Reactivity of guanine at m5CpG steps in DNA: evidence for electronic effects transmitted through the base pairs.

BACKGROUND: Mitomycin C (MC), a DNA cross-linking and alkylating agent, targets guanines in the m5CpG sequence with 2-3-fold preference over guanines in unmethylated CpG. Benzo[a]pyrenediolepoxide (BPDE) and several other aromatic carcinogens form guanine adducts with an identical selectivity for m5CpG, and in certain cancers G to T transversion mutation 'hotspots' in the p53 tumor suppressor gene are more frequent at this sequence than at guanines in other sequences. MC appears suitable to probe the general mechanism of this selectivity. RESULTS: A 162-bp DNA fragment containing C, m5C or f5C (5-fluoro cytosine) at all cytosine positions was cross-linked by MC at guanines in CpG steps. The extent of cross-linking increased in the order f5C < C < m5C. Monoalkylation or cross-linking of duplex 12-mer oligonucleotides containing a single CpG, f5CpG or m5CpG step gave yields of adducts that increased in the same order. The rates showed a correlation with the Hammett sigma constant of the methyl and fluoro substituents of the cytosine. Only the base-pair cytosine substituent influenced reactivity of guanine. CONCLUSIONS: The 2-amino group of guanine in the m5CpG sequence of DNA has a greater nucleophilic reactivity with mitomycin than CpG. Evidence is presented for a novel mechanism: transmission of the electron-donating effect of the 5-methyl substituent of the cytosine to guanine through H-bonding of the m5C.G base pair. The results explain the enhanced reaction of BPDE at m5CpG in DNA and the origin of G-T mutational hotspots in the p53 gene in cancer.     

Multi-dimensional simulation of thermal non-equilibrium channel flow

The Homogenous Relaxation Model (HRM) is used to study thermal non-equilibrium, two-phase flows with flash-boiling and condensation. Typically, such non-equilibrium phase-change models have been studied in one-dimensional flow, but the goal of the present work is to create and utilize a multi-dimensional CFD implementation. The simulations are able to handle general polyhedral meshes, an important convenience for irregular channel or nozzle shapes. The model is applied to flash-boiling flow in short channels and validated against experimental measurements. The simulations predict the multi-dimensional features that have been observed in the past in experiments. Nozzle choking is also observed in the calculations.     

Influence of post-deposition annealing on the structural and optical properties of ZnO thin films prepared by sol–gel and spin-coating method

Thin films of zinc oxide have been deposited onto (0001) sapphire substrate by sol–gel and spin-coating methods. The XRD pattern showed that the crystallinity of the annealed ZnO films had improved in comparison with that of the as-grown films. Photoluminescence spectra revealed a two-line structure, which is identified in terms of UV emission and defect-related emission. The emission intensity was found to be greatly dependent on heat treatment. Host phonons of ZnO and a shift of the _E2$E_2$ (high) peak from its position have been observed from Raman spectra. The surface morphologies of the film had been improved after annealing was observed from AFM images.     

Solvent effects in the reaction between (anthracen‐9‐yl)methyl sulfides and electron‐deficient acetylenes

Solvent‐dependent diverse reactivity of (anthracen‐9‐yl)methyl sulfides with a few electron‐deficient acetylenes is described. Diversity in reactivity is attributed to competition between one electron transfer, two electron transfer and Diels–Alder reaction of these sulfides with electron‐deficient acetylenes. We have proposed plausible mechanisms to account for various reactions observed by us. Copyright © 2015 John Wiley & Sons, Ltd.     

Organoruthenium Antagonists of Human A3 Adenosine Receptors

Human A₃ adenosine receptor (hA₃AR) is a membrane‐bound G protein‐coupled receptor implicated in a number of severe pathological conditions, including cancer, in which it acts as a potential therapeutic target. To derive structure–activity relationships on pyrazolo–triazolo–pyrimidine (PTP)‐based A₃AR antagonists, we developed a new class of organometallic inhibitors through replacement of the triazolo moiety with an organoruthenium fragment. The objective was to introduce by design structural diversity into the PTP scaffold in order to tune their binding efficacy toward the target receptor. These novel organoruthenium antagonists displayed good aquatic stability and moderate binding affinity toward the hA₃ receptor in the low micromolar range. The assembly of these complexes through a template‐driven approach with selective ligand replacement at the metal center to control their steric and receptor‐binding properties is discussed.     

Theoretical prediction of spectroscopic constants of 1-alkoxy radicals

Spectroscopic constants for the conformers of the 1-alkoxy radicals were computed by ab initio and density functional methods. These parameters include ground and excited state rotational constants, harmonic frequencies, and and excitation energies. Elements of the electronic spin–molecular rotation tensor have also been predicted for the ground electronic state utilizing a simple transformation. The transformation employed the experimentally observed spin-rotation tensor of the ethoxy radical as a reference and the calculated rotational constants of the ethoxy radical and the investigated 1-alkoxy radicals. The predicted spectroscopic parameters are in good agreement with the experimental ones where available, and found to be useful parameters for assigning the rotationally resolved spectral bands to given conformers.     

Preparation and studies of a new ammonium vanadium bronze, (NH4)xV2O5

A new bronze-type phase of composition (NH₄)_0.40±0.02V₂O₅ is obtained around 230°C during the thermal decomposition of NH₄VO₃ in hydrogen atmosphere. The bronze intermediate is characterized by X-ray diffraction, electrical conductivity, magnetic susceptibility, and ESR studies. It is found to be isostructural with other known β-type vanadium bronzes of general formula M_xV₂O₅, where M is usually a monovalent metal. Electrical conductivity and magnetic studies indicate the localized character of conduction electrons at V⁺⁴ sites. At high temperatures (>400°C), the bronze undergoes decomposition and subsequent reduction to V₂O₃ in hydrogen atmosphere.