Glutaric Anhydride Research Articles

Synthesis and Antibacterial Activity of 5-Phthalate and 5-Glutarate Derivatives of Milbemycins A3/A4*

Naturally occurring 16-membered macrolides milbemycins A3 and A4 were selectively esterified at their 5-OH group with phthalic and glutaric anhydrides. The obtained monoesters were further functionalized by amide formation. Propargylamide derivatives were demonstrated to undergo 1,2,3-triazole formation upon treatment with organic azides in the presence of copper catalyst. Some of the synthesized compounds exhibited useful levels of antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis.

Preparation and characterization of diethoxy- and monoethoxy phosphylated (‘aged’) serine haptens and use in the production of monoclonal antibodies

In this study, the first mechanism-based monoclonal antibodies have been produced that recognize and differentiate diethoxy- and monoethoxyphosphorylated serine residues. Haptens were synthesized as the stable phosphonate form of phosphoserine esters to improve the immunoresponse. Following condensation with a glutaric anhydride to link the phosphoserine moieties to carrier protein, the hapten densities attached to bovine serum albumin and keyhole limpet henocyanin were determined by partial trypsin digestion and MALDI mass spectrometry, and confirmed using a fluorescent assay (FITC) to quantify unmodified lysine residues. The conjugation reactions were pH optimized to improve hapten density. Screening of subclones led to the identification of two monoclonal antibodies: (a) N257/25.11 that specifically recognizes (EtO)2P(O)-Ser as the phosphylated or inhibited form, and (b) N262/16 that recognizes (EtO)(HO)P(O)-Ser as the ‘aged’ form. Analysis of blood samples treated with paraoxon (EtO)2P(O)-OPhNO2 showed a concentration dependent recognition of the phosphylated form.

Organocatalytic kinetic resolution of racemic secondary nitroallylic alcohols combined with simultaneous desymmetrization of prochiral cyclic anhydrides.

This study describes an organocatalytic kinetic resolution of racemic secondary nitroallylic alcohols (2) combined with simultaneous desymmetrization of prochiral cyclic anhydrides (1). The experimental results revealed that enantioselective alcoholysis of 3-substituted glutaric anhydrides afforded hemiesters (3) with high levels of enantioselectivities (up to 99% ee) in the presence of cinchonidine-derived thiourea catalyst (IV). The highly optical enrichment (up to 95% ee) of (S)-nitroallylic alcohols (2) was recovered.

Ultrasound-promoted Friedel-Crafts acylation of arenes and cyclic anhydrides catalyzed by ionic liquid of [bmim]Br/AlCl3

A simple and efficient method of Friedel-Crafts acylation of arenes with succinic anhydride, phthalic anhydride and glutaric anhydride under the action of 1-butyl-3-ethylimidazolium ([bmim]Br/AlCl3 ([bmim]+) cation (ionic liquid) and ultrasound irradiation is presented. Thy purity of products was tested by GC-MS and their structures evaluated by IR and 1H NMR spectroscopy.

Enzymatic desymmetrization of 3-(4-fluorophenyl)glutaric anhydride through enantioselective alcoholysis in organic solvents

The enzymatic desymmetrization of 3-(4-fluorophenyl)glutaric anhydride (3-FGA) was investigated through lipase-catalyzed enantioselective alcoholysis in organic solvents. An immobilized Lipase B from Candida Antarctica (Novozym 435) was found to be an efficient biocatalyst for the enantioselective alcoholysis of 3-FGA. Methyl tert-butyl ether (MTBE) and methanol were chosen as the suitable reaction medium and acyl acceptor, respectively. The optimum reaction temperature, molar ratio of methanol to 3-FGA and 3-FGA concentration were 25°C, 2:1 and 100 mM, respectively. Under these conditions, complete conversion was achieved and methyl (S)-3-(4-fluorophenyl)glutarate ((S)-MFG) was obtained in a moderate ee value of 80%. Furthermore, the reaction was performed on a gram scale and the ee value of (S)-MFG was enriched to 96% after treatment with a toluene/hexane (2/1, v/v) mixture.

High Voltage Spinel Lmno/Lto Li-Ion Batteries: Ageing Processes and Role of Electrolyte Additives on Interfaces

The combination of high voltage spinel oxides LiMn2-x Ni x O4 (LMNO, that can be charged up to 5V vs. Li+/Li) with Li4Ti5O12 (LTO, 1.5V vs. Li+/Li) is a very attractive solution to obtain Li-ion systems with a high power density and an increased safety with respect to systems using carbon negative electrodes [1,2]. LTO authorizes higher charge rates without any problem of lithium dendrites formation, which is suitable for electric vehicles (EVs) or hybrid electric vehicles (HEVs) for instance.However, conventional electrolytes made up of LiPF6 salt dissolved in a mixture of carbonates are not stable above 4.2 - 4.5V vs. Li+/Li and lead to a reactive cathode/electrolyte interface at high voltage [3]. This interfacial reactivity results in capacity fading and fast self-discharge of LMNO/LTO batteries, preventing up to now the commercial use of these systems [4,5]. To reduce this electrode/electrolyte reactivity at the cathode surface and to improve the electrochemical performances, it is possible to introduce additives in the electrolyte in order to stabilize interfaces. In this work we have focused on an organic additive: glutaric anhydride. A small amount (2 %) of this additive was found to show a beneficial effect by reducing the self-discharge and improving the cycle life and rate capability of these systems.To better understand the ageing processes in these systems and explain the beneficial role of this additive, we have investigated the cathode and anode/electrolyte interfaces by two complementary techniques: X-ray Photoelectron Spectroscopy (XPS) and Electrochemical Impedance Spectrocopy (EIS), which allow a chemical and an electrochemical analysis of the interfaces, respectively.Our study has shown that, whereas LTO is usually considered as a passivation-free electrode material, large amounts of organic and inorganic species are deposited at the surface of this electrode upon cycling in a conventional electrolyte, due to a cross-talk process with the LMNO cathode.The additive was found to significantly change the chemical composition of the passivation layer at both electrodes surfaces. In this case a large amount of oxygenated organic species accumulates at the surface of the cathode (and also at the anode side) upon cycling or storage in charged state. After long cycling, the characteristic XPS signals of LMNO strongly decrease, showing that the electrode's surface has been covered by a thick layer coming from degradation species of the additive (see figure 1). EIS electrical measurements support a more covering/homogenous and ionically conducting surface film on the cathode when the additive is used, suggesting that the passivation film behaves like a Polymer Electrolyte Interface (PEI).The deposition of this surface film is accompanied by an improvement of the electrochemical performances, and does not hinder Li+ ions diffusion but decreases the interfacial reactivity of the electrode towards the electrolyte.Moreover, the deposition of a thick layer was also observed at the surface of LTO negative electrode, but the nature of the oxygenated species is different, as shown by XPS spectra. This shows that two different mechanisms of degradation of the additive are involved at the cathode and the anode.

Diastereoselective synthesis of γ- and δ-lactams from imines and sulfone-substituted anhydrides.

Sulfone-substituted γ- and δ-lactams have been prepared in a single step with high diastereoselectivity. Sulfonylglutaric anhydrides produce intermediates that readily decarboxylate to provide δ-lactams with high diastereoselectivity. Substituents at the 3- or 4-position of the glutaric anhydride induce high levels of stereocontrol. Sulfonylsuccinic anhydrides produce intermediate carboxylic acids that can be trapped as methyl esters or allowed to decarboxylate under mild conditions. This method has been applied to a short synthesis of the pyrrolizidine alkaloid (±)-isoretronecanol.

Improvement of Electrode/Electrolyte Interfaces in High-Voltage Spinel Lithium-Ion Batteries by Using Glutaric Anhydride as Electrolyte Additive

High-voltage spinel oxides combined with Li4Ti5O12 result in 3 V Li-ion batteries with a high power capability, but electrochemical performances are limited by electrode/electrolyte interfacial reactivity at high potential. We have investigated glutaric anhydride (GA) as an electrolyte additive to improve the performances of LiNi0.4Mn1.6O4/Li4Ti5O12 cells. We showed that GA efficiently reduces both the capacity fading upon cycling and the self-discharge. From X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR), and electrochemical impedance spectroscopy (EIS) measurements, we showed that GA reduces salt (LiPF6) degradation. Addition of 2% GA in the electrolyte results in a passivation film at the surface of both electrodes, which is mainly composed of organic compounds resulting from degradation of GA. The film is much thicker but less resistive due to a better ionic conductivity, and behaves like a polymer electrolyte interface.

Dicarboxylated ethynylarenes as buffer-dependent chemosensors for Cd(II), Pb(II), and Zn(II)

Two dicarboxylated ethynylarenes were prepared efficiently from condensation of 1,3-bis(3-aminoph enylethynyl)benzene with two equivalents of either succinic anhydride or glutaric anhydride. These compounds behave as fluorescent chemosensors selective for Cd(II), Pb(II) and Zn(II) cations under buffered aqueous conditions, with analyte binding observed as bathochromically shifted, intensified fluorescence. It was noteworthy that the fluorescence responses varied significantly with buffer identity. A conformational restriction mechanism involving reversible interactions between the fluorophore, metal cation and buffer itself is proposed.

Fractionation effects of polystyrene on acylation reaction and their adhesive and corrosive properties

First, polystyrene (PS) was fractionated using solvent-precipitation methods; then the chemical modification of PS was investigated in the presence of Lewis acid [BF3·O(C2H5)2] catalyst with some anhydrides such as phthalic anhydride, glutaric anhydride, maleic anhydride, and propionic anhydride. The amount of the polyfunctional groups bonded to polymer structures changed depending on the molecular weight of the polymer, and more functional groups connected to the highest-molecular-weight fraction. The amount of the bonded functional groups was determined with the chemical analysis method. The structures of PS functionalized with anhydrides were confirmed by FTIR, 1H NMR, and thermogravimetric studies. Their adhesion capability and corrosion resistance against metals have been investigated under various conditions. The results showed that the addition of functional groups to PS increases its adhesion capability and corrosion resistance. This increase is attributed to the quantity of the functional groups bonded to PS.

Water-soluble paclitaxel by conjugation to hyperbranched polyglycidols

Chemical conjugates composed of paclitaxel (PTXL) and hyperbranched polyglycidols (HBP) were synthesized using glutaric anhydride as a “bridge” with esterification in dimethylformamide. A series of HBP–PTXL conjugates (HPCs) were synthesized using different molecular weights of HBP and varying ratios of HBP to PTXL, and they were characterized. An intact form of PTXL was regenerated from HPCs under acidic or basic pH conditions. Furthermore, water-soluble HPCs exhibit a more pronounced cytotoxic effect against cancer cells, suggesting that these HPCs can be utilized as tumor-specific therapeutic agents in the form of an injectable drug.

Nanoparticle-tethered NAD+ with in situ cofactor regeneration

A new and simple route for the preparation of immobilized NAD(+) on carboxyl-activated silica nanoparticles activated by γ-aminpropyltriethoxysilane and glutaric anhydride was developed. In addition, formate dehydrogenase, keto-reductase and the silica nanoparticle-attached NAD(+) were applied to catalyze the coupled reactions for production of L-lactate with the cofactor regenerated within the reaction cycle. As indicated by thermogravimetric analysis and FT-IR, the silica nanoparticles were successfully activated and the loading of carboxyl groups was 0.53mmolg(-1) particle. The amount of immobilized NAD(+) on the support was 73mgg(-1) particle. With 0.2M pyruvate and 3M formate, 0.16M L-lactate was produced after the coupled reactions. The immobilized system showed excellent efficiency and stabilities in recycling, and it retained 60% residual activity even after six reuses.

Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier

The aim of this study was to investigate the ability of a third-generation (G3) polyamidoamine (PAMAM) dendrimer-based carrier to enhance the permeability of paclitaxel (pac) and to overcome cellular barriers. G3 dendrimers were surface modified with lauryl chains (L) and conjugated with paclitaxel (pac) via a glutaric anhydride (glu) linker, followed by labeling with FITC. Biological evaluation of the dendrimer and conjugates was conducted using the human colon adenocarcinoma cell line (Caco-2) and primary cultured porcine brain endothelial cells (PBECs). LDH assay was used to evaluate the cytotoxicity of the dendrimer and conjugates. Cytotoxicity studies showed that the conjugation of lauryl chains and paclitaxel on G3 dendrimer significantly (p<0.05) increased the cytotoxicity against both cell types. Permeability studies of dendrimer-drug conjugates demonstrated an increase in the apparent permeability coefficient (P(app)) in both apical to basolateral A→B and basolateral to apical B→A directions across both cell monolayers compared to unmodified G3 and free drug. The B→A P(app) of paclitaxel was significantly (p<0.05) higher than the A→B P(app), indicating active function of P-gp efflux transporter system in both cell models. L6-G3-glu-pac conjugate had approximately 12-fold greater permeability across both cell monolayers than that of paclitaxel alone.

An enantiodivergent and formal synthesis of paroxetine enantiomers by asymmetric desymmetrization of 3-(4-fluorophenyl)glutaric anhydride with a chiral SuperQuat oxazolidin-2-one

The asymmetric desymmetrization of 3-(4-fluorophenyl)glutaric anhydride 9 with lithiated chiral oxazolidin-2-one 8 has been studied. The desymmetrized product was formed with >90% de and converted into known intermediates for both (+)- and (−)-paroxetines.

Thermal and photochemical oxidation of 2-acetylcyclopentanone with atmospheric oxygen

The major products of thermal (acetone, CaCl2 excess, reflux) and photochemical (acetone or CCl4, room temperature) oxidation of 2-acetylcyclopentanone with atmospheric oxygen are 2-acetyl-2-hydroxycyclopentanone, 2-acetyl-2-hydroxymethylcyclopentanone, 1,1′-diacetyl-1,1′-bicyclopentyl-2,2′-dione, 2-acetoxycyclopentanone, 5,6-dioxoheptanoic acid, glutaric acid, and glutaric anhydride. The formation of 2-acetyl-2-hydroxycyclopentanone is the first example of the direct α-hydroxylation of β-dicarbonyl compound under the conditions described.

Effect of glutaric anhydride additive on the LiNi0.4Mn1.6O4 electrode/electrolyte interface evolution: A MAS NMR and TEM/EELS study

Investigation of electrode/electrolyte interface of 5V spinel material LiNi0.4Mn1.6O4 was carried out in the presence of glutaric anhydride additive, using combined magic angle spinning NMR spectroscopy and electron energy-loss spectroscopy. After exposure to LiPF6 in EC/DMC liquid electrolyte, oxidation state of +III or lower has been evidenced by EELS for Mn ions, indicating that the presence of glutaric anhydride additive in the electrolyte, not only modifies the interphase, but does not prevent chemical reactions with the active material. Further investigation of the influence of the additive upon storage and cycling was performed using combined 7Li and 19F MAS NMR. The native interphase formed by simple contact of the active material with the electrolyte is partially destroyed at high potential but the new appearing interphase is overall increasing upon cycling, independently from the presence of glutaric anhydride. The use of glutaric anhydride is nevertheless beneficial as it clearly restrains the formation of lithiated interphasial species and alters the interphase composition since the formation of fluorophosphates is promoted, lowering the relative amount of resistive LiF. Although resistive LiF can be formed in significant amount, it is removed by the DMC rinsing while fluorophosphates display a stronger adherence to the active material.

Synthesis of periodic copolymers via ring‐opening copolymerizations of cyclic anhydrides with tetrahydrofuran using nonafluorobutanesulfonimide as an organic catalyst and subsequent transformation to aliphatic polyesters

AbstractTo synthesize polyesters and periodic copolymers catalyzed by nonafluorobutanesulfonimide (Nf2NH), we performed ring‐opening copolymerizations of cyclic anhydrides with tetrahydrofuran (THF) at 50–120 °C. At high temperature (100–120 °C), the cyclic anhydrides, such as succinic anhydride (SAn), glutaric anhydride (GAn), phthalic anhydride (PAn), maleic anhydride (MAn), and citraconic anhydride (CAn), copolymerized with THF via ring‐opening to produce polyesters (Mn = 0.8–6.8 × 103, Mn/Mw = 2.03–3.51). Ether units were temporarily formed during this copolymerization and subsequently, the ether units were transformed into esters by chain transfer reaction, thus giving the corresponding polyester. On the other hand, at low temperature (25–50 °C), ring‐opening copolymerizations of the cyclic anhydrides with THF produced poly(ester‐ether) (Mn = 3.4–12.1 × 103, Mw/Mn = 1.44–2.10). NMR and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectra revealed that when toluene (4 M) was used as a solvent, GAn reacted with THF (unit ratio: 1:2) to produce periodic copolymers (Mn = 5.9 × 103, Mw/Mn = 2.10). We have also performed model reactions to delineate the mechanism by which periodic copolymers containing both ester and ether units were transformed into polyesters by raising the reaction temperature to 120 °C. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Functionalization of Polystyrene with Cyclic Anhydrides and their Spectroscopic, Adhesive and Corrosive Characterizations

Abstract Polystyrene (PS) has been chemically modified with cyclic anhydrides such as glutaric anhydride (GA), citraconic anhydride (CA) and phthalic anhydride (PA) in the presence of BF3·O(C2H5)2 in chloroform and succinic anhydride (SA) in 1,2-dichloroethane. Some important reaction parameters were determined in order to optimize the acylation process. ATR FT-IR and 1H NMR studies indicate that the acylation reaction can introduce both carboxyl group and double bond (for only citraconic anhydride) onto pendant aromatic groups of the polymer. The adhesion properties and corrosion resistance of the acylated PS on metal surface under various conditions have been investigated.

Ageing effects on electrical, morphological, and mechanical properties of a low viscosity epoxy nanocomposite

This research highlights the influence of alumina nanoparticles on different ageing concepts in order to study ageing consequences on sub-micron structures for a novel nanocomposite based on glycerol diglycidyl ether (GDE) and 3,3-dimethyl glutaric anhydride (DGA). Electrochemical impedance spectroscopy (EIS) was used to evaluate thermal degradation and corrosion resistance of the epoxy in exposure to distilled water and 10 wt% sulphuric acid solution at various times. It was found that the resistance of the epoxy to corrosive electrolyte was significantly improved using alumina nanoparticles. The water uptake behaviour was also evaluated by EIS measurements. The results showed that ageing for 2 months led to increase in the charge transfer resistance. Surface topography and roughness were studied using Atomic Force microscopy (AFM). Ageing was confirmed by the flattening of the surfaces and observed to be significant for the system without nanoalumina. Results from tensile measurements showed that the nanocomposite system gives better mechanical properties after ageing in comparison to the neat GDE system.

Development and validation of a chemiluminescent ELISA for simultaneous determination of florfenicol and its metabolite florfenicol amine in chicken muscle

A competitive indirect chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) for florfenicol (FF) and its major metabolite florfenicol amine (FFA) residues in chicken muscle has been developed and validated according to Commission Decision 2002/657/EC criteria. The IC50 value of the method was 0.153 μg kg−1 for FFA with a cross-reactivity of 74.3% for FF under optimum conditions, in which FFA–F–BSA (FFA–formaldehyde–BSA) and FF–G–OVA (FF–glutaric anhydride–OVA) were used as an immunogen and a coating antigen, respectively. FFA and FF were easily extracted from chicken muscle with a 40:1 ethyl acetate–ammonia mixture, obtaining recoveries of 70.3–100% (FFA) and 71.8–102.0% (FF). Accuracy, precision, selectivity, robustness, limit of detection (LOD), limit of quantification (LOQ) and detection capability (CCβ) of the assay have been assessed during the validation process. LOD values in chicken muscle were 0.353 μg kg−1 for FFA and 0.526 μg kg−1 for FF (10-fold dilution) and 0.453 μg kg−1 for FFA and 0.657 μg kg−1 for FF (100-fold dilution). Furthermore, the CL-ELISA method gave CCβ values of 1.0 μg kg−1 for FFA and FF. Finally, real chicken muscle samples were analyzed with the CL-ELISA method, traditional ELISA and a previously reported gas chromatography-negative chemical ionization mass spectrometry (GC-MS), and results confirmed the utility of this new CL-ELISA for trace determination of FF and FFA, simultaneously.