Carboxy Acid Research Articles

Structural studies of DltA, a D-Alanine activating enzyme

DltA is a member of the adenylate forming family of enzymes which all show an ATP dependent activation of their substrates. This family of enzymes includes firefly luciferase, 4-coumarate-CoA ligases, oxidoreductases and the adenylation domains of nonribosomal peptide synthetases (NRPS). The NRPSs are large multimodular enzymes involved in biosynthesis of a large number of natural products with broad pharmacological relevance, such as antibiotics and immunosuppressive agents. Their substrates not only include proteinogenic aminoacids but also non-proteinogenic substrates such as D-amino acids, carboxy acids, glycosylated and N-methylated residues.

Calculating pesticide sorption coefficients ( Kd) using selected soil properties

Pesticide soil/solution distribution coefficients ( K d values), commonly referred to as pesticide soil sorption values, are utilized in computer and decision aid models to predict soil mobility of the compounds. The values are specific for a given chemical in a given soil sample, normally taken from surface soil, a selected soil horizon, or at a specific soil depth, and are normally related to selected soil properties. Pesticide databases provide K d values for each chemical, but the values vary widely depending on the soil sample on which the chemicals were tested. We have correlated K d values reported in the literature with the reported soil properties for an assortment of pesticides in an attempt to improve the accuracy of a K d value for a specific chemical in a soil with known soil properties. Mathematical equations were developed from regression equations for the related properties. Soil properties that were correlated included organic matter content, clay mineral content, and/or soil pH, depending on the chemical properties of the pesticide. Pesticide families for which K d equations were developed for 57 pesticides include the following: Carboxy acid, amino sulfonyl acid, hydroxy acid, weakly basic compounds and nonionizable amide/anilide, carbamate, dinitroaniline, organochlorine, organophosphate, and phenylurea compounds. Mean K d values for 32 additional pesticides, many of which had K d values that were correlated with specific soil properties but for which no significant K d equations could be developed are also included.

Metabolite production and kinetics of branched-chain aldehyde oxidation in Staphylococcus xylosus

The metabolite production of the gram positive bacterium Staphylococcus xylosus when cultivated in a defined medium containing 18 amino acids, 6 vitamins and 2 purines was characterised. Several compounds not previously reported as metabolites of this organism were identified including 2,5-methylpyrazine, 2-phenylethylacetate, 2-methyltetrahydrothiophen-3-one, 3-(methylthio)-propanoic acid and 3-(methylthio)-propanal. The organoleptic metabolites derived from branched-chain amino acid catabolism; 2-methylpropanal from valine, 2-methylbutanal from isoleucine and 3-methylbutanal from leucine were detected at levels ranging from 0.4 to 2.0 μM. The concentrations of the corresponding carboxy acids were 963, 858 and 1486 μM respectively. We demonstrated that α-ketoisocaproic acid was biotransformed to 3-methylbutanal which immediately was oxidised into 3-methylbutanoic acid. Kinetic studies of the conversion of 2-methylpropanal, 2-methylbutanal and 3-methylbutanal into their corresponding acids were also performed and we found K m values of 0.8, 0.9 and 1.6 μM, and V max values of 9.4, 7.1 and 5.9 μmol/min/10 12 CFU, respectively.

Multimodular biocatalysts for natural product assembly.

Nonribosomal peptides and polyketides represent a large class of natural products that show an extreme structural diversity and broad pharmacological relevance. They are synthesized from simple building blocks such as amino or carboxy acids and malonate derivatives on multimodular enzymes called nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), respectively. Although utilizing different substrates, NRPSs and PKSs show striking similarities in the modular architecture of their catalytic domains and product assembly-line mechanism. Among these compounds are well known antibiotics (penicillin, vancomycin and erythromycin) as well as potent immunosuppressive agents (cyclosporin, rapamycin and FK 506). This review focuses on the modular organization of NRPSs, PKSs and mixed NRPS/PKS systems and how modules and domains that build up the biosynthetic templates can be exploited for the rational design of recombinant enzymes capable of synthesizing novel compounds.

Mesogenic Behavtors of 4-Cafboxy- and 4-Propenyloxy-Benzo-15-Crown-5 Stilbazolyl Esters

Mesogens without terminal chain were obtained by connecting benzo-15-crown-5 and stilbazole with carboxy and propenoic acids. A nematic phase was observed for the later on cooling from 145 to 129°C. Hydrogen bond induced nematic and smectic A phases with wide temperature ranges were observed for mixtures containing para- and meta-atkyloxybenzoic acids as proton donors.

Comparison of Sorbents Using Semipolar to Highly Hydrophilic Compounds for a Sequential Solid-Phase Extraction Procedure of Industrial Wastewaters

Untreated and biologically cleaned industrial wastewaters contain huge amounts of both hydrophilic and hydrophobic compounds. Due to breakthrough effects, only a few percent of the dissolved organic carbon is usually extracted by solid-phase extraction methods. Methods for screening analysis have not faced that problem sufficiently yet. To extract more hydrophilic compounds, solid-phase sorbent characteristics had to be evaluated in this study. Recovery studies were carried out with 21 hydrophilic aromatics including carboxy acids, sulfonates, aldehydes, ketones, thiols, and phenols at a level of 1−2 μmol/L. Both silica gel based sorbents and polymeric materials were tested at neutral to acidic pH values and extraction volumes up to 200 mL. It was found that poly(styrene−divinylbenzene) sorbents are a powerful tool for the enrichment of hydrophilic aromatic substances. Most of the tested compounds could be extracted at recovery rates of >80%. The quantitative extraction of thiols as well as (aminohydroxy)...

Recent advances in phosphono- and phosphinopeptide synthesis

Phosphopeptides have been described as protease inhibitors as well as haptens for the preparation of abzymes exhibiting esterase activity. Phosphono- or phosphinopeptides have previously been prepared by solution synthesis, starting from the fully protected phosphoester dipeptide analogue. We have compared the reactivity of phosphonic versus carboxylic acid using BOP- or PyBOP-mediated activation. These reagents have been efficiently used for the preparation of mixed phosphonate diesters in the presence of an alcohol by phosphonic acid activation. We demonstrate their efficiency for solid phase synthesis of phosphonopeptides (or phosphinopeptides) in the presence of an amine by carboxy acid activation, starting from an unprotected phosphodipeptide analogue. In contrast, the efficient BroP-mediated monoesterification of α-amino-phosphonic acid is not suitable for phosphonopeptide preparation by SPPS.

Attempted synthesis of esters of tricarballylic acid and 3,5-dibromosalicylic acid. Structure and properties of tricarballylic acid, its anhydrides and some of their derivatives, and an investigation of the reaction pathways of anhydride formation by1H NMR spectroscopy, MNDO and molecular mechanics methods

Reactions ordinarily leading to the formation of esters of carboxy acids afford, in the case of tricarballylic acid, the cyclic anhydride. A comparison of the experimental and simulated 1H NMR spectra reveals that the product contains a five-membered ring structure. To explain the experimental findings, theoretical calculations were performed at the level of molecular mechanics and MNDO methods, in order to obtain information on the structure and thermodynamic stability of various substrate conformations and reaction products, as well as on the reaction pathways of anhydride formation. Theoretical predictions reveal that the formation of the five-membered ring structure is preferred in the case of tricarballylic acid anhydride.

Oxidative decomposition of oxirane and methyloxirane polyethers. II [1]. Autoxidation of Dipropylene Glycol Isomers

AbstractThe oxidative decomposition of two structural isomers of dipropylene glycol, i.e. 2,4‐dimethyl‐3‐oxapentandiol‐1,5 (1) and 4‐oxaheptandiol‐2,6 (2) was studied. The maximum rate of oxidation of glycol 1 was ca. 20 times lower than that of glycol 2. In the products of oxidation 15 different compounds were detected for the former glycol and 20 compounds for the latter. The products of decomposition were the mixtures of water and carboxy acid, acetal, alcohol, aldehyde, ketone, ester, unsaturated ether and hydroperoxy type of compounds of different structure. The mechanism of product formation is discussed.

Reactions in the presence of organic phosphites, II: Low‐temperature amidatior in solvent

AbstractPolyamides and related model compounds were prepared from carboxy acids and primary amines by reacting them with triphenylphosphite in an appropriate solvent at 100°C. The reactions proceeded in the absence of organic base but were accelerated by the addition of bases such as pyridine. Nevertheless, even the powerful combination of 13C and 31P NMR failed to indicate the presence of pyridinium phosphite in the reaction mixture. In the reaction of a primary amine and carboxyl groups a detectable amount of the diphenoxy aminophosphine intermediate was observed. The end products are the amides, phenol, and diphenyl phosphite. When primary amine was not present a slow formation of a phenyl ester of the carboxylic acid was evident. All the intermediate species and the end products were formed with or without added pyridine. A mixed anhydride of carboxylic acid and phosphite was never seen. The results in this article are fundamentally the same as those in the companion article (I) for which the data were obtained at 280°C in the absence of solvent and base. However, because the reaction went quickly to completion at 280°C, the diphenoxy aminophosphine intermediate was not observed. A mechanism for the amidation in which the diphenoxy aminophosphine is an initial reaction intermediate is proposed. This species reacts with the carboxylic acid through an intramolecular substitution to give an amide. This mechanism may be valid for the high‐temperature reactions as well. Several minor unclear points are indicated.

Absence of hydrocortisone from cytoplasmic hormone-protein complexes formed in vivo after administration of biologically active doses of [ 3H]hydrocortisone

After administration of [ 3H]hydrocortisone to adrenalectomized rats, hormone-protein complexes were isolated from liver cytosol by DEAE-cellulose chromatography. After application of biologically active and inactive doses of hydrocortisone five binding components were detected eluting at the same salt concentrations as the hormone-protein complexes observed after incubation of cytosol with [ 3H]hydrocortisone in vitro. The isolated hormone-protein fractions were acidified and extracted with ethylacetate and the steroids were analyzed by thin-layer chromatography. No significant amount of hydrocortisone could be detected in any of the complexes formed in vivo 5–60 min after administration of biologically active doses of hydrocortisone. 3ξ,11β,17α,20ξ, 21-Pentahydroxypregnane, steroidal carboxy acids, glucuronides and a very polar conjugate of hydrocortisone were found in the different fractions. After an in vivo dose of hydrocortisone of about 1/5000th of the minimal dose required for enzyme induction, hydrocortisone could be found in all cytoplasmic hormone-protein complexes formed. In contrast to the cytoplasmic hormone-protein complexes, hydrocortisone could be readily demonstrated in nuclei isolated after the administration of biologically active doses of hormone, although acid metabolites were found to represent the main part of the radioactive compounds present in the nuclei. These acid metabolites were located in ronide on the basis of its chromatographic behavior. The biological significance of this conjugate of hydrocortisone as well as that of the extremely polar conjugate found in fraction DE-3 cannot be understood on the basis of the published data pertaining to biological functions and metabolism of glucocorticosteroids. Our finding that no ‘classical’ glucocorticosteroid receptor can be detected in rat liver cytosol raises again the question of the way in which hydrocortisone and its active metabolites enter the nucleus. On the basis of the published data, the possibility cannot be ruled out that glucocorticosteroids are transported via the endoplasmic reticulum. A transport by this way has been inferred for the uptake of sodium and inulin by liver nuclei [40–42].

Induction of tryptophan oxygenase and tyrosine aminotransferase by metabolites of hydrocortisone

Metabolites of hydrocortisone were isolated from rat liver on a preparative scale, fractionated by column chromatography on Sephadex LH-20 and silica gel and tested for biological activity. Apart from the well known neutral metabolites, steroid glucuronides and sulfates, we obtained metabolite fractions containing non-conjugated steroidal carboxy acids and acid metabolites of unknown structure. One of these fractions induced tyrosine aminotransferase (EC 2.6.1.5) in adrenalectomized female rats but not trptophan oxygenase (EC 1.13.11.11), whereas another one mainly increased activity of tryptophan oxygenase. The doses necessary to significantly induce both enzymes were much lower in case of these metabolites than in the case of hydrocortisone itself. The active fractions eluting from silica gel column were analyzed by thin-layer chromatography in two different solvent systems. Absence of hydrocortisone in these fractions could be clearly demonstrated. Furthermore, the active fractions eluting from the silica gel column were characterized by treatment with an extract from Helix pomatia and/or diazomethane and subsequent analysis by thin-layer chromatography. We conclude, considering the biological activity of some synthesized derivatives of hydrocortisone, that the biologically active components are acid metabolites of hydrocortison which are not identical to any of the known metabolites.

A new relation between molar sound velocity and molar volume in carboxy acid solutions

A new relationship between molar sound velocity ‘R ’ and molar volume (M/ρ) in carboxy acid solutions has been established. Using the composite ultrasonic interferometer, both monocarboxylic and dicarboxylic acid solutions in common solvents like methyl alcohol, carbontetrachloride have been studied and it has been established that a linear relationshipR =a 0 +a 1 · M/ρ holds good in all solutions of homologous series of acids in a common solvent at a particular temperature. The constantsa 0 anda 1 for a number of carboxy acid solutions have been evaluated.

Catalytic carboxylation of fats: Carboxy acids from polyunsaturates

AbstractStudies with a palladium chloride‐triphenylphosphine catalyst have been extended to the carboxylation of polyunsaturated fats. Linseed, soybean, and safflower oils, acids, and esters were carboxylated catalytically with water‐carbon monoxide (4000 psig) at 120–160 C with or without acetone as a solvent. Main products were monocarboxy, 1,3‐ and 1,4‐dicarboxy and tricarboxy acids. Minor products were carbomethoxy esters and disubstituted 2‐cyclopentenone. Optimum reaction conditions were determined for the carboxylation of linseed oil and methyl esters by statistically designed experiments. Yields of total carboxy and tricarboxy acids were maximized at low triphenylphosphine and water levels, low temperatures, and high palladium‐chloride concentrations. Carboxylated soybean esters were separated by ether extraction of the palladium catalyst from sodium carbonate or hydroxide carboxylate salts. This salt extraction permits catalyst recycling.

Catalytic carboxylation of fats. Carboxy acids and esters from monounsaturates

AbstractA highly selective catalytic, one‐step synthesis converts oleic acid into 9(10)‐carboxystearic acid in high yields (85–99%). Hydrocarboxylation with water and carbon monoxide under pressure (3000–4000 psi) is catalyzed with a mixture of palladium chloride and triphenylphosphine at 120–150 C with or without acetone or acetic acid solvents. Palladium supported on carbon is also an effective hydrocarboxylation catalyst in the presence of triphenylphosphine and HCl. Methyl 9(10)‐carbomethoxystearate was prepared by catalytic carbomethoxylation of methyl oleate with methanol and carbon monoxide but in lower yields. The carboxystearic acids and esters consisted of the 9 and 10 isomers (87–94%) in approximately equal proportions. This catalytic carboxylation procedure is a more efficient route to carboxystearic acid and ester than the two‐step hydroformylation‐oxidation process reported previously. Carboxylated acids, methyl esters and triglycerides of potential industrial importance have been prepared.

Complex Aromatic Hydrocarbons in Low-Temperature Tar

FROM a tar produced by distillation of Pooley Hall-Wearmouth coal, carbonised at 600°, a fraction boiling at 313°-360° was obtained which yielded a complex mixture of aromatic hydrocarbons distinguished even in an impure state by their bright colours. Predominant among these hydrocarbons is β-methylanthracene which was identified by conversion into β-methylanthraquinone and anthraquinone-β-carboxylic acid. The identity of the β-methylanthraquinone obtained in our experiments was established by comparison with a specimen of synthetic β-methylanthraquinone furnished by Mr. W. H. Dawson of the British Alizarine Co. Additional proof of the identity of -methylanthracene was obtained by comparing its carboxy acid with the anthraquinone-β-carboxylic acid prepared by oxidising the β-methylanthraquinone from the British Alizarine Co.