Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations
Al-Subeihi, A.A. ; Alhusainy, W. ; Kiwamoto, R. ; Spenkelink, A. ; Bladeren, P.J. van; Rietjens, I.M.C.M. ; Punt, A. - \ 2015
Toxicology and Applied Pharmacology 283 (2015)2. - ISSN 0041-008X - p. 117 - 126.
human liver-microsomes - in-vitro data - alkenylbenzene methyleugenol - methyl eugenol - rat - glucuronidation - estragole - detoxification - derivatives - metabolism
The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1'-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1'-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1'-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1'-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1'-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1'-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment.
Polymer organogelation with chitin and chitin nanocrystals
Nikiforidis, C.V. ; Scholten, E. - \ 2015
RSC Advances : An international journal to further the chemical sciences 5 (2015)47. - ISSN 2046-2069 - p. 37789 - 37799.
mechanical characterization - supramolecular gels - lecithin organogel - molecular-weight - edible oils - chitosan - derivatives - morphology - chemistry - mixtures
In this paper, we show that biodegradable and biocompatible organogels can be formed with chitin as the filler material and triglycerides as the continuous hydrophobic phase. When crude chitin was used, a large degree of aggregation was observed that prevented the formation of stable organogels. Two approaches were used to diminish this degree of aggregation and increase the stability. Either surfactants were used to increase the dispersability of the crude chitin, or the crude chitin was transformed into smaller rod-like nanocrystals by acid hydrolysis. Both approaches led to the formation of stable organogels with storage moduli up to 106 Pa for high chitin concentrations (20 wt%). Three different types of surfactants were used, namely phosphatidylcholine, enzymatically modified phosphatidylcholine and sorbitan monostearate (Span 60). The choice of surfactant has a large influence on the gel strength and the temperature sensitivity of the gels. With chitin nanocrystals, in the presence of surfactants, larger gel strengths were observed for lower concentrations (1-10 wt%), indicating more efficient packing of the particles. Gels were stable even after addition of considerable amounts of water up to 25 wt%. The increase in gel strength in the presence of water (storage modulus) was most likely an effect of the water absorption ability of chitin that increased the effective volume fraction of the fillers.
Gac-mediated changes in pyrroloquinoline quinone biosynthesis enhance the antimicrobial activity of Pseudomonas fluorescens SBW25
Cheng, X. ; Voort, M. van der; Raaijmakers, J.M. - \ 2015
Environmental Microbiology Reports 7 (2015)1. - ISSN 1758-2229 - p. 139 - 147.
biological-control - systemic resistance - biocontrol bacteria - root-colonization - gluconic acid - brassicacearum - arabidopsis - derivatives - induction - pathogens
In Pseudomonas species, production of secondary metabolites and exoenzymes is regulated by the GacS/GacA two-component regulatory system. In P. fluorescens SBW25, mutations in the Gac-system cause major transcriptional changes and abolished production of the lipopeptide viscosin and of an exoprotease. In contrast to many other Pseudomonas species and strains, inactivation of the Gac-system in strain SBW25 significantly enhanced its antimicrobial activities against oomycete, fungal and bacterial pathogens. Here, random plasposon mutagenesis of the gacS mutant led to the identification of seven mutants with reduced or loss of antimicrobial activity. In four mutants, the plasposon insertion was located in genes of the pyrroloquinoline quinone (PQQ) biosynthesis pathway. Genetic complementation, ectopic expression, activity bioassays and RP-HPLC analyses revealed that a gacS mutation in SBW25 leads to enhanced expression of pqq genes, resulting in an increase in gluconic and 2-ketogluconic acid production, which in turn acidified the extracellular medium to levels that inhibit growth of other microorganisms. We also showed that PQQ-mediated acidification comes with a growth penalty for the gacS mutant in the stationary phase. In conclusion, PQQ-mediated acidification compensates for the loss of several antimicrobial traits in P. fluorescens SBW25 and may help gac mutants to withstand competitors.
Isohexide hydroxy esters: synthesis and application of a new class of biobased AB-type building blocks
Thiyagarajan, S. ; Wu, J. ; Knoop, J.R.I. ; Haveren, J. van; Lutz, M. ; Es, D.S. van - \ 2014
RSC Advances : An international journal to further the chemical sciences 4 (2014)89. - ISSN 2046-2069 - p. 47937 - 47950.
isosorbide - polyesters - derivatives - acid
Here we present the synthesis of a new family of sugar derived 1,4: 3,6-dianhydrohexitol based AB-type monomers, containing one methyl ester group and a secondary hydroxyl group in all four possible stereo isomers (RR, RS, SR, SS). Structural characterization of the monomers (5a-d) was established by 1D and 2D NMR analysis, which was further confirmed by single-crystal X-ray structure determination. The application of these monomers in step-growth polymerization afforded fully isohexide based stereo-regular polyesters. Homo polyesters based on the RR and RS monomers were obtained with reasonable molecular weights by melt polymerization (Mn 2400 and 2500 resp.). These materials showed unexpectedly low glass-transition temperatures of 20 degrees C and 15 degrees C respectively. In contrast, the monomers with SR and SS configuration yielded only low molecular weight oligomers. Surprisingly, copolymerization of the RR and SR monomers gave a polyester with higher molecular weight (Mn 4100) and a high T-g of 80 degrees C. These preliminary results show that isohexide hydroxyesters are an intriguing new class of biobased building blocks with many potential applications.
Hydrothermal Deoxygenation of Triglycerides over Pd/C aided by In Situ Hydrogen Production from Glycerol Reforming
Hollak, S.A.W. ; Jong, K.P. de; Es, D.S. van; Ariëns, M.A. - \ 2014
ChemSusChem 7 (2014)4. - ISSN 1864-5631 - p. 1057 - 1062.
catalytic deoxygenation - fatty-acids - supercritical water - reaction pathways - oil - carbon - hydrodeoxygenation - hydrocarbons - derivatives - selectivity
A one-pot catalytic hydrolysis–deoxygenation reaction for the conversion of unsaturated triglycerides and free fatty acids to linear paraffins and olefins is reported. The hydrothermal deoxygenation reactions are performed in hot compressed water at 250¿°C over a Pd/C catalyst in the absence of external H2. We show that aqueous–phase reforming (APR) of glycerol and subsequent water–gas-shift reaction result in the in situ formation of H2. While this has a significant positive effect on the deoxygenation activity, the product selectivity towards high-value, long-chain olefins remains high.
Regio- and stereoselective synthesis of (+)-6-ketoeuryfuran, (+)-6-ketowinterin, and (-)-7-ketoeuryfuran from accessible labdane diterpenoids (+)-larixol and (-)-sclareol
Vlad, P.E. ; Ciocarlan, A. ; Edu, C. ; Aricu, A. ; Biriiac, A. ; Coltsa, M. ; Ambrosio, M. D'; Deleanu, C. ; Nicolescu, A. ; Shova, S. ; Vornicu, N. ; Groot, Æ. de - \ 2013
Tetrahedron 69 (2013)2. - ISSN 0040-4020 - p. 918 - 926.
drimane-related sesquiterpenes - ring transfer-reaction - efficient synthesis - singlet oxygen - (+/-)-euryfuran - derivatives - euryfuran - sponge - (&/-)-isodrimenin - photooxygenation
Starting from (+)-larixol and (-)-sclareol, new syntheses of (+)-6-ketoeuryfuran, (+)-6-ketowinterin, and (-)-7-ketoeuryfuran have been elaborated in high yields. (+)-6-Ketowinterin was synthesized for the first time. Both euryfurans are excellent starting materials for the synthesis of important polyfunctional biologically active drimanic compounds. (C) 2012 Elsevier Ltd. All rights reserved.
Matrix-derived combination effect and risk assessment for estragole from basil-containing plant food supplements (PFS)
Berg, S.J.P.L. van den; Klaus, V. ; Alhusainy, W. ; Rietjens, I. - \ 2013
Food and Chemical Toxicology 62 (2013). - ISSN 0278-6915 - p. 32 - 40.
in-vivo - trans-anethole - rat - 1'-hydroxyestragole - derivatives - mouse - bioactivation - constituents - metabolism - safrole
Basil-containing plant food supplements (PFS) can contain estragole which can be metabolised into a genotoxic and carcinogenic 1'-sulfoxymetabolite. This study describes the inhibition of sulfotransferase (SULT)-mediated bioactivation of estragole by compounds present in basil-containing PFS. Results reveal that PFS consisting of powdered basil material contain other compounds with considerable in vitro SULT-inhibiting activity, whereas the presence of such compounds in PFS consisting of basil essential oil was limited. The inhibitor in powdered basil PFS was identified as nevadensin. Physiologically based kinetic (PBK) modeling was performed to elucidate if the observed inhibitory effects can occur in vivo. Subsequently, risk assessment was performed using the Margin of Exposure (MOE) approach. Results suggest that the consequences of the in vivo matrix-derived combination effect are significant when estragole would be tested in rodent bioassays with nevadensin at ratios detected in PFS, thereby increasing MOE values. However, matrix-derived combination effects may be limited at lower dose levels, indicating that the importance of matrix-derived combination effects for risk assessment of individual compounds should be done on a case-by-case basis considering dose-dependent effects. Furthermore, this study illustrates how PBK modeling can be used in risk assessment of PFS, contributing to further reduction in the use of experimental animals. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Nanomolar cholera toxin inhibitors based on symmetrical pentavalent ganglioside GM1os-sym-corannulenes
Mattarella, M. ; Garcia-Hartjes, J. ; Wennekes, T. ; Zuilhof, H. ; Siegel, J.S. - \ 2013
Organic & Biomolecular Chemistry 11 (2013)26. - ISSN 1477-0520 - p. 4333 - 4339.
heat-labile enterotoxin - receptor-binding - multivalent ligands - gm1 mimics - design - corannulene - derivatives - dendrimers - subunit
Eight symmetric and pentavalent corannulene derivatives were functionalized with galactose and the ganglioside GM1-oligosaccharide (GM1os) via copper-catalyzed alkyne-azide cycloaddition (CuAAC) reactions. The compounds were evaluated for their ability to inhibit the binding of the pentavalent cholera toxin to its natural ligand, ganglioside GM1. In this assay, all ganglioside GM1os-sym-corannulenes proved to be highly potent nanomolar inhibitors of cholera toxin.
Synthesis of Isoidide through Epimerization of Isosorbide using Ruthenium on Carbon
Notre, J.E.L. le; Haveren, J. van; Es, D.S. van - \ 2013
ChemSusChem 6 (2013)4. - ISSN 1864-5631 - p. 693 - 700.
dynamic kinetic resolution - chiral building-blocks - renewable resources - biodegradable polymers - secondary alcohols - catalytic isomerization - coating applications - succinic acid - polyesters - derivatives
A highly efficient procedure for obtaining resin-grade isoidide through catalytic epimerization of isosorbide using a ruthenium-on-carbon (Ru/C) catalyst is reported. A comprehensive reaction-parameter variation study involving substrate concentration, catalyst (type of metal, support, and loading), initial pH value, hydrogen pressure, solvent, and reaction temperature demonstrates that superior performance and high selectivity can be achieved. Epimerization of isosorbide in water (pH 8) at 220¿°C, under 40 bar of hydrogen, and using a Ru/C catalyst (5¿% Ru) for 2 h results in a thermodynamic equilibrium mixture containing 55¿% isoidide, 40¿% isosorbide, and 5¿% isomannide. In comparison with previously reported nickel-based catalysts, the Ru/C catalyst is advantageous because it is highly active (as low as 360 ppm Ru) and recyclable. High purity isoidide is obtained by high-vacuum distillation of an equilibrium mixture on a 200 g scale. The high substrate loading (50 wt¿% in water), high selectivity, and the possibility for substrate reuse makes this procedure highly atom efficient and therefore, highly attractive for industrial use
High molecular weight poly(ethylene-2,5-furanoate); critical aspects in synthesis and mechanical property determination
Knoop, J.R.I. ; Vogelzang, W. ; Haveren, J. van; Es, D.S. van - \ 2013
Journal of Polymer Science. Part A, Polymer Chemistry 51 (2013)19. - ISSN 0887-624X - p. 4191 - 4199.
semi-crystalline poly(ethylene-terephthalate) - equilibrium melting temperature - chiral building-blocks - renewable resources - aromatic polyesters - furan - behavior - polymerization - derivatives - morphology
Furan-2,5-dicarboxylic acid (FDCA) is a widely advocated renewable substitute for terephthalic acid (TA). Preparation of high molecular weight FDCA based polyesters by an industrially common combination of melt polymerization and subsequent solid state post condensation is described. Ultimately, poly(ethylene 2,5-furanoate) (PEF) with absolute Mn = 83,000 g mol-1 is obtained, determined by triple detection Size Exclusion Chromatography. The bulk polymer properties of FDCA based polyesters, necessary to evaluate their industrial potential were determined the Young's modulus of PEF is determined to be 2450 ± 220 MPa and the maximum stress 35 ± 8 MPa. The influence of crystallinity on the mechanical properties as function of temperature was determined by dynamic mechanical thermal analysis. A detailed differential scanning calorimetry study on the crystallization behavior of high molecular weight PEF allowed to calculate the equilibrium melting temperature (Tm0) of 239.3 and 239.7 °C for the first and second melting peak, respectively
Antioxidant potential of hydrolyzed polyphenolic extracts from tara (Caesalpinia spinosa) pods
Chambi, F. ; Chirinos, R. ; Pedreschi Plasencia, R.P. ; et al., - \ 2013
Industrial Crops and Products 47 (2013). - ISSN 0926-6690 - p. 168 - 175.
tropaeolum-tuberosum ruiz - betula-pubescens - tannic-acid - leaves - capacity - gallotannins - derivatives - sinensis - solvent - ability
The antioxidant potential of tara pod extracts rich in gallotannins submitted to chemical hydrolysis was evaluated. The increase in the release of gallic acid from the tara pod extracts during the hydrolysis process reached a maximum ratio of free gallic acid/total phenolics of 94.1% at 20 h, at this point, 100% hydrolysis degree (HD) was obtained. After 4 h of hydrolysis (38.8% of HD) the highest antioxidant capacity was obtained reaching values of 25.9, 23.8 and 8.8 µmol trolox equivalent/mg gallic acid equivalent measured by ABTS, FRAP and ORAC methods. Lipophilicity diminished from 0.8 to 0.3 (log P value). In addition, the antioxidant efficacy of 100 ppm total phenolics of hydrolyzates at 9 h (93.7% of HD) and 20 h showed to be significantly more efficient than a similar concentration of the synthetic antioxidant TBHQ to retard soybean oil oxidation. These results indicate that 4 and 9 h of chemical hydrolysis of tara pod extracts under the tested conditions are sufficient to obtain a product with good antioxidant properties to be used as an alternative source of antioxidants.
Quantitative Fate of Chlorogenic Acid during Enzymatic Browning of Potato Juice
Narvaez Cuenca, C.E. ; Vincken, J.P. ; Gruppen, H. - \ 2013
Journal of Agricultural and Food Chemistry 61 (2013)7. - ISSN 0021-8561 - p. 1563 - 1572.
performance liquid-chromatography - trap mass-spectrometry - oxidation-products - apple juice - covalent interactions - caffeoylquinic acid - proteins - tuber - derivatives
The quantitative fate of chlorogenic acid (ChA) during enzymatic browning of potato juice was investigated. Potato juice was prepared in water without the use of any antibrowning agent (OX treatment). As a control, a potato juice was prepared in the presence of NaHSO3 (S control). To study the composition of phenolic compounds in potato in their native states, also a potato extract was made with 50% (v/v) methanol containing 0.5% (v/v) acetic acid (MeOH control). Water-soluble low molecular weight fractions (LMWFs) and high molecular weight fractions (HMWFs) from S and OX extracts were obtained by ultrafiltration and dialysis, respectively. Pellets obtained after the OX treatment and the S and MeOH controls were also analyzed for ChA content. Whereas in the S-LMWF all ChA was converted to sulfonic acid adducts, no free ChA was found in the OX-LMWF, indicating its high reactivity upon enzymatic browning. Analysis of protein in the HMWFs showed a higher content of “reacted” ChA in OX (49.8 ± 7.1 mg ChA/100 g potato DW) than in S (14.4 ± 1.5 mg ChA/100 g potato DW), as evidenced by quinic acid release upon alkaline hydrolysis. The presence of quinic acid in S-HMWF was unexpected, but a mass balance incorporating the ChA content of LMWF, HMWF, and pellet for the three extractions suggested that ChA might have been attached to polymeric material, soluble in the aqueous environment of S but not in that of MeOH. Size exclusion chromatography, combined with proteolysis, revealed that ChA reacted with patatin and protease inhibitors to produce brown soluble complexes.
Phosphorescence Imaging of Living Cells with Amino Acid-Functionalized Tris(2-phenylpyridine)iridium(III) Complexes
Steunenberg, P. ; Ruggi, A. ; Berg, N.S. van den; Buckle, T. ; Kuil, J. ; Leeuwen, F.W.B. van; Velders, A.H. - \ 2012
Inorganic Chemistry 51 (2012)4. - ISSN 0020-1669 - p. 2105 - 2114.
cyclometalated iridium complexes - light-emitting-diodes - golgi-apparatus - energy-transfer - emission - ligand - microscopy - ir(iii) - accumulation - derivatives
A series of nine luminescent cyclometalated octahedral iridium(III) tris(2-phenylpyridine) complexes has been synthesized, functionalized with three different amino acids (glycine, alanine, and lysine), on one, two, or all three of the phenylpyridine ligands. All starting complexes and final compounds have been fully analyzed by one-dimensional (ID) and two-dimensional (2D) NMR spectroscopy, and photophysical data have been obtained for all the mono-, bis-, and tri- substituted iridium(III) complexes. Cellular uptake and localization have been studied with flow cytometry and confocal microscopy, respectively. Confocal experiments demonstrate that all nine substituted iridium(III) complexes show variable uptake in the tumor cells. The monosubstituted iridium(III) complexes give the highest cellular uptake, and the series substituted with lysines shows the highest toxicity. This systematic study of amino acid-functionalized Ir(ppy)(3) complexes provides guidelines for further functionalization and possible implementation of luminescent iridium complexes, for example, in (automated) peptide synthesis or biomarker specific targeting.
Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat
Al-Subeihi, A.A. ; Spenkelink, A. ; Punt, A. ; Boersma, M.G. ; Bladeren, P.J. van; Rietjens, I. - \ 2012
Toxicology and Applied Pharmacology 260 (2012)3. - ISSN 0041-008X - p. 271 - 284.
human liver-microsomes - estragole bioactivation - fischer-344 rat - methyl eugenol - dna-adducts - allylbenzene - genotoxicity - derivatives - metabolism - safrole
This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1'-hydroxymethyleugenol glucuronide (1'HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1'-oxomethyleugenol (1'OME) compared with male rat liver is observed. Furthermore, formation of 1'-sulfooxymethyleugenol (1'HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1'-hydroxymethyleugenol (1'HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1'-sulfooxymethyleugenol (1'HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1'-sulfooxymethyleugenol (1'HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD10) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation.
The oxidative esterification of glycerol to methyl glycerate in methanol using gold on oxidic supports: an insight in product selectivity
Pazhavelikkakath Purushothaman, R.K. ; Haveren, J. van; Es, D.S. van; Heeres, H.J. - \ 2012
Green Chemistry 14 (2012). - ISSN 1463-9262 - p. 2031 - 2037.
aqueous-phase oxidation - bimetallic catalysts - commodity chemicals - carbon-monoxide - au catalysts - lactic-acid - derivatives - adsorption - conversion - kinetics
Gold nanoparticles on different oxidic supports (TiO2, Al2O3 and ZnO) have been studied for the oxidation of glycerol in methanol, using molecular oxygen as the oxidizing agent in a batch set-up. The main oxidation products are methyl glycerate and dimethyl mesoxalate in over 95% selectivity at high glycerol conversion, indicating that C–C bond scission occurs at a significantly lower extent compared to glycerol oxidations in water. The product selectivity is a function of the support. Highest selectivity (82% at 72% conversion) to methyl glycerate is observed in the case of Au/TiO2 as the catalyst. The use of a base is not essential for the glycerol oxidation reaction to occur, although for TiO2 and Al2O3 higher initial activities are found in the presence of sodium methoxide. Au/ZnO gives comparable activity and selectivity both in the presence and absence of a base. Oxidation experiments with reaction intermediates indicate that oxidation of methyl glycerate to higher oxygenates does not occur to a significant extent in methanol. An alternative pathway for the formation of dimethyl mesoxalate involving dihydroxyacetone is proposed.
Separation of L-aspartic acid and L-glutamic acid mixtures for use in the production of bio-based chemicals
Teng, Y. ; Scott, E.L. ; Sanders, J.P.M. - \ 2012
Journal of Chemical Technology and Biotechnology 87 (2012)10. - ISSN 0268-2575 - p. 1458 - 1465.
nitrogen-containing chemicals - amino-acids - biobased production - derivatives - hydrolysis - proteins - kinetics
BACKGROUND: Amino acids are promising feedstocks for the chemical industry due to their chemical functionality. They can be obtained by the hydrolysis of potentially inexpensive protein streams such as the byproduct of biofuel production. However, individual amino acids are required before they can be used for the further production of chemicals. Here, the separation of L-aspartic acid (Asp) and L-glutamic acid (Glu) mixture, which can be isolated from protein hydrolysis solutions at low pH or from electrodialysis of complex amino acid mixtures, was studied. RESULTS: Glu was converted into L-pyroglutamic acid (pGlu) which can be separated from the mixture of Asp and Glu due to its higher solubility in water. The conversion was carried out under aqueous or melt conditions. Under aqueous conditions, the conversion was studied as a factor of time, temperature and the amount of Glu. The conversion was specific with high yield and not effected by Asp. After pGlu was separated from Asp and residual Glu by solubility difference, it can be transferred back to Glu through hydrolysis. CONCLUSION: The conversion of Glu to pGlu is specific and can be applied to separation Asp and Glu for their use in the production of bio-based chemicals
Renewable Rigid Diamines: Efficient, Stereospecific Synthesis of High Purity Isohexide Diamines
Thiyagarajan, S. ; Gootjes, L. ; Vogelzang, W. ; Haveren, J. van; Lutz, M. ; Es, D.S. van - \ 2011
ChemSusChem 4 (2011)12. - ISSN 1864-5631 - p. 1823 - 1829.
chiral building-blocks - polyesters - polycondensation - derivatives - polyamides - resources
We report an efficient three-step strategy for synthesizing rigid, chiral isohexide diamines derived from 1,4:3,6-dianhydrohexitols. These biobased chiral building blocks are presently the subject of several investigations (in our and several other groups) because of their application in high-performance biobased polymers, such as polyamides and polyurethanes. Among the three possible stereo-isomers, dideoxy-diamino isoidide and dideoxy-diamino isosorbide can be synthesized from isomannide and isosorbide respectively in high yield with absolute stereo control. Furthermore, by using this methodology dideoxy-amino isomannide—a tricyclic adduct—was obtained starting from isoidide in high yield. Our improved synthetic route is a valuable advance towards meeting scale and purity demands for evaluating the properties of new biobased performance materials, which will benefit the development of these plastics.
Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria.
Fiamegos, Y.C. ; Kastritis, P.L. ; Exarchou, V. ; Han, H. ; Bonvin, A.M. ; Vervoort, J.J.M. ; Lewis, K. ; Hamblin, M.R. ; Tegos, G.P. - \ 2011
PLoS ONE 6 (2011)4. - ISSN 1932-6203 - 12 p.
staphylococcus-aureus - multidrug-resistance - antibiotic-activity - chlorogenic acids - nora - transporter - derivatives - berberine - analogs - protein
Background Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purification and structural determination of compounds from plant sources have yielded a number of pump inhibitors which acted against gram positive bacteria. Methodology/Principal Findings In this study we report the identification and characterization of 4',5'-O-dicaffeoylquinic acid (4',5'-ODCQA) from Artemisia absinthium as a pump inhibitor with a potential of targeting efflux systems in a wide panel of Gram-positive human pathogenic bacteria. Separation and identification of phenolic compounds (chlorogenic acid, 3',5'-ODCQA, 4',5'-ODCQA) was based on hyphenated chromatographic techniques such as liquid chromatography with post column solid-phase extraction coupled with nuclear magnetic resonance spectroscopy and mass spectroscopy. Microbial susceptibility testing and potentiation of well know pump substrates revealed at least two active compounds; chlorogenic acid with weak antimicrobial activity and 4',5'-ODCQA with pump inhibitory activity whereas 3',5'-ODCQA was ineffective. These intitial findings were further validated with checkerboard, berberine accumulation efflux assays using efflux-related phenotypes and clinical isolates as well as molecular modeling methodology. Conclusions/Significance These techniques facilitated the direct analysis of the active components from plant extracts, as well as dramatically reduced the time needed to analyze the compounds, without the need for prior isolation. The calculated energetics of the docking poses supported the biological information for the inhibitory capabilities of 4',5'-ODCQA and furthermore contributed evidence that CQAs show a preferential binding to Major Facilitator Super family efflux systems, a key multidrug resistance determinant in gram-positive bacteria.
Biobased industrial chemicals from glutamic acid
Lammens, T.M. - \ 2011
Wageningen University. Promotor(en): Johan Sanders, co-promotor(en): Maurice Franssen; Elinor Scott. - [S.l.] : S.n. - ISBN 9789461730237
glutaminezuur - derivaten - chemicaliën uit biologische grondstoffen - synthese - biobased economy - glutamic acid - derivatives - biobased chemicals - synthesis - biobased economy
In dit onderzoek is op zoek gegaan naar routes om van glutaminezuur vier producten te maken die van waarde zijn voor de industrie, die nu uit olie gemaakt worden. Dat zijn grondstoffen voor allerlei soorten kunststof, zoals nylon en rubbers. Het onderzoek laat zien dat alle vier die producten inderdaad gemaakt kunnen worden uit glutaminezuur. Vervolgens is niet alleen gekeken naar de manier waarop dat zou kunnen, maar ook naar de praktische uitvoerbaarheid, de economische haalbaarheid en de impact op het milieu. Daarbij bleek dat er voor twee van de vier producten nog verbeteringen nodig zijn om te kunnen concurreren met de productie uit olie, maar dat de andere twee industrieel haalbaar kunnen zijn. Productie daarvan uit glutaminezuur vermindert onze afhankelijkheid van fossiele brandstoffen en is beter voor het milieu.
S-arylation of mercaptobenzimidazoles using Cu(I) catalysts-experimental and theoretical observations
Sekar, R. ; Srinivasan, M. ; Marcelis, A.T.M. ; Sambandam, A. - \ 2011
Tetrahedron Letters 52 (2011)26. - ISSN 0040-4039 - p. 3347 - 3352.
aryl halides - nucleophilic-substitution - coupling reactions - bond formation - thiols - efficient - derivatives - inhibitors - iodides - density
Substituted 2-mercaptobenzimidazoles (MBI) are an important class of bio-active and industrially important organic compounds. In this Letter, a new synthetic method is presented for the selective S-arylation of MBI with substituted aryl iodides using low cost copper (I) iodide and 1,10-phenanthroline as a catalytic system. The selective formation of S-arylated product was confirmed by several spectroscopic techniques and the vibrational spectrum was found to be in very good agreement with the theoretical spectrum calculated by density functional theory