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  • 1.
    Bökman, C Fredrik
    et al.
    Clinical Chemistry Laboratory, Falun Central Hospital.
    Bylund, Dan
    Department of Natural Sciences, Mid Sweden University.
    Markides, Karin E
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Relating chromatographic retention and electrophoretic mobility to the ion distribution within electrosprayed droplets.2006In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 17, no 3, p. 318-24Article in journal (Refereed)
    Abstract [en]

    Ions that are observed in a mass spectrum obtained with electrospray mass spectrometry can be assumed to originate preferentially from ions that have a high distribution to the surface of the charged droplets. In this study, a relation between chromatographic retention and electrophoretic mobility to the ion distribution (derived from measured signal intensities in mass spectra and electrospray current) within electrosprayed droplets for a series of tetraalkylammonium ions, ranging from tetramethyl to tetrapentyl, is presented. Chromatographic retention in a reversed-phase system was taken as a measure of the analyte's surface activity, which was found to have a large influence on the ion distribution within electrosprayed droplets. In addition, different transport mechanisms such as electrophoretic migration and diffusion can influence the surface partitioning coefficient. The viscosity of the solvent system is affected by the methanol content and will influence both diffusion and ion mobility. However, as diffusion and ion mobility are proportional to each other, we have, in this study, chosen to focus on the ion mobility parameter. It was found that the influence of ion mobility relative to surface activity on the droplet surface partitioning of analyte ions decreases with increasing methanol content. This effect is most probably coupled to the decrease in droplet size caused by the decreased surface tension at increasing methanol content. The same observation was made upon increasing the ionic strength of the solvent system, which is also known to give rise to a decreased initial droplet size. The observed effect of ionic strength on the droplet surface partitioning of analyte ions could also be explained by the fact that at higher ionic strength, a larger number of ions are initially closer to the droplet surface and, thus, the contribution of ionic transport from the bulk liquid to the liquid/air surface interface (jet and droplet surface), attributable to migration or diffusion will decrease.

  • 2.
    Danielsson, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bäckström, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Ullsten, Sara
    Rapid multivariate analysis of LC/GC/CE data (single or multiple channel detection) without prior peak alignment2006In: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 84, no 1-2, p. 33-39Article in journal (Refereed)
    Abstract [en]

    One- or two-dimensional data obtained with LC/GC/CE and single or multiple channel detection (MS, UV/VIS) are often used as 'fingerprints' in order to characterize complex samples. The relation between samples is then explored by multivariate data analysis (PCA, hierarchical clustering), but inevitable more or less random variation in separation conditions obstructs the analysis. Several methods for peak alignment have been developed, with more or less increase of time and efforts for computations. In this work another approach is presented, based on a correlation measure less sensitive for variations in retention/migration time. The merits of the method as a fast initial data exploration tool are demonstrated for a case study of urine profiling with CE/MS.

  • 3.
    Engman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    McNaughton, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Gajewska, Malgorzata
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Kumar, Sangit
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Birmingham, Anne
    Powis, Garth
    Thioredoxin reductase and cancer cell growth inhibition by organogold(III) compounds2006In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 17, no 5, p. 539-544Article in journal (Refereed)
    Abstract [en]

    Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon-gold bonds were evaluated for their capacity to inhibit TrxR and the growth of MCF-7 cancer cells in vitro. Compounds with up to two carbon-gold bonds were often potent inhibitors of TrxR with IC50 values as low as 2 nmol/l. In the presence of Trx and insulin the inhibiting capacity was much lower. However, the inhibitory concentrations of the compounds did not correlate with the ability to kill cells. Out of the organometallics tested, only compound 8 with two carbon-gold bonds was able to inhibit colony formation by MCF-7 breast cancer cells at low micromolar concentrations (IC50=1,6umol/l). Unfortunately, the compound did not show any anti-tumor activity against MCF-7 breast cancer and HT-29 colon cancer zenografts in scid mice.

  • 4.
    Eriksson, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Synthesis of 11C-labelled Alkyl Iodides: Using Non-thermal Plasma and Palladium-mediated Carbonylation Methods2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Compounds labelled with 11C (β+, t1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects.

    The feasibility of preparing [11C]methyl iodide from [11C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [11C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [11C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact.

    Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [11C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-11C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-11C]Propyl iodide and [1-11C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-11C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [11C]carbon monoxide. [1-11C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-11C]butyl iodide with 146 GBq/mmol from 8 GBq.

    Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-11C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield N-[carbonyl-11C]benzylacrylamide. In an alternative method, [carbonyl-11C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [11C]carbon monoxide, N-[carbonyl-11C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol.

    List of papers
    1. [C-11]methyl iodide from [C-11]methane and iodine using a non-thermal plasma method
    Open this publication in new window or tab >>[C-11]methyl iodide from [C-11]methane and iodine using a non-thermal plasma method
    2006 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, no 13, p. 1177-1186Article in journal (Refereed) Published
    Abstract [en]

    A method and an apparatus for preparing [C-11]methyl iodide from [C-11]methane and iodine in a single pass through a non-thermal plasma reactor has been developed. The plasma was created by applying high voltage (400 V/31 kHz) to electrodes in a stream of helium gas at reduced pressure. The [C-11]methane used in the experiments was produced from [C-11]carbon dioxide via reduction with hydrogen over nickel. [C-11]methyl iodide was obtained with a specific radioactivity of 412 +/- 32 GBq/mu mol within 6 min from approximately 24 GBq of [C-11]carbon dioxide. The decay corrected radiochemical yield was 13 +/- 3% based on [C-11]carbon dioxide at start of synthesis. [C-11]Flumazenil was synthesized via a N-alkylation with the prepared [C-11]methyl iodide.

    Keywords
    [C-11]methyl iodide, [C-11]methane, non-thermal plasma, specific radioactivity
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-94929 (URN)10.1002/jlcr.1135 (DOI)000242796700006 ()
    Available from: 2006-10-05 Created: 2006-10-05 Last updated: 2017-12-14Bibliographically approved
    2. Synthesis of [1-11C]ethyl iodide from carbon monoxide and its application in alkylation reactions
    Open this publication in new window or tab >>Synthesis of [1-11C]ethyl iodide from carbon monoxide and its application in alkylation reactions
    2004 (English)In: Journal of Labelled Compounds and Radiopharmaceuticals, ISSN 0362-4803, Vol. 47, no 11, p. 723-731Article in journal (Refereed) Published
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-94930 (URN)
    Available from: 2006-10-05 Created: 2006-10-05 Last updated: 2015-09-24
    3. Synthesis of [1-C-11]propyl and [1-C-11]butyl iodide from [C-11]carbon monoxide and their use in alkylation reactions
    Open this publication in new window or tab >>Synthesis of [1-C-11]propyl and [1-C-11]butyl iodide from [C-11]carbon monoxide and their use in alkylation reactions
    2006 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, no 12, p. 1105-1116Article in journal (Refereed) Published
    Abstract [en]

    A method to prepare [1-C-11]propyl iodide and [1-C-11]butyl iodide from [C-11]carbon monoxide via a three step reaction sequence is presented. Palladium mediated formylation of ethene with [C-11]carbon monoxide and hydrogen gave [1-C-11]propionaldehyde and [1-C-11]propionic acid. The carbonylation products were reduced and subsequently converted to [1-C-11]propyl iodide. Labelled propyl iodide was obtained in 58 +/- 4% decay corrected radiochemical yield and with a specific radioactivity of 270 +/- 33 GBq/mu mol within 15 min from approximately 12 GBq of [C-11]carbon monoxide. The position of the label was confirmed by C-13-labelling and C-13-NMR analysis. [1-C-11]Butyl iodide was obtained correspondingly from propene and approximately 8 GBq of [C-11]carbon monoxide, in 34 +/- 2% decay corrected radiochemical yield and with a specific radioactivity of 146 +/- 20 GBq/mu mol. The alkyl iodides were used in model reactions to synthesize [O-propyl-1-C-11]propyl and [O-butyl-1-C-11]butyl benzoate. Propyl and butyl analogues of etomidate, a (beta-11-hydroxylase inhibitor, were also synthesized.

    Keywords
    [C-11]carbon monoxide, [1-C-11]propyl iodide, [1-C-11]butyl iodide, carbonylation, formylation, alkylation
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-94931 (URN)10.1002/jlcr.1119 (DOI)000242335900009 ()
    Available from: 2006-10-05 Created: 2006-10-05 Last updated: 2017-12-14Bibliographically approved
    4. Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation
    Open this publication in new window or tab >>Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation
    2007 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 3, p. 455-461Article in journal (Refereed) Published
    Abstract [en]

    Two methods are presented for the synthesis of acrylamides labelled with C-11 (beta(+), t(1/2) = 20.4 min) and C-11 in the carbonyl position. In the first method, [1-C-11]acrylic acid is synthesised from [C-11]carbon monoxide by palladium-mediated hydroxy-carbonylation of acetylene. The labelled carboxylic acid is converted into the acyl chloride and subsequently treated with amine to yield N-benzyl[carbonyl(11)C]acrylamide, The second method utilizes [C-11]carbon monoxide in a palladium-mediated carbonylative cross-coupling of vinyl halides and amines. A higher radiochemical yield is achieved with the latter method and the amount of amine needed is decreased to 1/20. The C-11-labelled acrylamides were isolated in up to 81 % decay-corrected radiochemical yield. Starting from 10 +/- 0.5GBq of [C-11]carbon monoxide, N-benzyl[carbonyl-C-11]acrylamide was obtained in 4 min with a specific radioactivity of 330 +/- 4 GBq mu mol-(1). Co-labelling with C-11 and C-13 enabled confirmation of the labelled position by C-13 NMR spectroscopy.

    Keywords
    Carbonylation, Amides, Carbon monoxide, Isotopic labelling, Carbon-11, 11C, PET
    National Category
    Chemical Sciences
    Research subject
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-98592 (URN)10.1002/ejoc.200600700 (DOI)000243600100007 ()
    Available from: 2009-02-27 Created: 2009-02-27 Last updated: 2017-12-13Bibliographically approved
    5. [1-11C]Ethyl iodide and [1-11C]propyl iodide in the synthesis of two potential NK1-receptor ligands and initial PET-imaging
    Open this publication in new window or tab >>[1-11C]Ethyl iodide and [1-11C]propyl iodide in the synthesis of two potential NK1-receptor ligands and initial PET-imaging
    Show others...
    (English)Manuscript (Other academic)
    National Category
    Medicinal Chemistry
    Identifiers
    urn:nbn:se:uu:diva-94933 (URN)
    Available from: 2006-10-05 Created: 2006-10-05 Last updated: 2018-01-13
  • 5.
    Forsgard, Niklas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Nilsson, Eva
    Andersson, Marit
    Pettersson, Jean
    Investigation of matrix effects in boron determination using organic solvents as modifiers for liquid chromatography coupled to ICP-MS2006In: Journal of Analytical Atomic Spectrometry, ISSN 0267-9477, Vol. 21, no 3, p. 305 - 310Article in journal (Refereed)
  • 6. Hedberg, Christian
    et al.
    Källström, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Brandt, Peter
    Hansen, Lars-Kristian
    Andersson, Pher
    Asymmetric Hydrogenation of Trisubstituted Olefins with Iridium-Phosphine Thiazole Complexes: A Further Investigation of the Ligand Structure2006In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 128, no 9, p. 2995-3001Article in journal (Refereed)
    Abstract
  • 7.
    Kushnir, Mark M
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Rockwood, Alan L
    Roberts, William L
    Owen, William E
    Bunker, Ashely M
    Meikle, A Wayne
    Development and performance evaluation of a tandem mass spectrometry assay for four adrenal steroids: LC-MS/MS method for adrenal steroids2006In: Clinical Chemistry, ISSN 0009-9147, Vol. 52, no 8, p. 1559–1567-Article in journal (Refereed)
  • 8.
    Kushnir, Mark M
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Rockwood, Alan L
    Roberts, William L
    Pattison, Elithabeth G
    Bunker, Ashely M
    Fitzgerald, Robert L
    Meikle, A Wayne
    Performance characteristics of a novel tandem mass spectrometry assay for analysis of testosterone in serum: Testosterone analysis by LC-MS/MS2006In: Clinical Chemistry, ISSN 0009-9147, Vol. 52, no 1, p. 120–128-Article in journal (Refereed)
  • 9.
    Källström, Klas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Catalytic Asymmetric Ketone and Alkene Reductions Using Transition Metal Complexes2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis contains seven papers dealing with iridium and ruthenium based catalytic asymmetric reductions, either of ketones into chiral alcohols, or olefins into chiral alkanes. The first part of the thesis describes how we have designed and evaluated new bicyclic ligands containing either N,S or N,N chelating atoms. The ligands have been evaluated in the asymmetric Ir-catalyzed transfer hydrogenation of acetophenone. The complexes evaluated induced good enentioselectivity of the product. Moreover we have also utilized a commercially available chiral diamine (QCD-amine) as a ligand in the Ru-catalyzed hydrogenation of prochiral ketones, with excellent enantioselectivity for some of the substrates used. As part of this work we investigated, both theoretically and experimentally, the mechanism of this hydrogenation. Based on these results we have proposed a new reaction mechanism for this type of hydrogenations which involves active participation of the solvent in the catalytic cycle. The last part of the thesis describes the design, synthesis and evaluation of N,P and N2C-carbene,N ligands for the Ir-catalyzed hydrogenation of carbon-carbon double bonds. The selectivities obtained in these investigations are among the best reported so far for a broad variation of substrates. A selectivity model for this hydrogenation has been derived and used in the rationalization of the results. As a part of this work we have synthesized and evaluated a new class of substrates, vinyl silanes, and showed that the scope of the hydrogenation reaction can be expanded to this new substrate class.

    List of papers
    1. Synthesis and evaluation of N,S-compounds as chiral ligands for transfer hydrogenation of acetophenone.
    Open this publication in new window or tab >>Synthesis and evaluation of N,S-compounds as chiral ligands for transfer hydrogenation of acetophenone.
    Show others...
    2003 In: Organic & Biomolecular Chemistry, ISSN 1477-0520, Vol. 1, no 2, p. 358-366Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94448 (URN)
    Available from: 2006-04-28 Created: 2006-04-28Bibliographically approved
    2. Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation
    Open this publication in new window or tab >>Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation
    2004 In: Tetrahedron, ISSN 0040-4020, Vol. 60, no 15, p. 3393-3403Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94449 (URN)
    Available from: 2006-04-28 Created: 2006-04-28Bibliographically approved
    3. Mechanistic Insights into the Phosphine free RuCp*-Diamine Catalyzed Hy-drogenation of Arylketones: Experimental and Theoretical Evidence for an Alcohol-Mediated Dihydrogen Activation
    Open this publication in new window or tab >>Mechanistic Insights into the Phosphine free RuCp*-Diamine Catalyzed Hy-drogenation of Arylketones: Experimental and Theoretical Evidence for an Alcohol-Mediated Dihydrogen Activation
    Show others...
    2005 In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 127, no 43, p. 15083-15090Article in journal (Refereed) Published
    Abstract
    Identifiers
    urn:nbn:se:uu:diva-94450 (URN)
    Available from: 2006-04-28 Created: 2006-04-28 Last updated: 2016-08-17Bibliographically approved
    4. Rationally Designed Ligands for Asymmetric Iridium-Catalyzed Hydrogenation of Olefins
    Open this publication in new window or tab >>Rationally Designed Ligands for Asymmetric Iridium-Catalyzed Hydrogenation of Olefins
    Show others...
    2004 In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 126, no 44, p. 14308-14309Article in journal (Refereed) Published
    Abstract
    Identifiers
    urn:nbn:se:uu:diva-94451 (URN)
    Available from: 2006-04-28 Created: 2006-04-28 Last updated: 2016-08-17Bibliographically approved
    5. Asymmetric Hydrogenation of Trisubstituted Olefins with Iridium-Phosphine Thiazole Complexes: A Further Investigation of the Ligand Structure
    Open this publication in new window or tab >>Asymmetric Hydrogenation of Trisubstituted Olefins with Iridium-Phosphine Thiazole Complexes: A Further Investigation of the Ligand Structure
    Show others...
    2006 In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 128, no 9, p. 2995-3001Article in journal (Refereed) Published
    Abstract
    Identifiers
    urn:nbn:se:uu:diva-94452 (URN)
    Available from: 2006-04-28 Created: 2006-04-28 Last updated: 2016-08-17Bibliographically approved
    6. Asymmetric Hydrogenation of Trisubstituted Olefins with Ir-NHC-Thiazole Complexes
    Open this publication in new window or tab >>Asymmetric Hydrogenation of Trisubstituted Olefins with Ir-NHC-Thiazole Complexes
    In: Advanced Synthesis & Catalysis, ISSN 1615-4150Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-94453 (URN)
    Available from: 2006-04-28 Created: 2006-04-28Bibliographically approved
    7. Ir-Catalyzed Hydrogenation of Vinyl Silanes as a Route Towards Optically Active Silanes
    Open this publication in new window or tab >>Ir-Catalyzed Hydrogenation of Vinyl Silanes as a Route Towards Optically Active Silanes
    In: Journal of Organic Chemistry, ISSN 0022-3263Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-94454 (URN)
    Available from: 2006-04-28 Created: 2006-04-28Bibliographically approved
  • 10.
    Norgren, Anna S.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Organic Chemistry.
    Conformational Stability!?: Synthesis and Conformational Studies of Unnatural Backbone Modified Peptides2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The beauty of the wide functionality of proteins and peptides in Nature is determined by their ability to adopt three-dimensional structures. This thesis describes artificial molecules developed to mimic secondary structures similar to those found crucial for biological activities.

    In the first part of this thesis, we focused on post-translational modifications of a class of unnatural oligomers known as β-peptides. Through the design and synthesis of a glycosylated β3-peptide, the first such hybrid conjugate was reported. In this first report, a rather unstable 314-helical structure was found. Subsequently, a collection of six new glycosylated β3-peptides was synthesized with the aim to optimize the helical stability in water.

    The ability of natural proteins, i.e. lectins, to recognize the carbohydrate residue on these unnatural peptide backbones was investigated through a biomolecular recognition study.

    The second part of this thesis concerns the design of conformationally homogeneous scaffolds, which could be of importance for biomedical applications. In paper V, four- and five-membered cyclic all-β3-peptides were investigated for this purpose. In a subsequent paper, a completely different strategy was employed; herein, the ability of a single β2-amino acid to restrict the conformational freedom of a cyclic α-peptide was studied.

    In the third part of this thesis, we synthesized and investigated the folding propensities of novel backbone modified oligomers, i.e. β-peptoids (N-substituted β-Ala) with α-chiral side chains.

    The collective results of these studies have established the procedures required for synthesis of glycosylated β-peptides and deepened our understanding of the factors governing folding among such oligomers. Moreover, it was established that β-amino acids can be a useful tool to increase conformational stability of cyclic peptides.

    List of papers
    1. Glycosylated Foldamers: Synthesis of Carbohydrate-modified β3hSer and Incorporation into β-Peptides
    Open this publication in new window or tab >>Glycosylated Foldamers: Synthesis of Carbohydrate-modified β3hSer and Incorporation into β-Peptides
    2007 (English)In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 13, no 11, p. 717-727Article in journal (Refereed) Published
    Abstract [en]

    Fmoc-protected β3hserine (β3hSer) was prepared and O-linked to suitably protected N-acetylgalactosamine (GalNAc) and N-acetylglucosamine (GlcNAc) derivatives. Glycosylation of β3hSer was made by two independent routes: either by direct glycosyl linkage to the β3hSer, or linkage to natural L-Ser and then utilizing the carbohydrate moiety as a protecting group in an Arndt–Eistert homologation. Both procedures gave the novel glycosylated β3-amino acids Fmoc-β3hSer(α-D-GalNAc(Ac)3)-OH (1a), its β-anomer (1b), and Fmoc-β3hSer(β-D-GlcNAc(Ac)3)-OH (2), which were utilized in the solid-phase peptide synthesis of four glycosylated dipeptides (3a–d) and two heptapeptides (4a–b). The preparation of β-amino acids bearing common post-translational modifiers represents an important step towards functionalized foldamers with broad applications in biomedical research.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-95278 (URN)10.1002/psc.832 (DOI)000252622900004 ()17890640 (PubMedID)
    Available from: 2006-12-22 Created: 2006-12-22 Last updated: 2017-12-14Bibliographically approved
    2. Functionalized foldamers: synthesis and characterization of a glycosylated β-peptide 314-helix conveying the Tn-antigen
    Open this publication in new window or tab >>Functionalized foldamers: synthesis and characterization of a glycosylated β-peptide 314-helix conveying the Tn-antigen
    2005 In: Organic & Biomolecular Chemistry, ISSN 1477-0520, Vol. 3, no 8, p. 1359-1361Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-95279 (URN)
    Available from: 2006-12-22 Created: 2006-12-22Bibliographically approved
    3. Glycosylated β3-Peptides: Relationship Between Peptide Sequence and 314-Helical Stability in Water
    Open this publication in new window or tab >>Glycosylated β3-Peptides: Relationship Between Peptide Sequence and 314-Helical Stability in Water
    Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-95280 (URN)
    Available from: 2006-12-22 Created: 2006-12-22Bibliographically approved
    4. Biomolecular Recognition of Glycosylated β3-Peptides by GalNAc Specific Lectins
    Open this publication in new window or tab >>Biomolecular Recognition of Glycosylated β3-Peptides by GalNAc Specific Lectins
    2007 (English)In: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 20, no 2, p. 132-138Article in journal (Refereed) Published
    Abstract [en]

    The molecular recognition of a novel kind of hybrid conjugates, composed of artificial biomimetic β-peptide oligomers with an O-linked natural N-acetyl-galactosamine (the Tn-antigen) residue, by four different GalNAc specific lectins was investigated using surface plasmon biosensor technology. The influence of the peptide and the glycosyl moiety on the recognition was studied using two glycosylated β3-heptapeptides, a glycosylated α-heptapeptide, two β-amino acid containing dipeptides, and monomeric αGalNAc-O-Thr. Although all four lectins displayed a decreased affinity for the carbohydrate residue when attached to a peptide, as compared to the monomeric Tn-antigen, the peptide part was found to have distinct effects on the binding kinetics - indicating that varying degrees of protein-peptide interactions occurred in the recognition process. Likewise, the lectins did not discriminate between β3-peptides and the α-peptide, but the β- linkage of the galactose had a detrimental effect for at least two of the lectins.

    Keywords
    b-peptides, glycopeptides, lectins, molecular recognition, surface plasmon resonance
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-95281 (URN)10.1002/jmr.821 (DOI)000246169000008 ()17410519 (PubMedID)
    Available from: 2006-12-22 Created: 2006-12-22 Last updated: 2017-12-14Bibliographically approved
    5. Cyclic β-tetra- and pentapeptides: Synthesis through on-resin cyclization and conformational studies by X-ray, NMR and CD spectroscopy and theoretical calculations
    Open this publication in new window or tab >>Cyclic β-tetra- and pentapeptides: Synthesis through on-resin cyclization and conformational studies by X-ray, NMR and CD spectroscopy and theoretical calculations
    Show others...
    2005 In: Chemistry--A European Journal, ISSN 0947-6539, Vol. 11, no 21, p. 6145-6158Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-95282 (URN)
    Available from: 2006-12-22 Created: 2006-12-22Bibliographically approved
    6. β2-Amino Acids in the Design of Conformationally Homogeneous cyclo-Peptide Scaffolds
    Open this publication in new window or tab >>β2-Amino Acids in the Design of Conformationally Homogeneous cyclo-Peptide Scaffolds
    Show others...
    2006 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 71, no 18, p. 6814-6821Article in journal (Refereed) Published
    Abstract [en]

    Herein, we report studies on the influence of chiral, beta(2)-amino acids in the design of conformationally homogeneous cyclic tetrapeptide scaffolds. The cyclic alpha-tetrapeptide cyclo(-Phe-D-Pro-Lys-Phe-) (1) and its four mixed analogues, having one of the alpha-Phe replaced by either an (S)-or an (R)-beta(2)hPhe residue (i.e., cyclo(-(R)-beta(2)hPhe-D-Pro-Lys-Phe) (2a), cyclo(-(S)-beta(2)hPhe-D-Pro-Lys-Phe-) (2b), cyclo(-Phe-D-Pro-Lys-(R)-beta(2)hPhe-) (3a), and cyclo(- Phe- D- Pro- Lys-( R)-, 2hPhe-) ( 3b)), were all synthesized through solidphase procedures followed by solution- phase cyclization. Initially, all five cyclo- peptides were analyzed by H-1 NMR spectroscopic studies in different solvents and at variable temperatures. Subsequently, a detailed 2D NMR spectroscopic analysis of three of the mixed peptides in water was performed, and the information thus extracted was used as restraints in a computational study on the peptides' conformational preference. An X- ray crystallographic study on the side chain- protected (Boc) 2a revealed the solid- state structure of this peptide. The results presented herein, together with previous literature data on beta(3)-amino acid residues, conclusively demonstrate the potential of beta-amino acids in the design of conformationally homogeneous cyclic peptides that are homologous to peptides with known applications in biomedicinal chemistry and as molecular receptors.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-95283 (URN)10.1021/jo060854n (DOI)000240020100013 ()16930031 (PubMedID)
    Available from: 2006-12-22 Created: 2006-12-22 Last updated: 2017-12-14Bibliographically approved
    7. Synthesis and circular dichroism spectroscopic investigations of oligomeric β-peptoids with α-chiral side chains
    Open this publication in new window or tab >>Synthesis and circular dichroism spectroscopic investigations of oligomeric β-peptoids with α-chiral side chains
    2006 (English)In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 8, no 20, p. 4533-4536Article in journal (Refereed) Published
    Abstract [en]

    Biomimetic oligomers are of large interest both as targets for combinatorial and parallel synthetic efforts and as foldamers. For example, shorter peptoid derivatives of beta-peptides, i.e., oligo-N-substituted beta-Ala, have been described as potential lead structures. Herein, we describe a solid-phase synthetic route to beta-peptoids with alpha-chiral aromatic N-substituents up to 11 residues long. Furthermore, the folding propensities of these oligomers were investigated by circular dichroism (CD) spectroscopy.

    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-95284 (URN)10.1021/ol061717f (DOI)000240654700038 ()16986943 (PubMedID)
    Available from: 2006-12-22 Created: 2006-12-22 Last updated: 2017-12-14Bibliographically approved
  • 11. Schwartz, Lennart
    et al.
    Eilers, Gerriet
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Eriksson, Lars
    Gogoll, Adolf
    Lomoth, Reiner
    Ott, Sascha
    Iron hydrogenase active site mimic holding a proton and a hydride2006In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, no 5, p. 520-522Article in journal (Refereed)
  • 12.
    Schwartz, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Eilers, Gerriet
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Eriksson, Lars
    Gogoll, Adolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
    Lomoth, Reiner
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Ott, Sascha
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Iron hydrogenase active site mimic holding a proton and a hydride2006In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 5, p. 520-522Article in journal (Refereed)
    Abstract [en]

    The first model of the iron hydrogenase active site has been prepared which concomitantly carries a proton and a hydride; the title species was characterized by IR and NMR spectroscopy and is reduced at more positive potential than any other mimic of this kind.

  • 13.
    Toom, Lauri
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Bispidine Derivatives: Synthesis and Interactions with Lewis Acids2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, the improved synthesis and investigations into the properties of some 3,7-diazabicyclo[3.3.1]nonane (bispidine) derivatives are described. These compounds are structurally related to the naturally occurring lupanine alkaloids, they are of interest because of their cardiac antiarrhythmic function as well as their use as bases or ligands in organic chemical reactions. Their chemical properties are related to the presence of a rigid molecular scaffold with two nitrogen atoms that can be utilized for binding interactions with a variety of Lewis acids.

    An improved synthesis has been developed, providing access to bispidines via bispidinones while avoiding the use of highly toxic hydrazine, which is required as reducing agent in alternative methods.

    A series of bispidine derivatives with a variety of substituents were characterized regarding their basicity, which spans thirteen orders of magnitude. Correlations between structure and basicity are discussed and computational methods have been used to propose further derivatives with even higher basicity.

    The structures of several bispidine derivatives and their protonated forms have been characterized in the solid state by X-ray crystallography and in solution using NMR spectroscopy. Structure and solution dynamics in a sterically congested (π-allyl)palladium complex with a bispidine ligand have been investigated, revealing mechanistic insight into the dynamic process. Using a bulky bispidine as a temporary ligand for a (η3-propenyl) palladium complex, the novel adamantanoid [{(η3-propenyl)Pd}63-OH)4] cluster was prepared.

    List of papers
    1. Microwave-Assisted Raney Nickel Reduction of Bispidinone Thioketals to N,N’-Dialkylbispidines
    Open this publication in new window or tab >>Microwave-Assisted Raney Nickel Reduction of Bispidinone Thioketals to N,N’-Dialkylbispidines
    2006 (English)In: Synthesis (Stuttgart), ISSN 0039-7881, E-ISSN 1437-210X, no 12, p. 2064-2068Article in journal (Refereed) Published
    Abstract [en]

    A series of N,N′-dialkyl-3,7-diazabicyclo[3.3.1]nonanes was prepared by microwave-assisted reduction of a common dithiolane precursor with Raney nickel, using the corresponding alkanol as solvent. The method avoids the use of hydrazine.

    Keywords
    Alkylations, Bicyclic Compounds, Deoxygenation, Dexulfurization, Microwave-assisted Synthesis
    National Category
    Natural Sciences Organic Chemistry
    Research subject
    Chemistry with specialization in Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-94218 (URN)10.1055/s-2006-942394 (DOI)
    Funder
    Swedish Research Council
    Available from: 2006-04-06 Created: 2006-04-06 Last updated: 2017-12-14
    2. Substituent Effects on the Basicity of 3,7-Diazabicyclo[3.3.1]nonanes
    Open this publication in new window or tab >>Substituent Effects on the Basicity of 3,7-Diazabicyclo[3.3.1]nonanes
    Show others...
    2006 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 71, no 19, p. 7155-7164Article in journal (Refereed) Published
    Abstract [en]

    Basicity constants for a series of 3,7-diazabicyclo[3.3.1] nonane derivatives in acetonitrile with a variation over 13 orders of magnitude have been determined using a spectrophotometric titration technique. An excellent correlation between basicity and calculated proton affinities obtained at PCM-B3LYP/6-31+G-(d)//B3LYP/6-31G(d) level was found. The results are discussed in terms of substituent effects and compared to N-15 NMR chemical shifts.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-94219 (URN)10.1021/jo0604991 (DOI)000240371900004 ()
    Available from: 2006-04-06 Created: 2006-04-06 Last updated: 2017-12-14Bibliographically approved
    3. Solution structure and dynamics of a sterically congested (π-allyl)palladium complex
    Open this publication in new window or tab >>Solution structure and dynamics of a sterically congested (π-allyl)palladium complex
    In: Magnetic Resonance in ChemistryArticle in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-94220 (URN)
    Available from: 2006-04-06 Created: 2006-04-06Bibliographically approved
    4. Ligand-Induced Formation of an Adamantanoid Hexanuclear (π-Allyl)PdII(μ3-Hydroxo) Cluster Stacked as Hydrogen-Bonded Double Strands
    Open this publication in new window or tab >>Ligand-Induced Formation of an Adamantanoid Hexanuclear (π-Allyl)PdII(μ3-Hydroxo) Cluster Stacked as Hydrogen-Bonded Double Strands
    2005 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 44, no 30, p. 4729-4731Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-94221 (URN)10.1002/anie.200500750 (DOI)
    Available from: 2006-04-06 Created: 2006-04-06 Last updated: 2017-12-14
  • 14. Trifonova, Anna
    et al.
    Diesen, Jarle S.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Organic Chemistry.
    Andersson, Pher G.
    Hydrogenation of Imines and Olefins Using Phosphine-Oxazoline Iridium Complexes as Catalysts2006In: Chemistry-A European Journal, Vol. 12, no 8, p. 2318-2328Article in journal (Refereed)
  • 15. Ullsten, Sara
    et al.
    Danielsson, Rolf
    Bäckström, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Sjöberg, Per
    Bergquist, Jonas
    Urine profiling using capillary electrophoresis-mass spectrometry and multivariate data analysis2006In: Urine profiling using capillary electrophoresis-mass spectrometry and multivariate data analysis, ISSN 0021-9673, Vol. 1117, no 1, p. 6-Article in journal (Refereed)
  • 16.
    Ullsten, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Danielsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bäckström, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Sjöberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Urine profiling using capillary electrophoresis-mass spectrometry and multivariate data analysis2006In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1, no 1117, p. 87-93Article in journal (Refereed)
    Abstract [en]

    This work presents the development of a general and fast method for metabolic profiling of urine, using capillary electrophoresis-electrospray ionisation mass spectrometry (CE-ESIMS) and multivariate data analysis (DA). Human urine samples collected before and after ingestion of paracetamol were analysed at acidic and basic CE conditions, using both positive and negative ESI-MS detection. Analysis of the entire resulting data set, with no prior knowledge of the target compounds, using pair-wise 'fuzzy' correlation and eigenvalue analysis enabled the samples to be discriminated between on the basis of blank urine and urine collected after drug intake. By generating two-dimensional loadings plots, it was also possible to identify the m/z values of the substances responsible for the differentiation between control and dosed samples.

  • 17.
    Ullsten, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Danielsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bäckström, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Sjöberg, Per J. R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Urine profiling using capillary electrophoresis-mass spectrometry and multivariate data analysis.2006In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1117, no 1, p. 87-93Article in journal (Refereed)
    Abstract [en]

    This work presents the development of a general and fast method for metabolic profiling of urine, using capillary electrophoresis-electrospray ionisation mass spectrometry (CE-ESIMS) and multivariate data analysis (DA). Human urine samples collected before and after ingestion of paracetamol were analysed at acidic and basic CE conditions, using both positive and negative ESI-MS detection. Analysis of the entire resulting data set, with no prior knowledge of the target compounds, using pair-wise 'fuzzy' correlation and eigenvalue analysis enabled the samples to be discriminated between on the basis of blank urine and urine collected after drug intake. By generating two-dimensional loadings plots, it was also possible to identify the m/z values of the substances responsible for the differentiation between control and dosed samples.

  • 18.
    Zettersten, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Lomoth, Reiner
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Sjöberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    The influence of the thin-layer flow cell design on the mass spectra when coupling electrochemistry to electrospray ionisation mass spectrometry2006In: Journal of Electroanalytical Chemistry, ISSN 0022-0728, E-ISSN 1873-2569, Vol. 590, no 1, p. 90-99Article in journal (Refereed)
    Abstract [en]

    The influence of the flow cell configuration on the mass spectra obtained when coupling an electrochemical thin-layer flow cell to electrospray mass spectrometry (ESI-MS) has been investigated. It is shown that interferences due to the electrochemical reaction on the counter electrode and/or the absence of 100% conversion efficiency can alter the mass spectra when conventional thin-layer flow cells are used in conjunction with ESI-MS. The effects, which affect the intensities and distribution of the peaks in the mass spectra, can result in the inability to detect products formed at the working electrode. Comparisons of mass spectra, generated after the electrochemical oxidation of a dinuclear Mn complex (where bpmp = 2,6-bis[bis(2-pyridylmethyl) amino]methyl-4-methylphenol) using two different thin-layer flow cells clearly show that the potential dependence and appearance of the mass spectra depend on the flow cell configuration used. The use of a modified thin-layer flow cell, in which the counter electrode had been separated from the working electrode, gave rise to significantly increased intensities for the oxidised MnIII,IV state of the complex. With the conventional unmodified cell, the corresponding complex was only seen for considerably higher oxidation potentials. The different results can be explained by the reduced risk of redox cycling and interferences due to species generated at the counter electrode with the modified cell. As interferences due to the counter electrode reactions likewise may be expected with many coulometric flow cells, the electrochemical cell design clearly needs to be considered when using electrochemistry coupled to ESI-MS to study electrochemical reactions.

1 - 18 of 18
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