Abstract    Novel arene-ruthenium [2+2] metalla-rectangles 4 and 5 have been synthesized by self-assembly using dipyridyl amide ligand 3 and arene-ruthenium acceptors (arene: benzoquinone (1), naphthacenedione (2)) and characterized by NMR spectroscopy and ESI-MS. The solid-state structure of 5 was determined by X-ray diffraction and shows encapsulated diethyl ether molecule in the rectangular cavity of 5. The luminescent 5 was further used for anion sensing with the amidic linkage serving as a hydrogen-bond donor site for anions and the ruthenium moiety serving as a signaling unit. A UV/Vis titration study demonstrated that although 5 interacts very weakly with common monoanions as well as with flexible dicarboxylate anions such as malonate and succinate, it displays significant binding affinity (K>103 in MeOH) for rigid multi-carboxylate anions such as oxalate, citrate, and tartrate, exhibiting a 1:1 stoichiometry. It has been suggested that 1:1 bidentate hydrogen bonding assisted by appropriate geometrical complementarity is mainly responsible for the increased affinity of 5 towards such anions. A fluorescence titration study revealed a large fluorescence enhancement of 5 upon binding to multi-carboxylate anions, which can be attributed to the blocking of the photoinduced electron-transfer process from the arene-Ru moiety to the amidic donor in 5 as a result of hydrogen bonding between the donor and the anion.

Abstract  Enantioselective Pd-catalyzed allylic substitution of ()-()-1,3-diphenyl-3-acetoxyprop-1-ene with dimethyl malonate was studied in 3-butyl-1-methylimidazolium hexafluorophosphate ([bmim][PF]) as an ionic liquid. The reactions were catalyzed by Pd() complexes of three homochiral ferrocenylphosphine ligands, (,)-iPr-Phosferrox, (,)-iPr-Phosferrox, (,)-BCyPFA and ()-BINAP. Potassium carbonate and bis(trimethylsilyl)acetamide (BSA)/AcOK were tested as the bases and simple optimization of the reaction procedure was performed. Experiments with other soft nucleophiles also were carried out under optimized conditions.

Abstract  Enantioselective allylic substitution reactions of ()-()-1,3-diphenyl-3-acetoxyprop-1-ene with dimethyl malonate (DMM) are studied in 1-butyl-3-methylimidazolinium hexafluorophosphate ([bmim][PF]) as an ionic solvent; the reactions are catalyzed by Pd complexes of two homochiral ferrocenylphosphine ligands, ()-BPPFA and ()-BPPFDEA with the recycling of the catalytic system being tested. A similar reaction with 1-phenyl-3-acetoxyprop-1-ene is also studied with only a linear achiral product being isolated.

Abstract  Reactions of alpha-ketols with diethyl malonate at the molar ratio 2:1 in the presence of K(2)CO(3) were investigated. The heterospiranes obtained contained a dihydrofuran and a gamma-lactone rings. The optimum conditions for the synthesis of heterospiranes were found by varying the ratio of the initial compounds: alpha-ketoalcohol (or 2-ethoxycarbonyl-, 2-methoxycarbonyl-, 2-cyano-3,4,4-trimethyl-2-buten-4-olides), diethyl malonate, K(2)CO(3), by varying the environment, and also the temperature and the time of the reaction.

Abstract  LiClO4 is used as catalyst for direct Mannich-type reaction of aryl aldehydes, aryl amines, and diethyl malonic ester under solvent-free conditions. This three-component reaction afforded the corresponding-amino esters in good yields with simple and environmentally benign procedure.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Retention index monitoring using thermal desorption gas chromatographic analysis was developed as a method for the verification of compounds of chemical defense interest in environmental matrices. Gas chromatography retention indices were determined by loading solid adsorbent packed sampling tubes initially with the target compounds and subsequently with a series of n-alkaline probes. The resulting chromatographic performance and gas chromatography retention indices were shown to be independent of the tube loading method. A database of gas chromatography retention indices for chemical warfare agents and simulants was compiled and, in conjunction with simultaneous flame ionizatin and flame photometric detection, applied to the identification of triethyl phosphate, tributyl phosphate and diethyl malonate in water and soil samples.

Abstract  Adenosylcobalamin-dependent methylmalonyl-CoA mutase catalyzes the interconversion of methylmalonyl-CoA and succinyl-CoA. In humans, deficiencies in the mutase lead to methylmalonic aciduria, a rare disease that is fatal in the first year of life. Such inherited deficiencies can result from mutations in the mutase structural gene or from mutations that impair the acquisition of cobalamins. Recently, a human gene of unknown function, MMAA, has been implicated in methylmalonic aciduria. MMAA orthologs are widespread in bacteria, archaea, and eukaryotes. In Methylobacterium extorquens AM1, a mutant defective in the MMAA homolog meaB was unable to grow on C sub(1) and C sub(2) compounds because of the inability to convert methylmalonyl-CoA to succinyl-CoA. Here we demonstrate that this defect is not due to the absence of adenosylcobalamin but due to an inactive form of methylmalonyl-CoA mutase. The presence of active mutase in double mutants defective in MeaB and in the synthesis of either R-methylmalonyl-CoA or adenosylcobalamin indicates that MeaB is necessary for protection of mutase from inactivation during catalysis. MeaB and methylmalonyl-CoA mutase from M. extorquens were cloned and purified in their active forms. We demonstrated that MeaB forms a complex with methylmalonyl-CoA mutase and stimulates in vitro mutase activity. These results support the hypothesis that MeaB functions to protect methylmalonyl-CoA mutase from irreversible inactivation.

Abstract  The recovery of propionic acid from aqueous solutions such as fermentation broth and wastewater is an important problem where liquid extraction is the favorite process. Liquid-liquid equilibrium (LLE) data were investigated for mixtures of water+propionic acid+diethyl carbonate or diethyl malonate or diethyl fumarate at 298.15K. The solubility curves and the tie-line end compositions of liquid phases at equilibrium were determined experimentally, and the tie-line results compared with the data correlated by means of UNIQUAC model. The phase diagrams for the ternary mixtures including both the experimental and correlated tie-lines are presented. The reliability of the experimental tie-lines was confirmed by using Othmer-Tobias correlation. The distribution coefficients and the separation factors for the immiscibility region are calculated. In order to boost the distribution of propionic acid between aqueous and organic phases, the distribution was investigated by using organic solutions composed of amine {tributylamine (TBA)} and phosphorus containing compounds {trioctylphosphine oxide (TOPO) or tributyl phosphate (TBP)} dissolved in diethyl carbonate, diethyl malonate and diethyl fumarate, in the concentration range of about 0.06-1.00mol/l. It was observed that the used solvents may serve individually as adequate agents to extract propionic acid from its dilute aqueous solution; however, the extraction performance can be improved by using phosphorus containing compounds or amines, mostly by using tributylamine dissolved in diethylmalonate.

Abstract  The skin is a portal of entry and the largest organ of the body. It has been shown to contain the major enzymes found in other tissues of the body. Topically applied compounds may be metabolized in skin resulting in altered pharmacologic or toxicologic activity. The metabolism of benzo[a]pyrene applied to mouse skin floating in an organ culture demonstrated the potential importance of metabolism of chemicals during percutaneous absorption. A flow-through diffusion cell was subsequently developed to aid in quantitating skin absorption and metabolism. Viability of skin in the diffusion cell, which was assessed by light microscopy, was found to be maintained for at least 17 h. The viability of pig skin was maintained in flow-through cells by using tissue culture media; skin-mediated hydrolysis of diethyl malonate was observed. The suitability of these conditions to maintain skin viability was assessed in initial studies by the ability to graft the skin to nude mice.

Abstract  A piscicide screening program was conducted with 1,888 different chemicals mostly at concentrations of 10 ppm. The times at which fish lost their equilibrium and died are given for 2,552 separate 24-hour assays. The species tested were the northern squawfish (Ptychocheilus oregonensis), chinook salmon (Oncorhynchus tshawytscha), coho salmon (Oncorhynchus kisutch), and steelhead (Salmo gairdneri).

Abstract  A mild protocol for the asymmetric Michael addition of dimethyl malonate to various α,β-unsaturated carbonyl compounds was developed. The salient feature of this methodology is that a cheap and environmentally friendly Lewis acid, CaCl2, was used as a catalyst. An aminoindanol- and pyridine-derived ligand provided in the presence of CaCl2 Michael adducts in moderate to high enantioselectivities. The scope of the reaction was demonstrated.

Abstract  1. Caspases, key enzymes in the apoptosis pathway, have been detected in the brain of HD patients and in animal models of the disease. In the present study, we investigated the neuroprotective properties of a new, reversible, caspase-3-specific inhibitor, M826 (3-([(2S)-2-[5-tert-butyl-3-[[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]amino]-2-oxopyrazin-1(2H)-yl]butanoyl]amino)-5-[hexyl(methyl)amino]-4-oxopentanoic acid), in a rat malonate model of HD. 2. Pharmacokinetic and autoradiography studies after intrastriatal (i.str.) injection of 1.5 nmol of M826 or its tritiated analogue [(3)H]M826 indicated that the compound diffused within the entire striatum. The elimination half-life (T(1/2)) of M826 in the rat striatum was 3 h. 3. I.str. injection of 1.5 nmol of M826 10 min after malonate infusion induced a significant reduction (66%) in the number of neurones expressing active caspase-3 in the ipsilateral striatum. 4. Inhibition of active caspase-3 translated into a significant but moderate reduction (39%) of the lesion volume, and of cell death (24%), 24 h after injury. The efficacy of M826 at inhibiting cell death was comparable to that of the noncompetitive NMDA receptor antagonist MK801. 5. These data provide in vivo proof-of-concept of the neuroprotective effects of reversible caspase-3 inhibitors in a model of malonate-induced striatal injury in the adult rat.

Abstract  NADP(+)-dependent serine dehydrogenase [EC 1.1.1.-], which catalyzes the oxidation of the hydroxyl group of serine to form 2-aminomalonate semialdehyde, was purified to homogeneity from a crude extract of Agrobacterium tumefaciens ICR 1600. The enzyme had a molecular mass of about 100 kDa and consisted of four identical subunits. In addition to L-serine, D-serine, L-glycerate, D-glycerate, and 2-methyl-DL-serine were substrates. However, O-methyl-DL-serine and L-threonine were inert. The enzyme showed maximal activity at about pH 9 for the oxidation of L-serine. The enzyme required NADP+ as a coenzyme, NAD+ was inert. The enzyme was not inhibited by EDTA, o-phenanthroline, or alpha,alpha'-dipyridyl, but was inhibited by HgCl2, p-chloromercuribenzoate, L-cysteine, D-cysteine, malonate, 2-methylmalonate, and tartronate. The Michaelis constants for L-serine, D-serine, and NADP+ were 42, 44, and 0.029 mM, respectively.

Abstract  A bacterium in the genus Halomonas that grew on dimethylsulfoniopropionate (DMSP) or acrylate as sole carbon sources and that liberated the climate-changing gas dimethyl sulfide in media containing DMSP was obtained from the phylloplane of the macroalga Ulva. We identified a cluster that contains genes specifically involved in DMSP catabolism (dddD, dddT) or in degrading acrylate (acuN, acuK) or that are required to break down both substrates (dddC, dddA). Using NMR and HPLC analyses to trace 13C- or 14C-labelled acrylate and DMSP in strains of Escherichia coli with various combinations of cloned ddd and/or acu genes, we deduced that DMSP is imported by the BCCT-type transporter DddT, then converted by DddD to 3-OH-propionate (3HP), liberating dimethyl sulfide in the process. As DddD is a predicted acyl CoA transferase, there may be an earlier, unidentified catabolite of DMSP. Acrylate is also converted to 3HP, via a CoA transferase (AcuN) and a hydratase (AcuK). The 3HP is predicted to be catabolized by an alcohol dehydrogenase, DddA, to malonate semialdehyde, thence by an aldehyde dehydrogenase, DddC, to acyl CoA plus CO2. The regulation of the ddd and acu genes is unusual, as a catabolite, 3HP, was a co-inducer of their transcription. This first description of genes involved in acrylate catabolism in any organism shows that the relationship between the catabolic pathways of acrylate and DMSP differs from that which had been suggested in other bacteria.

Abstract  The measurement of matrix metalloproteinase (MMP) activity in diseases like inflammation, oncogenesis, or atherosclerosis in vivo is highly desirable. Fine-tuned pyrimidine-2,4,6-triones (barbiturates) offer nonpeptidyl lead structures for developing imaging agents for specifically visualization of activated MMPs in vivo. The aim of this study was to modify a C-5-disubstituted barbiturate and thus design a highly affine, nonpeptidic, optical MMP inhibitor (MMPI)-ligand for imaging of activated MMPs in vivo. A convergent 10 step synthesis was developed, starting with a malonic ester and (4-bromophenoxy)benzene to generate 5-bromo-pyrimidine-2,4,6-trione as the key intermediate. To minimize the interactions between activated MMPs and the dye of the conjugate 6, a PEGylated piperazine derivative was used as a spacer and an azide as a protected amino function. After linking both building blocks, reducing the azide ( Staudinger reaction) and labeling with Cy 5.5, we obtained the nonhydroxamate MMP inhibitor 6 with high affinity (IC 50-value: 48 nM for MMP-2) measured in a fluorogenic assay using commercially available MMP-substrates and the purified enzyme. Zymography revealed an efficient blocking of enzyme activity of purified MMP-2 and MMP-9 and of MMP-containing cell supernatants (HT-1080), (A-673) using the PEGylated barbiturate 5. Fluorescence microscopy studies using a highly (A-673) and a moderate (HT-1080) MMP-2 secreting cell line showed efficient binding of the Cy 5.5 labeled tracer 6 to the MMP-2 positive cells while MMP-2 negative cells (MCF-7) did not bind. Therefore, this new barbiturate-based MMP-probe has a high affinity and specificity toward MMP-2 and -9 and is thus a promising candidate for sensitive MMP detection in vivo.

Abstract  The PICs formed from 1,2-dichlorobenzene identified in this study resulted from three types of mechanisms. Chlorination by chlorine free radicals was the major reaction forming PICs. The second source of PICs was from fragmentation of the aromatic ring and recombination reactions and the third source of PICs was from disproportionation reactions. A scheme summarizing the various reactions is detailed.

Abstract  Palladium(II)-exchanged hydroxyapatite (PdHAP: for example, PdHAP-B has a Pd/Ca ratio = ca 1/200) was prepared by ion-exchanging with Ca(2+) from calcined hydroxyapatite and Pd(NO(3))(2) in water at 70 degrees C for 24 h. The ion-exchange was revealed by inductively coupled plasma analysis; Pd(2+) was almost absent in any filtrate that included over 1.6 equimolar amounts of Ca(2+) relative to the amount of Pd(2+) consumed. The PdHAP (1 mol% Pd) functioned as a catalyst for the allylic alkylation of allyl methyl carbonate with active methylene compounds such as diethyl malonate, 2-ethoxycarbonylcyclopentanone, 2-ethoxycarbonylcyclohexanone, and 2,2-dimethy1-1,3-dioxane-4,6-dione at 50 degrees C in water under air. Over 97% of the PdHAP was recovered by centrifugation followed by decantation, and the material could be reused. The catalytic activity of PdHAP accompanied by satisfactory yields of monoallylated products was maintained in ten repetitive uses for the allylic alkylation of allyl methyl carbonate with diethyl malonate at 50 degrees C for 24h in water under air. From the standpoints of yield and handling, using water as a solvent was superior to using an organic medium such as ethanol. THF or DMF. Thus, this heterogeneous PdHAP-catalyzed allylic alkylation will be one of the environmentally-benign organic syntheses. (C) 2010 Elsevier B.V. All rights reserved.

Abstract  Decontamination of chemical agents from the skin uses both dry and wet decontamination processes. Recent studies have shown that wet decontamination frequently results in stratum corneum hydration. To evaluate the hydration effect of wet decontamination on the skin barrier function and hence on the decontamination efficiency, a series of comparative studies were carried out on human skin contaminated with the nerve agent simulant diethylmalonate, using decontamination media having different salinity and surfactants. The results showed that, compared to non-decontaminated skin, remnant diethylmalonate on decontaminated skin penetrated at an accelerated rate in the immediate 2 h following decontamination. This transient enhancement effect, ranging from 20 to 98%, was depended on the nature of the decontamination media used and was more obvious in skin samples that were decontaminated 1 h postexposure. All decontamination media exhibited this effect, with the greatest enhancement observed in the following order: anionic surfactant > cationic surfactant > non-ionic surfactant > deionized water > 0.9% saline > 9% saline.

Abstract  For the exploration of pharmacophoric moiety of malloapelta B (1) possessing the inhibitory activity of NF-kappaB activation, structural variation of alpha,beta-unsaturated carbonyl motif was attempted. 1 was reduced by catalytic hydrogenation, sodium borohydride, and lithium aluminumhydride. Catalytic hydrogenation with 30 psi or 15 psi of H2 gas of 1 generated 8-butyl-5,7-dimethoxy-2,2-dimethylchroman (2) and 1-(5,7-dimethoxy-2,2-dimethylchroman-8-yl)butan-1-one (3), respectively. Reduction with sodium borohydride occurred at the double bond of alpha,beta-unsaturated ketone of 1 to give 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)butan-1-one (4). Reduction of 1 with lithium aluminumhydride and then quenched with methanol and water produced unexpected products, 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)-3-methoxy-1-butene (5) and 1-(5,7-dimethoxy-2,2-dimethyl-2H-chromen-8-yl)-3-hydroxy-l-butene (6). These are formed from the isomerization of initial product 9 through the continuous conjugate carbocation intermediate 11. Addition of ethylmagnesium bromide and dimethyl malonate anion to 1 gave the conjugate adducts 7 and 8. Ethylmagesium bromide and sodium borohydride reduction unusually gave the conjugate addition due to steric congestion around carbonyl group of 1. Compound 2 exhibits the reduced inhibitory activity against NF-kappaB activation and the others do not show the activity. Therefore alpha,beta-unsaturated carbonyl group of 1 should be important for its inhibitory activity.

Abstract  Retention factors on a minimum of eight stationary phases at various temperatures by gas-liquid chromatography and in acetonitrile-water and methanol-water mobile phases by reversed-phase liquid chromatography on a Synergi Polar-RP column were combined with further values taken from the literature and liquid-liquid partition coefficients for up to eight totally organic biphasic systems to estimate descriptors for 24 esters (phthalate, oleate, stearate, arbietate, adipate, succinate, sebacate, and diethylmalonate) widely used as plasticizers and solvents in industry. The descriptors facilitated the estimation of several properties of environmental interest (octanol-water, air-octanol, and air-water partition coefficients, and soil-water distribution coefficients, vapor pressure, and water solubility). The descriptors are suitable for use in the solvation parameter model and facilitate the estimation of a wide range of physicochemical, chromatographic, biological, and environmental properties using existing models.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM PYRUVATE MALONATE LACTATE ACETATE PROPIONATE BUTYRATE METHYLMALONATE VALERATE ISOVALERATE SUCCINATE FORMATE FUMARATE ISOBUTYRATE GROUND WATER POLLUTION

Abstract  A new highly efficient three-component reaction of alkyl acrylate, aldehyde and dialkyl malonate using ethyl diphenylphosphine as organocatalyst has been described. Various highly functional compounds bearing hydroxyl groups and the ester functions can be easily prepared in moderate to good yields according to our one-step procedure. The reactions are believed to proceed via Morita-Baylis-Hillman reactions of alkyl acrylate and aldehydes, followed by the Michael addition reactions of dialkyl malonates. Our reactions indicated that the intermediate species formed in the phosphine-catalyzed MBH reaction are an effective organic base to catalyze the Michael addition reactions of dialkyl malonates to the preformed MBH adducts.