Assessment of the N-oxidation of deprenyl, methamphetamine, and amphetamine enantiomers by chiral capillary electrophoresis: an in vitro metabolism study

A chiral capillary electrophoresis method using hydroxypropyl-beta-cyclodextrin as chiral selector was developed and validated for the quantification of the N-oxygenated metabolites of deprenyl, methamphetamine, and amphetamine enantiomers, formed in vitro. The influence of various parameters (selector concentration, buffer pH, temperature, polymer additive, etc.) on the simultaneous separation of the optical isomers of the parent drugs and their metabolites has been evaluated. The buffer pH had the greatest impact on the separation selectivity of the N-oxygenated compounds. Linear calibration curves were obtained over the concentration range of 2.5-50 microM for the enantiomers of amphetamine-hydroxylamine, methamphetamine-hydroxylamine, and deprenyl-N-oxide. The inter- and intra-assay precision and accuracy varied by less than 15% for all analytes at concentrations of 5, 10, and 30 microM, and less than 20% at the lower limit of quantitation (2.5 microM). The sample extraction recovery ranged between 109 and 129% at the three concentration levels. The drug enantiomers were incubated with recombinant human flavin-containing monooxygenase enzymes (FMO3 and FMO1), and human liver microsomes, respectively. The enantioselectivity of the substrate preference, as well as the stereoselective formation of the new chiral center upon the oxidation of the prochiral tertiary nitrogen of deprenyl were assessed. FMO1, the extrahepatic form of the enzyme in man, was shown to be more active in the N-oxygenation of both deprenyl and methamphetamine isomers than FMO3. Deprenyl enantiomers and S-methamphetamine were substrates of human recombinant FMO3. Conversion of amphetamine to its hydroxylamine derivative could not be observed on incubation with either FMO1 or FMO3. Formation of the new chiral center on the nitrogen, during N-oxidation of the tertiary amine deprenyl, was found stereoselective. The two FMO isoforms have shown opposite preference in the formation of this chiral center. Methamphetamine-hydroxylamine formed from methamphetamine was further transformed by FMO, amphetamine-hydroxylamine was identified as the product of a demethylation reaction.     

Selective hydrogenation of acrylonitrile over a supported Ni catalyst

Acrylonitrile can be selectively hydrogenated into propionitrile at about 400 K over a ceramic-supported Ni catalyst. At low surface coverages, the observed rates of hydrogenation are proportional to the first powers of the partial pressures of both acrylonitrile and dihydrogen, in agreement with Langmuir-Hinshelwood kinetics.

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400 . , , -.

     

Molecular Engineering of Conjugated Acetylenic Polymers for Efficient Cocatalyst‐free Photoelectrochemical Water Reduction

Conjugated polymers featuring tunable band gaps/positions and tailored active centers, are attractive photoelectrode materials for water splitting. However, their exploration falls far behind their inorganic counterparts. Herein, we demonstrate a molecular engineering strategy for the tailoring aromatic units of conjugated acetylenic polymers from benzene‐ to thiophene‐based. The polarized thiophene‐based monomers of conjugated acetylenic polymers can largely extend the light absorption and promote charge separation/transport. The C≡C bonds are activated for catalyzing water reduction. Using on‐surface Glaser polycondensation, as‐fabricated poly(2,5‐diethynylthieno[3,2‐b]thiophene) on commercial Cu foam exhibits a record H₂‐evolution photocurrent density of 370 μA cm^?2 at 0.3 V vs. reversible hydrogen electrode among current cocatalyst‐free organic photocathodes (1–100 μA cm^?2). This approach to modulate the optical, charge transfer, and catalytic properties of conjugated polymers paves a critical way toward high‐activity organic photoelectrodes.     

The ring closure and rearrangement of 1-(2-amino)-benzoyl-1-methylhydrazones of β-dicarbonyl compounds: on the formation and crystal structure of 3a,9a-dihydro- -1,3,3a,9a-tetramethyl-4H-pyrazolo[3,4-b]quinolin-4-one

The conversion of 1-(2-amino)-benzoyl-1-methylhydrazones of β-dicarbonyl compounds into heterocyclic derivatives yielded in addition to the already known type of product $\text{2}$ further three novel pyrazole derivatives $\text{3}$, $\text{4}$ and $\text{5}$. The structures of these products have been established by chemical and spectroscopic (MS) methods. The crystal structure of $\text{5}$ has been determined by X-ray diffraction.     

Application of ultrasonic irradiation for the degradation of chemical contaminants in water

The sonochemical degradation of a variety of chemical contaminants in aqueous solution has been investigated. Substrates such as chlorinated hydrocarbons, pesticides, phenols, explosives such as TNT, and esters are transformed into short-chain organic acids, CO₂, and inorganic ions as the final products. Time scales of treatment in simple batch reactors over the frequency range of 20 to 500 kHz are reported to range from minutes to hours for complete degradation. Ultrasonic irradiation appears to be an effective method for the rapid destruction of organic contaminants in water because of localized high concentrations of oxidizing species such as hydroxyl radical and hydrogen peroxide in solution, high localized temperatures and pressures, and the formation of transient supercritical water.

The degradation of chemical compounds by acoustic cavitation is shown to involve three distinct pathways: 1) oxidation by hydroxyl radicals, 2) pyrolytic decomposition and 3) supercritical water oxidation. Detailed reaction mechanisms for the degradation of p-nitrophenol, carbon tetrachloride, parathion, p-nitrophenyl acetate and trinitrotoluene are presented.     

Hypotensive effects of the Crotalus durissus cascavella venom: involvement of NO

Crotalus durissus cascavella is a snake native of northeastern Brazil. The aim of the study was to investigate the effects of C. d. cascavella venom on rat mean arterial pressure and vascular reactivity in the mesenteric vascular bed. The venom evoked a dose-dependent decrease in mean arterial pressure, cardiac and respiratory frequency with increased plasma nitrite levels. L-NAME (10 mg/kg) blunted both the hypotension and increased nitrite production observed after the venom administration. To investigate the effects of C. d. cascavella in resistance vessels, the vascular mesenteric bed was studied, and the results suggested that the hypotensive effect of the venom is not dependent on a direct vasodilatory activity. In conclusion, C. d. cascavella venom presented indirect hypotensive effects with the involvement of nitric oxide.     

Surface modification of cotton nanocrystals with a silane agent

The research herewith aims at obtaining cellulose nanocrystals with a reduced hydrophilic surface character using a silane with isocyanate groups (isocyanatepropyltriethoxysilane), which are very reactive to hydroxyl groups and thus, are readily able to react with the low quantity of free hydroxyl groups present in the cellulose nanocrystal surfaces, therefore, promoting surface modification. Cellulose nanocrystals were obtained by hydrochloric acid hydrolysis of cotton fiber and were characterized by X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and solid state ²⁹Si nuclear magnetic resonance (NMR) and their morphologies were investigated by scanning and transmission electron microscopy techniques. The nanocrystals presented a needle-like geometry with a 10 nm approximate diameter and a 166 nm average length. FTIR, ²⁹Si NMR and silicon mapping images showed that nanocrystal surface chemical modification was successfully achieved. Also, the results confirm that the chemical modification occurred mainly at the nanocrystal surface, keeping the morphological integrity of the nanocrystals. The applied methodology for surface modification of the cellulose nanocrystals provided nanofillers with more appropriate surface characteristics that allow the dispersion in polymeric matrices and the adhesion at filler-matrix interface to be obtained. This may result in a better performance of these nanocrystals as reinforcing agents of hydrophobic polymer matrices.     

Induced surface enhancement in coral Pt island films attached to nanostructured Ag electrodes

Coral Pt islands films are deposited via electrochemical reduction on silica-coated nanostructured Ag electrodes. From these devices surface-enhanced (resonance) Raman [SE(R)R] signals of molecules exclusively attached to Pt are obtained with intensity up to 50% of the value determined for Ag. SE(R)R spectroscopic investigations are carried out with different probe molecules, silica-coating thicknesses, and excitation lines. Additionally, field enhancement calculations on Ag-SiO(2)-Pt support geometries are performed to elucidate the influence of the Pt island film nanostructure on the observed Raman intensities. It is concluded that the nonperfect coating of the Pt island film promotes the efficiency of the induced Pt SER activity. Comparison with similar measurements on Ag-SiO(2)-Au electrodes further suggests that the chemical nature of the deposited metal island film plays a minor role for the SE(R)R intensity.     

Adsorption of sulfite oxidase on self-assembled monolayers from molecular dynamics simulations

Sulfite oxidase (SO) is an enzyme catalyzing the terminal step of the metabolism of sulfur-containing amino acids that is essential for almost all living organisms. The catalytic activity of SO in vertebrates strongly depends on the efficiency of the intramolecular electron transfer (IET) between the catalytic Moco domain and the cytochrome b5 (cyt b5) domain. The IET process is assumed to be mediated by large domain motions of the cyt b5 domains within the enzyme. Thus, the interaction of SO with charged surfaces may affect the mobility of the cyt b5 domain required for IET and consequently hinder SO activation. In this study, we present a molecular dynamics approach to investigating the ionic strength dependence of the initial surface adsorption of SO in two different conformations-the crystallographic structure and the model structure for an activated SO-onto mixed amino- and hydroxyl-terminated SAMs. The results show for both conformations at low ionic strengths a strong adsorption of the cyt b5 units onto the SAM, which inhibits the domain motion event required for IET. Under higher ion concentrations, however, the interaction with the surface is weakened by the negatively charged ions acting as a buffer and competing in adsorption with the cathodic cyt b5 domains. This competition prevents the immobilization of the cytochrome b5 units onto the surface, allowing the intramolecular domain motions favoring IET. Our predictions support the interpretation of recent experimental spectroelectrochemical studies on SO.