Salim Sioud

One-pot synthesis Of Cu/ZnO/ZnAl2O4 catalysts and their catalytic performance in glycerol hydrogenolysis

In this work, a series of Cu/ZnO/ZnAl2O4 catalysts with different metal molar fractions (Cu:Zn:Al) were successfully prepared using a one-pot method via the evaporation-induced self-assembly (EISA) of Pluronic P123 and the corresponding metal precursors. The catalysts were characterized using N2 adsorption, H2 temperature-programmed reduction (H2-TPR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectra (XPS). The catalytic properties of the resulting Cu/ZnO/ZnAl2O4 with different molar fractions of metals were investigated for the selective hydrogenolysis of glycerol to 1,2-propanediol (1,2-PDO). It was observed that the ZnAl2O4 support exerts a strong positive effect on the catalytic activity of the copper-based catalysts, and the presence of ZnO further improves the catalytic activity of the Cu/ZnAl2O4 catalysts. The Cu/ZnO/ZnAl2O4 catalyst (Cu10Zn30Al60, Cu/Zn/Al molar ratio is 10:30:60), which was the best catalyst, exhibited the highest yield (79%) of 1,2-PDO with 85.8% glycerol conversion and 92.1% 1,2-PDO selectivity at 180 °C reaction temperature in 80 wt% glycerol aqueous solution over 10 h reaction time. The high catalytic activity was attributed to the presence of the ZnAl2O4 support, the strong interaction between ZnO and Cu nanoparticles and the small particle size of ZnO and Cu. Moreover, the Cu/ZnO/ZnAl2O4 catalysts exhibited higher stability than Cu/ZnO and Cu/ZnO/Al2O3 catalysts prepared by a co-precipitation method during consecutive cycling experiments, which is due to the high chemical and thermal stability of crystalline ZnAl2O4 under harsh reaction conditions.

Bioequivalence assessment of two formulations of ibuprofen

Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz®, produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen®, manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%–125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen.

Unraveling the structure and chemical mechanisms of highly oxygenated intermediates in oxidation of organic compounds

Significance Highly oxygenated molecules are involved in autooxidation reactions leading to the formation of secondary organic aerosols (SOAs); they are also critical intermediates in autooxidation processes for liquid hydrogen degradation and the ignition of fuels in advanced combustion systems. However, these reactions are still poorly understood. In this study, we unveil a generalized reaction mechanism involving the autooxidation of peroxy radicals with at least three stages of sequential O2 addition. We elucidate important underlying kinetics and structural characteristics of autooxidation processes used for developing new technologies including those aimed at reducing climatically active SOAs and pollutants from fuel combustion. We show that advances can be made by bridging experimental and theoretical methods used by atmospheric and combustion scientists. Decades of research on the autooxidation of organic compounds have provided fundamental and practical insights into these processes; however, the structure of many key autooxidation intermediates and the reactions leading to their formation still remain unclear. This work provides additional experimental evidence that highly oxygenated intermediates with one or more hydroperoxy groups are prevalent in the autooxidation of various oxygenated (e.g., alcohol, aldehyde, keto compounds, ether, and ester) and nonoxygenated (e.g., normal alkane, branched alkane, and cycloalkane) organic compounds. These findings improve our understanding of autooxidation reaction mechanisms that are routinely used to predict fuel ignition and oxidative stability of liquid hydrocarbons, while also providing insights relevant to the formation mechanisms of tropospheric aerosol building blocks. The direct observation of highly oxygenated intermediates for the autooxidation of alkanes at 500–600 K builds upon prior observations made in atmospheric conditions for the autooxidation of terpenes and other unsaturated hydrocarbons; it shows that highly oxygenated intermediates are stable at conditions above room temperature. These results further reveal that highly oxygenated intermediates are not only accessible by chemical activation but also by thermal activation. Theoretical calculations on H-atom migration reactions are presented to rationalize the relationship between the organic compound’s molecular structure (n-alkane, branched alkane, and cycloalkane) and its propensity to produce highly oxygenated intermediates via extensive autooxidation of hydroperoxyalkylperoxy radicals. Finally, detailed chemical kinetic simulations demonstrate the influence of these additional reaction pathways on the ignition of practical fuels.

Synthesis of Fluoroalkoxy Substituted Arylboronic Esters by Iridium-Catalyzed Aromatic C–H Borylation

The preparation of fluoroalkoxy arylboronic esters by iridium-catalyzed aromatic C-H borylation is described. The fluoroalkoxy groups employed include trifluoromethoxy, difluoromethoxy, 1,1,2,2-tetrafluoroethoxy, and 2,2-difluoro-1,3-benzodioxole. The borylation reactions were carried out neat without the use of a glovebox or Schlenk line. The regioselectivities available through the iridium-catalyzed C-H borylation are complementary to those obtained by the electrophilic aromatic substitution reactions of fluoroalkoxy arenes. Fluoroalkoxy arylboronic esters can serve as versatile building blocks.

Investigation of the ionization mechanism of polycyclic aromatic hydrocarbons using an ethanol/bromobenzene/chlorobenzene/anisole mixture as a dopant in liquid chromatography/atmospheric pressure photoionization mass spectrometry

RATIONALE An ethanol-based multicomponent dopant consisting of ethanol/chlorobenzene/bromobenzene/anisole (98.975:0.1:0.9:0.025, v/v/v/v) has been used as a dopant for atmospheric pressure photoionization (APPI) of polycyclic aromatic hydrocarbons (PAHs). In this study the mechanism of ionization of PAHs assisted by the ethanol-based multicomponent dopant is investigated. METHODS The reactant background cluster ions of the ethanol-based multicomponent dopant observed in the positive ion APPI were studied. These studies were performed to investigate the mechanism behind the generation of a molecular radical cation (M(+•)) for PAHs by APPI assisted by the ethanol-based multicomponent dopant. Full scan and MS/MS analyses were conducted using an LTQ Orbitrap mass spectrometer. The effect of acidification of the mobile phase on the dopant cluster ion formation was also investigated. RESULTS With the ethanol-based multicomponent dopant, a single type of molecular radical cation M(+•) was observed for the studied PAHs. The characteristic ion signal of the multicomponent dopant mixture consisted of mainly anisole photoions at m/z 108.05697 and its adduct ions at m/z 124.05188 and 164.07061. The anisole ion response at m/z 108.05697 was stable in the presence of acetonitrile, methanol, water and 0.1% formic acid mobile phase composition. CONCLUSIONS The abundance formation of anisole photoions shows the universality of this multicomponent dopant in ionizing compounds with ionization energy ranging from 7.1-8.2 eV. Since the ionization energy of anisole is 8.2 eV and is lower than those of chlorobenzene (9.07 eV) and bromobenzene (9.0 eV), the mechanism of formation of anisole photoions even with its very minute amounts was not only governed by its photoionization by the krypton lamp photon energy (10.0 eV and 10.6 eV), but also by charge transfer from bromobenzene and chlorobenzene radical cations. PAH molecules were mainly ionized by charge transfer reaction from photoionized anisole and oxidized anisole radical cations as well as by the krypton lamp.

Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia’s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

Synthesis and evaluation of modified chalcone based p53 stabilizing agents

Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death in response to various cellular stresses thereby preventing cancer development. Activation and stabilization of p53 through small organic molecules is, therefore, an attractive approach for the treatment of cancers retaining wild-type p53. In this context, a series of nineteen chalcones with various substitution patterns of functional groups including chloro, fluoro, methoxy, nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt condensation. The compounds were characterized using NMR, HRMS, IR and melting points. Evaluation of synthesized compounds against human colorectal (HCT116) and breast (CAL-51) cancer cell lines revealed potent antiproliferative activities. Nine compounds displayed GI50 values in the low micromolar to submicromolar range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (SSE14108) showed GI50 of 0.473±0.043µM against HCT116 cells. Further analysis of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused rapid (4 and 8-h post-treatment) accumulation of p53 in HCT116 cells similar to its induction by positive control, Nutlin-3. Such activities were absent in 3-(4-methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of conjugated ketone for antiproliferative and p53 stabilizing activity of the chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX) and the results showed that the p53 stabilization was regulated at post-translational level through blockage of its degradation. These chalcones can, therefore, act as fragment leads for further structure optimization to obtain more potent p53 stabilizing agents with enhanced anti-proliferative activities.

The formation of [M-H]+ ions in N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during atmospheric pressure photoionization mass spectrometry.

RATIONALE The formation of ions during atmospheric pressure photoionization (APPI) mass spectrometry in the positive mode usually provides radical cations and/or protonated species. Intriguingly, during the analysis of some N-alkyl-substituted thieno[3,4-c]pyrrole-4,6-dione (TPD) derivatives synthesized in our laboratory, unusual [M-H](+) ion peaks were observed. In this work we investigate the formation of [M-H](+) ions observed under APPI conditions. METHODS Multiple experimental parameters, including the type of ionization source, the composition of the solvent, the type of dopant, the infusion flow rate, and the length of the alkyl side chain were investigated to determine their effects on the formation of [M-H](+) ions. In addition, a comparison study of the gas-phase tandem mass spectrometric (MS/MS) fragmentation of [M + H](+) vs [M-H](+) ions and computational approaches were used. RESULTS [M-H](+) ions were observed under APPI conditions. The type of dopant and the length of the alkyl chain affected the formation of these ions. MS/MS fragmentation of [M-H](+) and [M + H](+) ions exhibited completely different patterns. Theoretical calculations revealed that the loss of hydrogen molecules from the [M + H](+) ions is the most favourable condition under which to form [M-H](+) ions. CONCLUSIONS [M-H](+) ions were detected in all the TPD derivatives studied here under the special experimental conditions during APPI, using a halogenated benzene dopant, and TPD containing substituted N-alkyl side chains with a minimum of four carbon atoms. Density functional theory calculations showed that for [M-H](+) ions to be formed under these conditions, the loss of hydrogen molecules from the [M + H](+)  ions is proposed to be necessary.

Technical report: Development of a piezoelectric inkjet dopant delivery device for an atmospheric pressure photoionization source with liquid chromatography/mass spectrometry

This paper describes a simple, robust and integrated piezoelectric actuated printhead as a dopant delivery system for atmospheric pressure photoionization with liquid chromatography/mass spectrometry. The newly designed dopant delivery system avoids problems associated with traditional liquid delivery systems such as solvent immiscibility, backpressure and increased post-column dead volume issues. The performance of the new device was tested and evaluated using chlorobenzene as a dopant with a test mixture consisting of 18 different polycyclic aromatic hydrocarbons (PAHs). The results show that the new system works robustly at low dopant consumption level (1.6 uL min−1), consuming only approximately 5% of the amount used by conventional sources. The low dopant consumption has resulted in up to a 20-fold reduction in signal intensity of tested PAH molecules, but has led to less presence of background cluster ions and dopant trace contaminant background ions in the source area. Consequently, all tested PAHs were detected with excellent signal-to-noise ratio with at least two- to ten-fold improvements in the limit of detection and quantification compared to those obtained with traditional dopant assistance using a post-column addition method.

Identification of a 3-Alkylpyridinium Compound from the Red Sea Sponge Amphimedon chloros with In Vitro Inhibitory Activity against the West Nile Virus NS3 Protease

Viruses are underrepresented as targets in pharmacological screening efforts, given the difficulties of devising suitable cell-based and biochemical assays. In this study we found that a pre-fractionated organic extract of the Red Sea sponge Amphimedon chloros was able to inhibit the West Nile Virus NS3 protease (WNV NS3). Using liquid chromatography–mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the identity of the bioactive compound was determined as a 3-alkylpyridinium with m/z = 190.16. Diffusion Ordered Spectroscopy (DOSY) NMR and NMR relaxation rate analysis suggest that the bioactive compound forms oligomers of up to 35 kDa. We observed that at 9.4 μg/mL there was up to 40–70% inhibitory activity on WNV NS3 protease in orthogonal biochemical assays for solid phase extracts (SPE) of A. chloros. However, the LC-MS purified fragment was effective at inhibiting the protease up to 95% at an approximate amount of 2 µg/mL with negligible cytotoxicity to HeLa cells based on a High-Content Screening (HCS) cytological profiling strategy. To date, 3-alkylpyridinium type natural products have not been reported to show antiviral activity since the first characterization of halitoxin, or 3-alkylpyridinium, in 1978. This study provides the first account of a 3-alkylpyridinium complex that exhibits a proposed antiviral activity by inhibiting the NS3 protease. We suggest that the here-described compound can be further modified to increase its stability and tested in a cell-based assay to explore its full potential as a potential novel antiviral capable of inhibiting WNV replication.