Browsing by Subject "116 Chemical sciences"

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  • Fliri, Lukas; Partl, Gabriel; Gelbrich, Thomas; Kahlenberg, Volker; Laus, Gerhard; Schottenberger, Herwig (2017)
    The title compound, C$sb 21$H$sb 12$Br$sb 2$F$sb 13$NO$ot$2CH$sb 3$OH, was obtained by condensation of 4-methyl-1-(1it H,1it H,2it H,2it H-perfluorooctyl)pyridinium iodide and 3,5-dibromo-4-hydroxybenzaldehyde, followed by deprotonation. It crystallizes as a methanol disolvate and exhibits short O---H$ots$O hydrogen bonds and a disordered perfluoroalkyl chain [occupancy ratio 0.538(7):0.462(7)]. Significant $--$ stacking interactions are observed between the benzene and pyridine rings of neighbouring molecules along the it b-axis direction.
  • Aly, Ashraf A.; Hassan, Alaa A.; Bräse, Stefan; Ibrahim, Mahmoud A. A.; Abd Al-Latif, El-Shimaa S. M.; Spuling, Eduard; Nieger, Martin (2017)
    Bisthioureas reacted with either 2-(bis(methylthio)methylene)malononitrile or ethyl 2-cyano-3,3-bis(methylthio)acrylate to give 1,3,4-thiadiazoles and 1,3-thiazoles. Only, the reactive allyl derivative of bisthioureas reacted with the bis(methylthio)methylene compounds to give 1,3-thiazoles. The mechanism was discussed. The structures of products were proved by MS, IR, NMR and elemental analyses and X-ray structure analysis. [GRAPHICS]
  • Virjamo, Virpi; Fyhrquist, Pia; Koskinen, Akseli; Lavola, Anu; Nissinen, Katri; Julkunen-Tiitto, Riitta (2020)
    Knowledge about the defensive chemistry of coniferous trees has increased in recent years regarding a number of alkaloid compounds; in addition to phenolics and terpenes. Here, we show that Norway spruce (Picea abies (L.) H. Karst.), an important boreal zone tree species; accumulates 1,6-dehydropinidine (2-methyl-6-(2-propenyl)-1,6-piperideine) in its needles and bark. We reanalyzed previously published GC-MS data to obtain a full picture of 1,6-dehydropinidine in P. abies. 1,6-dehydropinidine appeared to especially accumulate in developing spring shoots. We used solid-phase partitioning to collect the alkaloid fraction of the sprouts and thin-layer chromatography to purify 1,6-dehydropinidine. The antibacterial properties of the 1,6-dehydropinidine fraction were tested using a broth microdilution method; with Streptococcus equi subsp. equi as a model organism. Based on our results 1,6-dehydropinidine is common in alkaloid extractions from P. abies (0.4 +/- 0.03 mg g(-1) dw in mature needles) and it is especially abundant in young spruce shoots (2.7 +/- 0.5 mg g(-1) dw). Moreover; 1,6-dehydropinidine extracted from P. abies sprouts showed mild antibacterial potential against Streptococcus equi subsp. equi (MIC 55 mu g mL(-1)). The antibacterial activity of a plant compound thought of as an intermediate rather than an end-product of biosynthesis calls for more detailed studies regarding the biological function of these coniferous alkaloids
  • McVey, Alyssa; Bartlett, Sean; Kajbaf, Mahmoud; Pellacani, Annalisa; Gatta, Viviana; Tammela, Päivi; Spring, David R.; Welch, Martin (2020)
    Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C-2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.
  • Pätsi, Henri T.; Kilpeläinen, Tommi P.; Auno, Samuli; Dillemuth, Pyry M. J.; Arja, Khaled; Lahtela-Kakkonen, Maija K.; Myöhänen, Timo T.; Wallen, Erik A. A. (2021)
    Different five-membered nitrogen-containing heteroaromatics in the position of the typical electrophilic group in prolyl oligopeptidase (PREP) inhibitors were investigated and compared to tetrazole. The 2-imidazoles were highly potent inhibitors of the proteolytic activity. The binding mode for the basic imidazole was studied by molecular docking as it was expected to differ from the acidic tetrazole. A new putative noncovalent binding mode with an interaction to His680 was found for the 2-imidazoles. Inhibition of the proteolytic activity did not correlate with the modulating effect on protein-protein-interaction-derived functions of PREP (i.e., dimerization of alpha-synuclein and autophagy). Among the highly potent PREP inhibiting 2-imidazoles, only one was also a potent modulator of PREP-catalyzed alpha-synuclein dimerization, indicating that the linker length on the opposite side of the molecule from the five-membered heteroaromatic is critical for the disconnected structure-activity relationships.
  • Batsyts, Sviatoslav; Vedmid, Roman; Namyslo, Jan C.; Nieger, Martin; Schmidt, Andreas (2019)
    1-Methylquinolinium salts substituted at the C3 position with phenyl, naphthalen-1-yl, phenanthren-9-yl, and pentaphenyl phenyl as well as aryl ethynyl substituents were prepared. The phenyl, naphthalen-1-yl, and phenanthren-9-yl substituents are in conjugation with the quinolinium ring, and the sterically crowded pentaphenyl phenyl residue causes a propeller-type molecule possessing a calculated dihedral angle between aryl substituent and the quinolinium ring of approximately 54 degrees. The different influences of the substituents including the aryl ethynyl residues on the pi-architecture is well reflected in their frontier orbital profiles, their spectroscopic properties, and in their ability to form N-heterocyclic carbenes. The latter were generated from the C3-aryl substituted quinolinium salts and trapped as sulfur and selenium adducts, whereas the aryl ethynyl substituted derivatives failed to undergo the NHC generation under the conditions applied. Se-77 NMR measurements of the corresponding selenones reveal that quinolin-2-ylidenes are electron poor carbenes with strong pi-acceptor character.
  • Bulatov, Evgeny; Lahtinen, Elmeri; Kivijärvi, Lauri; Hey-Hawkins, Evamarie; Haukka, Matti (2020)
    Selective laser sintering (SLS) 3d printing was utilized to manufacture a solid catalyst for Suzuki-Miyaura cross-coupling reactions from polypropylene as a base material and palladium nanoparticles on silica (SilicaCat Pd(0)R815-100 by SiliCycle) as the catalytically active additive. The 3d printed catalyst showed similar activity to that of the pristine powdery commercial catalyst, but with improved practical recoverability and reduced leaching of palladium into solution. Recycling of the printed catalyst led to increase of the induction period of the reactions, attributed to the pseudo-homogeneous catalysis. The reaction is initiated by oxidative addition of aryl iodide to palladium nanoparticles, resulting in formation of soluble molecular species, which then act as the homogeneous catalyst. SLS 3d printing improves handling, overall practicality and recyclability of the catalyst without altering the chemical behaviour of the active component.
  • Viidik, Laura; Seera, Dagmar; Antikainen, Osmo; Kogermann, Karin; Heinämäki, Jyrki; Laidmäe, Ivo (2019)
    Printing technologies combined with a computer-aided design (CAD) have found an increasing number of uses in pharmaceutical applications. In extrusion-based printing, the material is forced through a nozzle to form a three-dimensional (3D) structure pre-designed by CAD. The aim of this study was to evaluate the 3D-printability of biocompatible aqueous poly(ethylene oxide) (PEO) gels and to investigate the effects of three formulation parameters on the 3D printing process. The impact of PEO concentration (gel viscosity), printing head speed and printing plate temperature was investigated at three different levels using a full factorial experimental design. The aqueous PEO gels were printed with a bench-top extrusion-based 3D printing system at an ambient room temperature. The viscosity measurements confirmed that the aqueous PEO gels follow a shear-thinning behaviour suitable for extrusion-based printing. Heating the printing plate allowed the gel to dry faster resulting in more precise printing outcome. With the non-heated plate, the gel formed a dumbbell-shaped grid instead of straight lines. Higher concentration and more viscous PEO gels formed the best structured 3D-printed lattices. In conclusion, the accuracy and precision of extrusion-based 3D printing of aqueous PEO gels is highly dependent on the formulation (PEO concentration) and printing parameters (printing head speed, plate temperature). By optimizing these critical process parameters, PEO may be suitable for printing novel drug delivery systems.
  • Meister, Anne C.; Lang, Mathias; Nieger, Martin; Bräse, Stefan (2013)
  • Aly, Ashraf A.; El-Emary, Talaat; Mourad, Aboul-Fetouh E.; Alyan, Zainab Khallaf; Bräse, Stefan; Nieger, Martin (2019)
    5-Carbohydrazides and 5-carbonylazides of pyrazolo[3,4-b]pyridines are used to synthesize new heterocyclic derivatives. Some unexpected behaviors are observed in the reactions of the above two species. The structures of the obtained compounds are proved by spectroscopic studies together with elemental and X-ray structure analyses.
  • Donsbach, Carsten; Reiter, Kevin; Sundholm, Dage; Weigend, Florian; Dehnen, Stefanie (2018)
    The use of ionic liquids (C(n)C(1)Im)[BF4] with long alkyl chains (n=10,12) in the ionothermal treatment of Na-2[HgTe2] led to lamellar crystal structures with molecular macrocyclic anions [Hg8Te16](8-) (1), the heaviest known topological relative of porphyrin. [Hg8Te16](8-) differs from porphyrin by the absence of an electronic pi-system, which prevents a global aromaticity. Quantum chemical studies reveal instead small ring currents in the pyrrole-type five-membered rings that indicate weak local (sigma) aromaticity. As a result of their lamellar nature, the compounds are promising candidates for the formation of sheets containing chalcogenidometalate anions.
  • Linkens, Armand M. A.; van Best, Niels; Niessen, Petra M.; Wijckmans, Nicole E. G.; de Goei, Erica E. C.; Scheijen, Jean L. J. M.; van Dongen, Martien C. J. M.; van Gool, Christel C. J. A. W.; de Vos, Willem M.; Houben, Alfons J. H. M.; Stehouwer, Coen D. A.; Eussen, Simone J. M. P.; Penders, John; Schalkwijk, Casper G. (2022)
    Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.
  • Zhou, Qi-Hang; Qin, Wei-Wei; Finel, Moshe; He, Qing-Qing; Tu, Dong-Zhu; Wang, Chao-Ran; Ge, Guang-Bo (2021)
    Strong inhibition of the human UDP-glucuronosyltransferase enzymes (UGTs) may lead to undesirable effects, including hyperbilirubinaemia and drugiherb-drug interactions. Currently, there is no good way to examine the inhibitory effects and specificities of compounds toward all the important human UGTs, side-by-side and under identical conditions. Herein, we report a new, broad-spectrum substrate for human UGTs and its uses in screening and characterizing of UGT inhibitors. Following screening a variety of phenolic compound(s), we have found that methylophiopogonanone A (MOA) can be readily O-glucuronidated by all tested human UGTs, including the typical N-glucuronidating enzymes UGT1A4 and UGT2B10. MOA-O-glucuronidation yielded a single mono-O-glucuronide that was biosynthesized and purified for structural characterization and for constructing an LC-UV based MOA-O-glucuronidation activity assay, which was then used for investigating MOA-O-glucuronidation kinetics in recombinant human UGTs. The derived K-m values were crucial for selecting the most suitable assay conditions for assessing inhibitory potentials and specificity of test compound(s). Furthermore, the inhibitory effects and specificities of four known UGT inhibitors were reinvestigated by using MOA as the substrate for all tested UGTs. Collectively, MOA is a broad-spectrum substrate for the human UGTs, which offers a new and practical tool for assessing inhibitory effects and specificities of UGT inhibitors. (C) 2021 Elsevier B.V. All rights reserved.
  • Zhang, Rui; Eronen, Aleksi; Du, Xiangze; Ma, Enlu; Guo, Ming; Moslova, Karina; Repo, Timo (2021)
    The synthesis of new types of furan-based compounds other than 5-hydroxymethylfurfural from glucose is a very attractive yet underexploited strategy. We report here a catalytic conversion of glucose with acetylacetone (acac) to furan-centered chemicals, 2-methyl-3-acetylfuran (MAF) and 1-(5-(1,2-dihydroxyethyl)-2-methylfuran-3-yl)ethan-1-one (DMAF), which are potential building blocks for the synthesis of fine chemicals. The experimentally supported reaction mechanism is cascade-type, including glycolaldehyde (GA) formation by H2MoO4-catalysed retro-aldol condensation (C2 + C4) of glucose and immediate capture of transient C2 and C4 intermediates by acac to yield MAF and DMAF. To the best of our knowledge, this is the first report on the straightforward synthesis of MAF and DMAF from glucose, providing a new but generic synthesis strategy for GA-based C2 and erythrose-based C4 chemistry in biorefining.
  • Zhou, Kecheng; Dichlberger, Andrea; Martinez-Seara, Hector; Nyholm, Thomas K. M.; Li, Shiqian; Kim, Young Ah; Vattulainen, Ilpo; Ikonen, Elina; Blom, Tomas (2018)
    Membrane proteins are functionally regulated by the composition of the surrounding lipid bilayer. The late endosomal compartment is a central site for the generation of ceramide, a bioactive sphingolipid, which regulates responses to cell stress. The molecular interactions between ceramide and late endosomal transmembrane proteins are unknown. Here, we uncover in atomistic detail the ceramide interaction of Lysosome Associated Protein Transmembrane 4B (LAPTM4B), implicated in ceramide-dependent cell death and autophagy, and its functional relevance in lysosomal nutrient signaling. The ceramide-mediated regulation of LAPTM4B depends on a sphingolipid interaction motif and an adjacent aspartate residue in the protein's third transmembrane (TM3) helix. The interaction motif provides the preferred contact points for ceramide while the neighboring membrane-embedded acidic residue confers flexibility that is subject to ceramide-induced conformational changes, reducing TM3 bending. This facilitates the interaction between LAPTM4B and the amino acid transporter heavy chain 4F2hc, thereby controlling mTORC signaling. These findings provide mechanistic insights into how transmembrane proteins sense and respond to ceramide.
  • Huittinen, Nina; Virtanen, Sinikka; Rossberg, Andre; Eibl, Manuel; Lönnrot, Satu; Polly, Robert (2022)
    Adsorption reactions on mineral surfaces are influenced by the overall concentration of the adsorbing metal cation. Different site types (strong vs. weak ones) are often included to describe the complexation reactions in the various concentration regimes. More specifically, strong sites are presumed to retain metal ions at low sorbate concentrations, while weak sites contribute to metal ion retention when the sorbate concentration increases. The involvement of different sites in the sorption reaction may, thereby, also be influenced by competing cations, which increase the overall metal ion concentration in the system. To date, very little is known about the complex structures and metal ion speciation in these hypothetical strong- and weak-site regimes, especially in competing scenarios. In the present study, we have investigated the uptake of the actinide americium on corundum (alpha-Al2O3) in the absence and presence of yttrium as competing metal by combining extended X-ray absorption fine structure spectroscopy (EXAFS) with density functional theory (DFT) calculations. Isotherm studies using the radioactive Eu-152 tracer were used to identify the sorption regimes where strong sites and weak sites contribute to the sorption reaction. The overall americium concentration, as well as the presence of yttrium could be seen to influence both the amount of americium uptake by corundum, but also the speciation at the surface. More specifically, increasing the Am3+ or Y3+ concentrations from the strong site to the weak site concentration regimes in the mineral suspensions resulted in a decrease in the overall Am-O coordination number from nine to eight, with a subsequent shortening of the average Am-O bond length. DFT calculations suggest a reduction of the surface coordination with increasing metal-ion loading, postulating the formation of tetradentate and tridentate Am3+ complexes at low and high surface coverages, respectively.
  • Sanwald, Corinna; Robciuc, Alexandra; Ruokonen, Suvi-Katriina; Wiedmer, Susanne K.; Lammerhofer, Michael (2019)
    This work presents the development and validation of a quantitative HILIC UHPLC-ESI-QTOF-MS/MS method for amino acids combined with untargeted metabolic profiling of human corneal epithelial (HCE) cells after treatment with ionic liquids. The work included a preliminary metabotoxicity screening of 14 different ionic liquids, of which 9 carefully selected ionic liquids were chosen for a metabolomics study. This study is focused on the correlation between the toxicity of the ionic liquids and their metabolic profiles. The method development included the comparison of different MS/MS acquisition modes. A sequential window acquisition of all theoretical fragment ion mass spectra (SWATH) method with variable Q1 window widths and narrow Q1 target windows of 5 Da for most of the amino acids was selected as the optimal acquisition mode. Due to the absence of a true blank matrix, C-13,N-15-isotopically labelled amino acids were utilized as surrogate calibrants, instead of proteinogenic amino acids. Partial least squares (PLS) analysis of the median effective concentrations (EC50) of 9 selected ionic liquids showed a correlation with their metabolic profile measured by the untargeted screening.
  • Gomez Millan, Gerardo; Hellsten, Sanna; King, Alistair W. T.; Pokki, Juha-Pekka; Llorca, Jordi; Sixta, Herbert (2019)
    Furfural (FUR) was produced from xylose using a biphasic batch reaction system. Water-immiscible organic solvents such as isophorone, 2-methyltetrahydrofuran (2-MTHF) and cyclopentyl methyl ether (CPME) were used to promptly extract FUR from the aqueous phase in order to avoid the degradation to humins as largely as possible. The effect of time, temperature, organic solvent and organic-to-aqueous ratio on xylose conversion and FUR yield were investigated in auto-catalyzed conditions. Experiments at three temperatures (170, 190 and 210 degrees C) were carried out in a stirred microwave-assisted batch reactor, which established the optimal conditions for achieving the highest FUR yield. The maximum FUR yields from xylose were 78 mol% when using CPME, 48 mol% using isophorone and 71 mol% in the case of 2-MTHF at an aqueous to organic phase ratio of 1:1 (v/v). Birch hydrolysate was also used to show the high furfural yield that can be obtained in the biphasic system under optimized conditions. The present study suggests that CPME can be used as a green and efficient extraction solvent for the conversion of xylose into furfural without salt addition. (C) 2019 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
  • Oswald, R.; Ermel, M.; Hens, K.; Novelli, A.; Ouwersloot, H. G.; Paasonen, Pauli; Petäjä, Tuukka; Sipilä, Mikko; Keronen, Petri; Bäck, Jaana; Konigstedt, R.; Beygi, Z. Hosaynali; Fischer, H.; Bohn, B.; Kubistin, D.; Harder, H.; Martinez, M.; Williams, J.; Hoffmann, T.; Trebs, I.; Soergel, M. (2015)
  • Hassan, Alaa A.; Mohamed, Nasr K.; El-Shaieb, Kamal M. A.; Tawfeek, Hendawy N.; Bräse, Stefan; Nieger, Martin (2019)
    2-Substituted hydrazinecarbothioamides and N ,2-disubstituted hydrazinecarbothioamides react in high yield with dimethyl acetylenedicarboxylate (DMAD) to give 4-oxo-Z-(thiazolidin-5-ylidene) acetate derivatives. Several mechanistic options involving interaction are presented. The structures of thiazolidin-4-ones have been unambiguously confirmed by single crystal X-ray crystallography. (C) 2014 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.