Carboxylic Acid Precursors Research Articles

ChemInform Abstract: Synthesis and Investigation of Novel Spiro‐isoxazolines as Anticancer Agents.

AbstractSeveral spiro‐isoxazolines are prepared via 1,3‐dipolar cycloaddition followed by intramolecular cyclization of either alcohol or carboxylic acid precursors.

Temporal changes (1997–2012) of perfluoroalkyl acids and selected precursors (including isomers) in Swedish human serum

Concentrations (including isomer patterns) and temporal changes (1997–2012) of perfluoroalkyl acids (PFAAs) and selected perfluorooctane sulfonate (PFOS) and perfluoroalkyl carboxylic acid (PFCA) precursors were determined in serum samples from Swedish women. Perfluorooctane sulfonamide (FOSA) and perfluorooctane sulfonamidoacetic acid (FOSAA), as well as its N-methyl and N-ethyl derivatives (MeFOSAA and EtFOSAA) were consistently detected. Highest PFOS precursor concentrations were found for EtFOSAA (before year 2000) or MeFOSAA and FOSAA (after 2000). Disappearance half-lives for all PFOS precursors were shorter compared to PFOS. 4:2/6:2 and 6:2/6:2 polyfluoroalkyl phosphate diesters (diPAPs) were detected in <60% of the samples, whereas 6:2/8:2 and 8:2/8:2 diPAPs were detected in >60% of the samples, but showed no significant change in concentrations over time. Linear and sum-branched isomers were quantified separately for three PFAAs and three precursors. Significant changes between 1997 and 2012 in the % linear isomer were observed for PFOA and FOSA (increase) and PFOS (decrease).

Spatial distribution and importance of potential perfluoroalkyl acid precursors in urban rivers and sewage treatment plant effluent – Case study of Tama River, Japan

Production and use of perfluorooctane sulfonate (PFOS) is regulated worldwide. However, numerous potential precursors that eventually decompose into PFOS and other perfluoroalkyl acids (PFAAs) such as perfluorooctanoic acid (PFOA) are still being used and have not been studied in detail. Therefore, knowledge about the levels and sources of the precursors is essential. We investigated the total concentration of potential PFAA precursors in the Tama River, which is one of the major rivers flowing into the Tokyo Bay, by converting all the perfluorinated carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA) precursors into PFCAs by chemical oxidation. The importance of controlling PFAA precursors was determined by calculating the ratios of PFCAs formed by oxidation to the PFAAs originally present (ΣΔ[PFCAC4–C12]/Σ[PFAAs]before oxidation) (average = 0.28 and 0.69 for main and tributary branch rivers, respectively). Higher total concentrations of Δ[PFCAs] were found in sewage treatment plant (STP) effluents. However, the ratios found in the effluents were lower (average = 0.21) than those found in the river water samples, which implies the decomposition of some precursors into PFAAs during the treatment process. On the other hand, higher ratios were observed in the upstream water samples and the existence of emission sources other than the STP effluents was indicated. This study showed that although the treatment process converting a part of the PFAA precursors into PFAAs, STPs were important sources of precursors to the Tama River. To reduce the levels of PFAAs in the aquatic environment, it is necessary to reduce the emission of the PFAA precursors as well.

Dynamics of cold acclimation and complex phytohormone responses in Triticum monococcum lines G3116 and DV92 differing in vernalization and frost tolerance level

Cold stress response was compared in the crowns, leaves, and roots of Triticum monococcum DV92 spring line and G3116 winter line. The cold exposure was associated with a rapid increase of water saturation deficit, which resulted in a strong up-regulation of abscisic acid. Simultaneously, other stress hormones: salicylic acid, aminocyclopropane carboxylic acid (precursor of ethylene), and jasmonic acid decreased. The stress application resulted in a decrease of hormones associated with stimulation of cell growth and division (gibberellins, cytokinins, and auxin). During the acclimation phase of the stress response, the plants increased their frost tolerance and started the accumulation of dehydrins. Active gibberellin, cytokinins, and auxin were elevated; more rapidly in the spring line. Abscisic acid decrease was accompanied by a gradual increase of the other stress hormones. Simultaneously, the up-regulation of phenolic acids was observed, including ferulic and sinapic acids, which may be involved in the stabilization of auxin levels as well as antioxidative functions. After 21 days, the spring line DV92 exhibited its maximum of active cytokinins, which indicates the onset of the early stage of reproductive development. The winter line fulfilled its vernalization requirement after 42 days, as indicated by a decrease of frost tolerance and dehydrin levels, accompanied by similar growth hormone changes as in DV92. The similarities and differences between einkorn and common wheat in a long-term cold response are discussed.

Construction of terpyridine–Ln(iii) coordination polymers: structural diversity, visible and NIR luminescence properties and response to nerve-agent mimics

Reactions of Ln(III) salts with 4′-(2,4-disulfophenyl)-2,2′:6′2′′-terpyridine (H2DSPT) result in five types of coordination polymers, namely, {[Gd(DSPT)(OH)(H2O)2]·4H2O}n (type I, 1), {[Ln(DSPT)(ox)0.5]·H2O}n (type II, Ln = Nd (2), Eu (3), Tb (4), Er (5), Yb (6), Lu (7), ox = oxalate), {[Ln(DSPT)(ox)0.5(H2O)]·4H2O}n (type III, Ln = Yb (8), Lu (9)), {[Ln(DSPT)(pBDC)0.5·(H2O)2]·5H2O}n (type IV, Ln = Yb (10), Lu (11), H2pBDC = 1,4-benzenedicarboxylic acid), and {[Ln(DSPT)(pBDC)0.5·(H2O)2]·5H2O}n (type V, Ln = Dy (12), Er (13)). Type I is a 1D chain built from binuclear Ln2(DSPT)2 building blocks and OH− linkers. Type II is a 2D layer with (4,5)-connected topology constructed by binuclear Ln2(DSPT)2 building blocks and ox− anions. Type III is also a 2D network based on Ln(III), DSPT2−, and ox−, but with (3,4)-connected topology. The ox− anion is generated in situ from carboxylic acid precursor in type II and type III structures. The formation of Lu(III) complexes of type II or type III can be tuned by the addition of different carboxylic precursors. Type IV posseses a 2D layered structure based on the [Ln(DSPT)]n chain connected by pBDC2−. Type V exhibits a 3D framework formed by binuclear [Ln2(SO3)2(COO)2] secondary building blocks and DSPT2− and pBDC2− linkers, resulting in a uninodal 8-connected sqc4 topology. The Nd- and Yb-centered complexes show strong NIR luminescence, whereas the Tb- and Eu-centered complexes exhibit strong luminescence in the visible region at room temperature in both solid state and water emulsions. Their luminescence intensity can be strongly quenched by the addition of diethylchlorophosphonate (DCP), but significantly less influenced by dimethylmethylphosphonate (DMMP), diethylcyanophosphonate (DCNP) and other selected organophosphate, which make this material have a potential application in nerve-agent detection.

Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (<0.1%). “Known Provenance” samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

Integrating syngas fermentation with the carboxylate platform and yeast fermentation to reduce medium cost and improve biofuel productivity

To ensure economic implementation of syngas fermentation as a fuel-producing platform, engineers and scientists must both lower operating costs and increase product value. A considerable part of the operating costs is spent to procure chemicals for fermentation medium that can sustain sufficient growth of carboxydotrophic bacteria to convert synthesis gas (syngas: carbon monoxide, hydrogen, and carbon dioxide) into products such as ethanol. Recently, we have observed that wild-type carboxydotrophic bacteria (including Clostridium ljungdahlii) can produce alcohols with a longer carbon chain than ethanol via syngas fermentation when supplied with the corresponding carboxylic acid precursors, resulting in possibilities of increasing product value. Here, we evaluated a proof-of-concept system to couple syngas fermentation with the carboxylate platform to both lower medium costs and increase product value. Our carboxylate platform concept consists of an open culture, anaerobic fermentor that is fed with corn beer from conventional yeast fermentation in the corn kernel-to-ethanol industry. The mixed-culture anaerobic fermentor produces a mixture of carboxylic acids at dilute concentrations within the carboxylate platform effluent (CPE). Besides providing carboxylic acid precursors, this effluent may represent an inexpensive growth medium. An elemental analysis demonstrated that the CPE lacked certain essential trace metals, but contained ammonium, phosphate, sodium, chloride, potassium, magnesium, calcium, and sulphate at required concentrations. CPE medium with the addition of a trace metal solution supported growth and alcohol production of C. ljungdahlii at similar or better levels compared with an optimized synthetic medium (modified ATCC 1754 medium). Other expensive supplements, such as yeast extract or macro minerals (ammonium, phosphate), were not required. Finally, n-butyric acid and n-caproic acid within the CPE were converted into their corresponding medium-chain alcohols n-butanol and n-hexanol.

Aromatic Polyketides Produced by Bacterial Iterative Type I Polyketide Synthases

Polyketides comprise a large and highly diverse group of natural products produced by polyketide synthases (PKSs), and many of these compounds display remarkable biological activities. Although PKSs share a common mechanism in the assembly of polyketides from short carboxylic acid precursors, different types of PKSs have been classified according to their structures and modes of action. This review discusses a growing group of bacterial PKSs that are structurally type I but act in an iterative manner to produce aromatic polyketides. We summarize the genetic and biochemical features of these enzymes and compare them with other types of PKSs with an emphasis on the evolutionary relationship. We also discuss the different mechanisms for polyketide off-loading and the diverse post-PKS modifications on the resulting aromatic rings. Insights into bacterial iterative type I PKSs for aromatic polyketide formation and the relevant tailoring enzymes may guide rational bioengineering efforts to produce novel natural...

Aromatic units from the macromolecular material in meteorites: Molecular probes of cosmic environments

Ancient meteorites contain several percent of organic matter that represents a chronicle of chemical evolution in the early solar system. Aromatic hydrocarbon units make up the majority of meteorite organic matter but reading their record of organic evolution is not straightforward and their formation mechanisms have remained elusive. Most aromatic units reside in a macromolecular material and new perceptions of its structure have been provided by a novel on-line hydrogenation approach. When applied to the Orgueil (CI1) and Murchison (CM2) meteorites the technique releases a range of aromatic hydrocarbons along with some oxygen, sulphur and nitrogen-containing aromatic units. When on-line hydrogenation is compared to conventional pyrolysis, more high molecular weight units and a wider range of liberated entities are evident. Comparisons of results from Orgueil and Murchison reveal variations that are most likely related to differing levels of parent body alteration. The enhancement of straight-chain hydrocarbons (n-alkanes) in the hydrogenation products imply a source of these common contaminants from straight-chain carboxylic acid (n-alkanoic acid) precursors, perhaps from bacterial contributions on Earth. The on-line hydrogenation data also highlight a long-standing but unexplained observation related to the relative preference for specific isomers in methyl-substituted benzenes (meta-, ortho- and para-xylenes). The new hydrogenation approach appears to release and transform macromolecular material meta-structures (benzenes with substituents separated by single carbon atoms) into their free hydrocarbon counterparts. Their release characteristics suggest that the meta-structures are bound by oxygen-linkages. The meta-structures may be molecular probes of specific ancient cosmic environments. Parent body processing may have performed a similar function as hydrogenation to produce the most common meta configuration for free substituted benzenes. Notably, this isomeric preference for substituted benzenes is relatively distinctive for meteorites and can help in the discrimination of meteorite-derived and fossil biology-derived organic matter on Earth and on Mars.

Barton esters for initiator-free radical cyclisation with heteroaromatic substitution

S-(1-Oxido-2-pyridinyl)-1,1,3,3-tetramethylthiouronium hexafluorophosphate (HOTT) facilitates the first examples of efficient radical cyclisation with (hetero)aromatic substitution via Barton ester intermediates. Cyclopropyl and alkyl radicals allow access to five, six and seven-membered alicyclic-ring fused heterocycles with and without an additional fused cyclopropane, including the skeleton of the anti-cancer agent, cyclopropamitosene, expanded, and diazole analogues. Radical initiators are not required for cyclisation from carboxylic acid precursors.

Reduction of photosynthetic sensitivity in response to abiotic stress in tomato is mediated by a new generation plant activator.

BackgroundYield losses as a result of abiotic stress factors present a significant challenge for the future of global food production. While breeding technologies provide potential to combat negative stress-mediated outcomes over time, interventions which act to prime plant tolerance to stress, via the use of phytohormone-based elicitors for example, could act as a valuable tool for crop protection. However, the translation of fundamental biology into functioning solution is often constrained by knowledge-gaps.ResultsPhotosynthetic and transcriptomic responses were characterised in young tomato (Solanum lycopersicum L.) seedlings in response to pre-treatment with a new plant health activator technology, ‘Alethea’, followed by a subsequent 100 mM salinity stress. Alethea is a novel proprietary technology composed of three key constituent compounds; the hitherto unexplored compound potassium dihydrojasmonate, an analogue of jasmonic acid; sodium benzoate, a carboxylic acid precursor to salicylic acid, and the α-amino acid L-arginine. Salinity treatment led to a maximal 47% reduction in net photosynthetic rate 8 d following NaCl treatment, yet in Alethea pre-treated seedlings, sensitivity to salinity stress was markedly reduced during the experimental period. Microarray analysis of leaf transcriptional responses showed that while salinity stress and Alethea individually impacted on largely non-overlapping, distinct groups of genes, Alethea pre-treatment substantially modified the response to salinity. Alethea affected the expression of genes related to biotic stress, ethylene signalling, cell wall synthesis, redox signalling and photosynthetic processes. Since Alethea had clear effects on photosynthesis/chloroplastic function at the physiological and molecular levels, we also investigated the ability of Alethea to protect various crop species against methyl viologen, a potent generator of oxidative stress in chloroplasts. Alethea pre-treatment produced dramatic reductions in visible foliar necrosis caused by methyl viologen compared with non-primed controls.Conclusions‘Alethea’ technology mediates positive recovery of abiotic stress-induced photosynthetic and foliar loss of performance, which is accompanied by altered transcriptional responses to stress.

Oxidative Conversion as a Means of Detecting Precursors to Perfluoroalkyl Acids in Urban Runoff

A new method was developed to quantify concentrations of difficult-to-measure and unidentified precursors of perfluoroalkyl carboxylic (PFCA) and sulfonic (PFSA) acids in urban runoff. Samples were exposed to hydroxyl radicals generated by thermolysis of persulfate under basic pH conditions and perfluoroalkyl acid (PFAA) precursors were transformed to PFCAs of related perfluorinated chain length. By comparing PFCA concentrations before and after oxidation, the concentrations of total PFAA precursors were inferred. Analysis of 33 urban runoff samples collected from locations around the San Francisco Bay, CA indicated that PFOS (2.6-26 ng/L), PFOA (2.1-16 ng/L), and PFHxA (0.9-9.7 ng/L) were the predominant perfluorinated compounds detected prior to sample treatment. Following oxidative treatment, the total concentrations of PFCAs with 5-12 membered perfluoroalkyl chains increased by a median of 69%, or between 2.8 and 56 ng/L. Precursors that produced PFHxA and PFPeA upon oxidation were more prevalent in runoff samples than those that produced PFOA, despite lower concentrations of their corresponding perfluorinated acids prior to oxidation. Direct measurements of several common precursors to PFOS and PFOA (e.g., perfluorooctanesulfonamide and 8:2 fluorotelomer sulfonate) accounted for less than 25% of the observed increase in PFOA, which increased by a median value of 37%. Exposure of urban runoff to sunlight, advanced oxidation processes, or microbes could result in modest, but measurable, increases in concentrations of PFCAs and PFSAs.

Unconventional Titania Photocatalysis: Direct Deployment of Carboxylic Acids in Alkylations and Annulations

Under dry, anaerobic conditions, TiO(2) photocatalysis of carboxylic acid precursors resulted in carbon-carbon bond-forming processes. High yields of dimers were obtained from TiO(2) treatment of carboxylic acids alone. On inclusion of electron-deficient alkenes, efficient alkylations were achieved with methoxymethyl and phenoxymethyl radicals. In reactions with maleic anhydride or maleimides, phenoxyacetic acid produced chromenedione derivatives in addition to adducts. These photocatalytic reactions are simple and cheap to perform, and the TiO(2) is easily removed by filtration. The anaerobic photocatalysis strategy offers a range of synthetic possibilities.

Harnessing Unusual Precursors in Polyketide Biosynthesis

Polyketides biosynthesized by type I polyketide synthases (PKSs) are a large class of natural products that have a wide range of important biological and pharmacological properties. The diversity of activities of these natural products is due to the structural variations afforded by type I PKSs. These enzymes recognize thioesterified carboxylic acid precursors and condense these precursors to generate the polyketide backbone. While PKSs incorporate predominantly malonyl‐CoA and (2S)‐methylmalonyl‐CoA precursors, additional precursors are being identified. We identified two unusual PKS precursors with unique chemical attributes while studying zwittermicin A biosynthesis by Bacillus cereus. These precursors, (2S)‐aminomalonyl‐acyl carrier protein (ACP) and (2R)‐hydroxymalonyl‐ACP, introduce an amino or hydroxyl group, respectively, into the polyketide. Understanding how these precursors are recognized and incorporated into a polyketide backbone will provide a means for reprogramming other PKSs to incorporate these unusual precursors. This will extend the possibilities of polyketide structural variation. Our structure‐function analyses of precursor recognition by PKSs will be discussed

N-Acyl-N-carboxymethyl-2-nitroaniline and its analogues: a new class of water-soluble photolabile precursor of carboxylic acids

The synthesis and photochemistry of a new class of water-soluble, photolabile protecting group, the N-carboxymethyl-2-nitroanilinyl (CNA) group, are described. All three CNA-caging compounds synthesized underwent clean photochemical reaction in aqueous buffer solution to produce the intended product of acetic acid, along with the corresponding nitroso aromatic.

Mesomorphism from Bent-Core Based Ionic Dendritic Macromolecules

A wide variety of ionic dendritic macromolecules based on bent-shaped structures have been synthesized and fully characterized. Regular polypropyleneimine dendrimers (PPI) of different generations and a random hyperbranched polymer (PEI) were selected as dendritic cores. Different bent-core structures derived from the 3,4′-biphenyl angular core with 5 or 6 aromatic rings as well as short and long terminal chains and spacers have been used for this study. The bent-core structure acts as strong driving force for the supramolecular arrangement of this type of macromolecules. All of the ionic dendritic polymers prepared show mesogenic behavior over broad temperature ranges, even if the carboxylic acid precursors were not mesomorphous. An extensive chemical structure-supramolecular organization relationship has been proposed for first time for this kind of bent-core dendrimer. Two types of supramolecular packing with lamellar and columnar order have been proposed on the basis of polarizing optical microscopy, differential scanning calorimetry, and X-ray diffraction. Additionally, fibers that present anisotropic optical behavior can be drawn from the materials. These results open new and stimulating possibilities for both bent-core based and dendritic supramolecular systems, with interest in basic and applied supramolecular chemistry and materials science scenarios.

Production of volatile compounds by Lactobacillus sakei from branched chain α-keto acids

Lactobacillus sakei belongs to the main flora of raw fermented sausages and is used as starter culture. Bacterial starter cultures can convert amino acids to α-keto acids by aminotransferases. These α-keto acids are the precursors of aroma active aldehydes, alcohols and carboxylic acids. In this study the formation of aldehydes, alcohols and carboxylic acids from leucine, isoleucine, valine and the corresponding α-keto acids are analysed in model fermentations with two different strains of L sakei. In the absence and upon addition of leucine, isoleucine and valine they produced 1 μg/ml 3-methylbutanoic, 0.2 μg/ml 2-methylbutanoic acid and 3 μg/ml 2-methylpropanoic acid, respectively. Upon addition of α-ketoisocaproic acid, α-keto-3-methyl-pentanoic acid or α-ketoisovaleric acid the amount of the corresponding carboxylic acid was increased to 40 μg/ml 3-methylbutanoic acid, 20 μg/ml 2-methylbutanoic acid and 35 μg/ml 2-methylpropanoic acid. The response patterns of the strains and amounts of carboxylic acids produced were similar. This behaviour was typical when compared with other strains of L. sakei and suggests general lack of transaminase activity and a limit in the transport of branched chain amino acids and their conversion to volatiles, some of which can contribute to the aroma of fermented sausages.

Treatment of disinfection by‐product precursors

Formation of harmful disinfection by‐products (DBPs), of which trihalomethanes (THMs) and haloacetic acids (HAAs) are the major groups, can be controlled by removal of natural organic matter (NOM) before disinfection. In the literature, removal of precursors is variable, even with the same treatment. The treatment of DBP precursors and NOM was examined with the intention of outlining precursor removal strategies for various water types. Freundlich adsorption parameters and hydroxyl rate constants were collated from the literature to link treatability by activated carbon and advanced oxidation processes (AOPs), respectively, to physico‐chemical properties. Whereas hydroxyl rate constants did not correlate meaningfully with any property, a moderate correlation was found between Freundlich parameters and log KOW, indicating activated carbon will preferentially adsorb hydrophobic NOM. Humic components of NOM are effectively removed by coagulation, and, where they are the principal precursor source, coagulation may be sufficient to control DBPs. Where humic species remaining post‐coagulation retain significant DBP formation potential (DBPFP), activated carbon is deemed a suitable process selection. Anion exchange is an effective treatment for transphilic species, known for high carboxylic acid functionality, and consequently is recommended for carboxylic acid precursors. Amino acids have been linked to HAA formation and are important constituents of algal organic matter. Amino acids are predicted to be effectively removed by biotreatment and nanofiltration. Carbohydrates have been found to reach 50% of NOM in river waters. If the carbohydrates were to pose a barrier to successful DBP control, additional treatment stages such as nanofiltration are likely to be required to reduce their occurrence.

ChemInform Abstract: Synthesis of (1R,4S,5R)-endo-N,N-Dimethyl-2-azabicyclo(2.2.1) methanamine.

Starting from trans-4-hydroxy-L-proline, (1R,4S,5R)-endo-N,N-dimethyl-2-azabicyclo[2.2.1]methanamine 1 has been synthesized. The target compound is precursor of antibacterial quinolone carboxylic acids.

ChemInform Abstract: Aryl Trifluoromethyl Ketone Hydrates as Precursors of Carboxylic Acids and Esters.

ChemInform Abstract: Aryl Trifluoromethyl Ketone Hydrates as Precursors of Carboxylic Acids and Esters.