Ethyl Monoesters Research Articles

By-products of fish-oil refinery as potential substrates for biogas production in Norway: A preliminary study

Norway is one of the biggest fish exporters in the world, and the fish industry is the second biggest economy of the country after oil and natural gas. As fish industries expand rapidly, the resulting fish-oil refining by-products are also receiving an upsurge interest, giving an enormous window of opportunity in generating bioenergy through this route. A number of fish-oil refinery by-products such as soapstock, glycerol, ethyl monoesters (light and dark) were utilized in the present study where the anaerobic digestion feasibility of these by-products as co-substrates with fish ensilage (acidified fish waste) was investigated. The method utilized was biomethane potential experiment by employing a series of 0.5 ​L batch bottles as anaerobic digesters operated at total feeding of about 7.0 ​g with co-substrates feeding ranging between 0.6 and 2.0 ​g per bottle. The digestion environment was set at extreme mesophilic having temperature of 39 ​± ​1 ​°C. During the ~65 days of experiment, it was found that accumulated volumetric biogas yield (in mL) from co-digestion of monoesters and fish ensilage was much higher than that of the mono digester operated with fish ensilage alone. The accumulated yield from light and dark monoesters co-digesters amounted to ~2100 ​mL and ~1950 ​mL respectively. In terms of specific biogas yield, highest yield was obtained from the soapstock co-digesters with an average peaking to 775 mL/gTS. The average methane content in biogas for all the digesters over the course of the experiment was found as ca 61%. The study concludes that fish-oil refinery by-products as co-substrates with fish ensilage upon utilization to anaerobic digestion plants can potentially offer Norwegian fish refineries an excellent opportunity to contribute heavily in local bioeconomy.

Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment.

Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2% worldwide; it is commonly characterized by squamous lesions on the skin that present the typical pain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl vinyl ether-alt-maleic ethyl monoester) (PMVEMA-ES) nanofibers have been designed as a delivery vehicle for three therapeutic agents with palliative properties for the symptoms of this disease (salicylic acid, methyl salicylate, and capsaicin). For such a task, the production of these nanofibers by means of the electrospinning technique has been optimized. Their morphology and size have been characterized by optical microscopy and scanning electron microscopy (SEM). By selecting the optimal conditions to achieve the smallest and most uniform nanofibers, approximate diameters of up to 800–900 nm were obtained. It was also determined that the therapeutic agents that were used were encapsulated with high efficiency. The analysis of their stability over time by GC-MS showed no significant losses of the encapsulated compounds 15 days after their preparation, except in the case of methyl salicylate. Likewise, it was demonstrated that the therapeutic compounds that were encapsulated conserved, and even improved, their capacity to activate the transient receptor potential cation channel 1 (TRPV1) channel, which has been associated with the formation of psoriatic lesions.

Poly(methyl vinyl ether-alt-maleic acid) and ethyl monoester as building polymers for drug-loadable electrospun nanofibers

New biomaterials are sought for the development of bioengineered nanostructures. In the present study, electrospun nanofibers have been synthesized by using poly(methyl vinyl ether-alt-maleic acid) and poly(methyl vinyl ether-alt-maleic ethyl monoester) (PMVEMA-Ac and PMVEMA-ES, respectively) as building polymers for the first time. To further functionalize these materials, nanofibers of PMVEMA-Ac and PMVEMA-ES containing a conjugated polyelectrolyte (HTMA-PFP, blue emitter, and HTMA-PFNT, red emitter) were achieved with both forms maintaining a high solid state fluorescence yield without altered morphology. Also, 5-aminolevulinic acid (5-ALA) was incorporated within these nanofibers, where it remained chemically stable. In all cases, nanofiber diameters were less than 150 nm as determined by scanning and transmission electron microscopy, and encapsulation efficiency of 5-ALA was 97 ± 1% as measured by high-performance liquid chromatography. Both polymeric matrices showed rapid release kinetics in vertical cells (Franz cells) and followed Higuchi kinetics. In addition, no toxicity of nanofibers, in the absence of light, was found in HaCaT and SW480 cell lines. Finally, it was shown that loaded 5-ALA was functional, as it was internalized by cells in nanofiber-treated cultures and served as a substrate for the generation of protoporphyrin IX, suggesting these pharmaceutical vehicles are suitable for photodynamic therapy applications.

Glutathione adduct of methylmercury activates the Keap1-Nrf2 pathway in SH-SY5Y cells.

Methylmercury (MeHg) reacts readily with GSH, leading to the formation of a MeHg-SG adduct that is excreted into extracellular space through multidrug-resistance-associated protein (MRP), which is regulated by the transcription factor Nrf2. We previously reported that MeHg covalently modifies Keap1 and activates Nrf2 in human neuroblastoma SH-SY5Y cells. In the study presented here, we examined whether the MeHg-SG adduct could also modulate the Keap1-Nrf2 pathway because the formation of the Hg-S bond is believed to be reversible in the presence of a nucleophile. SH-SY5Y cells exposed to the synthetic ethyl monoester of the MeHg-SG adduct (which is hydrolyzed by cellular esterase(s) to give the MeHg-SG adduct) exhibited a concentration-dependent cellular toxicity that was enhanced by pretreatment with a specific MRP inhibitor. As expected, the MeHg-SG adduct was able to modify cellular proteins in the SH-SY5Y cells and purified Keap1. We also found that this prodrug, as well as MeHg, causes the cellular Keap1 in the cells to be modified, resulting in Nrf2 activation and, thereby, the upregulation of the downstream genes. These results suggest that the MeHg-SG adduct is not electrophilic but that it modifies protein thiols (including Keap1) through S-transmercuration and that rapid Nrf2-dependent excretion of the MeHg-SG adduct is essential in decreasing the cytotoxicity of MeHg.

Identification of Unknown Impurity of Azelaic Acid in Liposomal Formulation Assessed by HPLC-ELSD, GC-FID, and GC-MS

The identification of new contaminants is critical in the development of new medicinal products. Many impurities, such as pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, and tetradecanedioic acid, have been identified in samples of azelaic acid. The aim of this study was to identify impurities observed during the stability tests of a new liposomal dosage form of azelaic acid that is composed of phosphatidylcholine and a mixture of ethyl alcohol and water, using high-performance liquid chromatography with evaporative light-scattering detector (HPLC-ELSD), gas chromatography–flame ionisation detection (GC-FID), and gas chromatography–mass spectrometry (GC-MS) methods. During the research and development of a new liposomal formulation of azelaic acid, we developed a method for determining the contamination of azelaic acid using HPLC-ELSD. During our analytical tests, we identified a previously unknown impurity of a liposomal preparation of azelaic acid that appeared in the liposomal formulation of azelaic acid during preliminary stability studies. The procedure led to the conclusion that the impurity was caused by the reaction of azelaic acid with one of the excipients that was applied in the product. The impurity was finally identified as an ethyl monoester of azelaic acid. The identification procedure of this compound was carried out in a series of experiments comparing the chromatograms that were obtained via the following chromatographic methods: HPLC-ELSD, GC-FID, and GC-MS. The final identification of the compound was carried out by GC with MS.

Abundant Intramolecular Ring Rearrangements of 1-(N-Benzyloxycarbonylamino)arylmethylphosphonate Phenyl monoesters Under Electrospray Ionization Conditions

The mass spectrometric behavior of 1-(N-benzyloxycarbonylamino)arylmethyl-phosphonate phenyl monoesters was investigated under positive ion electrospray ionization conditions. All nitrogen-protonated title compounds undergo four- and/or six-membered ring rearrangements to yield nitrogen-containing fragment ions by consecutive or simultaneous loss of a carbon dioxide and phenyl hydrogen phosphonate or phenyl benzylphosphonate or an arylmethylimine. All oxygen-protonated title compounds undergo four- to six-membered ring rearrangements to produce fragment ions by loss of a carbon dioxide plus an arylmethylimine, or phenyl benzylphosphonate, by consecutive or simultaneous loss of benzyl phenyl ether and isocyanic acid. The fragmentation is obviously different from the corresponding methyl and ethyl monoesters, which show a tendency to undergo intramolecular four-membered ring rearrangements only.GRAPHICAL ABSTRACT

Synthesis of Alkyl‐ and Arylphosphonic Acid Monoesters by Direct Esterification of Dibasic Phosphonic Acids in the Presence of an Arsonic Acid Catalyst.

Partial hydrolysis of a diester, hydrolysis of the monochloro monoester, or alcoholysis of a phosphonic acid anhydride generally is used to prepare monoesters of alkyl- and arylphosphonic acids. Limited cases have been reported for the esterification of a dibasic phosphonic acid to yield the monoester, and none of these methods are as simple as the analogous method for preparing carboxylic acid esters, in which the carboxylic acid is esterified with an alcohol in the presence of an acid catalyst. Described is a method for preparing monoesters of alkyl- and arylphosphonic acids by direct esterification with an alcohol in the presence of a catalytic amount of phenylarsonic acid. The water formed during the reaction is removed azeotropically. For example, methylphosphonic acid was esterified in good yield to give its isopropyl, butyl, cyclohexyl, bornyl, and octadecyl monoesters. Similarly prepared are the ethyl, butyl, hexyl, and 2-(ethylthio)ethyl monoesters of phenylphosphonic acid, as well as 2-isopropox...

SYNTHESIS OF ALKYL- AND ARYLPHOSPHONIC ACID MONOESTERS BY DIRECT ESTERIFICATION OF DIBASIC PHOSPHONIC ACIDS IN THE PRESENCE OF AN ARSONIC ACID CATALYST

Partial hydrolysis of a diester, hydrolysis of the monochloro monoester, or alcoholysis of a phosphonic acid anhydride generally is used to prepare monoesters of alkyl- and arylphosphonic acids. Limited cases have been reported for the esterification of a dibasic phosphonic acid to yield the monoester, and none of these methods are as simple as the analogous method for preparing carboxylic acid esters, in which the carboxylic acid is esterified with an alcohol in the presence of an acid catalyst. Described is a method for preparing monoesters of alkyl- and arylphosphonic acids by direct esterification with an alcohol in the presence of a catalytic amount of phenylarsonic acid. The water formed during the reaction is removed azeotropically. For example, methylphosphonic acid was esterified in good yield to give its isopropyl, butyl, cyclohexyl, bornyl, and octadecyl monoesters. Similarly prepared are the ethyl, butyl, hexyl, and 2-(ethylthio)ethyl monoesters of phenylphosphonic acid, as well as 2-isopropoxyethyl hydrogen ethylphosphonate and 2-methoxyethyl hydrogen benzylphosphonate.

Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels.

Nrf2 is a basic leucine zipper transcriptional activator that is essential for the coordinate transcriptional induction of various antioxidant drug-metabolizing enzymes. Numerous studies have firmly established Nrf2's importance in protection from oxidative stress and certain chemical insults. Given the protective function of Nrf2, surprisingly few studies have focused on the relationship between Nrf2 and apoptosis. Therefore, we analysed how Nrf2 influences Fas signaling using Nrf2-deficient T cells. At a concentration of 1 microg/ml, the anti-Fas antibody induced 60% of cell death in Nrf2-deficient cultured thymocytes while, using the same treatment, only 40% of Nrf2 wild-type thymocytes died (P<0.05). Nrf2 deficiency enhances the sensitivity of Fas-mediated apoptosis in T cells. Next we examined the effect of Nrf2 deficiency during hepatocellular apoptosis in vivo. In comparison to wild-type mice, Nrf2-deficient mice displayed more severe hepatitis after induction with the anti-Fas antibody or tumor necrosis factor (TNF)-alpha. The enhanced sensitivity to anti-Fas or TNF-alpha stimulation was restored by preadministration of glutathione ethyl monoester, a compound capable of passing the cell membrane and upregulating the intracellular levels of glutathione. The results indicated that Nrf2 activity regulates the sensitivity of death signals by means of intracellular glutathione levels.

Reduced glutathione esters--antidotes to toxicity. Cytotoxicity induced by hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and menadione in murine P388D1 macrophages in vitro.

Repletion of depleted cellular reduced glutathione (GSH) levels in oxidative stress and exposure to arylating agents is a strategy for the development of antidotes to chemical toxicity. The effect of GSH, reduced glutathione ethyl monoester (GSHEt), and reduced glutathione ethyl diester (GSHEt2) on the cytotoxicity of hydrogen peroxide, 1-chloro-2,4-dinitrobenzene (CDNB), and menadione to P388D1 macrophages in vitro was investigated. The median toxic concentration TC50 values of the toxicants were hydrogen peroxide 24 +/- 2 mM (N = 19), CDNB 63 +/- 6 microM (N = 18), and menadione 30 +/- 4 microM (N = 22). Reduced glutathione, GSHEt, and GSHEt2 were poor antidotes to hydrogen peroxide toxicity. Indeed, the observed antidote effects were attributed to the nonenzymatic reaction of the GSH derivatives with hydrogen peroxide in the extracellular medium. Reduced glutathione ethyl diester was a more potent antidote of CDNB- and menadione-mediated toxicity than GSHEt and GSH. For cell incubations with the approximate median toxic concentration TC50 values of hydrogen peroxide, CDNB, and menadione, the respective median effective antidote concentration EC50 values were GSHEt 23.8 +/- 4.1 mM (N = 9), 3.6 +/- 0.6 mM (N = 11), and 226 +/- 93 microM (N = 12); and GSHEt2 20.4 +/- 1.9 mM (N = 6), 603 +/- 2 microM (N = 9), and 7.6 +/- 2.3 microM (N = 12). Reduced glutathione ethyl diester was a potent antidote to CDNB- and menadione-induced toxicities but not to hydrogen peroxide-induced toxicity under acute intoxication conditions.