Free Carboxylic Acid Research Articles

In Vitro Hydrolysis of Zinc Chlorophyllide a Homologues by a BciC Enzyme.

Chlorosomes in green photosynthetic bacteria are the largest and most efficient light-harvesting antenna systems of all phototrophs. The core part of chlorosomes consists of bacteriochlorophyll c, d, or e molecules. In their biosynthetic pathway, a BciC enzyme catalyzes the removal of the C132-methoxycarbonyl group of chlorophyllide a. In this study, the in vitro enzymatic reactions of chlorophyllide a analogues, C132-methylene- and ethylene-inserted zinc complexes, were examined using a BciC protein from Chlorobaculum tepidum. As the products, their hydrolyzed free carboxylic acids were observed without the corresponding demethoxycarbonylated compounds. The results showed that the in vivo demethoxycarbonylation of chlorophyllide a by an action of the BciC enzyme would occur via two steps: (1) an enzymatic hydrolysis of a methyl ester at the C132-position, followed by (2) a spontaneous (nonenzymatic) decarboxylation in the resulting carboxylic acid.

Robust, universal, and persistent bud secretion adhesion in horse-chestnut trees

Buds of horse-chestnut trees are covered with a viscous fluid, which remains sticky after long-term exposure to heat, frost, radiation, precipitation, deposition of aerosols and particles, attacks by microbes and arthropods. The present study demonstrates that the secretion does not dry out under arid conditions, not melt at 50 °C, and not change significantly under UV radiation or frost at a microscopic level. It is slightly swellable under wet conditions; and, it universally wets and adheres to substrates having different polarities. Measured pull-off forces do not differ between hydrophilic and lipophilic surfaces, ranging between 58 and 186 mN, and resulting in an adhesive strength up to 204 kPa. The mechanical and chemical properties of secretion resemble those of pressure-sensitive adhesives. The Raman, infrared, and nuclear magnetic resonance spectra show the clear presence of saturated aliphatic hydrocarbons, esters, free carboxylic acids, as well as minor amounts of amides and aromatic compounds. We suggest a multi-component material (aliphatic hydrocarbon resin), including alkanes, fatty acids, amides, and tackifying terpenoids embedded in a fluid matrix (fatty acids) comprising nonpolar and polar portions serving the universal and robust adhesive properties. These characteristics matter for ecological-evolutionary aspects and can inspire innovative designs of multifunctional, biomimetic pressure-sensitive adhesives and varnishes.

Bilberry (Vaccinium myrtillus L.) Extracts Comparative Analysis Regarding Their Phytonutrient Profiles, Antioxidant Capacity along with the In Vivo Rescue Effects Tested on a Drosophila melanogaster High-Sugar Diet Model.

Bilberries (Vaccinium myrtillus L.) have been reported to hold a plentitude of health-promoting properties beyond basic nutrition, mainly attributed to their anthocyanin content and antioxidant activity. In this article, we built the phytochemical profile of three wild bilberry fruit extract formulations (aqueous, methanolic, and hydro-methanolic) using UHPLC-ESI-MS/MS putative analysis, identifying 88 individual phytochemicals, mainly flavonoids (total content 8.41 ± 0.11 mg QE/g dw), free amino acids, polyphenols (total content 21.68 ± 0.19 mg GAE/g dw), carboxylic acids, and vitamins. Furthermore, the antioxidant activity of the extract was assessed, reaching 78.03 ± 0.16% DPPH free radical scavenging activity, comparable to literature values determined for bilberry extracts of other origin. Due to the increased prevalence of metabolic syndrome and based on the reviewed benefits of bilberries, we tested the most potent formulation of our bilberry extracts in this biological context. The in vivo rescue effect of a bilberry extract supplemented diet on Drosophila melanogaster was assessed by monitoring biochemical and genomic markers. Hemolymph trehalose levels were halved upon addition of 3% hydro-methanolic bilberry extract to a high-sugar (1.5 M sucrose) diet, as compared to the non-supplemented high-sugar diet. Noteworthy, the rescue seen for flies kept on the bilberry extract supplemented high-sugar diet appeared to parallel the trehalose levels observed in the case of the control diet (50 mM sucrose) flies. Moreover, next to the trehalose-lowering type of in vivo effects, other gene expression related rescues were also detected for genes such as InR, Akh, AstA, AstC, Irk, Npc2g, and CCHa2 upon supplementation of the high-sugar diet with our hydro-methanolic bilberry fruit extract. Our findings suggest that such a bilberry fruit extract could generate physiological and genomic type of compensatory mechanisms so that further translational approaches would advance the understanding of some human specific pathological conditions.

In-situ multi-step pulsed vapor phase surface functionalization of zirconia nanoparticles via copper-free click chemistry

We report on multi-step copper-free vapor phase azide-alkyne click reactions for the functionalization of metal oxide nanopowders, automated with the atomic layer deposition (ALD) technique. The synthetic approach consists of the following reaction steps: chemisorption of propiolic acid (PA) to ZrO2 from the gas phase, followed by the formation of a triazole ring through a click reaction with 1,4-bis(azidomethyl)benzene (BisA), and, in the final step, click-coupling of the pendant azide groups with a second dose of propiolic acid (PA). The chemical composition and nature of the chemical bonding in the samples obtained after each of the ALD processing steps were investigated in detail by ATR-FTIR and XPS. As confirmed by an additional ALD deposition of ZnO, the latter reaction step introduces free polar carboxylic acid functionalities to the nanomaterial surface, which enhance the stability of the chemically modified zirconia in ethanolic dispersion. This proof-of-concept study offers great potential toward the fabrication of functional organic layers on metal oxide surfaces by sequential azide-alkyne cycloadditions performed in ALD.

Direct β- and γ-C(sp3 )-H Alkynylation of Free Carboxylic Acids*.

In this study we report the identification of a novel class of ligands for palladium‐catalyzed C(sp3)−H activation that enables the direct alkynylation of free carboxylic acid substrates. In contrast to previous synthetic methods, no introduction/removal of an exogenous directing group is required. A broad scope of acids including both α‐quaternary and challenging α‐non‐quaternary can be used as substrates. Additionally, the alkynylation in the distal γ‐position is reported. Finally, this study encompasses preliminary findings on an enantioselective variant of the title transformation as well as synthetic applications of the products obtained.

Palladium-Catalyzed Proaromatic C(Alkenyl)-H Olefination: Synthesis of Densely Functionalized 1,3-Dienes.

An example of proaromatic C(alkenyl)-H olefination is reported. This protocol utilized a free carboxylic acid as a directing group for C(alkenyl)-H activation of 1,4-cyclohexadiene and coupled with various alkenes. Direct and sequential bisolefinations of proaromatic acids were achieved. The synthetic applicability has been exhibited by [4 + 2] cycloaddition and decarboxylative aromatization of the resulting proaromatic 1,3-dienes. Additionally, several kinetic studies also have been carried out to elucidate the reaction mechanism.

Glycerol Oxidation over Supported Gold Catalysts: The Combined Effect of Au Particle Size and Basicity of Support

Gold nanoparticles supported on various oxides (CeO2, CeO2/TiO2, MgO, MgO/TiO2, La2O3, La2O3/TiO2) (with 4 wt.% Au loading) were investigated in the liquid (aqueous) phase oxidation of glycerol by molecular oxygen under mild conditions, in the presence of alkaline earth (CaO, SrO and MgO) or alkaline (NaOH) bases. Full conversion and selectivity between 38 and 68% to sodium glycerate were observed on different Au supported catalysts (Au/MgO/TiO2, Au/La2O3/TiO2, Au/CeO2 and Au/CeO2/TiO2). The combined effect of Au particle size and basicity of the support was suggested as the determining factor of the activity. Agglomeration of gold nanoparticles, found after the reaction, led to the deactivation of the catalysts, which prevents the further oxidation of sodium glycerate into sodium tartronate. Promising results were obtained with the use of alkaline earth bases (CaO, SrO, MgO), leading to the formation of free carboxylic acids instead of salts, which are formed in the presence of the more usual base, NaOH.

Waste Cooking (Palm) Oil as an Economical Source of Biodiesel Production for Alternative Green Fuel and Efficient Lubricant

Here, a cost-effective route for the preparation of biodiesel (BD) from waste cooking oil (WCO) as an alternative eco-friendly fuel and lubricant via catalytic transesterification process using simple base catalyst was demonstrated. Physical and chemical characterization based on FT-IR, 1H-NMR, and 13C-NMR spectroscopy reveals that free carboxylic acid functionality successfully alters to methyl ester of same hydrocarbon chain during the reaction. The BD was characterized by its physical, fuel characteristics including density, viscosity, acid value, flash point, pour point, and foaming tendency, and compared with existing diesel fuel in accordance with ASTM test standard. Prepared BD showed excellent fuel efficiency with higher flash (142 °C) and fire point (147 °C) than the existing diesel fuel. In order to use these synthetic biodiesel esters as advanced green lubricants, their lubrication behavior was tested and compared with hydrocarbon base oil hexadecane (HD). The macrotribological results showed the biodiesel significantly reduced the coefficient of friction by a maximum ~ 43% and specific wear rate ~ 71% in comparison with that of HD at variable applied load. The lubricating efficiency of prepared BD was found to be a similar trend in microtribometric experiments with reciprocating sliding motion under variable loads with similar contact pressure (Pm ~ 1.36–1.95 GPa) as demonstrated in macrotribological rotating motion. Due to polar nature of biodiesel, it deposits on the contact interface and provides a thick molecular film, which may be responsible for enhanced tribological behavior compared with pristine hydrocarbon oil.

Electrochemical sensing by a covalently bonded biotin–avidin couple on a silver nanoparticle modified gold electrode

A gold electrode was modified with cysteamine by a self-assembly monolayer technique and covalently coupled with 3-mercaptopropionic acid functionalized silver nanoparticles. The free carboxylic acid groups of the 3-mercaptopropionic acid functionalized silver nanoparticles assembled on gold electrode were bonded with the amine groups of biotin or avidin trough amide linkages. The changes in the interfacial properties of gold electrode modified stepwise were examined by cyclic voltammetry and electrochemical impedance spectroscopy using the ferric/ferrous redox system. The electrochemical sensing properties of covalently bonded biotin or avidin on a gold electrode modified with silver nanoparticle were studied by cyclic voltammetry and electrochemical impedance spectroscopy by the varying concentrations of the bio-affinity molecules in the same redox system. The charge transfer resistance was directly proportional to the concentration of analyte while the response was weakly dependent upon the change in the respective peak anodic currents. The sensing mechanism was established to explain the role of the silver nanoparticles.

Chemical Synthesis of Fucosylated Chondroitin Sulfate Oligosaccharides.

Fucosylated chondroitin sulfates (FuCSs) are a unique type of polysaccharides occurring in sea cucumber that show a variety of biological activities. In particular, well-defined FuCS oligosaccharides, consisting of a trisaccharide repeating unit of β-d-GalNAc(4,6-diS)-(1→4)-[α-l-Fuc(2,4-diS)-(1→3)]-β-d-GlcUA, display potent anticoagulant activity via selective inhibition of the intrinsic tenase, which could be developed into anticoagulant drugs without bleeding risk. Herein, we report an effective approach to the synthesis of FuCS oligosaccharides, as demonstrated by the successful elaboration of FuCS tri-, hexa-, and nonasaccharides. The syntheses employ an orthogonally protected trisaccharide as a pivotal building block that can be readily converted into the donor and acceptor for glycosidic coupling. In addition, the internal patterns of protecting groups, involving N-trichloroacetyl for N-acetyl group, benzylidene and benzyl groups for sulfonated hydroxyl groups, and benzoyl and methyl esters for free hydroxyl and carboxylic acid, respectively, ensure stereoselective formation of the glycosidic linkages and sequential transformation into the desired FuCS oligosaccharides.

Distal γ-C(sp3 )-H Olefination of Ketone Derivatives and Free Carboxylic Acids.

Reported herein is the distal γ-C(sp3 )-H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino-acid directing group and using the ligand combination of a mono-N-protected amino acid (MPAA) and an electron-deficient 2-pyridone were critical for the γ-C(sp3 )-H olefination of ketone substrates. In addition, MPAAs enabled the γ-C(sp3 )-H olefination of free carboxylic acids to form diverse six-membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3 )-H bonds also could be functionalized to form 3,4-dihydroisocoumarin structures in a single step from 2-methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ-C(sp3 )-H olefinated products.

Distal γ‐C(sp3)−H Olefination of Ketone Derivatives and Free Carboxylic Acids

AbstractReported herein is the distal γ‐C(sp3)−H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino‐acid directing group and using the ligand combination of a mono‐N‐protected amino acid (MPAA) and an electron‐deficient 2‐pyridone were critical for the γ‐C(sp3)−H olefination of ketone substrates. In addition, MPAAs enabled the γ‐C(sp3)−H olefination of free carboxylic acids to form diverse six‐membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3)−H bonds also could be functionalized to form 3,4‐dihydroisocoumarin structures in a single step from 2‐methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ‐C(sp3)−H olefinated products.

Ligand-Enabled γ-C(sp3 )-H Olefination of Free Carboxylic Acids.

We report the ligand‐enabled C−H activation/olefination of free carboxylic acids in the γ‐position. Through an intramolecular Michael addition, δ‐lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium‐catalyzed activation of free carboxylic acids in the γ‐position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.

Peptidyl ω-Asp Selenoesters Enable Efficient Synthesis of N-Linked Glycopeptides.

Chemical synthesis is an attractive approach allows for the assembly of homogeneous complex N-linked glycopeptides and glycoproteins, but the limited coupling efficiency between glycans and peptides hampered the synthesis and research in the related field. Herein we developed an alternative glycosylation to construct N-linked glycopeptide via efficient selenoester-assisted aminolysis, which employs the peptidyl ω-asparagine selenoester and unprotected glycosylamine to perform rapid amide-bond ligation. This glycosylation strategy is highly compatible with the free carboxylic acids and hydroxyl groups of peptides and carbohydrates, and readily available for the assembly of structure-defined homogeneous N-linked glycopeptides, such as segments derived from glycoprotein EPO and IL-5.

2-Oxoester Phospholipase A2 Inhibitors with Enhanced Metabolic Stability.

2-Oxoesters constitute an important class of potent and selective inhibitors of human cytosolic phospholipase A2 (GIVA cPLA2) combining an aromatic scaffold or a long aliphatic chain with a short aliphatic chain containing a free carboxylic acid. Although highly potent 2-oxoester inhibitors of GIVA cPLA2 have been developed, their rapid degradation in human plasma limits their pharmaceutical utility. In an effort to address this problem, we designed and synthesized two new 2-oxoesters introducing a methyl group either on the α-carbon to the oxoester functionality or on the carbon carrying the ester oxygen. We studied the in vitro plasma stability of both derivatives and their in vitro inhibitory activity on GIVA cPLA2. Both derivatives exhibited higher plasma stability in comparison with the unsubstituted compound and both derivatives inhibited GIVA cPLA2, however to different degrees. The 2-oxoester containing a methyl group on the α-carbon atom to the oxoester functionality exhibits enhancement of the metabolic stability and retains considerable inhibitory potency.

Ligand-Enabled Monoselective β-C(sp3)-H Acyloxylation of Free Carboxylic Acids Using a Practical Oxidant.

The development of C-H activation reactions that use inexpensive and practical oxidants remains a significant challenge. Until our recent disclosure of the β-lactonization of free aliphatic acids, the use of peroxides in C-H activation reactions directed by weakly coordinating native functional groups was unreported. Herein, we report C(sp3)-H β-acetoxylation and γ-, δ-, and ε-lactonization reactions of free carboxylic acids enabled by a novel cyclopentane-based mono-N-protected β-amino acid ligand. Notably, tert-butyl hydrogen peroxide is used as the sole oxidant for these reactions. This reaction has several key advantages over other C-H activation protocols: (1) exclusive monoselectivity was observed in the presence of two α-methyl groups; (2) aliphatic carboxylic acids containing α-hydrogens are compatible with this protocol; (3) lactonization of free acids, affording γ-, δ-, or ε-lactones, has been achieved for the first time.

Synthesis of Near-Infrared Emitting Gold Nanoclusters for Biological Applications.

Over the past decade, fluorescent gold nanoclusters (AuNCs) have witnessed growing popularity in biological applications and enormous efforts have been devoted to their development. In this protocol, a recently developed, facile method for preparation of water soluble, biocompatible, and colloidally stable near-infrared emitting AuNCs have been described in detail. This room-temperature, bottom-up chemical synthesis provides easily functionalizable AuNCs capped with thioctic acid and thiol-modified polyethylene glycol in aqueous solution. The synthetic approach requires neither organic solvents or additional ligand exchange nor extensive knowledge of synthetic chemistry to reproduce. The resulting AuNCs offer free surface carboxylic acids, which can be functionalized with various biological molecules bearing a free amine group without adversely affecting the photoluminescent properties of the AuNCs. A quick, reliable procedure for flow cytometric quantification and confocal microscopic imaging of AuNC uptake by HeLa cells also been described. Due to the large Stokes shift, proper setting of filters in flow cytometry and confocal microscopy is necessary for efficient detection of near-infrared photoluminescence of AuNCs.

Cobalt-Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Acids by Homolytic H2 Cleavage.

The asymmetric hydrogenation of α,β-unsaturated carboxylic acids using readily prepared bis(phosphine) cobalt(0) 1,5-cyclooctadiene precatalysts is described. Di-, tri-, and tetra-substituted acrylic acid derivatives with various substitution patterns as well as dehydro-α-amino acid derivatives were hydrogenated with high yields and enantioselectivities, affording chiral carboxylic acids including Naproxen, (S)-Flurbiprofen, and a d-DOPA precursor. Turnover numbers of up to 200 were routinely obtained. Compatibility with common organic functional groups was observed with the reduced cobalt(0) precatalysts, and protic solvents such as methanol and isopropanol were identified as optimal. A series of bis(phosphine) cobalt(II) bis(pivalate) complexes, which bear structural similarity to state-of-the-art ruthenium(II) catalysts, were synthesized, characterized, and proved catalytically competent. X-band EPR experiments revealed bis(phosphine)cobalt(II) bis(carboxylate)s were generated in catalytic reactions and were identified as catalyst resting states. Isolation and characterization of a cobalt(II)-substrate complex from a stoichiometric reaction suggests that alkene insertion into the cobalt hydride occurred in the presence of free carboxylic acid, producing the same alkane enantiomer as that from the catalytic reaction. Deuterium labeling studies established homolytic H2 (or D2) activation by Co(0) and cis addition of H2 (or D2) across alkene double bonds, reminiscent of rhodium(I) catalysts but distinct from ruthenium(II) and nickel(II) carboxylates that operate by heterolytic H2 cleavage pathways.

Determination of Trace Amounts of Aliphatic Acids in Natural Waters Using Liquid‒Liquid Extraction

A procedure is developed and conditions are optimized for the preparation of natural water samples using liquid‒liquid extraction without the preliminary filtration of acidified water and subsequent derivatization for the determination of trace concentrations of aliphatic carboxylic acids C6–C21 by gas chromatography–mass spectrometry. It is shown that, at the stage of extraction with hexane, less than one half of free carboxylic acids of this homologous series passes into the extract, while a significant amount is adsorbed on the walls of the extraction vessel, and they must be washed off with a solution of sodium carbonate in an ethanol–water mixture (4 : 1). Liquid–liquid extraction with hexane in combination with the conversion of acids to pentafluorobenzyl esters significantly simplifies the analysis procedure of natural waters containing suspended particles, humic substances and ensures the attainment of a limit of detection of 0.05 μg/L for the analytes.

Investigations into the Structure-Function Relationship of the Naturally-Derived Surfactant Glycyrrhizin: Emulsion Stability

This study describes the emulsion stabilizing properties of the licorice root (Glycyrrhiza glabra L.) derived saponin glycyrrhizin and its corresponding aglycone 18β-glycyrrhetinic acid to further increase the understanding between structure and functional behavior. For this, we prepared 10% oil-in-water emulsions and investigated the emulsion stabilizing properties regarding environmental stresses including extreme pH, ionic strength, and temperature. Glycyrrhizin and its aglycone formed nano-sized emulsion droplets at neutral pH that were stable across a broad range of pH-values (pH 5–9), ionic strength (0–200 mM NaCl), and temperature (up to 60 °C). In contrast, emulsions were unstable at low pH (pH <5), as well as high ionic strength (>200 mM NaCl, >5 mM CaCl2) and temperature as well as after a freeze-thaw cycle. Thereby, the observed instability was mainly attributed to the reduction of electrostatic forces caused by the protonation of free carboxylic acid groups at low pH, screening of electrostatic forces at high ionic strengths, and thin interfaces causing coalescence during a freeze-thaw cycle. Overall, both molecules yielded remarkably stable emulsions at very low molecule-to-oil ratios, and therefore our results are relevant for ‘all-natural’ emulsion-based foods and beverages, as well as pharmaceutical and cosmetic products.