Series Of Carboxylic Acids Research Articles

Synthesis of Polycarboxylate Viscosity Reducer and the Effect of Different Chain Lengths of Polyether on Viscosity Reduction of Heavy Oil.

Since there are not many studies on the application of polymeric surfactants in viscosity reduction emulsification of heavy oil, a series of polyether carboxylic acid–sulfonate polymeric surfactants were synthesized. The viscosity reduction performance and the effect of different chain lengths on the viscosity reduction effect were also investigated. The viscosity reduction, emulsification, wetting, and foaming performance tests showed that the viscosity reduction performance of this series of polymeric surfactants was excellent, with the viscosity reduction rate exceeding 95%, and the viscosity was reduced to 97 mPa·s by the polymeric surfactant with a molecular weight of 600 polyethers. It was also concluded that among the three surfactants with different side chains, the polymeric surfactant with a polyether molecular weight of 600, which is the medium side-chain length, had the best viscosity reduction performance. The study showed that the polyether carboxylic acid–sulfonate polymer surfactant had a promising application in the viscosity reduction of heavy oil.

Visible-light photoredox-catalyzed selective carboxylation of C(sp2)−F bonds in polyfluoroarenes with CO2

Visible light-driven carboxylation with CO2 have emerged as a sustainable and powerful way to transfer waste to treasure. However, it is still challenging for aryl fluorides due to the low reactivities of both C(sp2)−F bonds and CO2. Herein, we report the first photocatalytic carboxylation of aryl C−F bonds with CO2. The visible-light photoredox catalysis enables selective carboxylation of strong C(sp2)−F bonds in diverse polyfluoroarenes, such as penta-, tetra-, and tri-fluoroarenes under mild conditions, providing a facile access to a series of important polyfluoroaryl carboxylic acids with good yields. In contrast to previous reports of direct capture of polyfluoroaryl radicals, mechanistic studies suggest that the reduction of fleeting polyfluoroaryl radicals into polyfluoroaryl anions might be involved in this transformation, which may open a new avenue for photocatalytic functionalization of aryl C−F bonds.

Metabolism of Benzalkonium Chloride by CYP‐Mediated ω‐Oxidation and C‐C Cleavage Followed by β‐Oxidation in Humans

IntroductionBenzalkonium chlorides (BACs) are widely used quaternary ammonium disinfectants. A recent study found that median levels of BACs in human blood have increased 174% during COVID from pre‐COVID levels, with BACs being detected in 98% of blood samples. Although the parent BACs are not readily excreted into urine, we have identified several BAC metabolites in anonymous human urine samples. Formation of these metabolites requires ω‐oxidation and oxidative C‐C cleavage of BAC alkyl chains followed by β‐oxidation to produce a series of chain‐shortened carboxylic acid (COOH) BAC metabolites.Here, we aim to elucidate the metabolic route(s) that can account for the observed urinary metabolites of BACs. Our approach includes LC‐MS‐based investigation of metabolite profiles in microsomes, hepatocytes, and recombinant CYPs in comparison with those observed in human urine. BACs of the alkyl chain lengths found in commercial mixtures (C12, C14, and C16) served as substrates. Authentic metabolite standards were synthesized and confirmed by NMR and LC‐MS/MS. Selective CYP inhibitors were employed to assign specific CYP isoform contributions to metabolite formation.ResultsAs an extension of our previous work, we confirmed that NADPH‐dependent ω‐oxidation in microsomes and recombinant CYPs produced ω‐OH and ω‐COOH metabolites, as well as ω‐1 oxidized products, of all BAC chain lengths. We further found that the responsible CYPs (2D6, 4F2, 4F11, and 4F12) are all capable of performing C‐C cleavage of BAC side chains’ terminal carbons. The resulting products were chain‐shortened ω‐COOH BACs having lost 1 or 2 carbons (‐CH2 or ‐C2H4). In hepatocytes, subsequent β‐oxidation of the ω‐COOH C10, C12, C14, and C16 BAC metabolites (having lost 0 or 2 carbons during CYP metabolism) produces a series of even‐carbon ω‐COOH products (C4, C6, and C8) given the successive 2 carbon removal (‐C2H4) from the even‐carbon starting chain lengths. Additionally, hepatocytes produce a series of odd‐carbon ω‐COOH products (C5, C7, and C9) that logically originate from β‐oxidation of ω‐COOH C11, C13, and C15 BAC metabolites (having lost 1 carbon during CYP metabolism). The ω‐COOH BAC metabolites produced in hepatocytes were the same as those detected in human urine samples, and the relative abundance among the various chain lengths of ω‐COOH products was similar between human hepatocytes and urine. In most urine samples, C8, C10, and C12 were the most abundant COOH metabolites of even‐carbon length, and C9 was most abundant among the odd‐carbon series. In hepatocytes, addition of HET0016 and quinidine to inhibit CYP4F/CYP2D6 abolished all metabolite formation, including the β‐oxidation products.ConclusionThe above data confirm that CYP4F and/or CYP2D6 are required to initiate BAC metabolism. The relative abundance of ω‐ and β‐oxidized products (ω‐COOH BACs C4 ‐ C16) observed in urine was consistent with the human cellular metabolism of BACs observed in hepatocytes. While parent BACs are commonly found in human blood, they are not readily excreted to urine. Thus, we propose to expand monitoring of human urine samples for chain‐shortened ω‐COOH BAC metabolites as a practical surrogate for assessing BAC exposure in the general population.

Neopentyl Esters as Robust Linkers for Introducing Functionality to Bis-MPA Dendrimers

A series of neopentyl carboxylic acids bearing functionality amenable to click chemistry were prepared and then appended to high-generation bis-MPA dendrons via fluoride-promoted esterification. The nucleophilic stability of neopentyl and non-neopentyl dendrons in acidic to basic phosphate buffers was compared by monitoring degradation via quantitative 1H nuclear magnetic resonance (NMR). The neopentyl periphery dendrons were found to be highly resistant to hydrolysis under all experimental conditions. The neopentyl groups also did not impede click functionalization onto the dendrons.

Cobalt-Catalyzed Highly Regioselective Three-Component Arylcarboxylation of Acrylate with Aryl Bromides and Carbon Dioxide.

Cobalt-catalyzed regioselective three-component arylcarboxylation of acrylate with aryl bromides and carbon dioxide has been developed. The reaction is carried out by using cobalt chloride as a precatalyst and zinc powder as a reducing reagent under CO2 (1 atm) at 40 °C. A range of aryl bromides are used for this reaction, leading to a series of valuable carboxylic acids with high regioselectivity and functional-group compatibility. Mechanistic experiments and DFT calculations indicate that this arylcarboxylation reaction involves the reaction of CO2 with a cobalt enolate intermediate to form the C-C bond.

Attaching a Dipeptide to Fullerene as an Antioxidant Hybrid against DNA Oxidation.

Emerging evidence has revealed that oxidative damages of DNA correlate with the pathogenesis of some diseases, and numerous investigations have also suggested that supplementation of antioxidants is beneficial for keeping health by rectifying in vivo redox status. Here, we construct antioxidative dipeptides with the Ugi four-component reaction (comprising p-aminobenzyl alcohol, benzaldehyde, or vanillin, a series of antioxidative carboxylic acids and isocyanides as reagents) and then attempt to attach the dipeptides to [60]fullerene by the Bingel reaction. However, this endeavor does not lead to the amelioration of the radical-scavenging property because abilities of fullerenyl dipeptides to trap 2,2'-diphenyl-1-picrylhydrazyl and galvinoxyl radicals are still dependent upon the phenolic hydroxyl group in the dipeptide scaffold rather than upon the fullerenyl group. Alternatively, when the obtained fullerenyl dipeptides are evaluated in a peroxyl radical-induced oxidation of DNA, it is found that introducing a fullerene moiety into dipeptide enables antioxidative effect to be enhanced 20-30% because the fullerene moiety facilitates the corresponding dipeptide to intercalate with DNA strands, and thus, to increase the antioxidative efficacy. Our results suggest that connecting an antioxidative skeleton with the hydrophobic fullerene moiety might lead to a series of novel antioxidant hybrids applied for the inhibition of DNA oxidation.

Effective surface passivation on CsPbBr3 nanocrystals via post-treatment with aromatic carboxylic acid

Surface defects on CsPbX3 nanocrystals (NCs) commonly lead to the degeneration of photoluminescence emission and stability of CsPbX3 NCs. Defect passivation by surface engineering provides an effective route to improve the optical properties and stability. In this work, a series of aromatic carboxylic acids were explored to modify the as-synthesized CsPbBr3 NCs. The surface defects of CsPbBr3 NCs are found to be effectively passivated via the binding of carboxyl group with uncoordinated Pb2+ on the surface of CsPbBr3 NCs. The coordination ability of carboxyl groups with Pb2+ can be regulated by the electron effect generated by different groups at the para-position of carboxyl groups, thereby adjusting the passivation of surface defects. Benefitting from the effective passivation of surface defects, the PL emission and stability of the CsPbBr3 NCs can be effectively enhanced. Among them, the CsPbBr3 NCs modified with the softest 4-(trifluoromethyl)benzoic acid show near-unity photoluminescence quantum yields, a single-exponential photoluminescence decay kinetics and excellent stability.

External Catalyst‐Free Oxidation of Benzyl Halides to Benzoic Acids Using NaOH/TBHP in Water

AbstractAn efficient and metal‐free methodology for the oxidation of benzyl halides to benzoic acids using an inexpensive and green oxidant (TBHP) in aqueous basic medium has been developed. This protocol offers an excellent way to avoid adding catalysts and involves the use of an in‐situ generated halide ion as catalyst. It is also the first report on the oxidation of benzyl iodides to benzoic acids. A series of carboxylic acids were prepared from benzyl halides in high yields under mild reaction conditions by this method which does not require chromatographic purification. Gram scale reactions for the synthesis of the carboxylic acids in good yields have been successfully carried out using benzyl chloride, bromide and iodide. As an industrial application, the synthesis of a key monomer used for the synthesis of polyethylene terephthalate (PET), i. e., terephthalic acid (PTA), has also been accomplished in good yields.

Nine Supramolecular Adducts of 4-dimethylaminopyridine and Carboxylic acids Assembled by Classical Hydrogen Bonds and Other Noncovalent Intermolecular Interactions

Cocrystallization of the widely available 4-dimethylaminopyridine, with a series of carboxylic acids gave nine molecular adducts 4-dimethylaminopyridinium trifluoroacetate (1), 4-dimethylaminopyridinium glycolate glycolic acid (2), 4-dimethylaminopyridinium 2-furoate dihydrate (3), tri(4-dimethylaminopyridinium) tri(o-chlorobenzoate) tetrahydrate (4), 4-dimethylaminopyridinium 4-bromobenzoate 4-bromobenzoic acid (5), 4-dimethylaminopyridinium 4-formylbenzoate 4-formylbenzoic acid (6), 4-dimethylaminopyridinium 2,4-dichlorobenzoate (7), 4-dimethylaminopyridinium 2-aminobenzoate 2-aminobenzoic acid (8) and bis(4-dimethylaminopyridinium) 5-nitroisophthalate 5-nitroisophthalic acid methanol solvate (9). The nine adducts have been characterised by X-ray diffraction, IR and elemental analysis, the melting points were also reported. Their structural and supramolecular aspects are fully analyzed.The result reveals that among the nine investigated crystals only the ring Ns in the 4-dimethylaminopyridine moieties are protonated when the carboxylic acids are deprotonated. The crystal packing is interpreted by the strong charge-assisted N-H⋯O hydrogen bond between the NH+ and the deprotonated acidic groups. Except the N-H⋯O hydrogen bonds, the charge assisted or neutral O-H···O hydrogen bonds were also found at 2-6, 8 and 9. The COOH···COO−synthon has been at 2, 5-6 and 8-9.Further analysis of the crystal packing indicated that a different family of additional CH-O/CH2-O/CH3-O, F-F, Br-Br, CH-Cl, CH3-Cl, CH-π/CH3-π, C-H···Cπ, C-π, Cl-O, O-C, O-π and π-π contacts contribute to the stabilization and expansion of the total high-dimensional (2D-3D) framework structures. For the synergism of the various nonbonding contacts there created homo/hetero supramolecular synthons or both.

Identification of 2,2-Dimethylbutanoic Acid (HST5040), a Clinical Development Candidate for the Treatment of Propionic Acidemia and Methylmalonic Acidemia.

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive disorders of propionyl-CoA (P-CoA) catabolism, caused by a deficiency in the enzymes P-CoA carboxylase and methylmalonyl-CoA (M-CoA) mutase, respectively. PA and MMA are classified as intoxication-type inborn errors of metabolism because the intramitochondrial accumulation of P-CoA, M-CoA, and other metabolites results in secondary inhibition of multiple pathways of intermediary metabolism, leading to organ dysfunction and failure. Herein, we describe the structure-activity relationships of a series of short-chain carboxylic acids which reduce disease-related metabolites in PA and MMA primary hepatocyte disease models. These studies culminated in the identification of 2,2-dimethylbutanoic acid (10, HST5040) as a clinical candidate for the treatment of PA and MMA. Additionally, we describe the in vitro and in vivo absorption, distribution, metabolism, and excretion profile of HST5040, data from preclinical studies, and the synthesis of the sodium salt of HST5040 for clinical trials.

Nontargeted Discovery of Novel Contaminants in the Great Lakes Region: A Comparison of Fish Fillets and Fish Consumers.

Sport fish fillets and human sera (fish consumers) were collected in the Lake Superior and Lake Michigan basin and screened for novel contaminants using the isotopic profile deconvoluted chromatogram (IPDC) algorithm. The IPDC algorithm was extended beyond traditional Cl/Br filters to detect additional potential bioaccumulative and toxic (PBT) such as perfluoroalkyl substances (PFAS). The IPDC algorithm screened for approximately 13.5 million theoretical molecular formulas. Additional algorithm modules were developed to detect data independent MS/MS fragmentation products and a retention time index calculator using a series of 13C-labeled perfluoroalkyl carboxylic acids (13C-PFCAs). Ten potential compound classes were isolated including six untargeted PFAS, six homologue groups of polyfluorinated carboxylic acids, polyfluorinated telomer alcohols (PoFTOHs), two hydroxylated polychlorobiphenyls, pesticides, herbicides, antifungals, pharmaceuticals, artificial sweeteners, and personal care products with minimal postprocessing efforts. The algorithm isolated 48 ubiquitous PoFTOHs in both fish fillet and serum of fish consumers suggesting a region wide distribution of this class of compounds. The 3, 4, and 7 fluorine substituted PoFTOH were the most abundant congeners in both biological matrices.

Promotion of auxin- and gibberellin-induced elongation of epicotyl segments of Vigna angularis by short-chain carboxylic acids.

Pollen tube growth is inhibited and promoted by long- and short-chain carboxylic acids, respectively, but is not affected by formic acid. For auxin- and gibberellin-induced elongation of in vitro cultured epicotyl segments of adzuki bean (Vigna angularis), a series of carboxylic acids showed similar effects as that on pollen tube growth except that formic acid showed the strongest promotive effect. The effects of formic acid and GA3 on IAA-induced elongation were additive and both were strongly inhibited by inhibitors of cellulose synthesis (coumarin) and microtubule formation (colchicine). Formic acid, possibly by incorporation into the segments, prolonged the promotion by IAA and GA3 of the elongation of epicotyl segments. Based on these results and later advances in our understanding of metabolism and the role of formic acid in protecting against oxidative stress, a possible role of formic acid on stem elongation is discussed.

Wear products and tribochemical reactions during friction of a brass-steel pair

An attempt was made to determine the influence of the nature of the lubricating medium on the qualitative composition of wear products during long-term frictional interaction of a brass-steel friction pair in model media. Copper nanoparticles deposited on the steel surface in the form of a tribo-film are formed in the lubricant composition. Using quantum chemical calculations, it was shown that carboxylic acids form complexes with copper ions and clusters. The concentration of iron ions decreases during the transition from formic to caproic acid in the homologous series of monobasic carboxylic acids. It is shown that particles of wear products agglomerate in a lubricating medium with an increase in the time of frictional interaction of friction pairs.

Year-round measurements of size-segregated low molecular weight organic acids in Arctic aerosol

Organic acids in aerosols Earth's atmosphere are ubiquitous and they have been extensively studied across urban, rural and polar environments. However, little is known about their properties, transport, source and seasonal variations in the Svalbard Archipelago. Here, we present the annual trend of organic acids in the aerosol collected at Ny-Ålesund and consider their size-distributions to infer their possible sources and relative contributions. A series of carboxylic acids were detected with a predominance of C2-oxalic acid. Pinic acid and cis-pinonic acid were studied in order to better understand the oxidative and gas-to-particle processes occurred in the Arctic atmosphere. Since the water-soluble organic fraction is mainly composed by organic acids and ions, we investigated how the seasonal variation leads to different atmospheric transport mechanisms, focusing on the chemical variations between the polar night and boreal summer. Using major ions, levoglucosan and MSA, the Positive Matrix Factorization (PMF) identified five different possible sources: a) sea spray; b) marine primary production; c) biomass burning; d) sea ice related process and e) secondary products.

Self-Assembly Behavior of Diacetylenic Acid Molecules upon Vapor Deposition: Odd-Even Effect on the Film Morphology.

A series of linear carboxylic acids containing diacetylenic units at different positions along the chain (C12 H25 (C≡C)2 (CH2 )n COOH, n=7-11) were vacuum-deposited on clean silica substrates. The morphologies of the initial films after UV irradiation were studied. A clear odd-even effect on the morphology of the initial film was observed in that, depending on the spacer length between the diacetylenic unit and carboxyl head group, rings or dendrites of acid dimer layers were obtained. A molecular dynamic simulation of the aggregation process suggests that two competing intermolecular interactions and thus aggregation directions are involved and modulated by the odd or even carbon chain length. Further modulation of the interaction by substitution of a phenyl group at the terminus of the chain or by changing the carboxyl head group to an amidobenzoic acid head group led to a similar odd-even effect but with different dimensions or trends, which can be rationalized similarly. These results give the opportunity to create aligned conjugated polymer chains of different dimensions through self-assembly for applications in molecular/organic electronics.

Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO2 . This visible-light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine- or phosphorus-containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional-group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5-hydrogen atom-transfer process, the rate-limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrII species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2 to generate carboxylates.

Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

AbstractRemote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO2. This visible‐light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine‐ or phosphorus‐containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional‐group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5‐hydrogen atom‐transfer process, the rate‐limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrIIspecies generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2to generate carboxylates.

Pyrrolyl Pyrazoles as Non-Diketo Acid Inhibitors of the HIV-1 Ribonuclease H Function of Reverse Transcriptase.

Due to the biological liability of diketo acid (DKA) chain, we transferred this element of our previously reported anti-HIV-1 pyrrolyl derivatives to a non-DKA scaffold, obtaining a series of pyrrolyl-pyrazole carboxylic acids as new RNase H inhibitors. Among the newly synthesized derivatives, oxyphenylpyrrolyl-pyrazoles demonstrated inhibitory activities within the low micromolar/submicromolar range with compound 11b being the most potent. Interestingly, all tested compounds showed up to 2 orders of magnitude of selectivity for RNase H vs integrase. Docking studies within the RNase H catalytic site, coupled with site-directed mutagenesis, showed the key structural features that could confer the ability to establish specific interactions within RNase H. Furthermore, they proved the ability of our compounds to interact with amino acids highly conserved among HIV-1 subspecies isolated among patients carrying drug-resistant variants. In the end, the newly discovered pyrazole carboxylic acid derivatives feature promising serum stability with respect to their corresponding DKAs.

PH-Responsive Tunable Mixed-Charge Polymers for pH-Selective Interaction with Anionic Biological Constituents

Abstract A pH-responsive mixed-charge polymer consists of uniformly distributed cationic and anionic units in the polymer chain. Carboxylic acid monomers are generally used as anionic monomers. The pH responsive range is confined to a relatively narrow pH of ∼5, which is limiting the biological application of pH-responsive polymers. Therefore, we investigated the effect of a series of carboxylic acid and neutral monomers on the pKa value of pH-responsive mixed-charge polymers. We synthesized the polymers using [2-(methacryloyloxy)ethyl]trimethylammonium chloride, carboxylic acid monomers, and neutral monomers as the spacer moiety. As the monomer hydrophobicity and the composition ratio of neutral monomers increased, the pKa shifted to higher values. Finally, the polymer pKa values were tuned from 4.6 to 6.1. We confirmed that the pH-dependent interaction between anionic tissue constituent and pH-responsive mixed-charge polymers depends on their pKa.

An Enzymatic N-Acylation Step Enables the Biocatalytic Synthesis of Unnatural Sialosides.

Chitin is one of the most abundant and cheaply available biopolymers in Nature. Chitin has become a valuable starting material for many biotechnological products through manipulation of its N-acetyl functionality, which can be cleaved under mild conditions using the enzyme family of de-N-acetylases. However, the chemoselective enzymatic re-acylation of glucosamine derivatives, which can introduce new stable functionalities into chitin derivatives, is much less explored. Herein we describe an acylase (CmCDA from Cyclobacterium marinum) that catalyzes the N-acylation of glycosamine with a range of carboxylic acids under physiological reaction conditions. This biocatalyst closes an important gap in allowing the conversion of chitin into complex glycosides, such as C5-modified sialosides, through the use of highly selective enzyme cascades.