Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells

The mechanism of cell death by pheophorbide a (Pba) which has been established to be a potential photosensitizer was examined in experimental photodynamic therapy (PDT) on Jurkat cells, a human lymphoid tumor cell line. In 30-60 min after irradiation, Pba treated cells exhibited apoptotic features including membrane blebbing and DNA fragmentation. Pba/PDT caused a rapid release of cytochrome c from mitochondria into the cytosol. Sequentially, activation of caspase-3 and the cleavage of poly ADP-ribose polymerase (PARP) were followed. Meanwhile, no evidence of activation of caspase-8 was indicated in the cells. In experiments with caspase inhibitors, it was found that caspase-3 alone was sufficient initiator for the Pba-induced apoptosis of the cells. Pba specific emission spectra were confirmed in the mitochondrial fraction and the light irradiation caused a rapid change in its membrane potential. Thus, mitochondria were entailed as the crucial targets for Pba as well as a responsible component for the cytochrome c release to initiate apoptotic pathways. Taken together, it was concluded that the mode of Jurkat cell death by Pba/PDT is an apoptosis, which is initiated by mitochondrial cytochrome c release and caspase-3-pathways.     

Synthesis, structure and heterogeneous catalytic activities of Cu-containing polymeric compounds: anion effect and comparison of homogeneous vs. heterogeneous catalytic activity

The structures of new polymeric compounds containing Cu(II) ions and btp (2,6-bis(N'-1,2,4-triazolyl)pyridine) ligands have been determined. The btp ligands bridge Cu(II) ions to form double zigzag chains, [Cu(ClO4)2(btp)2] 3 with perchlorate anions, and form single zigzag chains, [Cu(btp)(H2O)4](SO4).2H2O 4 with sulfate anions. The polymeric compound 3 was found to effectively catalyze the epoxide ring-opening reaction with methanol, while polymeric compound 4 was almost inactive with epoxides under the same conditions. The polymeric compound 3 showed an efficient catalytic activity and regioselective reactivity in the ring opening of epoxides and allowed reuse without a significant loss of activity through three runs with epoxides.     

Intramolecular nucleophilic carbonyl trapping of alpha-ketenyl radicals by an amino group

Free-radical carbonylation of omega-alkynylamines with tributyltin hydride gives a mixture of alpha-methylene lactams and alpha-stannylmethylene lactams. Nucleophilic addition of an internal amino group to the carbonyl group of alpha-ketenyl radicals is proposed as the cyclization step. The subsequent unusual 1,4-H shift from the resulting 1-hydroxyallyl radical, followed by elimination of the beta-tributyltin radical leads to the formation of alpha-methylene lactams.     

Anion complexation. A ditriphenylphosphonium calix[4]arene derivative as a novel receptor for anions

A novel anionic receptor 2 consisting of a calix[4]arene bearing two alkytriphenylphosphonium has been prepared by two different procedures. The complexation occurred at the phosphonium sites probably due to electrostatic and/or π-anion forces.     

Evaluation of biological monitoring markers using genomic and proteomic analysis for automobile emission inspectors and waste incinerating workers exposed to polycyclic aromatic hydrocarbons or 2,3,7,8,-tetracholrodedibenzo-p-dioxins

In this study, we investigated the effects of PAHs and dioxin on mRNA and plasma protein expression using genomic and proteomic analysis for automobile emission inspectors and waste incineration workers. About 54 workers from automobile emission inspection offices, 31 workers from waste incinerating company and 84 unexposed healthy subjects were enrolled in this study. Urine and air samples were collected and analyzed by HPLC and GC/MS. Comet assays were carried out to evaluate any DNA damage in mononuclear and polynuclear cells. A significant difference in Olive tail moments in mononuclear cells was observed between exposed and control subjects (P < 0.0001). To examine the differences of the gene expression profile in automobile emission inspectors and waste incineration workers, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 total genes. The gene expression profiles showed that 11 genes were up-regulated and 4 genes were down-regulated in waste incinerating workers as compared with controls. Plasma proteins were analyzed by 2-dimentional electrophoresis with pH 3-10 NL IPG Dry strip. The protein expression profiles showed that 8 proteins were up- regulated and 1 protein, haptoglobin, was down- regulated in automobile emission inspectors and waste incineration workers. Serum paraoxonase/ arylesterase was found only in the plasma of waste incineration workers. The expression of genes and proteins involved in oxidative stress were up-regulated in both automobile emission inspectors and waste incineration workers. Several proteins, such as transthyrethin, sarcolectin and haptoglobin, that were highly up- or down-regulated, could serve as biological monitoring markers for future study.     

Phosphorylation of phospholipase D1 and the modulation of its interaction with RhoA by cAMP-dependent protein kinase

Agents that elevate cellular cAMP are known to inhibit the activation of phospholipase D (PLD). We investigated whether PLD can be phosphorylated by cAMP-dependent protein kinase (PKA) and PKA-mediated phosphorylation affects the interaction between PLD and RhoA, a membrane regulator of PLD. PLD1, but not PLD2 was found to be phosphorylated in vivo by the treatment of dibutyryl cAMP (dbcAMP) and in vitro by PKA. PKA inhibitor (KT5720) abolished the dbcAMP-induced phosphorylation of PLD1, but dibutyryl cGMP (dbcGMP) failed to phosphorylate PLD1. The association between PLD1 and Val14RhoA in an immunoprecipitation assay was abolished by both dbcAMP and dbcGMP. Moreover, RhoA but not PLD1 was dissociated from the membrane to the cytosolic fraction in dbcAMP-treated cells. These results suggest that both PLD1 and RhoA are phosphorylated by PKA and the interaction between PLD1 and RhoA is inhibited by the phosphorylation of RhoA rather than by the phosphorylation of PLD1.     

Gold-catalyzed hydrosilyloxylation driving tandem aldol and mannich reactions

The chemoselective formation of an enolate from alkyne in the presence of a carbonyl and imine group was realized, which constructed a variety of structural motifs under exceedingly mild reaction conditions in a tandem process. Reaction driving tandem hydrosilyloxylation/aldol reactions was achieved through the formation of enol silyl ethers catalytically generated in situ from readily available alkynes. These reactions were expanded to obtain β-amino enol silyl ethers in good yields via the tandem hydrosilyloxylation/isomerization/Mannich reaction.     

Self-organization of bent rod molecules into hexagonally ordered vesicular columns

Bent-shaped rigid-core molecules with flexible chiral dendrons grafted to the outer side of the bend were synthesized and characterized by circular dichroism, differential scanning calorimetry, X-ray scatterings, and transmission electron microscopy in solution and the solid state. The bent aromatic rods based on hepta- and nonaphenylene with nitrile groups at both ends self-assemble into well-ordered hollow tubular structures in aqueous solution, while the bent rod based on heptaphenylene without nitrile groups showed no apparent aggregations in aqueous solution. In the solid state, the rigid-flexible molecules based on heptaphenylene rod without the nitrile group self-assemble into a 2D oblique columnar structure with the columnar cross-section containing two interlocked molecules. Remarkably, the rigid flexible molecules based on hepta-, nona-, and undecaphenylene with nitrile groups self-assemble into a hexagonal columnar structure with weak 3D order. A model of vesicular channel structure is proposed based on small- and wide-angle X-ray diffraction on oriented fibers, density measurement, reconstruction and simulation of electron density maps, and molecular dynamics simulation. In contrast to the hollow tubular structure found in solution, in the solid both the outside and the interior of the columns are filled by the pendant aliphatic coils. Filling of the interior of these vesicular channels is made possible by some bent rod molecules turning their obtuse apex inward. One in 7, 2 in 8, and 4 in 10 molecules are thus inverted in a column slice in compounds with hepta-, nona-, and undecaphenylene cores, respectively. These are new examples of vesicular double-segregated columnar structures recently discovered in some dendrons.     

Deprotection of dithioacetals with 30% hydrogen peroxide catalyzed by tantalum(V) chloride–sodium iodide or niobium(V) chloride–sodium iodide

The reaction of dithioacetals with 30% hydrogen peroxide in the presence of catalytic amounts of tantalum(V) and iodide ion effectively produced carbonyl compounds in high yields. Dithioacetals also can be deprotected using the niobium(V) catalyzed oxidation of iodide ion by hydrogen peroxide under mild conditions.