3-oxoglutarate Research Articles

(Invited) To Prepare 2D Au Nanoplates and Its Controlled Molecular Self-Assembly (MS) Mechanism

It is very important to prepare 2D noble-metal nanomaterials, but very little is known about their chemical synthesis at molecular level. In this paper, we found the classic citric (CA) reduction method can prepare 2D Au nanoplates with a large range for 2D size (3-150nm). Furthermore, these 2D Au nanoplates exhibit thin thickness (8-20nm), along with two kinds of single crystal structure as 2D Au (110) –dominated and Au (111) –dominated nanoplates. To explore their preparation, we adjusted the CA reduction kinetic as CA additive→ acetone dicarboxylic acid (DCA) →acetone, revealing the intermediate species of DCA is crucial for nanoplate formation. Our DFT (Density-Functional-Theory) model further clarifies that the DCA has molecular interaction, preferentially transferring 2D clusters (Au3-Au7) towards Au(111) facets though accompanying with some Au (100) facets. These soft-hard interaction help us establish two kinds of controlled MS mechanisms towards (111) –dominated nanoplates and Au (110) –dominated nanoplates, revealing the cluster origination and its essential 2D growth process in nucleation-growth process. Consequently, our preparation for 2D Au nanoplates and controlled MS mechanisms open a gate towards nucleation-growth process, thus having great significance and broad impact for future studies.

Novel functionalized phenyl acetate derivatives of benzo [e]-bispyrone fused hybrids: Synthesis and biological activities

Eighteen novel functionalized phenyl acetate derivatives of benzo[e]-bispyrone fused hybrids and their three precursors are developed in this study. The precursor acetic acid congeners of benzo[e]-bispyrone fused hybrids (Y1, Y8, and Y15) were created by combining acetone dicarboxylic acid and three resorcinol-based compounds. They were utilized in the preparation of novel functionalized phenyl acetate derivatives of benzo[e]-bispyrone fused hybrids (Y2-Y7, Y9-Y14, and Y16-Y21). Six in vitro biological activities were investigated for the synthesized precursors and their functionalized phenyl acetate derivatives. First, the reactive species-caging activity was tested against DPPH and hydroxyl radicals. Second, the cellular viability-terminating activity was assayed using MTT-visual probing methodology against six common cancerous cell lines. Third, fourth, and fifth activities, collectively termed microbial-shedding potential, were examined using a microdilution broth methodology against six aerobic pathogenic bacterial strains, four anaerobic pathogenic bacterial strains, and two pathogenic fungal strains, respectively. Finally, the blood sugar-dropping activity was assessed against two related enzymes. Moreover, the toxic effects of the twenty-one synthesized compounds were assessed against one normal human cell line and one non-pathogenic bacterial strain. The results showed that the fused hybrids' methoxyphenyl acetate derivatives (Y2, Y9, and Y16) had the greatest reactive species-caging, anaerobic pathogenic bacterial-shooting, and blood sugar-dropping activities. In terms of cellular viability-terminating activity, the fluorophenyl acetate derivatives (Y4, Y11, and Y18) demonstrated the greatest activity against the tested cancerous cell lines while causing the least toxicity to the normal cell line. Chlorophenyl acetate derivatives had the highest aerobic pathogen-shedding activity while causing the least toxicity on normal bacterial strains (Y5, Y12, and Y19). Finally, the precursors and derivatives with flourophenyl or chlorophenyl acetate demonstrated the highest levels of fungal-shooting activity, exceeding the reference. The researchers concluded from these observations that the synthesized precursors and their derivatives provided several biosafe scaffolds with multiple and selective activities.

Orthoamide und Iminiumsalze, CIV. Umsetzungen von Orthoamiden der Alkincarbonsäuren mit enolisierbaren Carbonylverbindungen – Cyclisierung der Kondensationsprodukte zu Pyran-Derivaten

Abstract Orthoamides of alkynecarboxylic acid 15 condense with enolisable β-dicarbonyl compounds and as well with acetophenones to give 3-acryl-1,1-bis(dimethyl-amino)-1,3-butadienes. Some acylbutadienes cyclize affording 2-pyranon-derivatives 33 upon heating with aqueous ethanol. 2H-pyranes are accessible from acetone dicarboxylic acid ester and orthoamides 15. The constitution of one 4-acyl-1,1-bis(dimethylamino)-1,3-butadiene (16f) and one 2H-pyrane (44b) was confirmed by crystal structure determinations.

Core-shell structured SiO2@ZrO2@SiO2 filler for radiopacity and ultra-low shrinkage dental composite resins

To overcome the interfacial problem between X-ray radiopaque ZrO2 fillers and polymer resin in dental composites, monodispersed SiO2@ZrO2@SiO2 (SZS) microspheres with narrow size distribution were prepared by a controlled sol-gel method. In the presence of SiO2 coating layer over SiO2@ZrO2 (SZ) microspheres, they were easily silanized same as SiO2 microspheres. Ethoxylated bisphenol A dimethacrylate (EBPADMA) with a higher molecular weight and a lower viscosity was used as base resin monomer mixed with a low amount of diluent triethylene glycol dimethacrylate (TEGDMA). Additionally, the addition of a small amount of pore agent acetone dicarboxylic acid (ADCA) produced some voids, thereby effectively reducing the polymerization shrinkage of the resin. The prepared dental composites combining 52 wt% monodispersed silica microsphere, 20 wt% SZS microspheres, exhibited significantly enhanced capacity in radiopacity (higher than tooth enamel) and very low shrinkage (<0.1%). It also has better mechanical properties than resin composites filled with SiO2 microspheres, and its strength can meet practical applications. The properties of the radiopaque dental composite were to be further tuned by varying the amount of SZS microspheres contents, and the radiopaque resin has an advantage over the commercial one in that it is clinically nondestructive.

Deciphering the Biosynthetic Mechanism of Pelletierine in Lycopodium Alkaloid Biosynthesis.

Pelletierine, a proposed building block of Lycopodium alkaloids (LAs), was demonstrated to be synthesized via the non-enzymatic Mannich-like condensation of Δ1-piperideine and 3-oxoglutaric acid produced by two new type III PKSs (HsPKS4 and PcPKS1) characterized from Huperzia serrata and Phlegmariurus cryptomerianus, respectively. The findings provide new insights for further understanding the biosynthesis of LAs such as huperzine A.

255-LB: Impaired Gsa/cAMP Signaling Exclusive to Pancreatic ß-Cells Exhibits a Unique Urinary Metabolome via Nontargeted Metabolomics in a Murine Model of Diabetes In Vivo

Background: β-cell dysfunction is a hallmark feature of diabetes mellitus. G protein a-subunit (Gsa) mediates receptor-stimulated intracellular cAMP production In β cells in order to increase glucose-stimulated insulin secretion, cell proliferation and survival. Growing interest in urinary metabolome has emerged as many drugs aim to improve outcomes by targeting kidney function. Given clinical significance of the Gsa pathway, we aimed to study changes of urinary metabolome as a result of Gsa deficiency. Methods: Mice with Gsα deficiency limited to β cells (Gsa βcell-/-) were generated by mating Gsα-floxed mice with MIPcreERT mice in order to directly examine Gsα/cAMP signaling role in β cells, in a similar method to Xie et.al. Urine was collected from (Gsa βcell-/-) mice and controls and stored at -80C until processed for non-targeted metabolomics using GCMS. Results: In a small cohort, 17 metabolites were significantly altered between the two groups (P&amp;lt;0.05). While pathway analysis somewhat echoed findings described in other models of diabetes (urea cycle, Malate-Aspartate shuttle, and amino acid metabolism), 4 metabolites were completely undetectable in (Gsa βcell-/-) urine including 3-Oxoglutaric acid and Methylglutarate. In addition, some changed in a different direction to what was previously described in other models of diabetes (e.g: Gsa βcell-/- mice exhibited decreased urinary adipic acid). Enrichment analysis of disease associated metabolite sets of the urine mimicked changes seen in enzymatic defects of 3-Hydroxy-3-Methylglutaryl-Coa Lyase, Kynureninase Deficiency, 2-Ketoglutarate Dehydrogenase and Wolcott-Rallison Syndrome (P&amp;lt;0.05). Conclusion: Gsa pathway deficiency in β cells produced a model of diabetes with unique metabolome. Studying changes of urine metabolome after treatment with antiglycemics in the future might highlight the drugs renal impact in the setting of Gsa deficiency. Disclosure A. Ilaiwy: None. M. Capozzi: None. J.L. Brown: None. D. D’Alessio: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Intarcia Therapeutics. Research Support; Self; Ansh Labs, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp. Other Relationship; Self; Novo Nordisk A/S. J. Campbell: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc. Speaker’s Bureau; Self; Merck Sharp &amp; Dohme Corp.

Formation of Benzodiazepines and Pyrazinylquinoxalines from Aromatic and Heteroaromatic Ketones via Deoximation

The report stated that the treatment of o-phenylenediamine with acetone dicarboxylic acid, acetone and acetophenone afforded 2,4,4-trimethyl-3H-5-hydro-1,5-benzodiazepine. However, direct reactions of o-phenylenediamine with oximes (acetone oxime, acetophenone oxime, and benzophenone oxime) as ketone equivalents did not occur. In the course of present investigations, it is found that dichloroamine-T can be an efficient reagent for the conversion of oximes into the corresponding carbonyl compounds. As a part of a research program related to the synthetic study of pharmacologically interesting benzodiazepine compounds, herein the synthesis of 1H-1,5-benzodiazepine derivatives from heteroaromatic ketones and acetone equivalents obtained using dichloroamine-T. On the other hand, when diamine (1,2-phenylene diamine or 1,2-naphthalene diamine) with heterocyclic ketone (acetyl pyridine or acetyl pyrazines) in the presenece of conc. HCl and SiO2 was refluxed, quinoxaline derivatives as yellow crystalline solids were isolated in high yields

A Study on N-Substituted Nortropinone Synthesis using Acetone Equivalents

Robinson′s synthesis has long been a classic in organic chemistry due to its simplicity and impact in the industry. Various modifications have been made to improve the system. Among them, replacing acetone with more acidic chemical equivalents such as calcium dicarboxylic acid or ethyl dicarboxylic acetone improved the yield. In line with this trend, our group previously reported the synthesis of mono- and di-N-substituted tropinone derivatives from the one-pot reaction of 2,5-dimethoxy tetrahydrofuran and various amines with acetonedicarboxylic acid in the presence of HCl and water at room temperature. In this study, the synthesis with acetone instead of acetone-dicarboxylic acid was examined. Mono- and di-N-substituted nortropinones were prepared in higher yields in all cases although there were extent to which yields increased depending on the nature of substituents

Life cycle assessment of novel consolidants and a photocatalytic suspension for the conservation of the immovable cultural heritage

Abstract Three innovative conservation materials were investigated by means of life cycle assessment (a calcium acetoacetate consolidant for carbonate surfaces, a TEOS-based consolidant for silicate substrates, and a photocatalytic suspension). So far not much attention has been paid to materials for the conservation of the built cultural heritage, with regard to their environmental performance. The main aim of this study was to assess the environmental footprint of the above-mentioned conservation materials which arises throughout their life cycle. In this way comparative data are made available for other future LCA studies on consolidants and photocatalytic suspensions. The most heavily polluting processes (i.e. “hotspots”) in the life cycle of the investigated conservation materials were identified, and, where possible, solutions for the further optimization of their environmental performance were proposed. In the case of life cycle of the two above-mentioned consolidants, the majority of emissions can be attributed to the synthesis of the constituent materials which are used to make the final products. Ethyl polysilicate is the largest contributor to the environmental footprint of the TEOS-based consolidant. On the other hand, in the life cycle of the calcium acetoacetate consolidant most of the environmental burdens are contributed by the synthesis of acetone-dicarboxylic acid. Around 0.47 kg of CO2 equivalent emissions affecting global warming are released to the air during the life cycle of 1 L of calcium acetoacetate (considering solely the upstream and core processes), whereas this value is higher in the case of the life cycle of the TEOS-based consolidant, i.e. 3.77 kg of CO2 equivalent emissions. In the case of the life cycle of the investigated photocatalytic suspension, although 1 L of this suspension is responsible for the release of only 0.1 kg of CO2 equivalent emissions over its life cycle (excluding the case-specific downstream processes) the heaviest environmental impact is caused by the production of packaging material (e.g. plastic buckets and other types of plastic containers). Taking into account the above-mentioned facts, there are not many possibilities for the reduction of the environmental burdens of the two investigated consolidants by the environmental optimization of the processes involved in the core and downstream stages of their life cycles. In the life cycle of the photocatalytic suspension, the environmental burdens related to greenhouse gas emissions could be reduced by more than 10% if a cleaner form of electricity production were to be adopted. A further aim of this paper is to promote sustainability in the field of management of the immovable cultural heritage. Although the described conservation materials have only a minor environmental effect in the field of the management of the immovable cultural heritage, the significance of sustainability is presented to conservators on a practical example.

New Insight into and Characterization of the Aqueous Metal-Enol(ate) Complexes of (Acetonedicarboxylato)copper.

Nearly 50 years have passed since the classic studies by Larson and Lister [LarsonD. W.; ListerM. W.Can. J. Chem.1968, 46, 823]and Hay and Leong [HayR. W.; LeongK. N.J. Chem. Soc. A1971, 0, 3639]on the copper-catalyzed decarboxylation of acetonedicarboxylic acid (H3Acdica). Although the authors laid the foundations for what we know about this reaction; still very little information exists regarding the underlying aqueous metal-enol(ate)s of (acetonedicarboxylato)copper. In this study, UV–visible titrations revealed three pK values, pK[Cu(H2A)], pK[Cu(HA)], and pK[Cu(A)]. We associated the first two with ionization of α-carbon CH2 groups in [CuII(H2Acdica)keto]1+ and [CuII(HAcdica)keto]0 to form unstable metal-enolates, {[CuII(HAcdica)enolate]} and {[CuII(Acdica)enolate]}, which through β-carbonyl oxygen protonation can form metal-enols [CuII(H2Acdica)enol]1+ and [CuII(HAcdica)enol]0. The square-planar CuII center (electron paramagnetic resonance results) plays a dual role of stabilizing negative electron density at the β-carbonyl oxygen and as an electron sink in [[CuI(HAcdica)enolate]0]‡ and [[CuI(Acdica)enolate]1–]‡ (confirmed through cyclic voltammetry as two single 1e– transfers). The π → π* transition associated with [CuII(HAcdica)enol]0 was used to determine pK[Cu(A)] (deprotonation of enol OH) and enolization rate constant (stopped-flow spectroscopy) but also exhibited a time-dependent decrease in absorbance (on the order of min–1), suggesting a new method to possibly obtain experimental values for the estimated “kCuL” decarboxylation rate constant of metal-enolate [CuL]1– calculated by Larson and Lister. On the basis of our results, we postulate that decarboxylation takes place primarily through {[CuII(HAcdica)enolate]} and [CuII(HAcdica)enol]0. These results add to our understanding of aqueous metal-enol(ate)s, which contain underlying CuII/I redox chemistry, “active methylenes” and enol tautomers and enolate anions, which play roles in many catalytic reactions of interdisciplinary importance.

Characterization method for relative Raman enhancement for surface-enhanced Raman spectroscopy using gold nanoparticle dimer array

In this paper, a characterization method for Raman enhancement for highly sensitive and quantitative surface-enhanced Raman spectroscopy (SERS) is reported. A particle dimer shows a marked electromagnetic enhancement when the particle connection direction is matched to the polarization direction of incident light. In this study, dimers were arrayed by nanotrench-guided self-assembly for a marked total Raman enhancement. By measuring acetonedicarboxylic acid, the fabricated structures were characterized for SERS depending on the polarization angle against the particle connection direction. This indicates that the fabricated structures cause an effective SERS enhancement, which is dominated by the electromagnetic enhancement. Then, we measured 4,4′-bipyridine, which is a pesticide material, for quantitative analysis. In advance, we evaluated the enhancement of the particle structure by the Raman measurement of acetonedicarboxylic acid. Finally, we compared the Raman intensities of acetonedicarboxylic acid and 4,4′-bipyridine. Their intensities showed good correlation. The advantage of this method for previously evaluating the enhancement of the substrate was demonstrated. This developed SERS characterization method is expected to be applied to various quantitative trace analyses of molecules with high sensitivity.

Photoanodic response of hematite electrode to citric acid in aqueous solution

The iron oxide film was prepared by the current pulse deposition on a titanium substrate in aqueous solution of 10mM FeCl2–0.15M NaCl under O2 bubbling. The hematite structure of the deposited film after heat treatment under air was confirmed by the measurement of XRD and Raman spectrum. The Mott-Schottky plots of the hematite electrode/aqueous Na2SO4 solution showed the flat-band potential of −0.57V vs. Ag/AgCl and the carrier density of 1.35×1018cm−3 for the hematite electrode. A marked increase in photocurrent was observed on the hematite electrode in the presence of citric acid under irradiation of visible light with wavelength of 490nm. The HPLC analysis indicated the occurrence of oxidation of citric acid to acetonedicarboxylic acid with the current efficiency of 100% in this photoanodic process.

A Decennary Journey towards the Efficient Asymmetric Hydrogenation of Highly Functionalized Ketones

Around 2006, our group launched a long-term project on the asymmetric hydrogenation of functionalized ketones by using ruthenium complexes with SunPhos ligands. In this review, we recount the burgeoning and blossoming of this project. At the outset, we attempted some benchmark reactions with an array of monofunctionalized ketones, including α- and β-keto esters/amides, β-keto sulfones, phosphonates, and α-hydroxy ketones. For α-keto esters and amides, we discovered that CeCl3 •7H2 O was an efficient additive for both activity and enantioselectivity. The element iodine was found to be a valid additive for β-keto sulfones. β,γ-Unsaturated α-keto acids and esters were also hydrogenated to the saturated chiral blocks with good enantioselectivity and a high turnover number. For the α-substituted β-keto esters and phosphonates, exceptionally high stereoselectivity was achieved through dynamic kinetic resolution. Based on these incipient successes, we diverted to bifunctionalized ketone substrates, such as γ-heteroatom-substituted β-keto esters and δ-ketal-β-keto esters. For the δ-ketal-β-keto esters, CaCO3 was added to stabilize the δ-ketal groups, which ensured the formation of δ-ketal-β-hydroxy esters in good yields and high ee values. More interestingly, γ-halo-γ,δ-unsaturated-β-keto esters were hydrogenated to afford highly enantiopure chiral allyl alcohols under mild and neutral conditions. The distance effect of the directing groups was investigated in β-, γ-, and δ-keto amides; the last two were hydrogenated with the Ru-SunPhos-diamine system. To implement the pinpoint recognition of two carbonyl groups in similar chemical propinquity, we compared the reaction rates of different β-keto acid derivatives. THF was found to be a helpful coordinative solvent to control the chemo- and enantioselectivity for more challenging polycarbonyl substrates, such as 3-oxo glutaric acid derivatives, β,δ-diketo carboxamides, and γ-heteroatom-substituted β-diketones. The effects of solvents and heteroatoms in these substrates were also studied. Applications of these hydrogenation reactions were also exemplified by the employment of the products for important pharmaceutical syntheses.

Synthesis of structural analogs of epibatidine

A convenient one-step method for the preparation of 8-azabicyclo[3.2.1]octan-3-one derivatives, analogs of epibatidine, was suggested, which consists in the reaction of succinic aldehyde with heterocyclic amines and acetonedicarboxylic acid in the presence of sodium hydrogen phosphate.

Growth behavior of anodic oxide formed by aluminum anodizing in glutaric and its derivative acid electrolytes

The growth behavior of anodic oxide films formed via anodizing in glutaric and its derivative acid solutions was investigated based on the acid dissociation constants of electrolytes. High-purity aluminum foils were anodized in glutaric, ketoglutaric, and acetonedicarboxylic acid solutions under various electrochemical conditions. A thin barrier anodic oxide film grew uniformly on the aluminum substrate by glutaric acid anodizing, and further anodizing caused the film to breakdown due to a high electric field. In contrast, an anodic porous alumina film with a submicrometer-scale cell diameter was successfully formed by ketoglutaric acid anodizing at 293K. However, the increase and decrease in the temperature of the ketoglutaric acid resulted in non-uniform oxide growth and localized pitting corrosion of the aluminum substrate. An anodic porous alumina film could also be fabricated by acetonedicarboxylic acid anodizing due to the relatively low dissociation constants associated with the acid. Acid dissociation constants are an important factor for the fabrication of anodic porous alumina films.

Synthesis of aromatic carbamates derivatives with a chromen-2-one fragment

Condensation of methyl N-(3-hydroxyphenyl)carbamate with ethyl trifluoromethylacetoacetate, 2-methoxyethyl acetoacetate in the presence of conc. sulfuric acid, and also with acetonedicarboxylic acid formed in situ from citric acid under the action of conc. sulfuric acid afforded chromene derivatives. The esterification of 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}acetic acid with methanol in the presence of TsOH provided the corresponding ester. The oxidation of its α-methylene group with selenium dioxide led to the formation of methyl 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}-2-oxo-acetate entering into a condensation with o-phenylenediamine resulting in a derivative with a dihydroquinoxaline fragment. The reaction of phenyl N-(4-formylphenyl)carbamate with 3-acetyl-2H-chromen-2-one in butanol in the presence of catalytic quantity of piperidine and acetic acid furnished 4-[(E)-3-oxo-2H-chromen-3-yl)-1-propenyl]phenyl N-phenylcarbamate.

Synergistic effect of acetonedicarboxylic acid diethyl ester and calcium/zinc stearates on poly(vinyl chloride) thermal stability

Acetonedicarboxylic acid diethyl ester (AADE) is obtained by the interaction of ethanol with acetonedicarboxylic acid that is prepared from anhydrous citric acid. The thermal stabilizing effect of calcium and zinc stearates (CaSt2/ZnSt2) combined with AADE on poly (vinyl chloride) (PVC) is evaluated by the Congo red test, conductivity test, thermal aging test, and thermogravimetric analysis. The results of thermal stability tests show that the addition of AADE can improve not only the thermal stability but also the color stability of PVC. The improvement in stabilizing effectiveness is ascribed to the synergistic effect between CaSt2/ZnSt2 and AADE. The thermal stability mechanism of AADE is also under discussion with the help of quantum chemical calculations. The results of quantum chemical calculations indicate that, besides having the ability to form complexes with zinc ion, AADE has an evident tendency to replace the allyl chloride of the PVC. The results of the thermal aging test and quantum chemical calculations show that the thermal stabilizing effectiveness of AADE is higher than that of stearoyl benzoyl methane (β‐Diketones). J. VINYL ADDIT. TECHNOL., 21:228–234, 2015. © 2014 Society of Plastics Engineers

Effect of metal ions on acetone dicarboxylic acid catalyzed peroxomonosulphate reactions

The oxidation of Fe(III), Ni(II) and Co(II) citrates by peroxomonosulphate (PMS) in the pH range 3.0–6.0 follows autocatalysis mechanism. The acetone dicarboxylic acid (ADC), the oxidative decarboxylation product from citrate, is found to catalyze the reaction. The added metal ions switch the reaction from the ADC catalyzed decomposition of PMS to the oxidation of citrates. Based on the results from alcohol quenching, a mechanism involving oxygen atom transfer is proposed.

ChemInform Abstract: Synthesis of Salts of New Arylamides of 2‐Hydroxy‐5‐nitroso‐4,6‐dimethylisophthalic Acid

Abstractvia intermolecular cyclization of arylamides of acetonedicarboxylic acid (I) with isonitrosoacetylacetone (II)

Synthesis of salts of new arylamides of 2-hydroxy-5-nitroso-4,6-dimethylisophthalic acid

via intermolecular cyclization of arylamides of acetonedicarboxylic acid (I) with isonitrosoacetylacetone (II)