Quantum chemical study on influence of substituents and solvents in reaction complexing ethylene with nickel dithiolene

The influences induced by various terminal substituents and solvents on the reaction mechanism and chemical dynamics of complexing ethylene with Ni dithiolene are theoretically studied by using B3LYP method and Onsager model. It is shown that the reaction should be a two-step process, and the first step is the rate-determining step. We find that the rate constant of the rate-determining step becomes small when the electron-donating ability of the substituents is increased, while it becomes large when the electron-withdrawing ability of the substituents is increased. Subsequently, we consider the solvent effects on the reaction adding ethylene to the simplified hydrogen-substituted nickel dithiolene. It is found that the solvents will make slight changes to the geometries of the reactants, transition states, intermediates and products. However, the corresponding molecular dipole moments become large with the increase of the solvent polarity, which is beneficial to accelerate the reaction. Moreover, we show that, as the solvent polarity becomes large, the activation energies of the reaction decrease exponentially, while the reaction rate constants increase exponentially. These results demonstrate that in polar solvents, the reaction complexing ethylene with Ni dithiolene may become easier and faster to occur, and the product rate is improved. We believe that this research can be seen as a reference for complex and solvent selection in olefin separation process.     

A novel model for the molecular dynamics simulation study on mechanical properties of HMX/F2311 polymer-bonded explosive

The ‘insert’ model for β-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX)-based polymer-bonded explosive (PBX) was proposed for finding the relation of temperatures with mechanical properties. This model was simulated by using molecular dynamics models. The elastic constants and the effective moduli were calculated with static analysis method. Cauchy pressure was also calculated. It is found that the rigidity is weakened and the ductibility is improved by adding a small amount of F₂₃₁₁ in the crystalline HMX. The rigidity is also weakened with increasing temperature. However, the ductibility of HMX/F₂₃₁₁ PBX changes as a parabola with increasing temperature duo to the enhancement of F₂₃₁₁ molecular chain movement and simultaneously the increment of high energy conformation ratio in this molecular chain, i.e. the increment of the molecular chain rigidity.     

ATM pathway is essential for ionizing radiation-induced autophagy

BackgroundATM plays an important role in response to DNA damage, while the roles of ATM in radiation-induced autophagy are still unclear in cervical cancer cells.MethodsHuman cervical cancer cells, Hela, were used, and cell models with ATM^?/? and MAPK14^?/? were established by gene engineering. Western blot was implemented to detect protein expression. MDC staining and GFP-LC3 relocalization were used to detect autophagy. CCK-8 was used to detect cell viability. Radiosensitivity was analyzed by colony formation assays. Co-immunoprecipitation was used to detect the interaction between different proteins, and apoptosis was detected by flow cytometry.ResultsAfter radiation autophagy was induced, illustrated by the increase of MAPLC3-II/MAPLC3-I ratio and decrease of p62, and phosphorylation of ATM simultaneously increased. ATM^?/? cells displayed hypersensitivity but had no influence on IR-induced apoptosis. Then inhibitor of ATM, KU55933, ATM and MAPK14 silencing were used, and autophagy was induced by IR more than 200% in control, and only by 35.72%, 53.18% and 24.76% in KU55933-treated cells, ATM^?/? and MAPK14^?/? cells, respectively. KU55933 inhibited IR-induced autophagy by activating mTOR pathways. ATM silencing decreased the expression of MAPK14 and mTOR signals significantly. Beclin's bond to PI3KIII and their interaction increased after IR, while in ATM^?/? and MAPK14^?/? cells this interaction decreased after IR. Both ATM and MAPK14 interacted with Beclin, while ATM^?/? and MAPK14^?/? cells showed no interaction.ConclusionsATM could promote IR-induced autophagy via the MAPK14 pathway, the mTOR pathway, and Beclin/PI3KIII complexes, which contributed to the effect of ATM on radiosensitivity.     

DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis

Hepatic stellate cell (HSC) activation plays an important role in liver fibrogenesis. Transdifferentiation of quiescent hepatic stellate cells into myofibroblastic-HSCs is a key event in liver fibrosis. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. MeCP2 binds to methylated CpG dinucleotides, which are abundant in the promoters of many genes. Treatment of HSCs with DNA methylation inhibitor 5-aza-2′- deoxycytidine (5-azadC) prevented proliferation and activation. Treatment with 5-azadC prevented loss of Patched (PTCH1) expression that occurred during HSCs activation. In a search for underlying molecular medchanisms, we investigated whether the targeting of epigenetic silencing mechanisms could be useful in the treatment of PTCH1-associated fibrogenesis. It was indicated that hypermethylation of PTCH1 is associated with the perpetuation of fibroblast activation and fibrosis in the liver. siRNA knockdown of MeCP2 increased the expressions of PTCH1 mRNA and protein in hepatic myofibroblasts. These data suggest that DNA methylation and MeCP2 may provide molecular mechanisms for silencing of PTCH1.     

Enantioselective Synthesis and Antimicrobial Activities of Tetrahydro‐Β‐Carboline Diketopiperazines

A series of single isomers tetrahydro‐β‐carboline diketopiperazines were stereoselectively synthesized starting from l ‐tryptophan methyl ester hydrochloride and six aldehydes through a four‐step reaction including Pictet‐Spengler reaction, crystallization‐induced asymmetric transformations (CIAT), Schotten‐Baumann reaction, and intramolecular ester amidation. The chemical structures were characterized by nuclear magnetic resonance (NMR) and elemental analysis, among which two compounds were determined by x‐ray single crystal diffraction. Moreover, antimicrobial activities of all the compounds were also tested. Chirality 25:656–662, 2013. © 2013 Wiley Periodicals, Inc.     

Design and Synthesis of Fluoroacylshikonin as an Anticancer Agent

A series of shikonin derivatives, selectively acylated by various fluorinated carboxylic acids at the side chain of shikonin, were synthesized and their anticancer activity evaluated, in which eight compounds are reported for the first time. Among all the compounds tested, compound S7 showed the most potent anticancer activity against B16‐F10 (malignant melanoma cells), MG63 (human osteosarcoma cells), and A549 (lung cancer cells) with IC₅₀ 0.39 ± 0.01, 0.72 ± 0.04 and 0.58 ± 0.02 µmol/L. Docking simulation of compound S7 was carried out to position S7 into a tubulin active site to determine the probable binding conformation. All the results suggested that compound S7 may be a potential anticancer agent. Chirality 25:757–762, 2013. © 2013 Wiley Periodicals, Inc.     

Life: Self-Directing with Unlimited Variability on Self-Speeding

Abstract

The crystal structure of the deoxyoctamer d(G-G-^Br U-A-^BrU-A-C-C) was refined to a resolution of 1.7Å using combined diffractometer and synchrotron data. The analysis was carried out independently in two laboratories using different procedures. Although the final results are identical the comparison of the two approaches highlights potential problems in the refinement of oligonucleotides when only limited data are available.

As part of the analysis the positions of 84 solvent molecules in the asymmetric unit were established. The DNA molecule is highly solvated, particularly the phosphate-sugar backbone and the functional groups of the bases. The major groove contains, in the central ^BrU-A-^BrU-A region, a ribbon of water molecules forming closed pentagons with shared edges. These water molecules are linked to the base O and N atoms and to the solvent chains connecting the O-1 phosphate oxygen atoms on each strand. The minor groove is also extensively hydrated with a continuous network in the central region and other networks at each end. The pattern of hydration is briefly compared with that observed in the crystal structure of a B-dodecamer.     

A possible strategy against head and neck cancer: in silico investigation of three-in-one inhibitors

Overexpression of epidermal growth factor receptor (EGFR), Her2, and uroporphyrinogen decarboxylase (UROD) occurs in a variety of malignant tumor tissues. UROD has potential to modulate tumor response of radiotherapy for head and neck cancer, and EGFR and Her2 are common drug targets for the treatment of head and neck cancer. This study attempts to find a possible lead compound backbone from TCM Database@Taiwan (http://tcm.cmu.edu.tw/) for EGFR, Her2, and UROD proteins against head and neck cancer using computational techniques. Possible traditional Chinese medicine (TCM) lead compounds had potential binding affinities with EGFR, Her2, and UROD proteins. The candidates formed stable interactions with residues Arg803, Thr854 in EGFR, residues Thr862, Asp863 in Her2 protein, and residues Arg37, Arg41 in UROD protein, which are key residues in the binding or catalytic domain of EGFR, Her2, and UROD proteins. Thus, the TCM candidates indicated a possible molecule backbone for evolving potential inhibitors for three drug target proteins against head and neck cancer.

An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:35     

Overexpression of TaHSF3 in Transgenic Arabidopsis Enhances Tolerance to Extreme Temperatures

Heat shock factors (HSFs) in plants regulate heat stress response by mediating expression of a set of heat shock protein (HSP) genes. In the present study, we isolated a novel heat shock gene, TaHSF3, encoding a protein of 315 amino acids in wheat. Phylogenetic analysis showed that TaHSF3 belonged to HSF class B2. Subcellular localization analysis indicated that TaHSF3 localized in nuclei. TaHSF3 was highly expressed in wheat spikes and showed intermediate expression levels in roots, stems, and leaves under normal conditions. It was highly upregulated in wheat seedlings by heat and cold and to a lesser extent by drought and NaCl and ABA treatments. Overexpression of TaHSF3 in Arabidopsis enhanced tolerance to extreme temperatures. Frequency of survival of three TaHSF3 transgenic Arabidopsis lines was 75–91 % after heat treatment and 85–95 % after freezing treatment compared to 25 and 10 %, respectively, in wild-type plants (WT). Leaf chlorophyll contents of the transformants were higher (0.52–0.67 mg/g) than WT (0.35 mg/g) after heat treatment, and the relative electrical conductivities of the transformants after freezing treatment were lower (from 17.56 to 18.6 %) than those of WT (37.5 %). The TaHSF3 gene from wheat therefore confers tolerance to extreme temperatures in transgenic Arabidopsis by activating HSPs, such as HSP70.