Carboxylic Acid Research Articles

Exploring the Significance and Cutting-Edge Applications of Terpenes and Terpenoid-Derived Inorganic Nanoparticles

Terpenoids are a group of secondary metabolites derived from isoprene and are among the most diverse natural products responsible for crucial role in the metabolism of organisms. They are found in various forms, including terpene hydrocarbons, alcohols, aldehydes, carboxylic acids, ketones, esters, and glycosides. Terpenes have a broad range of medicinal properties and are used to prepare drugs such as artemisinin. Metallic nanoparticles that are formed by plants have garnered significant interest across various fields, including medicine, the environment, food processing, and agriculture. Using plant extracts to reduce metals is regarded as both eco-friendly and affordable and has recently gained popularity for synthesizing various classes of nanoparticles. In this study, we reviewed plant-derived terpenes (monoterpenes, sesquiterpenes, diterpenes, sesquiterpenes, triterpenes, and meroterpenes), their applications in medicine, and for the synthesis of nanoparticles. This review is relevant to researchers interested in combating bacterial infections and cancers and in using terpenoids in the synthesis of nanoparticles.

A europium MOF-based turn-off fluorescent sensor for Cr2O72−, l-tryptophan, Dimethylnidazole detection in water

Various pollutants in water are a serious threat to human health. It is very important to identify and detect harmful substances in water. In this paper, an unprecedented new coordination polymer of luminescent sensor, [[Eu(L)2] Cl·H2O] n, (Eu-MOF), with excellent fluorescence sensing abilities for anions, amino acid and antibiotics was developed. It was synthesized by N-heterocyclic carboxylic acid ligands 1, 3-bis (4-carboxylbenzyl) triazole chloride and lanthanide metal ion Eu3+ under solvothermal conditions. The fluorescence results indicate that Eu-MOF has excellent fluorescence sensing abilities for Cr2O72−, l-tryptophan, and Dimethylnidazole via fluorescence quenching. The limit of detection (LOD) is 8.98 × 10−6 mol·L−1, 4.94 × 10−5 mol·L−1 and 5.50 × 10−5 mol·L−1, respectively. Furthermore, the possible mechanisms of fluorescence quenching in the sensing process were systematically studied by UV–vis and DFT. It is revealed that the rational design and utilization of such one multifunctional Eu-MOF can offer guidance for fluorescence detection with wide applications.

Two Lactones Non-toxic to Humans Are Effective Repellents for the German Cockroach.

Lactones are cyclic esters of hydroxy carboxylic acids, present in several fruits and animals consumed by humans. There is evidence that some lactones modify insect behavior. The aim of the present study was to evaluate the repellent effect of four lactones (γ- and δ-nonalactone, and γ- and δ-dodecalactone) in first instar nymphs of the German cockroach, Blattella germanica (Linnaeus). To assess repellency, a nymph was placed on a circle of filter paper, half of which had been treated with lactone dissolved in acetone and the other half with acetone alone. The behavior of the nymph was recorded and the time the nymph spent in each half of the paper was quantified using Ethovision XT 10.1 software. Values of Distribution Coefficient (DC) were calculated: DC = (Tt - TA) / Tt, where Tt is the experimental time and TA is the time the nymph spent in the area treated with the repellent agent. DC can vary between 0 and 1. Values significantly higher than 0.5 indicate repellency. N,N-diethyl-meta-toluamide (DEET) was used as a positive control. DEET, δ- and γ-nonalactone caused repellency as from 77.9µg/cm2, whereas γ- and δ-dodecalactone had a repellent effect starting at 779.0µg/cm2. The values of DC for these concentrations were 0.89 (DEET), 0.86 (γ-nonalactone), 0.87 (δ-nonalactone), 0.83 (γ-dodecalactone), and 0.72 (δ-dodecalactone). To our knowledge, this is the first report of repellency produced by lactones in the German cockroach. This work allowed to identify two lactones that have a repellent effect similar to DEET.

Recovery of Propionic Acid from Aqueous Phase using Alamine 336 in 1 - Octanol by Reactive Extraction

The by-products of carboxylic acids are useful in chemical industry, pharmaceutical industry, preservations, drug delivery towards a more economical energy efficient technology. Physical and chemical equilibria results are presented as equilibrium distribution, distribution co -efficient, extraction efficiency, loading ratio and volume percentage by varying concentrations. The distribution of propionic acid between aqueous phase and organic phase reaches equilibrium over a concentration range of 0.009 kmol/m3 – 0.055 kmol/m3 . The optimum TOA concentration is found to be 40% at which KD value for 1 - octanol is 16.7. The modified separation increases with decrease in TOA & acid concentration and alamine loading with acid Z decreases with increase in alamine concentration in 1 – octanol. Optimum extraction efficiency is 43.82% for a conc. of 40% TOA at 0.2 kmol/m3.

Optimisation of the Production of Bio-Based Basic Chemicals from Biogenic Secondary Waste Through Dispersion

Biogenic waste from waste treatment plants, also known as secondary waste, can be used to produce bio-based carboxylic acids. Conventionally, these are produced by chemically synthesis of petroleum-based raw materials or synthesis of natural oils (e.g. coconut or palm kernel oil). Using organic residues and waste materials in a cascade to produce bio-based products can contribute to the circular bioeconomy. In the biological treatment process for production of bio-based carboxylic acids, microorganisms that are already present in the secondary waste use ethanol to convert short-chain carboxylic acids (with one to three carbon atoms) into medium-chain carboxylic acids (with four to ten carbon atoms). During the treatment process, medium-chain carboxylic acids are separated from the secondary waste by using in-situ extraction (liquid-liquid extraction). In previous studies, bioreactors without a dispersing function were used on a laboratory scale. In order to optimise the production and extraction of the formed medium-chain carboxylic acids, the bioreactors should be upgraded with a device for dispersing the extraction solvent in the secondary waste. Dispersing can increase the surface area between the extraction solvent and the secondary waste and therefore also the ability to extract the medium-chain carboxylic acids. To evaluate the effects of dispersing on the production of bio-based carboxylic acids, the production and extraction rates of static bioreactors without dispersing are compared with those of dynamic bioreactors with dispersing on a laboratory scale. Leachate from a composting plant was used as secondary waste. According to the results of the current study, it can be confirmed that dispersion has a positive effect on the biological treatment process. In addition to the increased degradation of the nutrient ethanol, the production of medium-chain carboxylic acids in the secondary waste as well as the extracted medium-chain carboxylic acids could be increased by dispersing.

Desymmetric Hydrogenation of meso-Dicarboxylic Acids.

Efficient transformation of platform chemicals into key intermediates has been increasingly important for the pharmaceutical industry. The development of the catalytic reduction of abundant carboxylic acids with molecular hydrogen has been of both practical and theoretical value. We herein report the homogeneous hydrogenation of dicarboxylic acids with the strategy of desymmetrization. Using a rhodium/bisphosphine catalyst, one carboxyl group of meso-diacids was selectively reduced to yield chiral lactones with satisfactory enantioselectivity. This method provides a straightforward approach to produce chiral lactone intermediates for the manufacture of biotin, telaprevir, and other antivirus drugs. Both experimental and computational investigations were carried out, revealing a novel neighboring group coordination mechanism in the catalytic cycle.

Graphitic Carbon Nitride as a Photocatalyst for Decarboxylative C(sp2)-C(sp3) Couplings via Nickel Catalysis.

The development of robust and reliable methods for the construction of C(sp2)-C(sp3) bonds is vital for accessing an increased array of structurally diverse scaffolds in drug discovery and development campaigns. While significant advances towards this goal have been achieved using metallaphotoredox chemistry, many of these methods utilise photocatalysts based on precious-metals due to their efficient redox processes and tuneable properties. However, due to the cost, scarcity, and toxicity of these metals, the search for suitable replacements should be a priority. Here, we show the use of commercially available heterogeneous semiconductor graphitic carbon nitride (gCN) as a photocatalyst, combined with nickel catalysis, for the cross-coupling between aryl halide and carboxylic acid coupling partners. gCN has been shown to engage in single-electron-transfer (SET) and energy-transfer (EnT) processes for the formation of C-X bonds, and in this manuscript we overcome previous limitations to furnish C-C over C-O bonds using carboxylic acids. A broad scope of both aryl halides and carboxylic acids is presented, and recycling of the photocatalyst demonstrated. The mechanism of the reaction is also investigated.

Post-Ugi Acid-Catalyzed Fragmentation and Trapping: An Unprecedented Approach towards Novel Bis(indolyl)acetamides

AbstractAn unprecedented post-Ugi Brønsted acid catalyzed fragmentation followed by in situ trapping of the alkylideneindolenine intermediate by indole nucleophiles was developed to furnish novel bis(indolyl)acetamides. The amide fragment formed during this acid-catalyzed fragmentation of the Ugi adduct was also isolated and characterized. The carboxylic acid and amine components of the Ugi reaction were carefully chosen to permit a simple water wash for the removal of the amide fragment to obtain the desired bis(indolyl)acetamides in a pure form.

An Optimized Method for LC–MS-Based Quantification of Endogenous Organic Acids: Metabolic Perturbations in Pancreatic Cancer

Accurate and reliable quantification of organic acids with carboxylic acid functional groups in complex biological samples remains a major analytical challenge in clinical chemistry. Issues such as spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column hinder sensitivity, specificity, and reproducibility in multiple-reaction monitoring (MRM)-based LC–MS assays. We report a targeted metabolomics method using phenylenediamine derivatization for quantifying carboxylic acid-containing metabolites (CCMs). This method achieves accurate and sensitive quantification in various biological matrices, with recovery rates from 90% to 105% and CVs ≤ 10%. It shows linearity from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 and LODs as low as 0.01 ng/mL. The library included a wide variety of structurally variant CCMs such as amino acids/conjugates, short- to medium-chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids, and some ring-containing CCMs. Comparing CCM profiles of pancreatic cancer cells to normal pancreatic cells identified potential biomarkers and their correlation with key metabolic pathways. This method enables sensitive, specific, and high-throughput quantification of CCMs from small samples, supporting a wide range of applications in basic, clinical, and translational research.

Covalent-Organic-Framework-Modified Quartz Crystal Microbalance Sensor for Selective Detection of Hazardous Formic Acid.

Covalent organic frameworks (COFs) are a novel family of porous crystalline materials utilized in various advanced applications. However, applying COFs as a hazardous organic acid gas sensor is substantial but still challenging. Herein, a phenylenediamine-based covalent organic framework (TPDA-TPB COF) featuring excellent crystallinity, ultrastable thermal stability, and high surface area was successfully constructed. Then, the TPDA-TPB COF-modified quartz crystal microbalance (QCM) sensor is fabricated by immobilizing the TPDA-TPB COF thin film on the gold-QCM chip. The fabricated TPDA-TPB COF-modified QCM sensor demonstrates a rapid response, excellent reproducibility, high selectivity, and sensitivity to formic gas, arising from hydrogen-bonding interactions between formic acid and the outermost layer of the TPDA-TPB COF, as determined by extensive analysis and density functional theory calculations. The basic sites of the TPDA-TPB COF, which are numerous due to its high nitrogen content, and the carboxylic acid groups present in formic acid exhibit efficient interactions. The sensitivity of the TPDA-TPB COF-modified QCM sensor was found to be 7.75 Hz ppm-1 at standard room temperature and pressure conditions, with a limit of detection (LOD) of formic acid down to 1.18 ppm, which is significantly below the workplace olfactory threshold limit of 5.0 ppm established by the Occupational Safety and Health Administration. The TPDA-TPB COF-modified QCM sensor exhibits remarkable detecting capabilities, making it highly attractive for detecting organic acid vapors in diverse applications that require superior performance.

Human metabolism of the semi-synthetic cannabinoids hexahydrocannabinol, hexahydrocannabiphorol and their acetates using hepatocytes and urine samples.

Hexahydrocannabinol (HHC), hexahydrocannabiphorol (HHCP) and their acetates, HHC-O and HHCP-O, respectively, are emerging in Europe as alternatives to tetrahydrocannabinol (THC). This study aimed to elucidate the metabolic pathways of the semi-synthetic cannabinoids HHC, HHCP, HHC-O and HHCP-O from incubation with human hepatocytes. The metabolites of HHC were also identified in authentic urine samples. HHC, HHCP, HHC-O and HHCP-O were incubated with primary human hepatocytes for 1, 3 and 5 h. Authentic urine samples from cases screened positive for cannabis in blood using ELISA but confirmed negative were analysed both non-hydrolysed and hydrolysed for HHC metabolites. Potential metabolites were identified using ultra-high performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight mass spectrometer (QToF-MS). HHC and HHCP were primarily metabolised through monohydroxylation (monoOH), followed by oxidation to a carboxylic acid metabolite. HHC-O and HHCP-O were rapidly metabolised to HHC and HHCP, respectively. In authentic urine samples, 18 different metabolites were identified, and 99.3% of hydroxylated metabolites were glucuronidated. 11-OH-HHC, 5'OH-HHC and another metabolite with a monoOH on the side chain were the only metabolites present in all 16 urine samples. The metabolism of HHC and HHCP were similar, although the longer alkyl side chain of HHCP (heptyl) led to greater hydroxylation on the side chain than HHC (pentyl). The use of HHC and HHCP can be differentiated from the use of THC and other phytocannabinoids, but the use of the acetate analogues may not be differentiable from their non-acetate analogues.

Carbon-14 Labeling Synthesis of RORγt Inhibitor JNJ-61803534.

Carbon-14 labeling synthesis of RORγt inhibitor JNJ-61803534 (1) was accomplished in four steps with the C14 label located at the thiazole-2-carboxamide carbon. The synthesis featured a highly efficient conversion of nitrile [14C]-12 to ester [14C]-17 under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile 12 under either acidic or basic conditions. Since carbon-14 labeling via [14C]-nitrile installation and subsequent conversion to [14C]-carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses.

Sodium Hypochlorite Pentahydrate as a Chlorinating Reagent: Application to the Tandem Conversion of β,γ-Unsaturated Carboxylic Acids to α,β-Unsaturated Lactones

Sodium hypochlorite pentahydrate (NaClO·5H2O, 1) has recently been employed in organic synthesis as an oxidant for alcohols, sulfides, glycols, etc. In most of these reactions, however, reagent 1 functions just as a simple oxidant, and the variations of the reactions have not been well explored. In this study, we report another useful and fascinating reaction, in which reagent 1 functions as a green chlorinating reagent toward β,γ-unsaturated carboxylic acid (2). When substrate 2 was stirred at room temperature with 1 (2 eq) in acetonitrile for 1 h, α,β-unsaturated lactone (3) was obtained in moderate yields (up to 62%). The same reaction proceeded in various organic and aqueous solvents as well. When excess reagent 1 was employed, lactone 3 was further oxidized to the corresponding epoxide (4) for some cases. The conversion is initiated by electrophilic attack of HOCl to the C=C bond of 2 to generate a chloronium ion intermediate, which is cyclized to β-chlorolactone (5) and then 3 through the elimination of HCl. The usefulness of 1 as a chlorinating reagent was further demonstrated in the electrophilic substitution of activated aromatic compounds.

New insights in the computational pKb determination of primary amines and anilines.

Extensive research hasalreadyprovided reliable methods for thein-silicoprediction of pKa, while atrustworthy strategy for pKb determination is still being sought. Indeed,the approaches previously exploited for computing pKa have shown their weakness in predicting pKb. In the light of the exceptional reliability demonstrated in the pKa calculation of a wide panel of organic acids, in this work, we exploited our "easy to use methodology", based on the direct approach, to predict the pKb of primary amines. Herein, CAM-B3LYP was compared to WB97XD and B3PW91, exploring the solvation model based on density (SMD) and the polarizable continuum model (PCM), in the presence of two explicit water molecules. Noteworthy, CAM-B3LYP and WB97XD returned completely differentsolvent accessible surfaces(SAS) and electron potential maps (EPM) for the bases and the conjugated acids, independently from the nature of the substituents. Once again, CAM-B3LYP/SMD/2H2O method confirmed itsremarkable reliability, leading to a minimum average error (MAE) lower than 0.3. This outstanding result strengthens the trustworthiness of our method, already successfully applied to predict the pKa of different substituted phenols and carboxylic acids. Thus, our "easy-to-use" process can predict also the pKb of primary ammines and anilines, always ensuring consistent outputs.

Pyrolysis of multilayered plastic packets to hydrocarbon fuel feedstock: Thermal degradation behaviour, kinetics and thermodynamic analysis, and semi-batch studies

This study examines the kinetics and batch pyrolysis behavior of multilayered waste milk packets to optimize their conversion into valuable products. Using thermogravimetric analysis at heating rates of 5, 10, 15, and 20 °C/min and employing the model fitting and model-free methods such as the Kissinger-Akahira-Sunose (KAS), Flynn-Wall-Ozawa (FWO), and Kissinger methods, the process was found to follow an F1 order-based mechanism with an activation energy of 304 kJ/mol and a pre-exponential factor of 2.60 × 1012 min.−1 The maximum weight loss (97.2 %) occurs at 5 °C/min. The average changes in free energy, enthalpy, and entropy are 814.939 kJ/mol, 135.698 kJ/mol, and −903.846 × 10−3 kJK−1mol−1 respectively. At 450 °C, the maximum pyrolytic oil yield reaches 66.92 %, with FTIR analysis confirming the presence of diverse hydrocarbon components such as alkanes, alkenes, cycloalkanes, aromatic hydrocarbons etc. in the oil. Kinetic triplet and thermodynamic parameter data, alongside physical and chemical analyses, suggest that the pyrolytic oil from multilayered waste milk packets could serve as a superior substitute for petrochemical fuel oil.

The Transformation of Per- and Polyfluoroalkyl Substances in the Aquatic Environment of a Fluorochemical Industrial Park

Jiangsu High-Tech Fluorochemical Industrial Park in Changshu City, Jiangsu Province, is the largest fluorochemical industrial park in Asia. The occurrence of per- and polyfluoroalkyl substances (PFASs) in surface water and widespread local plants was investigated in Jiangsu High-Tech Fluorochemical Industrial Park. Thirty-two target PFASs were detected in dissolved-phase, particle-phase and plant samples. The concentrations of total PFASs ranged from 1650 to 8250 ng/L in the dissolved-phase samples, 132 to 6810 ng/g dw in the particle-phase samples and 25.8 to 9460 ng/g dw in different plant tissues. Perfluorohexanoic acid (PFHxA), Perfluorooctanoate acid (PFOA) and 6:2 fluorotelomer carboxylic acid (6:2 FTCA) were predominant PFASs and contributed 80−91% to ΣPFAS in water samples. A total of 67 emerging PFAS were identified in all samples using nontargeted analysis. Typha orientalis showed better accumulation ability, with an average ΣPFAS concentration of 3450 ng/g dw and the highest root concentration factor (RCF) of 171. Typha orientalis, Eichhornia crassipes and Alternanthera sessilis have potential for use in PFAS phytostabilization.

Nickel‐Catalyzed Highly Selective Radical C‐C Coupling from Carboxylic Acids with Photoredox Catalysis

The selective coupling of two different radicals is a long‐standing challenge due to the process occurring statistically. Generally, the cross‐coupling selectivity is achieved by the persistent radical effect (PRE), resulting in limited radical precursors. In this paper, a highly selective cross‐coupling of alkyl radicals with acyl radicals to construct C(sp2)‐C(sp3) bonds, or with alkyl radicals to construct C(sp3)‐C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (L1) to enable radical cross‐coupling process to Ni‐mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90% yield), and also a new solution for the challenging double decarboxylative C(sp3)‐C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late‐stage functionalization of natural‐occurring carboxylic acids and drugs.

Nickel-Catalyzed Highly Selective Radical C-C Coupling from Carboxylic Acids with Photoredox Catalysis.

The selective coupling of two different radicals is a long-standing challenge due to the process occurring statistically. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE), resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp2)-C(sp3) bonds, or with alkyl radicals to construct C(sp3)-C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (L1) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90% yield), and also a new solution for the challenging double decarboxylative C(sp3)-C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.

Pd-Catalyzed Decarbonylative sp2 C-H Arylation: Construction of Five- and Six-Membered (Hetero)Cyclic Compounds.

The cyclic compounds have wide applications in the design and synthesis of drugs and materials; thus, their efficient construction attracts much attention from the synthetic community. In this letter, we report an efficient method for preparing cyclic compounds starting from the readily available carboxylic acids. This reaction takes place through intramolecular decarbonylative sp2 C-H arylation, enabling efficient synthesis of a wide range of five- and six-membered cyclic compounds. Both carbo- and heterocycles can be produced under the reaction conditions. Moreover, this reaction features a wide substrate scope with high functional group tolerance. The scale-up experiments also show its practicality in organic synthesis. Those experimental results indicate that this reaction would find wide applications in the synthetic community.

Genome-wide identification and analysis of the cotton ALDH gene family

BackgroundAldehyde dehydrogenases (ALDHs) are a family of enzymes that catalyze the oxidation of aldehyde molecules into the corresponding carboxylic acid, regulate the balance of aldehydes and protect plants from the poisoning caused by excessive accumulation of aldehydes; however, this gene family has rarely been studied in cotton.ResultsIn the present study, genome-wide identification was performed, and a total of 114 ALDH family members were found in three cotton species, Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii. The ALDH genes were divided into six subgroups by evolutionary analysis. ALDH genes in the same subgroup showed similar gene structures and conserved motifs, but some genes showed significant differences, which may result in functional differences. Chromosomal location analysis and selective pressure analysis revealed that the ALDH gene family had experienced many fragment duplication events. Cis-acting element analysis revealed that this gene family may be involved in the response to various biotic and abiotic stresses. The RT‒qPCR results showed that the expression levels of some members of this gene family were significantly increased under salt stress conditions. Gohir.A11G040800 and Gohir.D06G046200 were subjected to virus-induced gene silencing (VIGS) experiments, and the sensitivity of the silenced plants to salt stress was significantly greater than that of the negative control plants, suggesting that Gohir.A11G040800 and Gohir.D06G046200 may be involved in the response of cotton to salt stress.ConclusionsIn total, 114 ALDH genes were identified in three Gossypium species by a series of bioinformatics analysis. Gene silencing of the ALDH genes of G. hirsutum revealed that ALDH plays an important role in the response of cotton to salt stress.