maleic-acid and fumaric-acid

The potential of fumaric acid as a raw material in the polymer industry and the increment of cost of petroleum-based fumaric acid raises interest in fermentation processes for production of this compound from renewable resources. Although the chemical process yields 112% w/w fumaric acid from maleic anhydride and the fermentation process yields only 85% w/w from glucose, the latter raw material is three times cheaper. Besides, the fermentation fixes CO2. Production of fumaric acid by Rhizopus species and the involved metabolic pathways are reviewed. Submerged fermentation systems coupled with product recovery techniques seem to have achieved economically attractive yields and productivities. Future prospects for improvement of fumaric acid production include metabolic engineering approaches to achieve low pH fermentations.

Topics: Bacteria; Fermentation; Fumarates; Industrial Microbiology; Maleates; Oxygen

Topics: Citric Acid Cycle; Fumarate Hydratase; Fumarates; Humans; Isoenzymes; Maleates; Metabolism, Inborn Errors; Mitochondria; Substrate Specificity

Thiabendazole is an anthelmintic drug used to treat strongyloidiasis (threadworm), cutaneous and visceral larva migrans, trichinosis, and other parasites. The active pharmaceutical ingredient is typically administered orally as tablets that should be chewed before swallowing. Current formulations combine the active ingredient with excipients, including sodium saccharinate as a sweetener. Thiabendazole's low aqueous solubility hinders fast dissolution and absorption through the mucous membranes. We sought to reformulate this medicine to improve both solubility and palatability. We utilized the possibility of protonation of the azole nitrogen atom and selected four different hydrogen donors: saccharin, fumaric, maleic, and oxalic acids. Solvothermal synthesis resulted in salts with each co-former, whereas neat and liquid-assisted grinding enabled the synthesis of additional formulations. Product formation was observed by powder X-ray diffraction. To better understand the structural basis of the proton transfer, we solved the crystal structures of the salts with saccharin, maleic acid, and oxalic acid using single-crystal X-ray diffraction. The structure of the salt with fumaric acid was solved by powder X-ray diffraction. We further characterized the salts with vibrational spectroscopic and thermoanalytical methods. We report a broad tunability of the aqueous solubility of thiabendazole by salt formation. Reformulation with maleic acid provided a 60-fold increase in solubility, while saccharin and oxalic acid gave a modest improvement. Fumaric acid resulted in a solid with only slightly higher solubility. Furthermore, saccharin is a sweetener, while the acids taste sour. Therefore, the salts formed also result in an intrinsic improvement of palatability. These results can inform new strategies for oral and chewable tablet formulations for treating helminthic infections.

Topics: Anthelmintics; Anti-Infective Agents; Oxalic Acid; Powders; Saccharin; Salts; Solubility; Sweetening Agents; Tablets; Thiabendazole; X-Ray Diffraction

Significant advances have been made in unknown metabolite identification and expansion of the number of quantifiable metabolites in human plasma, serum, and whole blood using NMR spectroscopy. However, reliable quantitation of metabolites is still a challenge. A major bottleneck is the lack of a suitable internal standard that does not interact with the complex blood sample matrix and also does not overlap with metabolite peaks apart from exhibiting other favorable characteristics. With the goal of addressing this challenge, a comprehensive investigation of fumaric and maleic acids as potential internal standards was made along with a comparison with the conventional standards, TSP (trimethylsilylpropionic acid) and DSS (trimethylsilylpropanesulfonic acid). Both fumaric acid and maleic acid exhibited a surprisingly high performance with a quantitation error <1%, while the TSP and DSS caused an average error of up to 35% in plasma, serum, and whole blood. Further, the results indicate that while fumaric acid is a robust standard for all three biospecimens, maleic acid is suitable for only plasma and serum. Maleic acid is not suited for the analysis of whole blood due to its overlap with coenzyme peaks. These findings provide new opportunities for improved and accurate quantitation of metabolites in human plasma, serum, and whole blood using NMR spectroscopy. Moreover, the use of protein precipitation prior to NMR analysis mirrors the sample preparation commonly used for mass spectrometry based metabolomics, such that these findings further strengthen efforts to combine and compare NMR and MS based metabolite data of human plasma, serum, and whole blood for metabolomics based research.

Topics: Fumarates; Humans; Magnetic Resonance Spectroscopy; Maleates; Metabolomics; Plasma; Serum

ST segment elevation myocardial infarction (STEMI) is one of the most common global causes of cardiovascular disease-related death. Several metabolites may change during STEMI. Hence, analysis of metabolites in body fluid may be considered as a rapid and accurate test for initial diagnosis. This study has therefore attempted to determine the variation in metabolites identified in the serum of STEMI patients (n = 20) and 15 controls. Samples collected from the Cardiology Department, Medical Faculty, Ataturk University, were extracted by liquid-liquid extraction and analysed using liquid chromatography quadrupole time-of-flight mass spectrometry. The METLIN database was used for the identification and characterization of metabolites. According to Q-TOF/MS measurements, 231 m/z values, which were significantly different between groups (P < 0.01 and fold analysis >1.5) were detected. Metabolite identification was achieved via the Human Metabolome database. According to the multivariate data analysis, leucine, isoleucine, l-proline, l-alanine, glycine, fumaric acid, citrate, succinate and carnitine levels were decreased, whereas levels of propionic acid, maleic acid, butyric acid, urea, oleic acid, palmitic acid, lysoPC [18:2(9Z)], glycerol, phoshpatidylethanolamine, caffeine and l-lactic acid were increased in STEMI patients compared with controls. In conclusion, malonic acid, maleic acid, fumaric acid and palmitic acid can be used as biomarkers for early risk stratification of patients with STEMI.

Topics: Amino Acids; Chromatography, Liquid; Female; Fumarates; Humans; Male; Maleates; Malonates; Mass Spectrometry; Metabolome; Metabolomics; Middle Aged; ST Elevation Myocardial Infarction

Agrobacterium tumefaciens strain SCUEC1 is a nicotine-degrading bacterium, which has been recently isolated from the tobacco waste-contaminated field soil. However, the mechanism for nicotine degradation in this strain remains unclear. Here, we analyze the function and biological properties of the agnH gene in the strain SCUEC1. The overexpression of the AgnH protein was detected by SDS-PAGE analysis, and functional insight of the AgnH protein was carried out with monitoring the changes of maleic acid into fumaric acid by high performance liquid chromatography (HPLC). Moreover, the effects of temperature, pH and metal ions on the enzymatic activities of the AgnH protein were also analyzed. The results demonstrated that the agnH gene was successfully ligated to the plasmid pET28a. The optimal condition for the enzymatic activities for the AgnH, approximately 28.0 kDa, was determined as 37 °C, pH 8.0 and 25 µM Mg2+. Conclusively, the agnH gene fulfils an important role in the conversion of maleic acid into fumaric acid involved in nicotine-degradation pathways in Agrobacterium tumefaciens strain SCUEC1.

Topics: Agrobacterium tumefaciens; Bacterial Proteins; Fumarates; Hydrogen-Ion Concentration; Maleates; Nicotine; Temperature

Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral infection of cancer cell lines as well as human tumor biopsies with several oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic and xenograft tumor models. This results in durable responses, even in models otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance viral spread results from its ability to inhibit type I interferon (IFN) production and response, which is associated with its blockade of nuclear translocation of the transcription factor nuclear factor κB (NF-κB). This study demonstrates that unconventional application of U.S. Food and Drug Administration-approved drugs and biological agents can result in improved anticancer therapeutic outcomes.

Topics: Animals; Cell Line, Tumor; Cytokines; Dimethyl Fumarate; Esters; Fumarates; Glutathione; Humans; Interferon Type I; Maleates; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B; Oncolytic Virotherapy; Oncolytic Viruses; Xenograft Model Antitumor Assays

The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0

Topics: Antimalarials; Crystallization; Crystallography, X-Ray; Fumarates; Hydrogen Bonding; Isomerism; Maleates; Molecular Conformation

With the aim of improving the solubility of ciprofloxacin, polybasic organic acids were utilized to react with ciprofloxacin in different stoichiometric proportions. The use of the solvent drop grinding (SDG) method, as well as the solvent evaporation method, resulted in the crystalline salts ciprofloxacin/fumaric acid (1:1, 2:1), ciprofloxacin/maleic acid (1:1) and ciprofloxacin/citric acid (2:1). The solubilities of these salts in pure water (pH 7.0) were determined using high-performance liquid chromatography (HPLC) at 310 K, with the salts showing considerably greater solubility than ciprofloxacin itself and, interestingly, ciprofloxacin/fumaric acid (2:1) being more soluble than ciprofloxacin/fumaric acid (1:1). Intrigued by this phenomenon, we undertook a comparison of the crystal structures of the salts: the three-dimensional sandwich-like structure observed in the 2:1 salt indicates that the preferred stacking may be a factor in increasing the solubility of ciprofloxacin.

Topics: Calorimetry, Differential Scanning; Ciprofloxacin; Citric Acid; Fumarates; Maleates; Organic Chemicals; Sodium Chloride; Solubility

Heterobis imine Schiff base probe L is able to discriminate geometrical isomers (maleic acid vs fumaric acid) through sharp colorimetric as well as fluorogenic responses even conspicuous with the naked eye. Colorimetric as well as fluorogenic sensing of maleic acid among various carboxylic acids was also demonstrated in ethanol-buffer medium. Sensing behavior of L was corroborated by (1)H NMR spectra, mass spectrometry, and theoretical calculations. Subsequently sensing behavior of L was used to probe maleic acid in starch rich food samples.

Topics: Colorimetry; Fluorescent Dyes; Fluorometry; Food Additives; Fumarates; Imines; Isomerism; Maleates; Molecular Structure; Schiff Bases; Solutions; Time Factors

The characterization of the metabolites accumulated in the grapes of specific cultivars grown in different climates is of particular importance for viticulturists and enologists. In the present study, the metabolite profiling of grapes from the cultivars, Alvarinho, Arinto and Padeiro de Basto, of two Portuguese Controlled Denomination of Origin (DOC) regions (Vinho Verde and Lisboa) was investigated by gas chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS) and an amino acid analyzer. Primary metabolites, including sugars, organic acids and amino acids, and some secondary metabolites were identified. Tartaric and malic acids and free amino acids accumulated more in grapes from vines of the DOC region of Vinho Verde than DOC Lisboa, but a principal component analysis (PCA) plot showed that besides the DOC region, the grape cultivar also accounted for the variance in the relative abundance of metabolites. Grapes from the cultivar, Alvarinho, were particularly rich in malic acid and tartaric acids in both DOC regions, but sucrose accumulated more in the DOC region of Vinho Verde.

Topics: Amino Acids; Chromatography, Gas; Citric Acid; Fructose; Fruit; Fumarates; Geography; Glucose; Malates; Maleates; Mass Spectrometry; Metabolome; Metabolomics; Portugal; Principal Component Analysis; Species Specificity; Succinic Acid; Sucrose; Tartrates; Vitis

An ion-exclusion chromatographic method for the simultaneous determination of organic acids in rice wine was developed. An IC-Pak Ion Exclusion column (300 mm x 7.8 mm, 7 microm) was used at 50 degrees C. The mobile phases were H2SO4 (phase A) and acetonitrile (phase B) (98:2, v/v) at a flow rate of 0.5 mL/min. The gradient elution program was as follows: 0-40 min, 0.01 mol/L H2SO4 to 0.02 mol/L H2SO4; 40-50 min, 0.01 mol/L H2SO4. The injection volume was 10 microL. The detection wavelength was set at 210 nm. The results showed that oxalic acid, maleic acid, citric acid, tartaric acid, malic acid, ascorbic acid, succinic acid, lactic, fumaric acid, acetic acid, propionic acid, isobutyric acid and butyric acid were completely separated and determined in 30 min. The linear correlation coefficients were above 0.999 7 in the range of 0.001- 1.000 g/L. Under the optimized conditions, the recoveries of organic acids in rice wine were in the range of 93.4% - 103.8% with the relative standard deviations (RSDs, n = 5) of 0.1% - 1.5%. This method is feasible, convenient, fast, accurate and applicable for the quantitative analysis of the organic acids in rice wine.

Topics: Acids; Chromatography, Gel; Fumarates; Malates; Maleates; Oryza; Oxalic Acid; Tartrates; Wine

Preferential binding of a new reagent to fumaric acid could be utilized for its estimation in aqueous medium and in commercial fruit juice.

Topics: Beverages; Fluorescence; Fluorescence Resonance Energy Transfer; Fruit; Fumarates; Maleates; Molecular Structure; Quantum Theory; Water

AZD1305 is a novel, water-soluble investigational antiarrhythmic agent for restoration and maintenance of sinus rhythm in atrial fibrillation patients. The present studies were performed to evaluate the possibility for further development of the compound.. A set of technical approaches were used, including X-ray powder diffractometry, differential scanning calorimetry, thermogravimetrical analysis, dynamic vapor sorption, scanning electron microscopy, salt screen, and liquid chromatography.. AZD1305 is a crystalline oxabispidine and its neutral form is a base with a pK(a) of 9.9. The substance degrades with higher temperature and lower pH. The free base of the solid substance is stable at 25°C (closed container), 40°C/75% relative humidity (open container), and at 50°C (closed container) for at least 3 months. The free base of AZD1305 is polymorphic with two known forms. Both forms are non-hygroscopic ansolvates with melting points of approximately 90°C. No salt was found with overall improved properties. The substance had a strong odor, which was reduced by increased particle size.. The free base of AZD1305 seemed to be the most suitable agent for product development even though it has a fairly low melting point and occurred as two different crystal forms. Form B was the most stable thermodynamically in the temperature interval of interest.

Topics: Administration, Oral; Azabicyclo Compounds; Calorimetry, Differential Scanning; Carbamates; Chemistry, Pharmaceutical; Chromatography, Liquid; Crystallization; Drug Stability; Fumarates; Humidity; Hydrogen-Ion Concentration; Infusions, Intravenous; Maleates; Microscopy, Electron, Scanning; Particle Size; Powders; Salts; Solubility; Solutions; Temperature; Thermogravimetry; Transition Temperature; Wettability; X-Ray Diffraction

The plasticizer di (2-ethylhexyl) phthalate (DEHP) and its metabolites are considered ubiquitous contaminants, which have a range of implications on the environment and human health. This work considered several alternative compounds with structural features similar to DEHP. This added to the understanding of why DEHP is so poorly biodegraded once it enters the environment. These alternative compounds were based on 2-ethylhexyl diesters of maleic acid (cis-isomer), fumaric acid (trans-isomer) and succinic acid (saturated analogue). The rates of biodegradation by the common soil bacterium Rhodococcus rhodocrous were shown to be dependent on the structure of the central unit derived from the diacid used to make the ester. The diacid components of DEHP and the maleate both had a cis orientation and they were the two that were slow to biodegrade. Plasticizing properties were also compared and, because the ester of the saturated succinic acid was degraded quickly and also had good plasticizing properties, it was concluded that the succinic esters of straight chain alcohols would make the best green plasticizers. The maleate ester had excellent plasticizing properties but this is mitigated by a significant resistance to biodegradation.

Topics: Biodegradation, Environmental; Diethylhexyl Phthalate; Fumarates; Maleates; Plasticizers; Rhodococcus; Succinic Acid

The paper presents an on-line transient moving chemical reaction boundary (MCRB) method for simply but efficiently stacking analytes in capillary electrophoresis (CE). The CE technique was developed for a rapid determination of fumaric and maleic acid. Based on the theory of MCRB, Effects of several important factors such as the pH and concentration of running buffer and the conditions of stacking analytes were investigated to acquire the optimum conditions. The optimized separations were carried out in a 20 mmol/L sulphate neutralized with ethylenediamine to pH 6.0 electrolytes using a capillary coated with poly (diallyldimethylammonium chloride) and direct UV detection at 214 nm. The optimized preconcentrations were carried out in 50 mmol/L borax (pH 9.0). The calibration curves were linear in the concentration range of 1.0×10⁻⁷-1.0×10⁻⁴ mol/L and 5.0×10⁻⁷-1.0×10⁻⁴ mol/L for fumaric and maleic acid with correlation coefficients higher than 0.9991. The detection limits were 5.34×10⁻⁸ mol/L for fumaric acid and 1.92×10⁻⁷ mol/L for maleic acid. This method was applied for determination of fumaric acid in apple juice and of fumaric and maleic acid in dl-malic, the recovery tests established for real samples were within the range 95-105%. This work provided a valid and simple approach to detect fumaric and maleic acid.

Topics: Alkalies; Borates; Electrophoresis, Capillary; Ethylenediamines; Fumarates; Hydrogen-Ion Concentration; Linear Models; Maleates; Reproducibility of Results; Sensitivity and Specificity; Sulfuric Acids

(rac)-1,1'-Binaphthyl-based simple receptors 1 and 2 have been designed, synthesized and studied theoretically. The receptors utilize naphthyridine as the binding motifs for complexation of dicarboxylic acids in CHCl(3). The emission of the BINOL moiety was monitored experimentally to ascertain the selectivity and sensitivity of the receptors. Receptor 1 distinguishes maleic acid from isomeric fumaric acid by exhibiting different fluorescence behavior and demonstrates stronger binding in the excited state. Modulation of the binding sites of 1 leads to a new receptor structure 2, which was found to be less efficient in distinguishing maleic from fumaric acid, fluorometrically. Both 1 and 2 also recognize other hydroxy di- and tricarboxylic acids. The binding interactions were monitored by (1)H NMR, fluorescence and UV-vis spectroscopic methods. Structures of apo-hosts, guests and host-guest complexes were determined using force-field based conformational searching. Low energy ensembles were grouped into geometrically similar families, and low energy structures from each family were verified using B3LYP/6-31G*/PB-SCRF(CHCl(3)) calculations. The atomistic calculations provide insight into the differential dicarboxylic acid binding behavior of receptors 1 and 2.

Topics: Computer Simulation; Fluorometry; Fumarates; Magnetic Resonance Spectroscopy; Maleates; Molecular Structure; Naphthalenes

To better understand the behavior of low molecular weight organic acids in subsurface environments, the transport of three dicarboxylic acids (phthalic, maleic, and fumaric acid) in water-saturated columns packed with a hematite-coated sand was investigated in single and binary organic acid systems. Experiments were conducted at a single ionic strength (0.1M) and at two pH values (4.1 and 5.3). In single-acid systems, the order of breakthrough at both pH values was fumaric acid, followed by maleic acid, and then phthalic acid. The shape of the breakthrough curves for the acids at the two pH values were similar except at pH 5.3 phthalic acid showed two adsorption fronts. The initial front only partially broke through, whereas the second front proceeded to complete breakthrough. This behavior resulted from a marked pH increase during phthalic acid adsorption and suggests that the single-acid systems behaved as dual-component systems with the organic acid and hydrogen ion as variables. The breakthrough curves for the binary organic acid systems showed organic acids with a higher adsorption affinity (e.g., phthalic acid) competitively displace organic acids with a lower adsorption affinity (e.g., fumaric acid). The dual-component effect observed for phthalic acid in the single-acid systems was suppressed in the mixed acid systems, perhaps reflecting pH changes that accompanied the desorption of the weakly-binding acids. These results may provide an important step toward further elucidating the processes controlling organic acid fractionation in the subsurface.

Topics: Adsorption; Chromatography; Fumarates; Hydrogen-Ion Concentration; Maleates; Phthalic Acids; Porosity; Silicon Dioxide

Low molecular weight organic acids comprise an important pool of reactive ligands in aquatic systems. These acids readily bind to nano-sized mineral particles and thereby strongly influence a particle's physicochemical behavior. Predicting this influence requires the integration of molecular-level details that control surface complexation mechanisms and structures with macro-scale observations of mineral colloid behavior. We report on the aggregation kinetics of nano-sized hematite in the presence of fumaric acid and maleic acid, which are naturally occurring dicarboxylic acids of similar size and structure. Our results indicate that the structure and orientation of the adsorbed dianion at the hematite surface, not the adsorption mechanism, defines the resulting effect. Maleate, which directs both carboxyl groups to the surface in the form of inner- and outer-sphere surface complexes, enhances colloidal stability. Fumarate, however, which binds to the hematite surface as an outer-sphere complex with just one carboxyl group only slightly influenced particle stability. This outcome suggests that subtle differences in the structure of adsorbed acids produce important differences in the physicochemical behavior of particles in dilute aquatic systems.

Topics: Adsorption; Colloids; Ferric Compounds; Fumarates; Magnetite Nanoparticles; Maleates; Surface Properties

Maleic acid and fumaric acid, the Z and E isomers of butenedioic acid, form 1:1 adducts with 2-amino-1,3-thiazole, namely 2-amino-1,3-thiazolium hydrogen maleate (2ATHM), C(3)H(5)N(2)S(+) x C(4)H(3)O(4)(-), and 2-amino-1,3-thiazolium hydrogen fumarate (2ATHF), C(3)H(5)N(2)S(+) x C(4)H(3)O(4)(-), respectively. In both compounds, protonation of the ring N atom of the 2-amino-1,3-thiazole and deprotonation of one of the carboxyl groups are observed. The asymmetric unit of 2ATHF contains three independent ion pairs. The hydrogen maleate ion of 2ATHM shows a short intramolecular O-H...O hydrogen bond with an O...O distance of 2.4663 (19) A. An extensive hydrogen-bonded network is observed in both compounds, involving N-H...O and O-H...O hydrogen bonds. 2ATHM forms two-dimensional sheets parallel to the ab plane, extending as independent parallel sheets along the c axis, whereas 2ATHF forms two-dimensional zigzag layers parallel to the bc plane, extending as independent parallel layers along the a axis.

Topics: Butyric Acid; Crystallography, X-Ray; Fumarates; Hydrogen Bonding; Isomerism; Maleates; Models, Molecular; Molecular Structure; Thiazoles

Fumarate, a four-carbon trans dicarboxylic acid, is the allosteric activator of the human mitochondrial NAD(P)(+)-dependent malic enzyme (m-NAD(P)-ME). In this paper, we discuss the effects of the structural analogues of fumarate on human m-NAD(P)-ME. Succinate, a dicarboxylic acid with a carbon-carbon single bond, can also activate the enzyme, but the activating effect of succinate is less than that of fumarate. Succinamide, a diamide of succinate, cannot activate the enzyme and is a poor active-site inhibitor. The cis isomer of fumarate, maleic acid, significantly inhibits the ME activity, suggesting that the trans configuration of fumarate is crucial for operating the allosteric regulation of the enzyme. Other dicarboxylic acids, including glutaconic acid, malonic acid and alpha-ketoglutarate, cannot activate the enzyme and inversely inhibit enzyme activity. Our data suggest that these structural analogues are mainly active-site inhibitors, although they may enter the allosteric site to inhibit the enzyme. Furthermore, these data also suggest that the dicarboxylic acid must be in a trans conformation for allosteric activation of the enzyme.

Topics: Allosteric Regulation; Allosteric Site; Crystallography, X-Ray; Dicarboxylic Acids; Fumarates; Humans; Malate Dehydrogenase; Malates; Models, Molecular; Molecular Structure; Mutagenesis, Site-Directed; Protein Binding; Succinic Acid

Both maleic and fumaric acid readily form adducts or complexes with other organic molecules. The 1:1 adduct formed by quinolin-8-ol (oxine) with maleic and fumaric acid are salts, namely 8-hydroxyquinolinium hydrogen maleate, C(9)H(8)NO(+).C(4)H(3)O(4)(-), (I), and 8-hydroxyquinolinium hydrogen fumarate, C(9)H(8)NO(+).C(4)H(3)O(4)(-), (II). The cations and anions of both salts are linked by ionic N(+)-H...O(-) hydrogen bonds. The maleate salt crystallizes in the space group P2(1)2(1)2(1), while the fumarate salt crystallizes in P\\overline{1}. The maleic and fumaric acids in their complex forms exist as semimaleate and semifumarate ions (mono-ionized state), respectively. Classical N-H...O and O-H...O hydrogen bonds, together with short C-H...O contacts, generate an extensive hydrogen-bonding network. The crystal structures of the maleate and fumarate salts of oxine have been elucidated to study the importance of noncovalent interactions in the aggregation and interaction patterns of biological molecules. The structures of the salts of the Z and E isomers of butenedioic acid (maleic and fumaric acid, respectively) with quinolin-8-ol are compared.

Topics: Crystallography, X-Ray; Fumarates; Hydrogen Bonding; Isomerism; Maleates; Models, Molecular; Oxyquinoline

Polycarboxylate-type green surfactants with either sulfide- (S-) or imino- (N-) linkages were prepared in high yields by a single addition reaction of fatty mercaptan or fatty amine with unsaturated polycarboxylic acids such as fumaric, maleic, itaconic and aconitic acids. They exhibited surfactant properties and excellent biodegradabilities. Also, green surfactants with S-linkages showed better calcium ion sequestration abilities compared to the corresponding surfactant having an N-linkage. Among these surfactants, aconitic acid-derived polycarboxylate with an S-linkage exhibited calcium ion sequestration capacities similar to that of disodium 3-oxapentanedioate (ODA), a conventional calcium ion sequestrant on a molar basis of the surfactant.

Topics: Aconitic Acid; Biodegradation, Environmental; Calcium; Carboxylic Acids; Cations; Fumarates; Imines; Maleates; Propofol; Succinates; Sulfhydryl Compounds; Sulfides; Surface Properties; Surface-Active Agents

(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes between three organic acids: maleic, fumaric, L-tartaric acids and betaCD. In aqueous medium, the complexation was confirmed by (1)H NMR spectroscopy using two-dimensional technique. The stable geometries of the complexes were determined by molecular modeling. Experimental infrared frequencies were assigned on the base of the vibrational normal mode calculation at the fully optimized geometry for the inclusion complexes. All the results point out the presence of stable inclusion complexes between acids and betaCD at the solid state. These results show the double role of the acid. Correlated with the theoretical and experimental data previously obtained for the miconazole/CD/acids complexes, in function of both acids and CDs structures, the acids can either stabilize the complexes by formation of a multicomponent complex or form acid/CD inclusion complexes, hindering the guest inclusion.

Topics: beta-Cyclodextrins; Dicarboxylic Acids; Fumarates; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Maleates; Miconazole; Models, Molecular; Pharmaceutical Vehicles; Spectroscopy, Fourier Transform Infrared; Tartrates; Thermodynamics

A general synthetic procedure leading to isotopomeric dihydro-2(3H)furanones (gamma-butyrolactones) containing two, four, or six deuterium atoms has been developed. The labeled dihydro-2(3H)furanones were synthesized in quantitative yield from the saturated diacid C4 (succinic) or unsaturated diacids C4 (fumaric, maleic, or acetylendicarboxylic) in the presence of Ru4H4(CO)8(PBu3)4 using a deuterium pressure of 180 bar at 180 degrees C. This methodology was applied to the total synthesis of a hexadeuterated matairesinol lignan: The 3,4-bis[[3-methoxy-4-(phenylmethoxy)phenyl]methyl]dihydro-2(3H)furanone-[7,7',8,8',9',9'-D6] (benzyl-protected matairesinol-D6) was fully characterized.

Topics: 4-Butyrolactone; Deuterium; Fumarates; Furans; Isotope Labeling; Lignans; Maleates; Ruthenium; Succinic Acid

Four new colorimetric receptors (1-4) were synthesized and characterized. Upon addition of maleate to receptor in DMSO, the appearance of the solution of receptor 1 showed a color change from dark-blue to dark-red, which can be detected by the naked eye at parts per million. Similar experiments were repeated using receptors 2-4; the solution showed a distinct color change from blue to violet for receptor 2 and from blue-green to purple for both receptors 3 and 4, when they are formed as complexes with maleate. The striking color changes are thought to be due to the deprotonation of the thiourea moiety of the 4-nitronaphthyl chromophore. Whereas, in the addition of fumarate to receptors 1-4, the color of the solution changed from dark-blue to bright yellow for receptor and did not induce any color change for receptors 2-4. Thus, for a distinct color change, receptors 1-4 can act as optical chemosensors for recognition of maleate versus fumarate. Especially, only receptor 1 has a unique color change for the recognition of fumarate, accordingly it can be used for detection of the fumarate anion. In this research it was also found that the performance of the receptor is highly dependent on the substituent group on the phenyl ring; a stronger electron-withdrawing group resulted in a receptor with a higher binding constant with the maleate anion.

Topics: Anions; Colorimetry; Dicarboxylic Acids; Fumarates; Hydrogen Bonding; Isomerism; Kinetics; Magnetic Resonance Spectroscopy; Maleates; Protons; Spectrophotometry, Ultraviolet

Tris(2,4,6-trimethoxyphenyl)phosphonium propylamine bromide (TMPP) has been used for the derivatisation of maleic, fumaric, sorbic and salicylic acids to facilitate determination using liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI-MS/MS) in positive ion mode. Detection limits, achieved using multiple reaction monitoring mode, were 2, 4, 0.4 and 540 fmol (5 muL injection) for derivatised fumaric, sorbic, maleic and salicylic acids, respectively. In comparison, detection limits achieved in negative ion mode for the underivatised acids were 24, 51, 2, and 117 fmol, respectively. The method was successfully used for the determination of sorbic acid in a sample of Panadol. The derivatisation of salicylic acid was not as successful, probably due to poor reaction efficiency.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Bridged Bicyclo Compounds, Heterocyclic; Carboxylic Acids; Chromatography, High Pressure Liquid; Fumarates; Maleates; Salicylic Acid; Sorbic Acid; Spectrometry, Mass, Electrospray Ionization

Benzylsuccinate synthase catalyzes a highly unusual reaction: the addition of toluene to fumarate to form (R)-benzylsuccinic acid. The stereochemistry of this reaction has been examined using [d3-methyl]toluene and either fumarate or its cis stereoisomer, maleate, as the substrates. We demonstrate that when fumarate is the cosubstrate, deuterium is transferred from toluene to the C-3 pro-(R) position of benzylsuccinate, implying a syn addition of toluene to the double bond of fumarate. However, when maleate is the cosubstrate, the addition of toluene occurs in an anti fashion, so that deuterium transfer to the C-3 pro-(R) position of benzylsuccinate is also observed. This is consistent with the formation of the C-3 radical of benzylsuccinate as an intermediate, in which rotation about the C-2-C-3 bond can occur to relieve the sterically unfavorable cis conformation of the carboxylate groups when maleate is the cosubstrate.

Topics: Carbon-Carbon Lyases; Deuterium; Fumarates; Hydrogen; Maleates; Nuclear Magnetic Resonance, Biomolecular; Stereoisomerism; Succinates; Toluene

The chemometric resolution and quantification of overlapped peaks from comprehensive two-dimensional (2D) liquid chromatography (LCxLC) data are demonstrated. The LCxLC data is produced from an in-house LCxLC analyzer that couples an anion-exchange column via a multi-port valve with a reversed-phase column connected to a UV absorbance detector. Three test mixtures, each containing a target analyte, are subjected to partial LCxLC separations to simulate likely cases of signal overlap. The resulting unresolved target-analyte signals are then analyzed by the standard-addition method and two chemometric methods. The LCxLC analyses of a test mixture and its corresponding standard-addition mixture results in two data matrices, one for each mixture. The stacking of these two data matrices produces a data structure that can then be analyzed by trilinear chemometric methods. One method, the generalized rank annihilation method (GRAM), uses a non-iterative eigenvalue-based approach to mathematically resolve overlapped trilinear signals. The other method, parallel factor analysis (PARAFAC), uses an iterative approach to resolve trilinear signals by the optimization of initial estimates using alternating least squares and signal constraints. In this paper, GRAM followed by PARAFAC analysis is shown to produce better qualitative and quantitative results than using each method separately. For instance, for all three test mixtures, the GRAM-PARAFAC approach improved quantitative accuracy by at least a factor of 4 and quantitative precision by more than 2 when compared to GRAM alone. This paper also introduces a new means of correcting run-to-run retention time shifts in comprehensive 2D chromatographic data.

Topics: Benzoic Acid; Chemical Fractionation; Chlorobenzoates; Chromatography, Ion Exchange; Chromatography, Liquid; Factor Analysis, Statistical; Fumarates; Maleates; Organophosphorus Compounds; Pyruvic Acid; Uracil

The strength of the low-barrier hydrogen bond in hydrogen maleate in the gas phase was investigated by low-temperature photoelectron spectroscopy and ab initio calculations. Photoelectron spectra of maleic and fumaric acid monoanions (cis-/trans-HO(2)CCH=CHCO(2)(-)) were obtained at low temperatures and at 193 nm photon energy. Vibrational structure was observed for trans-HO(2)CCH=CHCO(2)(-) due to the OCO bending modes; however, cis-HO(2)CCH=CHCO(2)(-) yielded a broad and featureless spectrum. The electron binding energy of cis-HO(2)CCH=CHCO(2)(-) is about 1 eV blue-shifted relative to trans-HO(2)CCH=CHCO(2)(-) due to the formation of intramolecular hydrogen bond in the cis-isomer. Theoretical calculations (CCSD(T)/ aug-cc-pVTZ and B3LYP/aug-cc-pVTZ) were carried out to estimate the strength of the intramolecular hydrogen bond in cis-HO(2)CCH=CHCO(2)(-). Combining experimental and theoretical calculations yields an estimate of 21.5 +/- 2.0 kcal/mol for the intramolecular hydrogen bond strength in hydrogen maleate.

Topics: Chemical Phenomena; Chemistry, Physical; Fumarates; Gases; Hydrogen Bonding; Maleates; Molecular Conformation; Molecular Structure; Spectrum Analysis

The photoinduced gelation system based on 1 (non-gelling) to 2 (gelling) molecular photoisomerization in water results by microspheres (1) to gel fibers (2) transformation at the supramolecular level.

Topics: Amides; Delayed-Action Preparations; Fumarates; Gels; Maleates; Microspheres; Molecular Conformation; Phenylalanine; Photochemistry; Water

High-level ab initio calculations (B3LYP/6-31+G and QCISD(T)/6-311+G**) were carried out to resolve the disagreement between recent experimental and computational estimates of the relative strength of the intramolecular hydrogen bond in Z-hydrogen maleate anion with respect to the normal hydrogen bond in maleic acid. The computational estimates for the strength of the intramolecular hydrogen bond in the gas-phase maleate anion are in a range of 14-28 kcal/mol depending on the choice of the reference structure. Computational data suggest that the electrostatic influence of a counterion such as a tetraalkylammonium cation can considerably weaken the hydrogen bonding interaction (by 1.5-2 times) in the complexed hydrogen maleate anion relative to that in the naked anion. The estimated internal H-bonding energies for a series of Z-maleate/R4N+ salts (R = CH3, C2H5, CH3CH2CH2CH2) range from 8 to 13 kcal/mol. The calculated energy differences between the E- and Z-hydrogen maleates complexed to Me4N+, Et4N+, and Bu4N+ cation are 4.9 (B3LYP/6-31+G(d,p)) and 5.7 and 5.8 kcal/mol (B3LYP/6-31G(d)). It is also demonstrated that the sodium cation exerts a similar electrostatic influence on the hydrogen bond strength in bifluoride anion (FHF-). The present study shows that while low-barrier short hydrogen bonds can exist in the gas phase (the barrier for the hydrogen transfer in maleate anion is only 0.2 kcal/mol at the QCISD(T)/6-311+G//QCISD/6-31+G level), whether they can also be strong in condensed media or not depends on how their interactions with their immediate environment affect their strength.

Topics: Enzyme Inhibitors; Fumarates; Hydrogen Bonding; Maleates; Models, Molecular; Molecular Conformation; Molecular Structure; Quaternary Ammonium Compounds; Thermodynamics

A reliable method for the simultaneous determination of oxalic, fumaric, maleic, and succinic acids in tartaric and malic acids for pharmaceutical use by reversed-phase ion-suppression high performance liquid chromatography is presented. HPLC was achieved on a Nova-Pak C18 column by isocratic elution using water adjusted to pH 2.10-2.15 with perchloric acid, and detection was by UV adsorption at a wavelength of 210 nm. This method was found to be superior to previous liquid chromatography as well as other classical assay, and to be an attractive choice for the analysis of these compounds.

Topics: Chromatography, High Pressure Liquid; Dicarboxylic Acids; Drug Contamination; Evaluation Studies as Topic; Fumarates; Hydrogen-Ion Concentration; Malates; Maleates; Oxalic Acid; Perchlorates; Reproducibility of Results; Succinic Acid; Tartrates

The ortho-cleavage pathways of catechol and 3-chlorocatechol are central catabolic pathways of Pseudomonas putida that convert aromatic and chloroaromatic compounds to tricarboxylic acid (TCA) cycle intermediates. They are encoded by the evolutionarily related catBCA and clcABD operons, respectively. Expression of the cat and clc operons requires the LysR-type transcriptional activators CatR and ClcR, respectively, and the inducer molecules cis,cis-muconate and 2-chloro-cis,cis-muconate, respectively. The regulation of the cat and clc promoters has been well studied, but the extent to which these operons are repressed by growth in TCA cycle intermediates has not been explored. We demonstrate by transcriptional fusion studies that the expression from the clc promoter is repressed when the cells are grown on succinate, citrate, or fumarate and that this repression is ClcR dependent and occurs at the transcriptional level. The presence of these organic acids did not affect the expression from the cat promoter. In vitro transcription assays demonstrate that the TCA cycle intermediate fumarate directly and specifically inhibits the formation of the clcA transcript. No such inhibition was observed when CatR was used as the activator on either the cat or clc template. Titration studies of fumarate and 2-chloromuconate show that the fumarate effect is concentration dependent and reversible, indicating that fumarate and 2-chloromuconate most probably compete for the same binding site on ClcR. This is an interesting example of the transcriptional regulation of a biodegradative pathway by the intracellular sensing of the state of the TCA cycle.

Topics: Bacterial Proteins; Biodegradation, Environmental; Catechols; Chlorophenols; Citric Acid Cycle; Enzyme Repression; Fumarates; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Maleates; Operon; Pseudomonas putida; Sorbic Acid; Trans-Activators; Transcription, Genetic

Fumarate restores to flagella of cytoplasm-free, Che Y-containing envelopes of Escherichia coli and Salmonella typhimurium the ability to switch from one direction of rotation to another. To examine the specificity of this effect, we studied flagellar rotation of envelopes which contained, instead of fumarate, one of its analogues. Malate, maleate and succinate promoted switching, but to a lesser extent than fumarate. These observations were made both with wild-type envelopes and with envelopes of a mutant which lacks the enzymes succinate dehydrogenase and fumarase, indicating that the switching-promoting activity of the analogues was not caused by their conversion to fumarate. Aspartate and lactate did not promote switching. Using strains defective in specific enzymes of the tricarboxylic acid cycle and lacking the cytoplasmic chemotaxis proteins as well as some of the chemotaxis receptors, we demonstrated that, in intact bacteria, unlike the situation in envelopes, fumarate promoted clockwise rotation via its metabolites acetyl phosphate and acetyladenylate, but did not promote switching (presumably because of the presence of cytoplasmic fumarate). All of the results are consistent with the notion that fumarate acts as a switching factor, presumably by lowering the activation energy of switching. Thus fumarate and some of its metabolites may serve as a connection point between the bacterial metabolic state and chemotactic behaviour.

Topics: Aspartic Acid; Bacterial Proteins; Chemotaxis; Escherichia coli; Flagella; Fumarates; Lactic Acid; Malates; Maleates; Membrane Proteins; Methyl-Accepting Chemotaxis Proteins; Rotation; Salmonella typhimurium; Succinates; Succinic Acid

The sorbitol fermentation by Actinomyces viscosus and Actinomyces naeslundii was studied with washed sorbitol-grown cells. The fermentation was followed by titration of acids produced at pH 7.0 under anaerobic conditions. Metabolic end-products and intracellular levels of NAD, NADH and glycolytic intermediates during the fermentation were also analyzed. Cell extracts were examined for certain enzyme activities. Bicarbonate was required for acid production from sorbitol and from a mixture of glucose and sorbitol. Malate and fumarate could also support the acid production of A. viscosus. The main end-products were succinate and lactate but not ethanol. Cell extracts showed no activities of alcohol and aldehyde dehydrogenases, but they had activities of malate dehydrogenase and fumarate reductase. In the absence of bicarbonate, malate or fumarate, the intracellular NADH/NAD ratio increased and the levels of 3- and 2-phosphoglycerate and phosphoenolpyruvate decreased. The results indicate that oral sorbitol-fermenting actinomyces lack the ethanol pathway that can contribute to NADH oxidation. To maintain intracellular redox balance during anaerobic sorbitol fermentation, these bacteria can oxidize surplus NADH through a succinate pathway.

Topics: Actinomyces; Actinomyces viscosus; Dental Plaque; Fermentation; Fumarates; Glucose; Glycolysis; Humans; Lactates; Maleates; NAD; Sodium Bicarbonate; Sorbitol; Succinates

Topics: Acids; Adrenochrome; Epinephrine; Fumarates; Maleates; Oxidation-Reduction

Topics: Fumarates; Maleates; Oxalates; Oxalic Acid; Tartrates