes, using each of those short nanotubes as a template for growing much longer nanotubes of the same type, and then repeating the process. The result would be an amplification of the original tube type: a parent SWNT serving as the prolific progenitor of future identical SWNT types. As a proof-of-concept, we use here a short SWNT seed as a template for vapor liquid solid (VLS) amplification growth of an individual long SWNT. The original short SWNT seed was a polymer-wrapped SWNT, end-carboxylated, and further tethered with Fe salts at its ends. The Fe salts were to act as the growth catalysts upon subsequent reductive activation. Deposition of the short SWNT-Fe tipped species upon an oxide surface was followed by heating in air to consume the polymer wrappers, then reducing the Fe salts to Fe(0) under a H2-rich atmosphere. During this heating, the Fe(0) can etch back into the short SWNT so that the short SWNT acts as a template for new growth to a long SWNT that occurs upon introduction of C2H4 as a carbon source. Analysis indicated that the templated VLS-grown long SWNT had the same diameter and surface orientation as the original short SWNT seed, although amplifying the original n,m type remains to be proven. This study could pave the way for an amplified growth process of SWNTs en route to any n,m tube type synthesis from a starting sample of pure nanotubes.     

Brocaenols A-C: novel polyketides from a marine derived Penicillium brocae

Chemical investigation of a Penicillium brocae, obtained from a tissue sample of a Fijian Zyzyya sp. sponge, yielded two known diketopiperazines and three novel cytotoxic polyketides, brocaenols A-C. The brocaenols contain an unusual enolized oxepine lactone ring system that to the best of our knowledge is unprecedented in the literature. The structures were elucidated by using 2D-NMR methods including an INADEQUATE experiment. The absolute stereochemistry of brocaenol A was established by using a modified Mosher method. The taxonomy of the producing fungus was elucidated by using both morphological and rDNA sequence analysis.     

Similarity searching using reduced graphs

Reduced graphs provide summary representations of chemical structures. In this work, the effectiveness of reduced graphs for similarity searching is investigated. Different types of reduced graphs are introduced that aim to summarize features of structures that have the potential to form interactions with receptors while retaining the topology between the features. Similarity searches have been carried out across a variety of different activity classes. The effectiveness of the reduced graphs at retrieving compounds with the same activity as known target compounds is compared with searching using Daylight fingerprints. The reduced graphs are shown to be effective for similarity searching and to retrieve more diverse active compounds than those found using Daylight fingerprints; they thus represent a complementary similarity searching tool.     

Thermoresponsive Copolymers of Ethylene Oxide and N,N‐Diethyl Glycidyl Amine: Polyether Polyelectrolytes and PEGylated Gold Nanoparticle Formation

The synthesis of diblock as well as gradient copolymers of N,N‐diethyl glycidyl amine (DEGA) with ethylene oxide (EO) via anionic ring‐opening polymerization is presented. The polymers exhibit low polydispersities (≤1.13) and molecular weights in the range of 3300–10 200 g mol⁻¹. In PEG‐co‐PDEGA copolymers, incorporation of 4%–29% DEGA results in tailorable cloud point temperatures in aqueous solution and melting points depending on DEGA content. mPEG‐b‐PDEGA block copolymers can be quaternized to generate cationic double‐hydrophilic polyelectrolyte copolymers with polyether backbone. Furthermore, mPEG‐b‐PDEGA has been used as dual reducing and capping agent for gold nanoparticle synthesis.