Carboxylic Acid Functionality Research Articles

Advantages of Covalent Immobilization of Metal‐Salophen on Amino‐Functionalized Mesoporous Silica in Terms of Recycling and Catalytic Activity for CO2 Cycloaddition onto Epoxides

AbstractNiII and MnIII Schiff base complexes (Salophen‐Ni and Salophen‐MnCl) bearing a pending carboxylic group were prepared and characterized. Both complexes were grafted onto a mesoporous amino‐functionalized SBA‐15 silica, by formation of an amide function between the propylamine groups of the support and the carboxylic acid functions of the salophen ligand (corresponding respective to 1.30 wt.% of Ni and 1.06 wt.% of Mn). The co‐catalytic behaviour of the free and grafted complexes was then evaluated in the CO2 cycloaddition reaction onto styrene oxide, using tetra‐butylammonium bromide (n−Bu4NBr) as the main catalyst. In homogeneous conditions, the MnIII Schiff base complex and the NiII one, to a lesser extent, behave as efficient co‐catalysts for this reaction (styrene conversion of 100 % and 65 % respectively after 3 h at 120 °C, under 15 bars of CO2). Upon immobilization at the surface of the amino‐functionalized SBA‐15, we showed that the co‐catalytic activity of the less efficient one, i. e. Ni2+ salophen complex, could be enhanced (reaching a full conversion after 7 h), hence highlighting a potential synergistic effect between the unused amine functions of the support and the Ni2+ salophen co‐catalyst. Both salophen complexes were successfully re‐used in homogeneous conditions or after their immobilization without any appreciable loss of activity. This work is only a first step towards a completely heterogeneous catalytic system, in which the tetraalkylammonium halide catalyst and the metal‐salophen co‐catalyst will both be covalently anchored on the same support.

Tuning the Acceptor Unit of Push-Pull Porphyrazines for Dye-Sensitized Solar Cells.

A family of four push–pull porphyrazines of A3B type, where each unit A contains two peripheral propyl chains and the unit B is endowed with a carboxylic acid, were prepared. The carboxylic acid was attached to the β-position of the pyrrolic unit, either directly (Pz 10), or through cyanovinyl (Pz 11) and phenyl (Pz 7) groups. The fourth Pz (14) consisted in a pyrazinoporphyrazine wherein the dinitrogenated heterocycle provided intrinsic donor–acceptor character to the macrocycle and contained a carboxyphenyl substituent. The direct attachment of the carboxylic acid functions and their linkers to the porphyrazine core produces stronger perturbation on the electronic properties of the macrocycle, with respect to their connection through fused benzene or pyrazine rings in TT112 and 14, respectively. The HOMO and LUMO energies of the Pzs, which were estimated with DFT calculations, show little variation within the series, except upon introduction of the cyanovinyl spacer, which produces a decrease in both frontier orbital energetic levels. This effective interaction of cyanovinyl substitution with the macrocycle is also evidenced in UV/Vis spectroscopy, where a large splitting of the Q-band indicates strong desymmetrization of the Pz. The performance of the four Pzs as photosensitizers in DSSCs were also investigated.

Recent Advances in External-Directing-Group-Free C–H Functionalization of Carboxylic Acids without Decarboxylation

The selective functionalization of C–H bonds is an extremely important topic in present-day organic synthesis, as it utilizes the most abundant portion of a molecule as a tool for synthetic manipul...

Preparation of a hyperbranched hybrid curing agent for epoxidized novolac resin

A hyperbranched hybrid curing agent (CSD) for epoxidized novolac resin (ENR) was prepared by grafting silica nanoparticles modified with poly(amidoamine) (PAMAM) dendritic structure (SD) to carbon nanotube (CNT) using an esterification reaction between the amino functional groups of SD and carboxylic acid functionalities of oxidized CNT. ENR was prepared by a reaction between novolac resin and epichlorohydrin. Curing of ENR was carried out with two different contents of CSD as the hyperbranched hybrid curing component of the epoxidized matrix. The amino-rich structure of CSD could result in its high dispersion in the ENR matrix and consequently high thermal stability of the hybrid composites. Fourier-transform infrared spectroscopy and thermal gravimetric analysis (TGA) showed successful modification of silica nanoparticles and CNT with the PAMAM dendritic structure and SD, respectively. Structure of the resulting hybrid curing agents (SD and CSD) was investigated by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Thermal investigation of the resulted composites by TGA showed that the cured ENR with higher content of CSD has high thermal properties with a char residue of 44.4% among the other hybrid composites.

Electrografted Interfaces on Metal Oxide Electrodes for Enzyme Immobilization and Bioelectrocatalysis

AbstractIn this work, we demonstrate that diazonium electrografting of biocompatible interfaces on transparent conducting oxide indium tin oxide (ITO) can be controlled and optimized to achieve low charge transfer resistance, allowing highly efficient electron transfer to an immobilized model enzyme, the oxygen‐tolerant [NiFe]‐hydrogenase from Ralstonia eutropha. The use of a radical scavenger enables control of the interface thickness, and thus facilitates maximization of direct electron transfer processes between the enzyme's active center and the electrode. Using this approach, amine and carboxylic acid functionalities were grafted on ITO, allowing enzyme immobilization both under moderate electrostatic control and covalently via amide bond formation. Despite an initial decrease in catalytic activity, covalent immobilization led to an improvement in current stability compared to just electrostatically immobilized enzyme. Given the superior stability of electrografted interfaces in comparison to adsorbed or self‐assembled interfaces, we propose electrografting as an alternative approach for the functional immobilization of redox‐active enzymes on transparent conducting oxide (TCO) electrodes in bioelectronic devices.

Identification of the carboxylic acid functionality in protonated drug metabolite model compounds by using tandem mass spectrometry based on ion-molecule reactions coupled with high performance liquid chromatography

The carboxylic acid functionality is among the many functionalities that drug metabolites, degradation products and impurities may contain. Therefore, analytical techniques that can be used to rapidly identify the carboxylic acid functionality are important for pharmaceutical industry. In this study, a tandem mass spectrometric approach based on diagnostic gas-phase ion-molecule reactions with (isopropenoxy)trimethylsilane (ITS) was developed for the identification of protonated compounds containing the carboxylic acid functionality in a modified linear quadrupole ion trap mass spectrometer. All protonated carboxylic acid, N-oxide, sulfoxide, carboxamide, ketone, amine, hydroxylamine, sulfone, sulfonamide, amide, ether, ester and aldehyde model compounds studied react with ITS to form protonated ITS and an adduct that has lost an acetone molecule, [adduct – acetone]+. Protonated compounds containing the carboxylic acid functionality can be differentiated from most other types of protonated compounds based on the formation of a secondary product, 2° [adduct – acetone]+, upon reactions of the [adduct – acetone]+ primary product with a second ITS molecule via addition and elimination of an acetone molecule. Quantum chemical calculations suggest that both addition/acetone elimination reactions are initiated by proton transfer to ITS. Nucleophilic substitution of acetone at the silicon atom by the carbonyl oxygen atom of the carboxylic acid or the primary reaction product leads to elimination of acetone. An equimolar mixture of 4-aminobenzoic acid, clozapine N-oxide, oxcarbamazepine, diphenylsulfoxide, naproxen and celecoxib was subjected to analogous HPLC/tandem mass spectrometry experiments to demonstrate the utility of this method for high-throughput drug metabolite characterization. A limitation of this method is that compounds that contain a phenol group and an additional basic functionality can show a false positive result.

The Emergence of Palladium-Catalyzed C(sp3 )-H Functionalization of Free Carboxylic Acids.

Palladium-catalyzed directing group assisted C-H bond activation has emerged as a powerful tool in synthetic organic chemistry. However, only recently, among various directing groups, widely available carboxylate moiety is recognized as a versatile candidate for the regioselective transformations. Notably, palladium-catalyzed carboxylate directed C(sp3 )-H bond activation and diverse functionalization is highly challenging and has gained huge attention for its versatile applications. Mono- and bidentate ligands have proven to be useful for accelerating the C(sp3 )-H bond activation step, which helps to control reactivity and selectivity (including enantioselectivity). In this Minireview, we discuss the recent progress made in palladium-catalyzed C(sp3 )-H bond functionalization reactions for the construction of C-C and C-Heteroatom bonds with the direction of free carboxylic acid.

Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

New Naproxen Analogs: Synthesis, Docking and Anti-Inflammatory Evaluation

Naproxen is a well-known nonsteroidal anti-inflammatory drug belonging to aryl propanoic acid family; it nonselectively inhibits major cyclo-oxygenase (COX) isoforms causing GIT irritation as a side effect. A series of Naproxen analogs with modifiable carboxylic acid functionality (2–14) have been synthesized aiming to retain anti-inflammatory activity with reduced ulcerogenic effect. Docking studies of the new compounds into cyclo-oxygenase-2 complexes with its bound inhibitor SC-558 (1CX2) were performed in order to predict the binding affinities and orientations of these compounds at the active site. Best fit Naproxen analogs, 3, 5b, 9, 10f, 14 to COX-2 active site were screened for their anti-inflammatory activity by carrageenan-induced rat paw edema test method. The target compound, 3 showed higher inhibition rate (74.71%) than the reference standard, Naproxen (71.11%), compound 10f showed comparable inhibition rate (68.94%) to Naproxen, while the other targets 5b, 9, 14 elicited moderate anti-inflammatory activities (47.98–40.27%). All the test compounds were devoid of ulcerogenicity effect compared to Naproxen. Detailed synthesis, spectroscopic, and pharmacological data are disclosed. ICM values of compounds 3 and 10f are –87.69 and –105.57 kcal/mol respectively and the number of hydrogen bonding to COX-2 prove their affinity and showed good agreement with their remarkable pharmacological data.

Synthesis of <i>Capsicum chinense</i> Citric Acid Esters-Its Methanol Trans-esterification Investigations with hplc Analysis and Its valorization as Gels-Crystals Ca-Salts

The esterification between citric acid molecules and raw material-<i>Capsicum chinense</i> organic molecules in excess was carried out at 137°C-410.15°K. The kinetics of the reaction showed that this reaction was second order compared with citric acid and the calculated initial and global speed constant were respectively 1.43×10^-1[L²×mol^-2×s^-1] and 3.84×10^-2 [L²×mol^-2×s^-1]. The synthesized raw material’s-<i>Capsicum chinense</i>’s citric acid esters solutions colors was from light yellow-1.5[mn] to highly orange yellow-60[mn] confirming the esterification between citric acid molecules and the main bioactive molecules constituting the Capsicum chinense including capsaïcine, quercetin and luteolin whose densities were superior to one and explained the high densities of the Capsicum chinense citric acid esters solutions between 0.9825[g/ml] to 1.0636[g/ml]. Then, the alkene concentrations in esters solutions recorded an increase initially and at the middle of the time reaction respectively due to citric acid dehydration and alkenes from the raw material’s-<i>Capsicum chinense</i>’s bioactive molecules. But, the diminution of these alkene concentrations recorded from 900[s] time reaction confirmed their etherification with carboxylic acid and/or alcohol organic functions catalyzed by citric acid’s protonic acid-H⁺. Second, the trans-esterification mechanisms of the raw materials’ citric acid esters solutions with methanol was explored, inventoried and carried out in order to extract its bioactive molecules and their derivatives synthesized during this trans-esterification reaction where citric acid’s protonic acid-H⁺ sites functioned as catalyst. Thus, a trans-esterification using reflux-assembly followed by an extraction procedures were established in this manuscript. Indeed, the hplc analysis of the dichloromethane extracts allowed to identify the <i>Capsicum chinense</i>’s bioactive molecules and these derivatives. Third, procedures to synthesize crystals and gel calcium salts of raw material’s citric acid esters solutions was established. An inventory of these gel-crystals structure was done in this manuscript and it was deduced that the first step of these procedures was the esters solution titration with NaOH-0.05N in order to determine the optimum quantities of calcium hydroxide for the synthesis using reflux assembly at 137°C followed by evaporations procedures. Then, once synthesized gel was suffered under thermic treatment until having solid crystals well-structured, both could be characterized by an established EDTA-0.01N and alkene procedures titrations established in this manuscript. Finally, an established titration procedure with NaOH-0.05N allowed to determine their equivalent citric acid molecules concentrations. It was noticed that their citric acid and calcium weight concentration ratio was respectively 4.354/1.67 (≈2/1) which confirmed the well-structured of the product regarding to the exploration salts synthesis-mechanisms figures done in this manuscript.

Synergistic effect of hydrophobic and hydrogen bonding interaction-driven viologen-pyranine charge-transfer aggregates: adenosine monophosphate recognition.

Understanding the role of non-covalent interactions that dictate and fine-tune the direction of self-assembly of functional molecules is crucial for developing stimuli responsive materials. Herein, we systematically designed and synthesized viologen derivatives with hydrophobic dodecyl chains and alkyl carboxylic acid functionalities. The complementary electronic and electrostatic counterpart of viologens was chosen as pyranine. Viologens comprising of a hydrophobic dodecyl chain on one terminal and hydrogen bonding alkyl carboxylic acid on the other (V1 and V2) underwent aggregation to a varying extent upon interaction with pyranine. The length of the alkyl carboxylic acid had a greater impact on the nature and morphology of the aggregates. Control molecules (V3 and V4) in which 4,4'-bipyridine was symmetrically quaternized with alkyl carboxylic acids did not aggregate upon interaction with pyranine. The delicate balance existing between the hydrophobicity of the dodecyl chains and the intermolecular hydrogen bonding interaction between the alkyl carboxylic acid groups in V1 or V2 of the corresponding charge transfer (CT) complexes was instrumental in driving the aggregation. The CT aggregates of [V1-Pyr] and [V2-Pyr] exhibited excellent stability in water which disaggregated at physiological pH. We emphasize on the importance of synergy between hydrophobic and hydrogen bonding interactions in reinforcing each other to drive the supramolecular aggregation of the CT complexes. Such pH dependent CT aggregates are of importance as scaffolds in pH controlled drug release. In the present study, the CT aggregates were evaluated for adenosine nucleotide recognition in water; [V1-Pyr] and [V2-Pyr] exhibited selective response towards adenosine monophosphate via deprotonation induced dissolution of aggregates in water leading to emission enhancement.

Total Synthesis of a Structurally Complex Tetrasaccharide Repeating Unit of &lt;i&gt;Vibrio cholerae&lt;/i&gt; O43

Vibrio cholerae is a causative agent of the deadly pandemic - cholera. Among ~200 serogroups of V. cholerae, the O1 and O139 serogroups are mainly responsible for virulent cholera. Some other serogroups are also found to be associated with diarrhoea and minor outbreaks of cholera type diseases. The deadly pathogen is a threat for many developing countries, predominately in Asia and Africa, and still causes millions of deaths every year. A multicomponent glycoconjugate vaccine covering all the strains of V. cholerae is highly desired to prevent the spread of this disease. Here, we report the first total synthesis of a densely functionalized tetrasaccharide repeating unit of V. cholerae O43, which contains rare deoxy amino sugars D-quinosamine and D-viosamine attached with a rare amino acid N-acetyl-L-allothreonine. Synthesis of orthogonally protected rare sugars and unnatural amino acid building blocks, stereoselective construction of three consecutive 1,2-cis glycosidic linkages and the presence of five nitrogen atoms dispersed over four sugar units as well as carboxylic acid functionality makes the total synthesis a formidable task. The tetrasaccharide was assembled via a highly regio- and stereoselctive [3+1] glycosylation of fully functionalized, amino acid-bearing D-viosamine donor with the trisaccharide diol. The assembly of all-1,2-cis linked trisaccharide diol was expeditiously achieved in one-pot manner. Judicious selection of protecting groups and reaction conditions enabled access to the structurally complex, amino acid-attached tetrasaccharide repeating unit, which can be used for future biological studies directed towards development of vaccine. The synthetic strategy will be useful for accessing other structurally related complex bacterial glycans.

Comparing the host behaviour of roof-shaped compounds trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid and its dimethyl ester in the presence of mixtures of xylene and ethylbenzene guests

Each p-Xy guest molecule is surrounded by six dicarboxylic acid host molecules, forming a continuous intermolecular hydrogen-bonded motif through their carboxylic acid functionalities to form a cage-like structure in which the guests are trapped.

Synthesis of bis-azobenzene derivatives with reactive bromohexyl unit and carboxylic acid group based on Disperse Yellow 7

In this work, two types of azobenzene derivatives based on Disperse Yellow 7 (DY7, 4-[4-(phenylazo)phenylazo]-o-cresol) were synthesized, which are bis-azobenzenes bearing flexible functional 6-bromohexyl chain or carboxylic acid moiety. The first one was synthesized by alkylation of DY7 with an excess of 1,6-dibromohexane in the presence of a mild base (K2CO3). The second one (azo dye with carboxylic acid functionality) was obtained by the alkaline hydrolysis of the ester bond of the newly obtained DY7 derivative with the ethoxycarbonyl group. The synthesized compounds were characterized by different spectral analytical techniques such as 1H NMR, 13C NMR, FT-IR, and UV-Vis. They can be employed for the synthesis of a wide variety of azo-based materials, which may be suitable for photochromic systems and molecular electronics applications.

Modified silicates and carbon nanotubes for immobilization of lipase from Rhizomucor miehei: Effect of support and immobilization technique on the catalytic performance of the immobilized biocatalysts

Lipase from Rhizomucor miehei (RML) was covalently immobilized on different supports, two silica gels and two carbon nanotube samples, using two different strategies. RML was immobilized on 3-carboxypropyl silica gel (RML@Si−COOH) and multi-wall carbon nanotubes containing carboxylic acid functionalities (RML@MCNT−COOH) using a two-step carbodiimide activation/immobilization reaction. Moreover, the enzyme was also immobilized on 3-aminopropyl silica (RML@Si-Glu) and single-wall carbon nanotubes functionalized with 3-APTES and activated with glutaraldehyde (RML@SCNT-Glu). Before and after RML immobilization, the structurel properties of supports were characterized and compared in detail. After immobilization, the expressed activities were 36.9, 90.2, 16.9, and 26.1 % for RML@Si−COOH, RML@Si-Glu, RML@MCNT−COOH, and RML@SCNT-Glu, respectively. The kinetic parameters of free and immobilized RML samples were determined for three substrates, p-nitrophenyl acetate, p-nitrophenyl butyrate and p-nitrophenyl palmitate, and RML@Si-Glu showed higher catalytic efficiency than the other immobilized RML samples. RML@Si−COOH, RML@Si-Glu, RML@MCNT−COOH, and RML@SCNT-Glu exhibited 5.8, 7.6, 4.2 and 4.6 folds longer half-life values than those of the free enzyme at pH 7.5 and 40 °C. Recyclability studies showed that all the immobilized RML biocatalysts retained over 90 % of their initial activities after ten cycles in the hydrolysis of p-nitrophenyl butyrate.

Terpyridine-Functionalized Calixarenes: Synthesis, Characterization and Anion Sensing Applications.

Lanthanide complexes have been developed and are reported herein. These complexes were derived from a terpyridine-functionalized calix[4]arene ligand, chelated with Tb3+ and Eu3+. Synthesis of these complexes was achieved in two steps from a calix[4]arene derivative: (1) amide coupling of a calix[4]arene bearing carboxylic acid functionalities and (2) metallation with a lanthanide triflate salt. The ligand and its complexes were characterized by NMR (1H and 13C), fluorescence and UV-vis spectroscopy as well as MS. The photophysical properties of these complexes were studied; high molar absorptivity values, modest quantum yields and luminescence lifetimes on the ms timescale were obtained. Anion binding results in a change in the photophysical properties of the complexes. The anion sensing ability of the Tb(III) complex was evaluated via visual detection, UV-vis and fluorescence studies. The sensor was found to be responsive towards a variety of anions, and large binding constants were obtained for the coordination of anions to the sensor.

Targeted Nanoparticles for Fluorescence Imaging of Folate Receptor Positive Tumors.

This report presents the synthesis and folate receptor target-specificity of amino-functionalized polyacrylamide nanoparticles (AFPAA NPs) for near-infrared (NIR) fluorescence imaging of cancer. For the synthesis of desired nano-constructs, the AFPAA NPs (hereafter referred to as NPs) were reacted with a NIR cyanine dye (CD) bearing carboxylic acid functionality by following our previously reported approach, and the resulting conjugate (NP-CD) on further reaction with folic acid (FA) resulted in a new nano-construct, FA-NP-CD, which demonstrated significantly higher uptake in folate receptor-positive breast cancer cells (KB+) and in folate receptor over-expressed tumors in vivo. The target-specificity of these nanoparticles was further confirmed by inhibition assay in folate receptor-positive (KB+) and -negative (HT-1080) cell lines. To show the advantages of polyacrylamide (PAA)-based NPs in folate receptor target-specificity, the CD used in preparing the FA-NP-CD construct was also reacted with folic acid alone and the synthetic conjugate (CD-FA) was also investigated for its target-specificity. Interestingly, in contrast to NPs (FA-NP-CD), the CD-FA conjugate did not show any significant in vitro or in vivo specificity toward folate receptors, showing the advantages of PAA-based nanotechnology in delivering the desired agent to tumor cells.

Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram-Positive Pathogens.

New 5-substituted vitamin E derivatives were semisynthesized, and their antibacterial activity against human Gram-positive and Gram-negative pathogens was evaluated. Several vitamin E analogues were active against methicillin-resistant Staphylococcus aureus (MRSA) and/or methicillin-resistant Staphylococcus epidermidis (MRSE); structure-activity relationships (SARs) are discussed. As a result, it is shown that the presence of a carboxylic acid function at the C-5 position and/or at the end of the side chain is crucial for the antibacterial activity. The bactericidal or bacteriostatic action of three compounds against MRSA and MRSE was confirmed in a time-kill kinetics study, and the cytotoxicity on human cells was evaluated. The preliminary mechanism study by confocal microscopy indicated that those vitamin E analogues led to bacterial cell death through membrane disruption.

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

In this paper we describe the synthesis of a new carbohydrate-based building block functionalized with azido or amino groups on the 2 and 4 positions. The building block can be synthesized in anomerically pure form in only five scalable steps starting from commercially available levoglucosan. It was shown that the building block could undergo alkylations under strongly basic conditions. The building block with azido groups could furthermore take part in CuAAC reactions, generating derivatives with ester or carboxylic acid functionalities. In addition, the anomeric mixture of the building block was used for the synthesis of a molecule that could act as an emulsifier only in the presence of Zn2+ ions.

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.