Uzma I. Zakai

Electrochemical and chemical oxidation of dithia-, diselena-, ditellura-, selenathia-, and tellurathiamesocycles and stability of the oxidized species.

The diverse electrochemical and chemical oxidations of dichalcogena-mesocycles are analyzed, broadening our understanding of the chemistry of the corresponding radical cations and dications. 1,5-Diselenocane and 1,5-ditellurocane undergo reversible two-electron oxidation with inverted potentials analogous to 1,5-dithiocane. On the other hand, 1,5-selenathiocane and 1,5-tellurathiocane undergo one-electron oxidative dimerization. The X-ray crystal structures of the Se-Se dimer of the 1,5-selenathiocane one-electron oxidized product and the monomeric two-electron oxidized product (dication) of 1,5-tellurathiocane are reported. 1,5-Dithiocanes and 1,5-diselenocanes with group 14 atoms as ring members undergo irreversible oxidation, unlike the reversible two-electron oxidation of the corresponding silicon-containing 1,5-ditellurocanes. These results demonstrate the chemical consequences of the dication stabilities Te(+)-Te(+) > Se(+)-Se(+) > S(+)-S(+), as well as Se(+)-Se(+) > Se(+)-S(+) and Te(+)-Te(+) > Te(+)-S(+).

Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide.

Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions.

Hydrodeoxygenation of Phenol and Derivatives over an Ionic Liquid‐Like Copolymer Stabilized Nanocatalyst in Aqueous Media

Using phenolic bio‐oil as feedstock for sustainable production of alkane fuels is of great significance. Here, the hydrodeoxygenation of phenol and its derivatives has been systematically investigated in aqueous media with a dual‐functional catalyst system consisting of water‐soluble, ionic liquid‐like copolymer A‐stabilized nanocatalysts and the mineral acid H3PO4. The developed Ru/A‐H3PO4 catalyst system achieved a complete phenol conversion with cyclohexane selectivity higher than 99 %, making it by far one of the most efficient systems for phenol hydrodeoxygenation. Mercury poisoning experiments revealed that the in situ generated Ru nanoparticles are true a heterogeneous catalyst for hydrogenation. The catalytic activity of metal site for phenol hydrodeoxygenation to cyclohexane decreased with the order of Ru>Rh>Pt≫Pd. Our findings also demonstrated the delicate balance between activity and stability of ionic liquid‐like copolymer‐stabilized nanocatalysts. The research highlights an efficient catalyst system of transforming phenols into alkanes.

Synthesis and structure of m-terphenyl thio-, seleno-, and telluroethers.

Several routes for the synthesis of m-terphenyl thio-, seleno-, and telluroethers were investigated. m-Terphenyl iodides react with diphenyl diselenides or ditellurides (CsOH·H(2)O, DMSO, 110 °C) to give the desired compounds in 19-84% yield which significantly extends the previously reported such reactions because o-benzyne cannot be an intermediate as previously suggested. However, the most general synthetic route was that involving reaction of 2,6-diaryl Grignard reagents with sulfur, selenium, or tellurium electrophiles. The m-terphenyl thio-, seleno-, and telluroethers were characterized spectroscopically and, in one case, by single-crystal X-ray analysis. Certain of these compounds showed atropisomerism and barriers for interconversion of isomers were determined by variable-temperature NMR spectroscopy. The barriers for interconverting the syn and anti atropisomers increase on going from the analogous S to Se to Te compounds. Calculations on this isomerization revealed that the barriers are due to rotation about the aryl-aryl bond and that the barriers for rotation about the aryl-chalcogen bond are much lower.

Anodic oxidation of m -terphenyl thio-, seleno- and telluroethers: Lowered oxidation potentials due to chalcogen···π interaction

The electrochemistry of m-terphenylthio-, seleno-, and telluroethers was studied using cyclic voltammetry in acetonitrile. All of the compounds studied showed irreversible oxidations. The first oxidation potentials for the thio- and selenoethers are less positive than expected. This facilitation in oxidation is ascribed to through-space S···π and Se···π inter-action, respectively, on removal of an electron. No evidence for a comparable effect was found for the phenyltelluro-ethers studied.

Synthesis and Biological Screening of Silicon-Containing Ibuprofen Derivatives: A Study of Their NF-κβ Inhibitory Activity, Cytotoxicity, and Their Ability to Bind IKKβ

The synthesis and characterisation of new silicon-containing amides and esters derived from ibuprofen is reported. These compounds were tested against nuclear transcription factor κβ (NF-κβ). Higher inhibition values than those of ibuprofen were achieved by the new amides 10a–10d; ester derivatives did not show inhibitory activity. The cytotoxicity of these new derivatives was screened; none of them displayed significant toxicity at the screened doses. A molecular docking calculation on IKKβ (an enzyme related to NF-κβ activation) was carried out and the results showed that the amides interact better than ibuprofen with key residues, which are important to the inhibition of IKKβ.

2-[3-(Methyl­diphenyl­silyl)prop­yl]isoindoline-1,3-dione

In the title compound, C24H23NO2Si, the dihedral angle between the planes of the phenyl rings attached to the Si atom is 80.78 (10)°. In the crystal, the molecules form sheets lying perpendicular to [101] via C—H⋯O interactions. These sheets are stacked and linked in a three-dimensional framework by additional C—H⋯O interactions in the [10] direction.

2-{[(4-Methoxy-phen-yl)dimethyl-silyl]meth-yl}isoindoline-1,3-dione.

In the course of our studies of silicon-containing anticancer compounds, the title compound, C18H19NO3Si, was synthesized. The molecular geometry including bond distances and angles involving the Si atoms are typical. Torsion angles associated with the isoindoline ring and the silyl group [C—N—Cmethylene—Si = 90.5 (2) and −93.1 (2)°] indicate that there is no interaction between the O and Si atoms despite silicon’s high affinity for oxygen.

2-[2-(Trimethyl­silyl)eth­yl]isoindoline-1,3-dione

In the course of our studies of silicon-containing anticancer compounds, the title compound, C13H17NO2Si, was synthesized. The geometrical parameters including the geometry about the Si atom are typical. The molecules form dimers via a weak C—H⋯O interaction described by the graph set R 2 2(10). The dimers are assembled in rows stacked in the crystallographic b-axis direction via π–π interactions with a 3.332 (3) Å separation between the rows.

Chemistry of Mixed Sulfur-, Selenium-, or Tellurium- and Silicon-, or Tin-Containing Heterocycles

Lone pair ionization energies for 1,5-dichalcogenocanes containing endocyclic 3,7-R2Si groups and the parent 1,5-dichalcogenocanes, estimated from the TCNE charge-transfer wavelength maxima, are in good agreement with ionization energies directly obtained from photoelectron spectroscopy. These data indicate the occurrence of substantial intra-annular interaction between the chalcogen atoms and silyl groups, consistent with the well-known β -effect of silicon and the novel β-disilyl effect, when R (in R 2 Si) is Me 3 Si.