Stable Ester Research Articles

Synthesis of poly(vinyl alcohol) combs via MADIX/RAFT polymerization

Poly(vinyl acetate) combs have been prepared via macromolecular design via interchange of xanthate (MADIX)/reversible addition–fragmentation chain-transfer (RAFT) polymerization using xanthate functionalized polymer cores. The comb backbones were prepared using well-defined poly(vinyl alcohol) PVA polymers with a degree of polymerization of 20, 100 and 170, respectively. Functionalization with xanthates via R-group or a Z-group approach resulted in the formation of macromolecular MADIX agents. While Z group designed macromolecular xanthate agents appeared to inhibit the polymerization of vinyl acetate (VAc), R group designed macromolecular xanthate agents achieved to mediate efficiently the bulk polymerization of VAc affording PVAc combs. However, the growth of the combs was accompanied at low conversions by the formation of linear polymer chains as a result of the constant initiation (AIBN) and shoulders, which can be attributed to intermolecular coupling reactions. The proportions of single chains and termination products were observed to increase with the degree of polymerization of the macromolecular MADIX agents broadening the molecular weight distribution. As a result of a stable ester link between the branches and the PVA backbone, the branched PVAc architectures were finally hydrolyzed to afford poly(vinyl alcohol) combs.

Mechanism of α-oxoamine synthases: identification of the intermediate Claisen product in the 8-amino-7-oxononanoate synthase reaction

The reactive beta-ketoacid pyridoxal-5'-phosphate aldimine formed in the condensation step of the 8-amino-7-oxononanoate synthase reaction was 'trapped' in the enzyme-bound form by carrying out the reaction with l-alanine methyl ester and pimeloyl-CoA affording the more stable methyl ester of the putative intermediate, the characterisation of which provides the first definitive evidence for a beta-ketoacid intermediate in an alpha-oxamine synthase mechanism.

Concise Approach to the “Higher Sugar” Core of the Nucleoside Antibiotic Hikizimycin

A highly productive synthesis of phenylthio glycoside 33 is described which constitutes a fully functional surrogate for the hikosamine core of hikizimycin 1, a complex nucleoside antibiotic endowed with promising anthelmintic properties. The chosen approach to this undecose derivative starts from mannofuranose 7 which was one-carbon homologated to alkyne 8 in one step on treatment with lithio (trimethylsilyl)diazomethane. Alkynyl iodide 12 derived from 8 was combined with the tartrate-derived aldehyde 17 by a Nozaki-Hiyama-Kishi reaction that can either be performed using overstoichiometric amounts of CrCl2 or by means of a catalytic manifold based on the turnover of a cat. CrCl2/chlorosilane/manganese redox couple. Semi-hydrogenation of the resulting alkyne 18 to (Z)-olefin 19 required the use of Pd/C as the catalyst, whereas conventional Lindlar reduction was unsatisfactory. Attempted cis-dihydroxylation of alkene 22 (formed from 19 by a Mitsunobu reaction with phthalimide) by using catalytic amounts of OsO4 and NMO as the stoichiometric oxidant essentially failed, whereas a stoichiometric osmylation afforded the stable osmate ester 26 a as a single diastereomer. Since the use of OsO4 in stoichiometric amounts deemed inappropriate for a total synthesis project, recourse was taken to catalytic "Blitz dihydroxylation" with RuO4 in the presence of FeCl2.4H2O as co-catalyst. Application of these conditions to alkene 30 bearing a free aldehyde function at the terminus of the "higher sugar" chain furnished pyranose 32 in good yield and excellent diastereoselectivity, which was converted into the targeted thioglycoside 33 on treatment with PhSSPh/Et3P. It is particularly noteworthy that the conformational constraints of the acyclic substrate 30 enforce the dihydroxylation to violate Kishi's empirical rule for transformations of this type.

Rigidity and Flexibility of Dipeptidyl Peptidase IV: Crystal Structures of and Docking Experiments with DPIV

Dipeptidyl peptidase IV (DPIV) is an alpha,beta-hydrolase-like serine exopeptidase, which removes dipeptides, preferentially with a C-terminal l-Pro residue, from the N terminus of longer peptide substrates. Previously, we determined the tetrameric 1.8A crystal structure of native porcine DPIV. Each monomer is composed of a beta-propeller and a catalytic domain, which together embrace an internal cavity housing the active centre. This cavity is connected to the bulk solvent by a "propeller opening" and a "side opening". Here, we analyse DPIV complexes with a t-butyl-Gly-Pro-Ile tripeptide, Pro-boroPro, a piperazine purine compound, and aminoethyl phenyl sulfonylfluoride. The latter two compounds bind to the active-site groove in a compact and a quite bulky manner, respectively, causing considerable shifts of the catalytic Ser630 side-chain and of the Tyr547 phenolic group, which forms the oxyanion hole. The tripeptide, mimicking a peptide substrate, is clamped to the active site through tight interactions via its N-terminal alpha-ammonium group, the P2 carbonyl group, the P1-l-Pro side-chain, the C-terminal carboxylate group, and the stable orthoacid ester amide formed between the scissile peptide carbonyl group and Ser630 O(gamma). This stable trapping of the tripeptide could be due to stabilization of the protonated His740 imidazolium cation by the adjacent negatively charged C-terminal carboxylate group, preventing proton transfer to the leaving group nitrogen atom. Docking experiments with the compact rigid 58 residue protein aprotinin, which had been shown to be processed by DPIV, indicate that the Arg1-Pro2 N terminus can access the DPIV active site only upon widening of its side openings, probably by separation of the first and the last propeller blades, and/or of the catalytic and the propeller domain.

The B2–B7 phase transition in symmetrical bent‐shaped mesogens with methoxy substitution

New mesogens composed of achiral bent molecules with thermally stable ester linkages, and laterally substituted by a methoxy group symmetrically near the central benzene ring, were synthesized. Texture, calorimetric, electro‐optical, X‐ray and dielectric measurements were performed. In most of studied compounds the antiferroelectric B2 phase was found on cooling from the isotropic phase, followed by the B7 phase at lower temperatures. Undulation of layers in the B7 phase was confirmed by precise synchrotron studies.

Grafting of cotton with β‐cyclodextrin via poly(carboxylic acid)

AbstractCyclodextrins are cyclic oligosaccharides. Cyclodextrin molecules can form inclusion complexes with a large number of organic molecules. The properties of cyclodextrins enable them to be used in a variety of different textile applications. Cyclodextrins can act as auxiliaries in washing and dyeing processes, and they can also be fixed onto different fiber surfaces. Because of the complexing abilities of cyclodextrins, textiles with new functional properties can be prepared. Poly(carboxylic acid)s such as 1,2,3,4‐butane tetracarboxylic acid (BTCA) are well‐known non‐formaldehyde crosslinking reagents. BTCA has four carboxylic acid groups, which can react with hydroxyl groups of cellulose and form stable ester bonds. We crosslinked β‐cyclodextrin molecules on hydroxyl groups of cellulose via BTCA. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1323–1328, 2005

Hyperbranched Polymer-Drug Conjugates with High Drug Payload for Enhanced Cellular Delivery

To synthesize and evaluate hyperbranched polymer (HBP)-drug conjugates with high drug payload for enhanced cellular delivery. Polyol- and polyglycerol-ibuprofen conjugates with or without imaging agent fluorescein isothiocyanate (FITC) were synthesized using dicyclohexilcarbodiimide (DCC) as a coupling agent. Drug-polymer conjugates were characterized using 13C NMR, 1H NMR, and gel permeation chromatography (GPC). Stability of the drug-conjugates was studied using free drug release through a dialysis membrane. Cellular entry of FITC-labeled HBP conjugates was studied using fluorescence activated cell sorter (FACS), and cell supernatant was analyzed by UV-visible spectrophotometer. The intracellular localization of FITC-labeled conjugates in A549 lung epithelial cells was imaged using fluorescence microscopy. Anti-inflammatory activity of the HBP-ibuprofen conjugates was estimated in vitro by measuring the concentration of prostaglandin (PGE2) using an ELISA kit. The average number of ibuprofen molecules conjugated per molecule of HBP was estimated to be 50 for polyol and 53 for polyglycerol. The HBP-drug conjugates did not release the drug up to 72 h in methanol, indicating the presence of stable ester bonds. Both the polymer-drug conjugates entered the cells rapidly. The conjugates were localized in the cell cytosol as evidenced by fluorescence microscopy. Within 30 min, the HBP-drug conjugates showed rapid suppression of PGE2 synthesis, whereas free ibuprofen did not show any activity. At later times, the conjugates showed comparable activity. For the first time, we report HBP conjugates with a high drug payload. HBP-drug conjugates entered the cells rapidly and produced the desired pharmacological action. This study demonstrates that hyperbranched polyol and polyglycerol are promising nanovehicles for achieving enhanced cellular delivery of drugs.

A specific enzyme hydrolyzing 6- O(4- O)-indole-3-ylacetyl- β- d-glucose in immature kernels of Zea mays

The purification of 6-O(4-O)-indole-3-ylacetyl-beta-D-glucose (IAGlc) hydrolase from immature kernels of maize (Zea mays) was undertaken to separate this enzyme from 1-O-IAGlc hydrolase and beta-glucosidase. Partially purified 6-O(4-O)-IAGlc hydrolase was found to be the specific enzyme catalyzing hydrolysis of stable esters of IAA and glucose. Among a range of ester conjugates tested as substrates, only 6-O(4-O)-IAA-glucose and IBA-glucose isomers were effectively hydrolyzed. No activity against p-nitrophenyl-beta-D-glucopyranoside, a synthetic substrate for beta-glucosidase, was detected in the enzyme preparation. The enzyme is probably involved in the regulation of the IAA levels by the target release of free auxin from ester-linked conjugates, its inactive storage forms.

Banana-Shaped Mesogens Derived from 2,7-Dihydroxynaphthalene and 1,3-Dihydroxybenzene: Novel Columnar Mesophases

The synthesis and mesomorphic properties of a number of compounds belonging to different homologous series and derived from 2,7-dihydroxynaphthalene are described. In addition, several compounds derived from 1,3-dihydroxybenzene have also been synthesized for comparison. All these compounds are relatively stable esters of E-p-n-alkoxycinnamic acids and E-p-n-alkoxy-α-methylcinnamic acids which are incorporated in the arms of these bent-core compounds. Many of these compounds show interesting mesophases including a novel antiferroelectric columnar phase with a rectangular lattice. Direct transitions from a rectangular columnar B1 phase, an antiferroelectric B2 phase, and an intercalated B6 phase to a nematic phase have also been obtained. In addition, a direct transition from a novel columnar phase with an oblique lattice to a nematic phase has also been observed for the first time. The X-ray diffraction pattern of an oriented sample of the mesophase with an oblique lattice exhibited by a bent-core materia...

Poly(phosphoester) ionomers as tissue-engineering scaffolds.

Regenerative medicine requires scaffolds of divergent physicochemical properties for different tissue-engineering applications. To this end, a series of biodegradable poly(phosphoester) ionomers of the general composition [p(BHET-EOP-HOP/TC)] was synthesized, with BHET(bis-hydroxyl ethylene phosphate):EOP(ethylene phosphate):HOP(free phosphate) ratios of 60:20:20, 70:10:20, and 75:5:20, respectively. The 60/20/20 ionomer possessed the best tensile properties, exhibiting an average tensile modulus of 68 MPa and strain at break of 31%. Calcium treatment of the ionomer films led to significantly higher hardness and elastic moduli as measured by indentation. Calcium binding was evident from the increase in glass transition and melting temperatures, and a shift in the P-->O absorption in the FTIR spectrum. Stable N-hydroxysuccinimide ester (NHS) of the ionomers could be synthesized to facilitate derivatization, as demonstrated by conjugation of GRGDS in this study. The polymers conjugated with NHS were hydrolyzed in a biphasic mode, with a fast initial phase occurring in the first few hours, followed by a slower phase in the next few days. These ionomers represent a novel class of biomaterials with readily controllable physical and chemical attributes for tissue engineering.

Preparation, properties, reactions, and adenosine receptor affinities of sulfophenylxanthine nitrophenyl esters: toward the development of sulfonic acid prodrugs with peroral bioavailability.

Many currently known antagonists for P2 purinergic receptors are anionic molecules bearing one or several phenylsulfonate groups. Among the P1 (adenosine) receptor antagonists, the xanthine phenylsulfonates are a potent class of compounds. Due to their high acidity, phenylsulfonates are negatively charged at physiologic pH values and do not easily penetrate cell membranes. The present study was aimed at developing lipophilic, perorally bioavailable prodrugs of sulfonates by converting them into chemically stable nitrophenyl esters. Initial stability tests at different pH values using nitrophenyl tosylates as model compounds showed that m-nitrophenyl esters were stable over a wide pH range, while the ortho and para isomers were less stable under strongly acidic or basic conditions. A series of m- and p-nitrophenyl esters of p-sulfophenylxanthine derivatives were synthesized as model compounds. The target xanthine derivatives were obtained in high yields by condensation of the appropriate 5,6-diaminouracils with 4-(nitrophenoxysulfonyl)benzoic acids in the presence of a carbodiimide, followed by ring closure with polyphosphoric acid trimethylsilyl ester. The chemical and enzymatic stability of the m-nitrophenyl esters was investigated in vitro by means of capillary electrophoresis. High stability in aqueous solution, in artificial gastric acid, and in serum was observed. However, compound 5d, used as a prototypic xanthine m-nitrophenylsulfonate, was hydrolyzed by rat liver homogenate indicating an enzymatic pathway of hydrolysis. Thus, nitrophenyl esters of sulfonic acids have a potential as peroral prodrugs of drugs bearing a sulfonate group. The nitrophenyl esters of sulfophenylxanthines were additionally investigated for their adenosine receptor affinities. They showed high affinity at A(1), A(2A), and A(2B), but not at A(3) ARs. One of the most potent compounds was 1-propyl-8-[4-[[p-nitrophenoxy]sulfonyl]phenyl]xanthine (9d), a mixed A(1)/A(2B) antagonist (K(i)A(1) 3.6 nM, K(i)A(2B) 5.4 nM) selective versus the other subtypes. As a further result of this study, the m-nitrophenoxy group was found to be a suitable protecting group for sulfonates in organic synthesis due to its high lipophilicity and stability; it can be split off under strongly basic conditions. This new protection strategy allowed for the upscaling of the synthesis of 1-propyl-8-p-sulfophenylxanthine (PSB-1115), a selective A(2B) antagonist.

Protein immobilization on carbon nanotubes via a two-step process of diimide-activated amidation

Ferritin and bovine serum albumin (BSA) proteins are chemically bonded to nitrogen-doped multi-walled carbon nanotubes (CNx MWNTs) through a two-step process of diimide-activated amidation. First, carboxylated CNx MWNTs were activated by N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC), forming a stable active ester in the presence of N-hydroxysuccinimide (NHS). Second, the active ester was reacted with the amine groups on the proteins of ferritin or BSA, forming an amide bond between the CNx MWNTs and proteins. This two-step process avoids the intermolecular conjugation of proteins, and guarantees the uniform attachment of proteins on carbon nanotubes. TEM and AFM measurements clearly confirmed the successful attachment. This approach provides a universal and efficient method to attach biomolecules to carbon nanotubes at ambient conditions.

The effects of copper oxides on the thermal degradation of bismaleimide triazine prepreg

The effect of copper oxides on the thermal degradation of bismaleimide triazine (BT) prepreg has been studied with infrared spectroscopy (IR), attenuated total reflection infrared spectroscopy (ATR), and thermogravimetric analysis (TGA). The results of IR and ATR analyses indicate that the thermal degradation in the bulk BT is mainly from the epoxy constituent while that in the copper oxides contacted BT happens not only from the epoxy but also from the more stable cyanate ester constituent. From ATR, it is concluded that the BT contacted with copper oxides have a different degradation behaviour from the bulk BT and this surface related effect can extend to two microns deep into the BT prepreg from the BT/Cu interface. This is partly due to the composition difference in the BT/Cu interfaces resulting from the preferential adsorption on copper surfaces. The TGA results indicate that the BT contacted with the copper oxides degrade at a lower temperature than the bulk BT resin, and the presence of copper oxides would also change the degradation mechanisms of the BT resin.

Studies on synthesis of water-borne epoxy ester based on RBO fatty acids

The film formers, containing water as solvent and providing water-borne compositions, usually represent oligomers or polymers containing a significant number of ionogen and non-ionogen polar groups in their molecules. Most of the resin system do not give films with acceptable drying and gloss rather exhibit poor hydrolytic, storage stability and colour retention. Stable esters have been derived from the maleinized fatty acids that are suitable for industrial use. Water solubilization of the completely defunctionalized or the partial epoxy ester was performed via esterification of epoxy resin with maleinized fatty acids followed by hydration and neutralization.

Stable enols from Grignard addition to 1,2-diesters: serendipity rules

The temperature-dependent formation of a remarkably stable enol from the reaction of EtMgBr with a 1,2-diester was accidentally discovered. This compound was spectroscopically characterized ( 1H and 13C NMR, IR), and both methyl carbonate and trimethylsilyl ether derivatives were prepared. A mechanism for the selective formation of the stable enol ester and its corresponding keto form was suggested, and the kinetic stability of the enol was also documented. The generality of the observation of such a stable enol ester was demonstrated with the use of other Grignard reagents, and also other 1,2-diesters. The reaction of EtMgBr with a series of 1,2-amide esters also produced stable enol amides. The remarkable stability of the enol esters was attributed to the steric hindrance present in the aryl ester moiety of these compounds, and further studies will address the origin of this effect.

The Structure of the Sugar Residue in Glycated Human Serum Albumin and Its Molecular Recognition by Phenylboronate.

Quantification of the extent of glycation of human serum albumin (HSA) and of haemoglobin provides a record of average mid- and long-term blood-sugar concentrations, respectively; this is very useful for the management of diabetes. The reaction of D-glucose with propylamine affords the corresponding Schiff base, N-propylamino-D-glucoside, in the cyclic form. This compound is not stable: upon standing or treatment with acid it is converted, by an Amadori rearrangement, into N-propylfructosamine. Both amino sugars occur predominantly in the beta-pyranose form. Phenylboronate forms highly stable boronate esters through binding of the cis 1,2-diol moiety in the furanose form of N-propylfructosamine. Between pH 5 and 10, an electrostatic interaction between the protonated amino group and the negatively charged boronate moiety affords an additional stabilisation of the ester. The Schiff base, however, has no observable interaction with phenylboronate. In aqueous solution the Schiff base is in equilibrium with propylamine and glucose. Upon addition of phenylboronate, this equilibrium shifts to the side of glucose due to the formation of highly stable phenylboronate esters of the beta-furanose form of this compound. After Amadori rearrangement, the sugar moieties in glycated human serum albumin have a similar structure, they occur as an equilibrium of the beta-pyranose (59%), alpha-furanose (19%) and beta-furanose (24%) anomers. The open form was not observed. The beta-furanose anomer is selectively recognised by phenylboronate.

1,1,2,2‐Tetraphenyl‐1,2‐ethanediol: A New Protecting Group for the Synthesis of Cyclopropylboronic Esters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

3-Nitrotyrosine Butyl Ester: A Novel Derivative to Assess Tyrosine Nitration in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry Detection

A novel, sensitive, and specific method is presented for the quantification of endogenous 3-nitrotyrosine in rat plasma based on isotope dilution liquid chromatography–electrospray ionization tandem mass spectrometry, using 3-nitro-2,5,6-d3-l-tyrosine as an internal standard. The extraction and cleanup method entails three major steps: protein precipitation, solid-phase extraction with an aminopropyl cartridge, followed by derivatization of 3-nitrotyrosine to the corresponding butyl ester. The analysis of the stable butyl ester derivative circumvented matrix interferences, which were encountered on the analysis of the nonderivatized analyte in plasma, and thus significantly improved sensitivity. The mass spectral acquisition of 3-nitrotyrosine butyl ester was done in the positive ion mode using selected reaction monitoring of two specific transitions. The response was linear over the concentration range 1.4–28.5 nM, and the recoveries of spiked 3-nitrotyrosine in rat plasma exceeded 75%. The detection and quantification limits of 3-nitrotyrosine in rat plasma (165 μL equivalent injected) approached 0.43 and 1.4 nM (0.07 and 0.23 pmol, on column), respectively. This study also addresses the potential artifactual formation of 3-nitrotyrosine, which may lead to an overestimation of the background levels of the biomarker. Solid-phase extraction of 3-nitrotyrosine was required prior to esterification to avoid artifactual nitration of tyrosine. In this context, analysis of eight rat plasma samples showed quantifiable levels in only four of the samples of the order of 1.4–1.5 nM.

Siderophore production and induction of iron-regulated proteins by a microorganism from rhizosphere of barley.

This study provides new information on the Fe uptake system capable of supporting growth of the organism. Pseudomonas fluorescens isolated from the rhizosphere of barley, a gramineous plant, produced a siderophore under iron-limiting conditions. Its chemical structure was identified as pyochelin, on the basis of 1H and 13C NMR data of a stable methyl ester derivative. The same iron-limiting conditions induced a new set of outer membrane proteins (75 and 55 kDa), consistent with a siderophore-mediated iron-uptake system.

1,1,2,2-Tetraphenyl-1,2-ethanediol: A New Protecting Group for the Synthesis of Cyclopropylboronic Esters

While enantiomerically pure auxiliaries and protecting groups for boronic acids are well established, much less attention has been paid to achiral derivatives. The commercially available benzpinacol (9) proved to yield highly stable boronic esters. The new derivatives contributed to the substrate-controlled diastereo­selective synthesis of cyclopropylboronic esters 20, 22, and 25.