Unsaturated Aliphatic Acids Research Articles

The comparison researches of cis/trans-butenedioic acids in regulating solid crystalline forms and improving pharmaceutical properties of antifungal drug econazole

To highlight the preponderance of excipients maleic acid (MA) and fumaric acid (FA) in perfecting physicochemical peculiarities of antifungal drug econazole (ENZ), furthermore get some innovative cognitions on the regulation of solid crystalline form and antifungal activity of ENZ through regioisomers of unsaturated aliphatic dicarboxylic acids, two novice crystalline complexes of ENZ involving one cocrystal with FA, ENZ-FA (1), and one molecular salt with MA, ENZ-MA (2), are gained and structurally identified. The single-crystal X-ray diffraction analysis confirms that the component ratios of 2:1 and 1:1 for ENZ and corresponding acid molecules severally in 1 and 2. Both the cocrystallized solids have sandwich layer structures with hydrophobic surfaces and hydrophilic inner supramolecular networks with varied supramolecular aggregates, resulting in the simultaneous increasement in their dissolubility and permeability, thereinto, 1 owns higher permeability, while 2 is more ascendent in dissolubility, which are demonstrated by the combination of theory with experiment approaches. Specifically, compared with parent drug ENZ, the optimized physicochemical properties have endowed these cocrystallized complexes with strengthened in vitro antifungal activities, displaying larger inhibition rings and smaller MIC values, comparatively, 2 showcases stronger antifungal ability than that of 1. All the outcomes supply different molecular crystalline solids for ENZ, and fill the gap of its cocrystal investigations.

Isolation of achiral aliphatic acid derivatives from Piper kadsura using preparative two-dimensional chiral supercritical fluid chromatography

The separation of structural analogues in natural products has always been one of the challenges in separation science, where supercritical fluid chromatography (SFC) with chiral stationary phases (CSPs) is an unconventional but potential solution. In this study, a preparative two-dimensional chiral SFC (2D cSFC) method that was established with two kinds of CSPs was applied in the isolation of the aliphatic acid derivatives in Piper kadsura (P. kadsura). The RPLC unseparated peaks of two samples A and B of P. kadsura were evenly scattered on the CSP-1 column while they clustered into two groups on the CSP-2 column by SFC. There was impressively complementary selectivity between CSP-1 and CSP-2, which were used for construction of 2D cSFC. The first dimension (1D) separation with CSP-1 fractionated the sample A into six parts by a heart-cutting method and the sample B into nine parts for a comprehensive 2D analysis; then 29 and 71 peaks were respectively found in these parts in the second dimension (2D) separation with CSP-2. Further through 2D preparative separation, 19 high purity components were obtained, and the chemical structures of two of them were confirmed, including a novel unsaturated aliphatic acid compound (8Z,10Z)-12-methoxyheptadeca-8,10-dienoic acid and a known octadecadienoic acid lactone Lactariolide. The 2D cSFC method presented the superiority of separating the achiral compounds of complex samples.

Structure and Mechanism of Pseudomonas aeruginosa PA0254/HudA, a prFMN-Dependent Pyrrole-2-carboxylic Acid Decarboxylase Linked to Virulence.

The UbiD family of reversible (de)carboxylases depends on the recently discovered prenylated-FMN (prFMN) cofactor for activity. The model enzyme ferulic acid decarboxylase (Fdc1) decarboxylates unsaturated aliphatic acids via a reversible 1,3-cycloaddition process. Protein engineering has extended the Fdc1 substrate range to include (hetero)aromatic acids, although catalytic rates remain poor. This raises the question how efficient decarboxylation of (hetero)aromatic acids is achieved by other UbiD family members. Here, we show that the Pseudomonas aeruginosa virulence attenuation factor PA0254/HudA is a pyrrole-2-carboxylic acid decarboxylase. The crystal structure of the enzyme in the presence of the reversible inhibitor imidazole reveals a covalent prFMN–imidazole adduct is formed. Substrate screening reveals HudA and selected active site variants can accept a modest range of heteroaromatic compounds, including thiophene-2-carboxylic acid. Together with computational studies, our data suggests prFMN covalent catalysis occurs via electrophilic aromatic substitution and links HudA activity with the inhibitory effects of pyrrole-2-carboxylic acid on P. aeruginosa quorum sensing.

Poly(ethylene glycol) Supported Metal Nitrates as Well-Organized Reagents for Hunsdiecker Conversion of α,β-Unsaturated Acids to β-Nitrostyrenes under Solvent and Acid-Free Conditions

Poly(ethylene glycol) (PEG) supported metal nitrates such as ferric nitrate and manganese nitrate were accomplished as well-organized reagents for Hunsdiecker conversion of α,β-unsaturated acids to β-nitrostyrenes under acid-free and solvent free conditions using grind-stone technique. However, in the case of unsaturated aliphatic acids, nitro alkene derivatives were obtained as products. PEG-400 was found the best among the other PEGs (PEG-200,300, 400, 600, 3000 and 6000) used in this protocol.

Prenylated FMN: Biosynthesis, purification, and Fdc1 activation.

Prenylated flavin mononucleotide (prFMN) is a recently discovered flavin cofactor produced by the UbiX family of FMN prenyltransferases, and is required for the activity of UbiD-like reversible decarboxylases. The latter enzymes are known to be involved in ubiquinone biosynthesis and biotransformation of lignin, aromatic compounds, and unsaturated aliphatic acids. However, exploration of uncharacterized UbiD proteins for biotechnological applications is hindered by our limited knowledge about the biochemistry of prFMN and prFMN-dependent enzymes. Here, we describe experimental protocols and considerations for the biosynthesis of prFMN in vivo and in vitro, in addition to cofactor extraction and application for activation of UbiD proteins.

Stepwise extraction, chemical modification, GC–MS separation, and determination of amino acids in human plasma#

AbstractA method for isolation of enriched fractions of amino acids from human plasma followed by derivatization, gas chromatography separation and mass spectrometry identification is described. The method involves a stepwise extraction of plasma constituents with the use of two solvents: (a) extraction with methanol yields a concentrate of polyols, urea, carbohydrates and most long‐chain saturated and unsaturated aliphatic acids, and (b) further solubilization with water produces mainly a concentrate of amino acids. Chemical modification of amino acids with methyl chloroformate/methanol gives rise to methyl esters of methoxycarbonyl derivatives. The derivatization products are stable and quite suitable for gas chromatography with mass spectrometry analysis. The electron ionization mass spectra of the derivatization products reveal specific fragmentation patterns applicable for structure elucidation. The efficiency of the method is demonstrated by gas chromatography with mass spectrometry identification of 19 amino acids as their methyl esters of methoxycarbonyl derivatives in Standard Reference Material 1950 Metabolites in Frozen Human Plasma.

The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerization, and catalysis

The UbiD family of reversible decarboxylases act on aromatic, heteroaromatic, and unsaturated aliphatic acids and utilize a prenylated flavin mononucleotide (prFMN) as cofactor, bound adjacent to a conserved Glu–Arg–Glu/Asp ionic network in the enzyme's active site. It is proposed that UbiD activation requires oxidative maturation of the cofactor, for which two distinct isomers, prFMNketimine and prFMNiminium, have been observed. It also has been suggested that only the prFMNiminium form is relevant to catalysis, which requires transient cycloaddition between substrate and cofactor. Using Aspergillus niger Fdc1 as a model system, we reveal that isomerization of prFMNiminium to prFMNketimine is a light-dependent process that is largely independent of the Glu277–Arg173–Glu282 network and accompanied by irreversible loss of activity. On the other hand, efficient catalysis was highly dependent on an intact Glu–Arg–Glu network, as only Glu → Asp substitutions retain activity. Surprisingly, oxidative maturation to form the prFMNiminium species is severely affected only for the R173A variant. In summary, the unusual irreversible isomerization of prFMN is light-dependent and probably proceeds via high-energy intermediates but is independent of the Glu–Arg–Glu network. Our results from mutagenesis, crystallographic, spectroscopic, and kinetic experiments indicate a clear role for the Glu–Arg–Glu network in both catalysis and oxidative maturation.

Recombinant expression and characterisation of the oxygen-sensitive 2-enoate reductase from Clostridium sporogenes.

‘Ene’-reductases have attracted significant attention for the preparation of chemical intermediates and biologically active products. To date, research has been focussed primarily on Old Yellow Enzyme-like proteins, due to their ease of handling, whereas 2-enoate reductases from clostridia have received much less attention, because of their oxygen sensitivity and a lack of suitable expression systems. A hypothetical 2-enoate reductase gene, fldZ, was identified in Clostridium sporogenes DSM 795. The encoded protein shares a high degree of homology to clostridial FMN- and FAD-dependent 2-enoate reductases, including the cinnamic acid reductase proposed to be involved in amino acid metabolism in proteolytic clostridia. The gene was cloned and overexpressed in Escherichia coli. Successful expression depended on the use of strictly anaerobic conditions for both growth and enzyme preparation, since FldZ was oxygen-sensitive. The enzyme reduced aromatic enoates, such as cinnamic acid or p-coumaric acid, but not short chain unsaturated aliphatic acids. The β,β-disubstituted nitroalkene, (E)-1-nitro-2-phenylpropene, was reduced to enantiopure (R)-1-nitro-2-phenylpropane with a yield of 90 %. By contrast, the α,β-disubstituted nitroalkene, (E)-2-nitro-1-phenylpropene, was reduced with a moderate yield of 56 % and poor enantioselectivity (16 % ee for (S)-2-nitro-1-phenylpropane). The availability of an expression system for this recombinant clostridial 2-enoate reductase will facilitate future characterisation of this unusual class of ‘ene’-reductases, and expand the biocatalytic toolbox available for enantioselective hydrogenation of carbon-carbon double bonds.

Isobutylhydroxyamides from Zanthoxylum bungeanum and Their Suppression of NO Production.

Four new unsaturated aliphatic acid amides, named zanthoamides A–D (1–4), and eight known ones—tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E (10), bugeanumamide A (11), and (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (12)—were isolated from the pericarps of Zanthoxylum bungeanum. The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound 4 contained a rare C6 fatty acid unit with an acetal group. Results revealed that compounds 1, 5, 6, and 12 showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC50 values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC50 > 60 μM). They could contribute to the anti-inflammatory effects of Z. bungeanum by suppression of NO production.

Dissolved organic matter in pore water of Arctic Ocean sediments: Environmental influence on molecular composition

Marine organic matter (OM) sinks from surface water to the seafloor via the biological pump. Benthic communities, which use this sedimented OM as an energy and carbon source, produce dissolved OM (DOM) in the process of degradation, enriching the sediment pore water with fresh DOM compounds. In the oligotrophic deep Arctic basin, particle flux is low but highly seasonal. We hypothesized that the molecular signal of freshly deposited, primary produced OM would be detectable in surface sediment pore water, which should differ in DOM composition from bottom water and deeper sediment pore water. The study focused on (i) the molecular composition of the DOM in sediment pore water of the deep Eurasian Arctic basins, (ii) the signal of marine vs. terrigenous DOM represented by different compounds preserved in the pore water and (iii) the relationship between Arctic Ocean ice cover and DOM composition. Composition based on mass spectrometric information, obtained via 15T Fourier transform ion cyclotron resonance mass spectrometry, was correlated with environmental parameters with partial least square analysis. The fresh marine detrital OM signal from surface water was limited to pore water from <5cm sediment depth. The productive ice margin stations showed a higher abundance of peptide, unsaturated aliphatic and saturated fatty acid molecular formulae, indicative of recent phytodetritus deposition, than the multiyear ice-covered stations, which had a stronger aromatic signal. The study contributes to the understanding of the coupling between Arctic Ocean productivity and its depositional regime, and how it may be altered in response to sea ice retreat and increasing river runoff.

Removal of unsaturated aliphatic carboxylic acid from aqueous effluent using quaternary amine

Maleic acid, present in the effluent from organic intermediate producing industries, is an industrially important raw material. Its use in manufacture of alkyd and polyester resins, surface coatings, lubricant additives, plasticizers, co-polymers and agricultural chemicals, makes it necessary to explore for best possible techniques to recover it from aqueous solutions. The present work investigates the recovery of maleic acid from aqueous solution at ambient temperature. N–Methyl–n, n–dioctyloctan–1–ammonium chloride, (commercially known as Aliquat 336) is used as an extractant with three different diluents, belonging to different chemical classes: an aromatic hydrocarbon, a ketone, and an acetate. The chemical extraction results are reported in the terms of distribution coefficient, degree of extraction, and loading ratios. The results were modeled by mass action equilibria model as well as differential evolution technique. Differential evolution algorithm has been prepared. The model and experimental observations were compared and fairly good agreement was observed.

Structural features of two polymorphs of ammonium uranyl crotonate

X-ray crystallography, FTIR spectroscopy and thermal analysis were conducted for crystals of two polymorphs of NH4UO2(C3H5COO)3, which are the first examples of uranyl tricarboxylate complexes with ions of unsaturated aliphatic monocarboxylic acid. The main structural units of both polymorphs are anionic complexes [UO2(C3H5COO)3]−. Uranium atoms adopt hexagonal bipyramidal coordination polyhedron, and crotonate ions realize bidentate cyclic type of coordination. Due to different packing of ammonium ions and [UO2(C3H5COO)3]− complexes triclinic crystals of α-polymorph have layer structure and cubic crystals of β-polymorph have three dimensional structure. Features of three dimensional packing of R+ ions and [UO2L3]− complexes in structures of 25 known R[UO2L3] compounds are discussed.

Interacting blends of Styrenated unsaturated poly (ester–amide)s with commercial unsaturated polyester resin (o-phthalic anhydride based)

Unsaturated poly (ester–amide)s resins (UPEAs) were prepared by the reaction between an epoxy resin, namely diglycidyl ether of bisphenol-A (DGEBA) and unsaturated aliphatic bisamic acids (B1–4) using a base catalyst. These UPEAs were then diluted by styrene and blended with commercial unsaturated polyester resin (o-phthalic anhydride based) to produce a homogeneous resin. The curing of these Styrenated UPEAs–UPR blends was carried out using Benzoyl peroxide (BPO) as a catalyst and N,N′-Dimethyl aniline (DMA) as a promoter. The glass fiber reinforced composites (i.e. laminates) of these Styrenated UPEAs–UPR (o-phthalic anhydride based) blends were fabricated. The mechanical and chemical resistance properties of the glass fiber composites have also been evaluated. The unreinforced cured samples of the Styrenated UPEAs–UPR (o-phthalic anhydride based) blends were also analyzed by thermogravimetry (TGA).

Odor-Active (&lt;em&gt;E&lt;/em&gt;)-4-Methyl-3-hexenoic Acid in Roasted Coffee Generated in the Maillard Reactions of L-Isoleucine with Sugars

This study describes a novel odor-active unsaturated aliphatic acid in roasted Brazilian Arabica coffee. (<em>E</em>)-4-Methyl-3-hexenoic acid ((<em>E</em>)-4M3H), which is responsible for a sweaty odor, was identified for the first time using Gas Chromatography-Mass Spectrometry/Olfactometry (GC-MS/O), Aroma Extract Dilution Analysis (AEDA) and Multidimensional Gas Chromatography-Mass Spectrometry (MDGC-MS); its (<em>Z</em>)-isomer was also determined. Additionally, we conducted a model formation experiment to detect the presence of 4M3H in coffee and found that it may be produced nonstereoselectively in the Maillard reactions of L-isoleucine with sugars (xylose, fructose, glucose, rhamnose and sucrose). We also found that 2-methylbutanal derived from L-isoleucine and sugar degradation compounds such as &alpha-dicarbonyl compounds (glyoxal, 2-oxopropanal, 2, 3-butanedione and 2, 3-pentanedione) and α-hydroxy ketones (1-hydroxy-2-propanone and 3-hydroxy-2-butanone) are key factors in the formation of 4M3H. Based on these results, we propose a series of potential nonstereoselective formation pathways for 4M3H.

First identification of the odour‐active unsaturated aliphatic acid (E)‐4‐methyl‐3‐hexenoic acid in yuzu (Citrus junos Sieb. ex Tanaka)

ABSTRACTWe have investigated the aroma of yuzu (Citrus junos Sieb. ex Tanaka). Application of the aroma extract dilution analysis technique allowed us to determine a sequence of the odour‐active compounds in yuzu volatile oil. In this study, we confirmed the presence of an unknown odorant that possesses a sweaty odour and a relatively high flavour dilution factor. In order to identify the unknown compound, the concentrated volatile acid fraction of yuzu volatile oil was obtained, using an enrichment procedure consisting of the combination of the sub‐extraction of an acidic component with a basic aqueous solution and subsequent affinity chromatography with an Oasis MAX cartridge. Gas chromatography–olfactometry and multi‐dimensional gas chromatography–mass spectrometry analyses revealed that the unknown compound was (E)‐4‐methyl‐3‐hexenoic acid [(E)‐4M3H]. (E)‐4M3H was identified for the first time as an odour‐active unsaturated aliphatic acid in yuzu. Additionally, both (Z)‐ and (E)‐4M3H were stereoselectively synthesised over two steps comprised of the iron‐catalysed carbometalations of homopropargylic alcohols with Grignard reagents, followed by oxidation. On the basis of sensory evaluation, the orthonasal odour detection threshold of the (E)‐isomer was 10‐fold to 100‐fold lower than that of the (Z)‐isomer. Copyright © 2012 John Wiley &amp; Sons, Ltd.

VOLATILE COMPOUNDS DURING THE RIPENING OF COLOMBIAN SOURSOP (&lt;I&gt;Annona muricata&lt;/I&gt; L. cv. Elita)

Fruits of soursop (Annona muricata L. cv. Elita) were evaluated at different ripening stages to determine the changes in their physicochemical characteristics: total soluble solid content, percentage of acidity, pH, and ripeness index. The change in volatile compounds were determined through Headspace-Solid Phase Microextraction and subsequent Gas Chromatography-Mass Spectrometry analyses. The volatile compounds were identified through the comparison of their chromatographic and spectral properties against the ones exhibited by reference substances. The sensorial quality factors showed values that changed according to the ripening stage. It was established that the ester levels, particularly those from C6, C4, and C8 saturated and unsaturated aliphatic acids, increased with ripening. C6 aliphatic compounds, such as (Z)-3-hexenol and (Z)-3-hexenal, were observed to be the major volatile constituents in the green stage. In contrast, methyl hexanoate and methyl (E)-2-hexenoate were the main volatile in ripe, overripe and half ripe fruits. The overripe stage was characterized by an increase in the ethyl acetate, methyl butanoate and ethyl butanoate levels, and the appearance of butanoic and hexanoic aliphatic acids. These facts could be used as an indicator of the beginning of the fermentation stage and the loss of fruit sensory quality.

Coordination polymers constructed from d10 ions, saturated or unsaturated aliphatic carboxylic acids, and bidentate nitrogen ligands: synthesis, characterization, and fluorescence

Five new coordination polymers synthesized from d10 metal ions, aliphatic carboxylic acids, and bidentate nitrogen ligands have been characterized with single crystallographic X-ray analysis, IR, and TG. Compound 1 has a twofold 3-D network. During the synthesis of 1, fumaric acid reacts with water giving malic acid, which coordinates Cd forming 2. If we use Zn instead of Cd, 1-D chain-like 3 is formed. With hydrogen bonds and π–π interactions, the 1-D covalent chains form a 3-D supramolecular network. The 3-D supramolecular networks connect together and form a twofold interpenetration structure. Compound 4 shows a 2-D layer structure. Compound 5 exhibits 1-D double-chain structure composed by hydrogen bonds. We studied the fluorescence of 1, 2, 3, and 5.

Antitumor components from Naematoloma fasciculare.

The bioassay-guided fractionation of MeOH extract from Naematoloma fasciculare afforded a petroleum ether fraction (NFPF) and four known compounds, which showed good antitumor activities to inhibit MCF-7 cell line proliferation in vitro and tumor growth in H(22) implanted mice in vivo. In addition, a number of unsaturated aliphatic acids were identified in NFPF by GC analysis. These results showed that NFPF inhibits tumor growth through the activity of unsaturated aliphatic acids together with two active compounds, ergosterol peroxide (1: 62.17 mg/g in NFPF) and ergosterol (2: 3.13 mg/g in NFPF), and indicate the potential utility of NFPF as an antitumor drug.

Enantioselective hydrogenation of (E)-2-methyl-2-butenoic acid over cinchonidine modified Pd catalyst. Effect of the structure of achiral amine additives

The effect of the structure of the achiral primary amine additive on the enantioselective heterogeneous catalytic hydrogenation of (E)-2-methyl-2-butenoic acid over cinchonidine modified Pd/Al2O3 was studied. It was found that a variety of amines increase the enantioselectivity, which was always accompanied by decrease in the initial rate of the hydrogenations. Based on these results, the participation of the amine additive in the formation of the intermediate complex responsible for enantioselection was suggested. A decrease in the reaction temperature resulted in further increase in the optical purity of the product up to 67%, the highest value reported in the hydrogenation of unsaturated aliphatic acids in this heterogeneous catalytic system so far.

Preparative argentation reversed-phase high performance liquid chromatography

In this study, a preparative chromatography method named preparative argentation reversed-phase high performance liquid chromatography (Ag-RP-HPLC) was developed by adding silver ion to the mobile phase of preparative HPLC. Firstly, an analytical Ag-RP-HPLC method was developed, and the effects of silver content and acid content in the mobile phase on the column efficiency were studied. Based on the method of linear amplification, a preparative Ag-RP-HPLC technique with optimized separation conditions was developed. The new technique was applied successfully to the separation of the unsaturated aliphatic acid amide isomers contained in Asarum forbesii Maxim. Compared with the commonly used technique of argentation normal phase chromatography, this method with little solvent consumption is simple, fast, efficient, and flexible for the isolation and purification of the unsaturated compounds.