Β-mercaptopropionic Acid Research Articles

Quality conversion of H2S into β-mercaptopropionic acid by CETSA-based ionic liquid

With respect to the detrimental hydrogen sulfide (H2S), a whole new range of hydrophilic ionic liquids (ILs) could conveniently catalyze into more widely needed chemical reagents. ILs could be beneficial to increase the solubility and ionization of H2S, resulting in the Michael addition reaction with acrylic acid to produce β-mercaptopropionic acid. In this study, four kinds of hydrophilic ILs were synthesized by using carboxyethiosuccinic acid (CETSA), which contains three carboxyl groups with different chemical properties, as anions and combined with basic cations. The effect of the structure and reaction conditions of ILs on the catalytic activity of the system was studied. The result showed that the CETSA-based ILs with N, N, N′, N' -tetramethyl-1, 6-hexamethylenediamine (TMHDA) as cation had the best catalytic effect. ILs catalyst can greatly improve the selectivity and yield of the target product in addition reaction, which could be used for eight times at least without a noticeable decrease in its activity and conversion. In the absence of H2S cylinders, the conversion of acrylic acid can reach 99.21%, and the selectivity and yield of mercaptopropionic acid can reach 92.57% and 91.84% with [TMHDAH]CETSA. The ILs was characterized by FTIR, 1H NMR, 13C NMR and MS in order to determine the structure of the ILs. The thermal stability of ILs in the reaction system was observed by TG and DSC, and the ionization of ILs in solvent was measured by pH meter.

Reactions of 3,5-di-tert-butyl-1,2-benzoquinone with mercapto carboxylic acids

Heating of an equimolar mixture of 3,5-di-tert-butyl-1,2-benzoquinone with thiosalicylic acid led to 2-[(4,6-di-tert-butyl-2,3-dihydroxyphenyl)thio]benzoic acid. In the case of β-mercaptopropionic acid, 2-[(4,6-di-tert-butyl-2,3-dihydroxyphenyl)thio]propionic acid was formed, which upon reflux in Ac2O was converted to 6,8-di-tert-butyl-9-hydroxy-3,4-dihydro-2H-1,5benzoxathiepin-2-one.

3P110 Direct electrochemical analyses of cytochromes b5 with a mutated heme pocket at a gold electrode modified with β-mercaptopropionic acid(Heme proteins,The 48th Annual Meeting of the Biophysical Society of Japan)

3P110 Direct electrochemical analyses of cytochromes b5 with a mutated heme pocket at a gold electrode modified with β-mercaptopropionic acid(Heme proteins,The 48th Annual Meeting of the Biophysical Society of Japan)

Ethanol Enhances Hepatitis C Virus Replication through Lipid Metabolism and Elevated NADH/NAD+

Ethanol has been suggested to elevate HCV titer in patients and to increase HCV RNA in replicon cells, suggesting that HCV replication is increased in the presence and absence of the complete viral replication cycle, but the mechanisms remain unclear. In this study, we use Huh7 human hepatoma cells that naturally express comparable levels of CYP2E1 as human liver to demonstrate that ethanol, at subtoxic and physiologically relevant concentrations, enhances complete HCV replication. The viral RNA genome replication is affected for both genotypes 2a and 1b. Acetaldehyde, a major product of ethanol metabolism, likewise enhances HCV replication at physiological concentrations. The potentiation of HCV replication by ethanol is suppressed by inhibiting CYP2E1 or aldehyde dehydrogenase and requires an elevated NADH/NAD(+) ratio. In addition, acetate, isopropyl alcohol, and concentrations of acetone that occur in diabetics enhance HCV replication with corresponding increases in the NADH/NAD(+). Furthermore, inhibiting the host mevalonate pathway with lovastatin or fluvastatin and fatty acid synthesis with 5-(tetradecyloxy)-2-furoic acid or cerulenin significantly attenuates the enhancement of HCV replication by ethanol, acetaldehyde, acetone, as well as acetate, whereas inhibiting beta-oxidation with beta-mercaptopropionic acid increases HCV replication. Ethanol, acetaldehyde, acetone, and acetate increase the total intracellular cholesterol content, which is attenuated with lovastatin. In contrast, both endogenous and exogenous ROS suppress the replication of HCV genotype 2a, as previously shown with genotype 1b. Therefore, lipid metabolism and alteration of cellular NADH/NAD(+) ratio are likely to play a critical role in the potentiation of HCV replication by ethanol rather than oxidative stress.

Effects of the substitution of photoreactive groups in positions 4 and 8 of vasopressin

In an effort to synthesize potent vasopressin analogs containing photoreactive groups, we prepared, by solid phase synthesis, three analogs with proline or hydroxyproline substitutions in positions 4 and/or 7, lysine in positions 4 or 8, and beta-mercaptopropionic acid in position 1. From these three parent analogs, 1-desamino[4-proline,8-lysine]VP, 1-desamino[4-hydroxyproline,8-lysine]VP, and 1-desamino[4-lysine,7-hydroxyproline]AVP, we then prepared the corresponding azido compounds using the epsilon-amino group of lysine as the attachment point. These six analogs were then assayed for antidiuretic and pressor activities in rats. One of the resulting analogs, 1-desamino[4-lysine(N epsilon-4-azidobenzoyl),7-hydroxyproline)]AVP has the highest antidiuretic activity of any photoreactive compound reported to date.

Preparation of Conjugated p-Aminobenzamidine on Thermosensitive Poly(NIPAM) by Irradiation Grafted Process

A thermosensitive polymer that can either be soluble or insoluble in water was synthesized by electron beam irradiation N-isopropylacrylamide (NIPAM) and β-mercaptopropionic acid (MPA) without the presence of initiator. The polymer was then reacted with p-aminobenzamidine (PABA) using water-soluble carbodiimide (WSC) to introduce an affinity ligand. Radiation grafting of poly(NIPAM) and conjugation of ligand was successfully completed. It was found that the graft reaction could be done at higher dose and carboxyl group was introduced during irradiation of samples in air. Production and precipitate of the carboxylated poly(NIPAM) were investigated. Some results of direct radiation polymerization in this system are also given. The effect of radiation characteristics such as irradiation dose on the lower critical solution temperature (LCST) and conjugation of PABA on the prepared poly(NIPAM) has also been investigated. The precipitate of the grafted polymer has thermal sensitivity and their LCST is close to 35°C.

An approximation to the mechanism of inhibition of cystein proteases: nucleophilic sulphur addition to Michael acceptors type compounds

The cysteine proteases are proteolytic enzymes that act via nucleophilic attack of the sulphide anion, in the active site, to the peptidic bond. Compounds such as Michael type acceptors are inhibitors of these enzymes. In this work, PM3 quantum-chemical models of the nucleophilic addition of the sulphide anion to Michael acceptors are presented. In a first model, β-mercaptopropionic acid was the nucleophilic agent, and acrylonitrile, acrylamide and methyl acrylate were used as electrophiles. In the second one, mercaptoacetic acid, β-mercaptopropionic acid, dl-homocysteine, N-acetylcysteine and cysteine were used as nucleophilic agents, and acrylonitrile as the electrophile. The proposed mechanism involves the formation of an arrangement of the reactants that diminish the system energy in order to facilitate the formation of a reactive tetrahedral intermediary that is the rate-determining step. Good correlations between the reported second-order rate constant and the value of the exponential term in the Arrhenius equation, calculated from the activation energy of the rate-determining step, were found.

Control of polymer structure by a chain-transfer reaction in the radical polymerization of acrylamide by β-mercaptopropionic acid and 1,2,6-hexanetriol trithioglycolate

Star polymer synthesis by radical polymerization of acrylamide (AM) in the presence of thiol compounds was investigated. When 1,2,6-hexanetriol trithioglycolate (HTTG), as a trithiol compound, was used the molecular weights of the polymers were about 3 times those obtained in the presence of β-mercaptopropionic acid, as a monothiol compound, at the same concentration of thiol compounds in the feed. From viscosity measurements of the polymers and analysis of the 1H NMR spectra of the polymers, we presumed that a star-shaped polymer of AM could be synthesized by radical polymerization in the presence of HTTG.

Immobilization of α-chymotrypsin to a temperature-responsive reversibly soluble-insoluble oligomer based onN-isopropylacrylamide

A temperature-responsive N-isopropylacrylamide (NIPAAm) oligomer with an ester functional end group and a molecular weight of 3300 was prepared by chain-transfer polymerization using β-mercaptopropionic acid and subsequently activated by N-hydroxysuccinimide (NHS). This oligomer was coupled to α-chymotrypsin to yield a thermo-sensitive reversibly soluble-insoluble oligomer-enzyme conjugate, which is water-soluble at temperatures below 34°C and that precipitates above 36°C, The conjugated enzyme showed higher activity, and improved thermal stability compared with native enzyme. Kinetic properties and optimum conditions for activity were compared with those of native enzyme. More than 93% enzyme activity of the conjugate was recovered after eight cycles of thermal-induced precipitation. The oligomer-enzyme complex was used for repeated hydrolysis of casein; the biocatalyst was recovered between runs by thermal-induced precipitation and showed good stability.

Immobilization of α-chymotrypsin to a temperature‐responsive reversibly soluble–insoluble oligomer based on N-isopropylacrylamide

A temperature-responsive N-isopropylacrylamide (NIPAAm) oligomer with an ester functional end group and a molecular weight of 3300 was prepared by chain-transfer polymerization using β-mercaptopropionic acid and subsequently activated by N-hydroxysuccinimide (NHS). This oligomer was coupled to α-chymotrypsin to yield a thermo-sensitive reversibly soluble–insoluble oligomer–enzyme conjugate, which is water-soluble at temperatures below 34°C and that precipitates above 36°C. The conjugated enzyme showed higher activity, and improved thermal stability compared with native enzyme. Kinetic properties and optimum conditions for activity were compared with those of native enzyme. More than 93% enzyme activity of the conjugate was recovered after eight cycles of thermal-induced precipitation. The oligomer–enzyme complex was used for repeated hydrolysis of casein; the biocatalyst was recovered between runs by thermal-induced precipitation and showed good stability. © 1998 Society of Chemical Industry

Activity of enzymes immobilized on microspheres with thermosensitive hairs

Poly( N-isopropylacrylamide)s (PNIPAMs) carboxylated at one chain end or both ends were prepared by polymerization using 4,4-azobis( N,N,-cyanopentanoic acid) (V-501) as an initiator and β-mercaptopropionic acid (MPA) as a chain transfer reagent. One end group of PNIPAM carboxylated at both ends was conjugated with latex particles, and another with trypsin using carbodiimide. Differential scanning calorimetry (DSC) revealed that PNIPAM on the particles exhibited a drastic phase transition, and that the transition temperature was largely elevated when the enzyme was immobilized at the chain end. Therefore, PNIPAM on the particles showed two phase transitions because of the coexistence of the enzyme-conjugated and non-conjugated PNIPAMs. The activity of trypsin immobilized on the particles with the PNIPAM spacer showed significant temperature dependence. The apparent relative activity increased above the transition temperature of non enzyme-conjugated PNIPAM on the particles. One of the reasons for this is that the diffusion of the substrate changed discontinuously around the transition temperature. Therefore, the temperature dependence of the enzymatic activity was significantly affected by the molecular size of the substrates. The enzymatic activity was also influenced by the surface density of trypsin and PNIPAM on the particle, and the molecular weight of the PNIPAM spacer.

Ferrocene compounds XXII. Synthesis and reactions of some ferrocenylthiaaliphatic acids

Condensation of several ferrocenylcarbinols ( 1) with thioglycolic acid, β-mercaptopropionic acid or β-mercaptoisobutyric acid in the presence of trifluoroacetic acid have given the corresponding ferrocenylthiaaliphatic acids ( 2–4) with 65–99% yields. Instead of the expected intramolecularly cyclized products, reactions of the acids 2–4 with trifluoroacetic anhydride give 23–30% ofthe 1,2-disubstituted 1,2-diferrocenylethanes ( 8), 15–26% of trimeric species ( 9), and about 30% of oligomeric species ( 10). The mechanism of the reactions is discussed.

Synthesis and characterization of amphipathic poly(methyl methacrylate)-b-poly(ethylene oxide) diblock copolymers

This paper describes the synthesis and characterization of amphipathic diblock copolymers of poly(methyl methacrylate) (PMMA) and poly(ethylene oxide) (PEO). The synthesis involved the coupling of acyl chloride-terminated PMMA block with methoxy poly(ethylene oxide) (MPEO). Carboxylic acid chloride-terminated PMMA was generated by treating with thionyl chloride the parent carboxylic PMMA, which was prepared by free radical polymerization of methyl methacrylate (MMA) using benzoyl peroxide (BPO) as the initiator and β-mercaptopropionic acid (MPA) as the chain transfer agent. The proposed mechanism of MMA polymerization is in good agreement with the experimental results which indicate that as a side reaction nonfunctional (aromatic) counterpart is produced in a small quantity. The coupling of the acyl chloride-terminated PMMA with MPEO was quantitative.

Determination of the aminoglycoside antibiotics sisomicin and netilmicin in dried blood spots on filter discs, by high-performance liquid chromatography with pre-column derivatization and fluorimetric detection.

A simple method for the determination of the aminoglycoside antibiotic sisomicin or its 1-N-ethyl derivative, netilmicin in whole blood, using dried blood spots (DBSs) on filter-paper punched discs has been developed. Sisomicin or netilmicin in the DBSs were recovered most effectively in 0.5 M Na2HPO4 using ultrasonication. The eluates from the DBSs were treated by ultrafiltration for deproteinization and subjected to pre-column fluorescent derivatization using o-phthalaldehyde and beta-mercaptopropionic acid in 0.05 M KH2PO4-borate buffer (pH 9.0), followed by determination by reversed-phase high-performance liquid chromatography. The detection limits of sisomicin and netilmicin in the DBSs on punched discs (10.1 microliters of whole blood) were 0.053 and 0.50 micrograms per ml of whole blood, respectively (signal-to-noise ratio greater than or equal to 2). The method permits a simple collection of blood at the microlitre level and should prove particularly useful for monitoring sisomicin and netilmicin in blood at therapeutic levels in geriatric and paediatric patients.

Determination of sisomicin in eluate from dried blood spot on filter paper disc for monitoring of blood level in rat, by reversed-phase high-performance liquid chromatography after pre-column fluorimetric derivatization.

About 20 microliters of whole blood obtained by venipuncture from rat tail vein was spotted onto a filter paper and the blood spot was punched out (5 mm diameter). Sisomicin (SISO) in the dried blood spot (DBS) was extracted effectively into 0.5 M Na2HPO4 solution by ultrasonication and determined by reversed-phase high-performance liquid chromatography with pre-column derivatization using o-phthalaldehyde and beta-mercaptopropionic acid. This method could be used for the pre-clinical study of SISO blood levels of a number of mice or rats without killing. The results were identical with those for SISO in serum, if corrected for hematocrit values, and were used for the calculation of pharmacokinetic parameters for individual rats. The detection limit of SISO in DBS (10.1 microliters of whole blood) was 1.0 microgram per ml of whole blood.

ChemInform Abstract: Hydrophilic Tetrachloroferrate(III) Salts of Ferricenyl‐Substituted Carboxylic Acids.

As part of a project to provide hydrophilic ferricenium compounds for biomedical investigations, several ferrocenyl-alkanoic and -alkanedioic acids, including ferrocenylacetic, β-ferrocenylpropionic and γ-ferrocenylbutyric acids, ferrocylmalonic acid, and the two thioether derivatives, S-ferrocyl- β-mercaptopropionic acid and S-ferrocylthiomalic acid, are chemically oxidized to the respective ferricenium salts. While oxidation with the nitromethane/tetrafluoroboroboric acid system affords poorly crystallizing tetrafluoroborate salts, for the most part possessing unsatisfactory solubility characteristics, more hydrophilic salts containing the tetrachloroferrate(III) (FeCl) counterion, albeit contaminated with FeCl2, are obtained by treatment of the substrate acids with excess iron(III) chloride. The most promising method of ferricenium generation investigated in this study involves oxidation by means of the p-benzoquinone-HCL-FeCl3 system, which directly provides the respective ferricenium tetrachloroferrate salts. The IR and Mossbauer spectra confirm the expected ferricenium structures. The method appears attractive enough to be utilized in future investigations involving more complex notably polymeric, derivatives of the ferrocene parent compound.

Fluorometric determination of sisomicin, an aminoglycoside antibiotic, in dried blood spots on filter paper by reversed-phase high-performance liquid chromatography with pre-column derivatization.

A simple method for the determination of sisomicin (SISO) in dried blood spots (DBS) on filter paper has developed. SISO in DBS was recovered most effectively by ultrasonication in 0.05M KH2PO4-borate buffer (pH 9.0). The eluates from the DBS were treated with a carboxymethyl-Sephadex column, followed by determination be reversed-phase high-performance liquid chromatography after pre-column fluorescence derivatization using o-phthalaldehyde and β-mercaptopropionic acid in 0.05M KH2PO4-borate buffer (pH 9.0). The detection limit of SISO was below 0.05μg per ml of whole blood (100μl). The method permits a simple blood collection method for monitoring of aminoglycoside antibiotics at therapeutic levels.

Pre-column derivatization of sisomicin with o-phthalaldehyde-β-mercaptopropionic acid and its application to sensitive high-performance liquid chromatographic determination with fluorimetric detection

The stability of the o-phthalaldehyde (OPA) derivatives of sisomicin obtained using β-mercaptopropionic acid was investigated by reversed-phase high-performance liquid chromatography. One of the fluorescent derivatives of sisomicin was stable at least for 6 h in 50% methanol under the optimal conditions used (OPA concentration, pH and temperature). When plasma samples spiked with sisomicin were analysed, the response was linear in the calibration range 136–900 pg of sisomicin per injected volume (40 μl). As little as 0.06 μg of sisomicin per 1 ml of plasma could be detected with signal-to-noise ratio ≥2. For plasma samples spiked with 0.2 μg/ml sisomicin, the recovery was 97.1 ± 6.6% (mean ± S.D., n = 5) with a within-run coefficient of variation of 6.8% and a day-to-day coefficient of variation of 7.2%. The method was also applied to plasma samples from rabbit after a subcutaneous injection of 1 mg/kg sisomicin.

An on-line clean-up procedure for large sample volume analysis of serum aminoglycoside antibiotics by reversed-phase high-performance liquid chromatography.

A reversed-phase (RP) liquid chromatography procedure using column switching was applied to assay one of the aminoglycoside antibiotics, sisomicin. The drug in serum was derivatized with o-phthalaldehyde (OPA) and β-mercaptopropionic acid (β-MP) in 0.05M borate buffer (pH 9.0), then directly injected onto a RP pre-column (ODS-silica, 50×4 mm i.d.) to remove protein and interfering compounds (confirmed by ultraviolet monitoring at 280nm). The sisomicin derivatives retained on the pre-column were desorbed by back-flushing onto an analytical column (5μm ODS-silica 200×4mm i.d.) with 0.05M potassium dihydrogen phosphate-0.05M disodium hydrogen phosphate buffer (pH 7) and were separated by elution with a mixture of methanol, ethylene glycol and counter ion solution (sodium 1-heptanesulfonate/acetic acid/water, 2.5g/42ml/208ml). This system could be utilized for more than 50 samples with a 1ml injection volume. A good linear response curve was found between the injected sample amounts and the peak heights for the concentration range of 0.5 to 5μg/ml of sisomicin. The limit of detection for sisomicin in serum was 62.5.ng/ml for 0.1ml of sample. The mean recovery from serum was 97.5%.

Derivatization of keto fatty acids, X: Synthesis of thiazanones.

The synthesis of alkyl chain-substituted thiazanones from oxo fatty esters and a long chain aldehyde is reported. Four oxo compounds-methyl 10-oxoundecanoate, methyl 9-oxooctadecanoate, methyl 9,10-dioxooctadecanoate and octadecanal-were allowed to react with β-mercaptopropionic acid in the presence of ammonium carbonate in benzene to give the corresponding 4-m-thiazanones in high yields. The structures of these compounds were confirmed by combustion and spectral data.