Ring-opening carbonyl–olefin metathesis of norbornenes

A computational and experimental study of the hydrazine-catalyzed ring-opening carbonyl–olefin metathesis of norbornenes is described. Detailed theoretical investigation of the energetic landscape for the full reaction pathway with six different hydrazines revealed several crucial aspects for the design of next-generation hydrazine catalysts. This study indicated that a [2.2.2]-bicyclic hydrazine should offer substantially increased reactivity versus the previously reported [2.2.1]-hydrazine due to a lowered activation barrier for the rate-determining cycloreversion step, a prediction which was verified experimentally. Optimized conditions for both cycloaddition and cycloreversion steps were identified, and a brief substrate scope study for each was conducted. A complication for catalysis was found to be the slow hydrolysis of the ring-opened hydrazonium intermediates, which were shown to suffer from a competitive and irreversible cycloaddition with a second equivalent of norbornene. This problem was overcome by the strategic incorporation of a bridgehead methyl group on the norbornene ring, leading to the first demonstrated catalytic carbonyl–olefin metathesis of norbornene rings.

A computational and experimental study has uncovered a second generation hydrazine that enables the catalytic ring-opening carbonyl–olefin metathesis of norbornenes.     

Polypyridyl-Based Copper Phenanthrene Complexes: Combining Stability with Enhanced DNA Recognition

We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (K_app) rising from 10⁵ to 10⁷ m ⁻¹ with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine–cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumour cells with in-vitro results surpassing the clinical platinum(II) drug oxaliplatin.     

In Vitro Inhibitory Analysis of Rationally Designed siRNAs against MERS-CoV Replication in Huh7 Cells

MERS-CoV was identified for the first time in Jeddah, Saudi Arabia in 2012 in a hospitalized patient. This virus subsequently spread to 27 countries with a total of 939 deaths and 2586 confirmed cases and now has become a serious concern globally. Camels are well known for the transmission of the virus to the human population. In this report, we have discussed the prediction, designing, and evaluation of potential siRNA targeting the ORF1ab gene for the inhibition of MERS-CoV replication. The online software, siDirect 2.0 was used to predict and design the siRNAs, their secondary structure and their target accessibility. ORF1ab gene folding was performed by RNAxs and RNAfold software. A total of twenty-one siRNAs were selected from 462 siRNAs according to their scoring and specificity. siRNAs were evaluated in vitro for their cytotoxicity and antiviral efficacy in Huh7 cell line. No significant cytotoxicity was observed for all siRNAs in Huh7 cells. The in vitro study showed the inhibition of viral replication by three siRNAs. The data generated in this study provide preliminary and encouraging information to evaluate the siRNAs separately as well as in combination against MERS-CoV replication in other cell lines. The prediction of siRNAs using online software resulted in the filtration and selection of potential siRNAs with high accuracy and strength. This computational approach resulted in three effective siRNAs that can be taken further to in vivo animal studies and can be used to develop safe and effective antiviral therapies for other prevalent disease-causing viruses.     

Surface Interaction of Ionic Liquids: Stabilization of Polyethylene Terephthalate-Degrading Enzymes in Solution

The effect of aqueous solutions of selected ionic liquids solutions on Ideonella sakaiensis PETase with bis(2-hydroxyethyl) terephthalate (BHET) substrate were studied by means of molecular dynamics simulations in order to identify the possible effect of ionic liquids on the structure and dynamics of enzymatic Polyethylene terephthalate (PET) hydrolysis. The use of specific ionic liquids can potentially enhance the enzymatic hydrolyses of PET where these ionic liquids are known to partially dissolve PET. The aqueous solution of cholinium phosphate were found to have the smallest effect of the structure of PETase, and its interaction with (BHET) as substrate was comparable to that with the pure water. Thus, the cholinium phosphate was identified as possible candidate as ionic liquid co-solvent to study the enzymatic hydrolyses of PET.     

Characterization of superparamagnetic Mg x Zn1−x Fe2O4 powders

Structural and magnetic properties of Mg _x Zn_1−x Fe₂O₄ powders have been studied with respect to the application for thermal cancer therapy (magnetic hyperthermia). Mg _x Zn_1−x Fe₂O₄ (x=0.1–0.5) powders with particle sizes between 5 and 8 nm were produced by citrate method. The X-ray diffraction patterns of the samples correspond to a spinel phase. The lattice constant and the volume of the elementary cell increase when x changes from 0.1 to 0.5. The FTIR-spectra ascertain the spinel phase formation. The Mossbauer studies reveal the presence of extremely small particles, which undergo superparamagnetic relaxation at room temperature. The core-shell model has been applied to explain quadruple doublets. The quadruple splitting at “shells” is bigger than those at “cores” whereas the isomer shifts remain close. Magnetic studies confirm the presence of extremely small particles that behave as superparamagnetic ones.      

Chemical analysis of size-tailored magnetic colloids using slurry nebulization in ICP-OES

In this work, inductively coupled plasma emission spectroscopy was utilized to directly determine the chemical composition of magnetic fluids constituted of size-sorted ferrite nanoparticles in aqueous solution. Nickel and cobalt nanoferrites were chemically synthesized following a bottom-up route and dispersed under various pH conditions. Size and structural characteristics of nanograins were investigated by X-ray diffraction using a synchrotron source. Chemical analysis was then carried out by directly introducing diluted magnetic fluid samples (slurries) into the spectrometer. To achieve reliable measurements, sample conditions and apparatus parameters were carefully investigated. Slurry stability must be optimized in order to obtain reproducible and accurate analysis. The instrument must also be calibrated to minimize the difference between the signal produced by slurries and that of aqueous ordinary solutions. Furthermore, slurry sample introduction offers many advantages over conventional sample digestion, including reduced sample pretreatment time, less possibility of contamination and the use of direct calibration with aqueous solutions.     

Finite Genome Length Corrections for the Mean Fitness and Gene Probabilities in Evolution Models

Using the Hamilton–Jacobi equation approach to study genomes of length L, we obtain 1/L corrections for the steady state population distributions and mean fitness functions for horizontal gene transfer model, as well as for the diploid evolution model with general fitness landscapes. Our numerical solutions confirm the obtained analytic equations. Our method could be applied to the general case of nonlinear Markov models.     

Assessment of coal and ash environmental impact with the use of gamma- and X-ray spectrometry

Gamma-ray spectrometry (GS), energy dispersive X-ray fluorescence (EDXRF) analysis methods and wavelength dispersive X-ray fluorescence (WDXRF) were applied for the studies of some coal components, e.g., sulphur, light and heavy metal element concentrations and naturally occurring radioactive isotope contents. Hundred fifty coal samples originating mostly from eight different coal mines from Upper Silesian Coal Basin and 150 samples of ash obtained from these coal samples in laboratory by total combustion at final temperature of 820°C, were analyzed. Such comparitive analyses can be helpful in selection of most suitable kind of coal for burning in electrical power and heat plants to minimize the environmental pollution.     

Isolation,characterization, and quantification of curcuminoids and their comparative effects in cerebral ischemia

The study reports a rapid and short analytical technique for separation, characterization, and quantitation along with comparative pharmacological effect of curcuminoids in cerebral ischemia. Flash chromatography, using silica and diol columns along with gradient mobile phase, was utilized to separate three curcuminoids, i.e., curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) for the first time. The separated peaks were monitored at 200–360?nm, whereas the purity of compounds (96.2–97.6%) was determined through qualitative analysis such as infrared and ¹H and ¹³C-nuclear magnetic resonance spectroscopy, mass spectrometry (MS), and differential scanning calorimetry. Furthermore, chitosan nanoparticles (CS-NPs) for curcuminoids were prepared and characterized through zeta sizer, zeta potential, scanning electron microscopy, and transmission electron microscopy. The developed ultra performance of liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry/mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) method showed simplified automation and shorter run time for Combi flash over conventional separation techniques. The CS-NPs for all the three curcuminoids and combined-curcuminoids (CCr) (combined and administered together for a synergistic effect), following intranasal administration in middle cerebral artery–occluded rats were evaluated for grip strength, locomotor activity, and histopathological examination where the anti-ischemic activity was observed, in terms of potency, for all three CS-NPs and CCr as CCr>Cur>DMC>>BDMC. Cur-CS-NPs exhibited more potency among Cur, DMC, and BDMC, whereas CCr was the more potent anti-ischemic drug compared to Cur, DMC, and BDMC. For Cur the characteristic activity is proposed because of the presence of methoxy group on the phenyl ring whereas for CCr it is synergistic effect of curcuminoids.     

Adsorption and preconcentration of divalent metal ions in fossil fuels and biofuels: gasoline, diesel, biodiesel, diesel-like and ethanol by using chitosan microspheres and thermodynamic approach

Biodiesel and diesel-like have been obtained from soybean oil by transesterification and thermal cracking process, respectively. These biofuels were characterized as according to ANP standards by using specific ASTM methods. Ethanol, gasoline, and diesel were purchased from a gas station. Deacetylation degree of chitosan was determined by three distinct methods (conductimetry, FTIR and NMR), and the average degree was 78.95%. The chitosan microspheres were prepared from chitosan by split-coating and these spheres were crosslinked using glutaraldehyde. The surface area of microspheres was determined by BET method, and the surface area of crosslinked microspheres was 9.2 m² g⁻¹. The adsorption isotherms of cooper, nickel and zinc on microspheres of chitosan were determined in petroleum derivatives (gasoline and diesel oil), as well as in biofuels (alcohol, biodiesel and diesel-like). The adsorption order in all fuels was: Cu > Ni > Zn. The elution tests presented the following preconcentration degrees: >4.5 to ethanol, >4.4 to gasoline, >4.0 to diesel, >3.8 to biodiesel and >3.6 to diesel-like. The application of chitosan microspheres in the metal ions preconcentration showed the potential of this biopolymer to enrich fuel sample in order to be analyzed by flame atomic absorption spectrometry.