Ketone Structure Research Articles

Activation of Nrf2 target enzymes conferring protection against oxidative stress in PC12 cells by ginger principal constituent 6-shogaol.

Natural compounds containing phenoxyl groups and/or Michael acceptor units appear to possess antioxidant and cytoprotective properties. The ginger principal constituent 6-shogaol (6-S) represents one of such compounds. In this study, we reported that 6-S efficiently scavenges various free radicals in vitro, and displays remarkable cytoprotection against oxidative stress-induced cell damage in the neuron-like rat pheochromocytoma cell line, PC12 cells. Pretreatment of PC12 cells with 6-S significantly upregulates a series of phase II antioxidant molecules, such as glutathione, heme oxygenase 1, NAD(P)H: quinone oxidoreductase 1, thioredoxin reductase 1, and thioredoxin 1. A mechanistic study revealed that 6-S enhanced the translocation of Nrf2 from the cytosol to the nucleus and knockdown of Nrf2 abolished such protection, indicating that this cytoprotection is mediated by the activation of the transcription factor Nrf2. Another ginger constituent 6-gingerol (6-G), having a similar structure of 6-S but lacking the alpha,beta-unsaturated ketone structure (Michael acceptor moiety), failed to shelter PC12 cells from oxidative stress. Our results demonstrate that 6-S is a novel small molecule activator of Nrf2 in PC12 cells, and suggest that 6-S might be a potential candidate for the prevention of oxidative stress-mediated neurodegenerative disorders.

From cats and blackcurrants: structure and dynamics of the sulfur-containing cassis odorant cat ketone.

Sulfur-containing odorants and flavors play an important role in flavor and food industry, especially when meaty, garlic, onion, and vegetable scents are needed. Still, many S-containing flavors also possess fruity scents and may be used in compositions of perfumes that require a fresh and fruity odor perception. They are naturally abundant in various fruits, essential oils, and food. Most of these compounds possess strong scents, and their scent composition is highly dependent on the concentration applied. At higher concentrations, they usually feature repellent off-odors, while their sweet and fruity nature is only experienced at very low concentrations. This represents a challenge for their application in perfumery, as well as in food industry. From a molecular point of view, the endless structural and scent variety of these compounds makes them fascinating, especially as their O-analogs are usually free of any malodors. Here, we report on the investigation of the gas-phase structure and dynamics of the S-containing blackcurrant odorant cat ketone (4-methyl-4-sulfanylpentan-2-one). The work was performed by combining quantum-chemical calculations and molecular-beam Fourier-transform microwave spectroscopy as complementary tools. Using this technique, we are able to determine the structures of sizeable molecules where energy differences are small and conformational distinction is not always possible by quantum-chemical calculations alone. The presented results can be used for further structure-activity correlation studies, as well as for benchmarks to improve theoretical models, especially, as there is still significant interest in characterizing the various conformers of organic molecules in terms of relative energies, structures, and dipole moments.

Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin

Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice.

Friedländer reaction/quinoxalinone–benzimidazole rearrangement sequence: expeditious entry to diverse quinoline derivatives with the benzimidazole moieties

A protocol has been developed for the efficient synthesis of structurally diverse 4-(benzimidazol-2-yl)quinolines via reactions of 3-(2-aminophenyl)quinoxalin-2(1H)-ones and ketones, including acetone, acetophenones, 1,3-pentanedione and ethyl acetoacetate. The selective formation of the very different quinoline derivatives depends on the structure of ketones. The key steps are proposed to involve the new acid-catalyzed rearrangement of the spiro-quinoxalinone derivatives formed in situ from the reaction of 3-(2-aminophenyl)quinoxalin-2(1H)-ones and ketones under the modified Friedländer reaction. This transformation would facilitate the synthesis by short reaction times, large-scale synthesis, simple and prompt isolation of the products, which are the main advantages of this procedure.

High Temperature Laser Sintering (HT-LS): An investigation into mechanical properties and shrinkage characteristics of Poly (Ether Ketone) (PEK) structures

This paper presents an investigation into the properties of Poly Ether Ketone (PEK) components using the commercial high temperature laser sintering system, EOSINT P800. The shrinkage and the mechanical performance of components across the entire build chamber have been tested and a non-linear shrinkage profile has been obtained. The middle of the build chamber recorded the highest degree of shrinkage and the shrinkage in Z direction had the largest variation. The laser sintered components built in X and Y directions recorded a 10% lower tensile strength than the injection moulded samples of the same material where those built in the Z direction showed an approximately 50% decrease in strength in comparison with the injection moulded test specimens. The crystallinity between the skin and the core of the sintered samples was different; varied with the position within the build chamber and coincided with noticeable sample colour changes.

Proton conducting membranes prepared by radiation grafting of styrene and various comonomers

Proton conducting membranes are synthesized by radiation grafting a fluoropolymer matrix, poly(ethylene-alt-tetrafluoroethylene) (ETFE), with styrene and various non-crosslinking comonomers: methacrylonitrile (MAN), acrylonitrile (AN), methyl methacrylate (MMA), and methacrylic acid (MAA). During sulfonation, hydrolysis of nitrile and ester groups takes place to different extents. Solid-state NMR spectroscopy confirms the cyclic ketone structure formed in styrene/MAA co-grafted membranes. The comonomer influence on the membrane properties is studied by characterizing the ion exchange capacity (IEC), water uptake, proton conductivity, and the nano-scale morphology via small-angle X-ray scattering (SAXS). In water swollen state, the proton conductivities of grafted membranes with similar IEC are comparable, while at reduced relative humidity (<80%) the co-grafted membranes exhibit lower proton conductivity compared to the styrene grafted membrane, regardless of the type of comonomer. It is proposed, based on the SAXS analysis, that this is a consequence of an increased average distance between the acid groups in co-grafted membranes.

Sulfonated polyether ether ketone – sulfonated graphene oxide composite membranes for polymer electrolyte fuel cells

Sulfonated polyether ether ketone – sulfonated graphene oxide composite membranes for polymer electrolyte fuel cells have been prepared. Sulfonic acid functionalised graphene oxide nanosheets were incorporated into the sulfonated polyether ether ketone structure to interconnect the proton transport channels. The composite membranes were characterised by SEM, which revealed a uniform distribution of nanosheets into the polymer structure. FTIR showed the chemical interactions of functionalised graphene oxide with SPEEK membranes. Proton conductivity of the composite membrane was measured at various temperatures and relative humidities; the SGO/SPEEK composite membrane showed a very good conductivity of 0.055 S cm−1 at 80 °C and 30% RH, which was greater than that of recast SPEEK which was about 0.015 S cm−1. The fuel cell performance of SGO/SPEEK at 80 °C and 30% RH was 378 mW cm−2, which was higher than that of recast SPEEK.

ChemInform Abstract: Reactions of N,N‐Dimethylamino(diphenylphosphoryl)chloromethane with Alkan‐2‐ones.

AbstractThe title reaction gives α‐phosphorylated alcohols according to an Abramov‐type reaction [→ (III)] or phosphorylated Mannich bases (V) depending on the ketone structure.

A Copper‐Catalyzed Multicomponent Reaction and ‘Click Strategy’ for the Stereoselective Synthesis of a New Series of Oxazolone Peptidomimetics withα‐Acylamino Amide andβ‐Amido Ketone Structures

AbstractA novel ‘click ligation’ strategy for the stereoselective synthesis of a medium‐size library of structurally complex and functionally diverse oxazolone peptidomimetics, which containα‐acylamino carboxamide orβ‐amido ketone residues, is presented. Most of these molecules have lipophilicity constant values (logP) in the qualifying range for cell permeability, and that indicates the possibilities of these new molecules to be used in the search for potential inhibitors for a broad spectrum of enzymes.

Cooligomerization of carbon monoxide with cyclic olefins on supported palladium catalysts

The cooligomerization of CO with cyclic olefins, such as norbornene, 5-vinyl-2-norbornene, and dicyclopentadiene, in toluene in the presence of supported palladium catalysts containing 2,2’-bipyridine as a ligand is studied. It is shown that, during copolymerization, opening of the double bond in a ring occurs, while in the case of 5-vinyl-2-norbornene, vinyl bond C=C is not involved in the reaction. When ethylene is added to the reaction mixture, it does not participate in polymer-chain growth. The yield of the process is commensurable with the yield attained in the case of a homogeneous catalytic system, and the conversion of olefins is as high as 47%. The copolymers in the solid state occur in the form of spiroketal structures that, during dissolution, transform into ketone structures to different extents.

Synthesis and Antiproliferative Effect of Novel Curcumin Analogues

Novel curcumin analogues with α,β-unsaturated ketone moiety and/or α,β-saturated ketone structure were synthesized from curcumin via alkylation at the central carbon and the phenolic hydroxy groups, and hydrogenation of α,β-unsaturated ketone moiety. The antiproliferative activities were tested in five human solid tumor cell lines in vitro. Most of the compounds exhibited increased antiproliferative activities comparing with that of curcumin. Structure-activity relationship (SAR) analysis revealed that the α,β-unsaturated ketone structure was not required for antiproliferative activity of these curcumin analogues. Among these compounds, 1,7-bis(3-methoxy-4-(3-(4-methylpiperazinyl-1-yl)propoxy)phenyl)-4,4-dibenzylheptane-3,5-dione (16f) was the most effective one with IC50 value below 1 µM, which was 9- to 81-fold more potent than curcumin.

Carbocyclization of unsaturated thioesters under palladium catalysis

An intramolecular thioester–olefin cross-coupling reaction for the preparation of cyclic ketone structures from unsaturated thioesters is described. This method capitalizes on the unique reactivity of thioesters with low-valent palladium catalysts and copper(I) salts to form acyl-metal species. Trapping of such intermediates with alkene functional groups generates the corresponding exo-methylene cycloalkanone products. Unsaturated thioester substrates, which can be accessed using a suite of modern synthetic methods, can now be regarded as precursors to complex carbocyclic derivatives.

Reactions of ketones with aromatics in acid media. The effect of trifluoromethyl groups and the acidity media. A theoretical study

The reactions of acetone, 2,2,2-trifluoroacetone and hexafluoroacetone in methanesulfonic (MSA) and triflic acids (TFSA) with benzene have been studied at M06-2X/6-311+G(d,p) level using cluster-continuum model, where the carbonyl group is explicitly solvated by acid molecules. The introduction of a trifluoromethyl group into the ketone structure reduces the activation energy of the tetrahedral intermediates formation due to an increase of the electrophilicity of the carbonyl group and raises the activation and the reaction energies of the C-O bond cleavage in formed carbinol due to the destabilization of the corresponding carbocation. The introduction of the second trifluoromethyl group inhibits the hydroxyalkylation reaction due to a very strong increase of the reaction and activation energies of the C-O bond cleavage which becomes the rate determining step. The most important catalytic effect of TFSA compared to MSA is not the protonation of the ketone carbonyl, but the reduction of the activation and reaction energies of the carbinol C-O bond cleavage due to better protosolvation properties. Even for TFSA no complete proton transfer to carbonyl oxygen has been observed for free ketones. Therefore, the protonation energies of free ketones cannot be considered as a measure of ketone reactivity in the hydroxyalkylation reaction.

Reactions of N,N-dimethylamino(diphenylphosphoryl)chloromethane with alkan-2-ones

The direction of the reaction of N,N-dimethylamino(diphenylphosphoryl)chloromethane with alkan-2-ones depends on the ketone structure. N,N-Dimethylamino(diphenylphosphoryl)-chloromethane reacts with linear alkan-2-ones following the Abramov-type reaction to give α-phosphorylated alcohols, while the reaction with branched alkan-2-ones and acetophenone proceeds as the Mannich-type reaction affording the phosphorylated Mannich bases.

A mechanistic analysis of the quantitation of α-hydroxy ketones by the bicinchoninic acid assay

A new class of compounds amenable to quantification by the bicinchoninic acid (BCA) assay was identified, allowing an expansion of compounds quantifiable within the assay’s capacity. In this article, we demonstrate that compounds containing the α-hydroxy ketone structure are easily measured under standard BCA assay conditions. A nonchromophore analyte containing the α-hydroxy ketone structure, 1,3-dihydroxypropan-2-one (commonly known as dihydroxyacetone), and various structural derivatives were explored on an equimolar basis in the BCA assay. Combined with earlier studies exploring α-hydroxy ketones within copper oxidation systems, the data support the mechanism of this class of compound’s ability to enolize through an enediol intermediate to generate a strong signal in the BCA assay. This new quantification technique also highlights the potential for α-hydroxy ketones to interfere with other analytes quantified by the BCA assay.

ChemInform Abstract: Conjugate Addition of Unactivated Thiols to α,β‐Unsaturated Ketones Catalyzed by a Bifunctional Rhenium(V)‐oxo Complex.

AbstractA moisture‐tolerant complex is described as convenient catalyst for the title reaction which affords biologically interesting β‐sulfanyl ketone structures.

Ketone physics – structure, conformations, and dynamics of methyl isobutyl ketone explored by microwave spectroscopy and quantum chemical calculations

The microwave spectrum of methyl isobutyl ketone was recorded using a molecular beam Fourier transform microwave spectrometer and analyzed to determine the rotational constants A=4.7517(17)GHz, B=1.496115(79)GHz, C=1.324364(39)GHz, and centrifugal distortion constants. A–E splittings from 250MHz up to 1GHz were observed due to internal rotation of the acetyl methyl group with a potential barrier of 250.3(19)cm−1. 59 A and 57 E species lines were fitted to experimental accuracy. The experimental rotational constants were compared with results from quantum chemical calculations to validate the molecular structure.

ChemInform Abstract: Synthesis of Silyloxy Dienes by Silylene Transfer to Divinyl Ketones: Application to the Asymmetric Synthesis of Substituted Cyclohexanes.

AbstractThe Ag‐catalyzed treatment of divinyl ketones with the silicon compound (II) results in formation of regioisomeric silyloxy dienes whose ratio is dependent on the structure of the divinyl ketone.

Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi

Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) both enzymatically and chemically, and inhibited glutathione reductase activity. 7-Benzyl derivative, which was obtained by reduction of the olefin group in α,β-unsaturated ketone structure of BNTX, also exhibited CQ-resistance reversing effect, but its potency was significantly lower than that of BNTX. These outcomes suggested that the decrease in GSH level could be one of the mechanisms of CQ-resistance reversing effects induced by BNTX derivatives.

Synthesis and Properties of Anion Conductive Ionomers Containing Tetraphenyl Methane Moieties

A series of anion conductive aromatic ionomers, poly(arylene ether)s containing various polymer backbones and quaternary ammonium basic group functioned tetraphenyl methane moieties, were synthesized via nucleophilic substitution polycondensation, chloromethylation, quaternization, and the subsequent alkalization reactions. The structures of poly(arylene ether)s (PAEs), chloromethylated poly(arylene ether)s (CMPAEs), and quaternizated poly(arylene ether)s (QPAEs) ionomers were confirmed by (1)H NMR technique. Their thermal stabilities were evaluated by thermo gravimetric analysis (TGA). The water uptakes, ion exchange capacities (IEC), hydroxide ion conductivities, mechanical properties, and chemical stabilities of the membranes derived from the synthesized ionomers were assessed as anion exchange membranes. The QPAEs membranes were tough and thermally stable up to 170 °C. The IEC of the ionomers varied from 0.21 to 2.38 meq g(-1) which can be controlled by chloromethylation reaction conditions. The ion conductivities of QPAEs membranes increase dramatically with increasing temperature. The hydroxide ion transport activation energy, Ea, of the QPAEs membranes varied from 13.18 to 42.30 kJ mol(-1). The QPAE-d membrane with lower IEC value of 1.04 meq g(-1), derived from copolymer CMPAE-d bearing sulfone/ketone structure, displayed the highest hydroxide ion conductivity of 75 mS cm(-1) at 80 °C and showed strong tensile strength (29.2 MPa) at 25 °C. The QPAE-e membrane with IEC value of 1.09 meq g(-1), derived from copolymer CMPAE-e bearing sulfone/ketone-ketone structure, demonstrated 68 mS cm(-1) at 80 °C. The QPAE-d membrane kept 90% of mechanical properties and 82% of hydroxide ion conductivity after being conditioned with 1 M NaOH at 60 °C for 170 h. These properties of the ionomers membranes show their potential as an anion exchange membrane of alkaline fuel cells.