Change search
Refine search result
1234567 101 - 150 of 4437
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 101.
    Andersson, C. David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hillgren, J. Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Chemistry and Molecular Biology - Medicinal Chemistry, University of Gothenburg.
    Lindgren, Cecilia
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Qian, Weixing
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Laboratories for Chemical Biology Umeå, Umeå University.
    Akfur, Christine
    Berg, Lotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ekström, Fredrik
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Benefits of statistical molecular design, covariance analysis, and reference models in QSAR: a case study on acetylcholinesterase2015In: Journal of Computer-Aided Molecular Design, ISSN 0920-654X, E-ISSN 1573-4951, Vol. 29, no 3, p. 199-215Article in journal (Refereed)
    Abstract [en]

    Scientific disciplines such as medicinal- and environmental chemistry, pharmacology, and toxicology deal with the questions related to the effects small organic compounds exhort on biological targets and the compounds' physicochemical properties responsible for these effects. A common strategy in this endeavor is to establish structure-activity relationships (SARs). The aim of this work was to illustrate benefits of performing a statistical molecular design (SMD) and proper statistical analysis of the molecules' properties before SAR and quantitative structure-activity relationship (QSAR) analysis. Our SMD followed by synthesis yielded a set of inhibitors of the enzyme acetylcholinesterase (AChE) that had very few inherent dependencies between the substructures in the molecules. If such dependencies exist, they cause severe errors in SAR interpretation and predictions by QSAR-models, and leave a set of molecules less suitable for future decision-making. In our study, SAR- and QSAR models could show which molecular sub-structures and physicochemical features that were advantageous for the AChE inhibition. Finally, the QSAR model was used for the prediction of the inhibition of AChE by an external prediction set of molecules. The accuracy of these predictions was asserted by statistical significance tests and by comparisons to simple but relevant reference models.

  • 102.
    Andersson, C David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Karlberg, Tobias
    Ekblad, Torun
    Lindgren, Anders E G
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thorsell, Ann-Gerd
    Spjut, Sara
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Uciechowska, Urszula
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Niemiec, Moritz S
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wittung-Stafshede, Pernilla
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Weigelt, Johan
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Schüler, Herwig
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening2012In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, no 17, p. 7706-7718Article in journal (Refereed)
    Abstract [en]

    The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.

  • 103.
    Andersson, C. David
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Martinez, Nicolas
    Zeller, Dominik
    Allgardsson, Anders
    Koza, Michael M.
    Frick, Bernhard
    Ekström, Fredrik
    Peters, Judith
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Influence of Enantiomeric Inhibitors on the Dynamics of Acetylcholinesterase Measured by Elastic Incoherent Neutron Scattering2018In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, no 36, p. 8516-8525Article in journal (Refereed)
    Abstract [en]

    The enzyme acetylcholinesterase (AChE) is essential in humans and animals because it catalyzes the breakdown of the nerve-signaling substance acetylcholine. Small molecules that inhibit the function of AChE are important for their use as drugs in the, for example, symptomatic treatment of Alzheimer's disease. New and improved inhibitors are warranted, mainly because of severe side effects of current drugs. In the present study, we have investigated if and how two enantiomeric inhibitors of AChE influence the overall dynamics of noncovalent complexes, using elastic incoherent neutron scattering. A fruitful combination of univariate models, including a newly developed non-Gaussian model for atomic fluctuations, and multivariate methods (principal component analysis and discriminant analysis) was crucial to analyze the fine details of the data. The study revealed a small but clear increase in the dynamics of the inhibited enzyme compared to that of the noninhibited enzyme and contributed to the fundamental knowledge of the mechanisms of AChE-inhibitor binding valuable for the future development of inhibitors.

  • 104.
    Andersson, David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate design of molecular docking experiments: An investigation of protein-ligand interactions2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    To be able to make informed descicions regarding the research of new drug molecules (ligands), it is crucial to have access to information regarding the chemical interaction between the drug and its biological target (protein). Computer-based methods have a given role in drug research today and, by using methods such as molecular docking, it is possible to investigate the way in which ligands and proteins interact. Despite the acceleration in computer power experienced in the last decades many problems persist in modelling these complicated interactions. The main objective of this thesis was to investigate and improve molecular modelling methods aimed to estimate protein-ligand binding. In order to do so, we have utilised chemometric tools, e.g. design of experiments (DoE) and principal component analysis (PCA), in the field of molecular modelling. More specifically, molecular docking was investigated as a tool for reproduction of ligand poses in protein 3D structures and for virtual screening. Adjustable parameters in two docking software were varied using DoE and parameter settings were identified which lead to improved results. In an additional study, we explored the nature of ligand-binding cavities in proteins since they are important factors in protein-ligand interactions, especially in the prediction of the function of newly found proteins. We developed a strategy, comprising a new set of descriptors and PCA, to map proteins based on their cavity physicochemical properties. Finally, we applied our developed strategies to design a set of glycopeptides which were used to study autoimmune arthritis. A combination of docking and statistical molecular design, synthesis and biological evaluation led to new binders for two different class II MHC proteins and recognition by a panel of T-cell hybridomas. New and interesting SAR conclusions could be drawn and the results will serve as a basis for selection of peptides to include in in vivo studies.

  • 105.
    Andersson, David C.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chen, Brian Y.
    Howard Hughes Institute, Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Columbia University..
    Linusson Jonsson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Design of target-tailored virtual screening experimentsManuscript (preprint) (Other academic)
    Abstract [en]

    Discovering molecules with a desired biological function is one of the great challenges in drug research. To discover new lead molecules, in silico virtual screens (VS) are often conducted, in which databases of molecules are screened for potential binders to a specific protein, using molecular docking. The choice of docking software and parameter settings within the software can significantly influence the outcome of a VS. In this study, we have applied chemometric methods such as DoE, principal component analysis (PCA) and partial least-square projections to latent structure (PLS) to simulated VS experiments to find and compare suitable conditions for performing VS against six protein targets selected from the DUD databases. The docking parameters in FRED, and scoring functions in both FRED and GOLD docking software, were varied according to a statistical experimental design and a PLS model was calculated to correlate the experimental setup to the VS outcome. The study revealed that the choice of scoring function has the greatest influence on VS outcome, and that other parameters have varying influence, depending on the protein target. We also found that substantial bias can be introduced by the lack of variation of molecule properties in the databases used in the screening. The results indicate that docking experiments should be tailored to the protein target in order to obtain satisfactory VS results and that our methodology provides a suitable approach for such tailoring.

  • 106.
    Andersson, David C.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chen, Brian Y
    Linusson Jonsson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mapping of ligand-binding cavities in proteins2010In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 78, no 6, p. 1408-1422Article in journal (Refereed)
    Abstract [en]

    The complex interactions between proteins and small organic molecules (ligands) are intensively studied because they play key roles in biological processes and drug activities. Here, we present a novel approach to characterize and map the ligand-binding cavities of proteins without direct geometric comparison of structures, based on Principal Component Analysis of cavity properties (related mainly to size, polarity, and charge). This approach can provide valuable information on the similarities and dissimilarities, of binding cavities due to mutations, between-species differences and flexibility upon ligand-binding. The presented results show that information on ligand-binding cavity variations can complement information on protein similarity obtained from sequence comparisons. The predictive aspect of the method is exemplified by successful predictions of serine proteases that were not included in the model construction. The presented strategy to compare ligand-binding cavities of related and unrelated proteins has many potential applications within protein and medicinal chemistry, for example in the characterization and mapping of "orphan structures", selection of protein structures for docking studies in structure-based design, and identification of proteins for selectivity screens in drug design programs.

  • 107.
    Andersson, David C.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Martinez, N.
    Zeller, D.
    Rondahl, S. H.
    Koza, M. M.
    Frick, B.
    Ekstrom, F.
    Peters, J.
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Changes in dynamics of alpha-chymotrypsin due to covalent inhibitors investigated by elastic incoherent neutron scattering2017In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, no 37, p. 25369-25379Article in journal (Refereed)
    Abstract [en]

    An essential role of enzymes is to catalyze various chemical reactions in the human body and inhibition of the enzymatic activity by small molecules is the mechanism of action of many drugs or tool compounds used to study biological processes. Here, we investigate the effect on the dynamics of the serine protease alpha-chymotrypsin when in complex with two different covalently bound inhibitors using elastic incoherent neutron scattering. The results show that the inhibited enzyme displays enhanced dynamics compared to the free form. The difference was prominent at higher temperatures (240-310 K) and the type of motions that differ include both small amplitude motions, such as hydrogen atom rotations around a methyl group, and large amplitude motions, such as amino acid side chain movements. The measurements were analyzed with multivariate methods in addition to the standard univariate methods, allowing for a more in-depth analysis of the types of motions that differ between the two forms. The binding strength of an inhibitor is linked to the changes in dynamics occurring during the inhibitor-enzyme binding event and thus these results may aid in the deconvolution of this fundamental event and in the design of new inhibitors.

  • 108.
    Andersson, David C.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thysell, Elin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindström, Anton
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bylesjö, Max
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Raubacher, Florian
    Linusson Jonsson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    A multivariate approach to investigate docking parameters' effects on docking performance2007In: Journal of chemical information and modeling, ISSN 1549-9596, Vol. 47, no 4, p. 1673-1687Article in journal (Refereed)
    Abstract [en]

    Increasingly powerful docking programs for analyzing and estimating the strength of protein-ligand interactions have been developed in recent decades, and they are now valuable tools in drug discovery. Software used to perform dockings relies on a number of parameters that affect various steps in the docking procedure. However, identifying the best choices of the settings for these parameters is often challenging. Therefore, the settings of the parameters are quite often left at their default values, even though scientists with long experience with a specific docking tool know that modifying certain parameters can improve the results. In the study presented here, we have used statistical experimental design and subsequent regression based on root-mean-square deviation values using partial least-square projections to latent structures (PLS) to scrutinize the effects of different parameters on the docking performance of two software packages: FRED and GOLD. Protein-ligand complexes with a high level of ligand diversity were selected from the PDBbind database for the study, using principal component analysis based on 1D and 2D descriptors, and space-filling design. The PLS models showed quantitative relationships between the docking parameters and the ability of the programs to reproduce the ligand crystallographic conformation. The PLS models also revealed which of the parameters and what parameter settings were important for the docking performance of the two programs. Furthermore, the variation in docking results obtained with specific parameter settings for different protein-ligand complexes in the diverse set examined indicates that there is great potential for optimizing the parameter settings for selected sets of proteins.

  • 109.
    Andersson, Emma K.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Bengtsson, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Evans, Margery L.
    Chorell, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Sellstedt, Magnus
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Lindgren, Anders E.G.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hufnagel, David A.
    Bhattacharya, Moumita
    Tessier, Peter M.
    Wittung-Stafshede, Pernilla
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Chapman, Matthew R.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). University of Michigan, USA.
    Modulation of Curli Assembly and Pellicle Biofilm Formation by Chemical and Protein Chaperones2013In: Chemistry and Biology, ISSN 1074-5521, E-ISSN 1879-1301, Vol. 20, no 10, p. 1245-1254Article in journal (Refereed)
    Abstract [en]

    Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation. The ability of inhibitor compounds to stop growing CsgA fibers was compared to the same property of the CsgA chaperone, CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors prevented biofilm formation by Escherichia coli at the air-liquid interface of a static culture. We demonstrate that curli amyloid assembly and curli-dependent biofilm formation can be modulated not only by protein chaperones, but also by "chemical chaperones."

  • 110.
    Andersson, Emma K.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chapman, Matthew
    Small Molecule Disruption of B-subtilis Biofilms by Targeting the Amyloid Matrix2013In: Chemistry and Biology, ISSN 1074-5521, E-ISSN 1879-1301, Vol. 20, no 1, p. 5-7Article in journal (Other academic)
    Abstract [en]

    Small molecule inhibitors of amyloid aggregation have potential as treatment for a variety of conditions. In this issue of Chemistry & Biology, Romero and colleagues use amyloid-dependent B. subtilis biofilm formation to screen for amyloid inhibitors, identifying compounds that not only inhibit B. subtilis biofilm formation but also ones that disrupt preformed biofilms.

  • 111.
    Andersson, Emma K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Strand, Mårten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Enquist, Per-Anders
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Spjut, Sara
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Small molecule screening using a whole cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel anti-adenoviral compound2010In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 54, no 9, p. 3871-3877Article in journal (Refereed)
    Abstract [en]

    Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their anti-adenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential anti-adenoviral compounds. The assay is unique in that it is based on a replication competent adenovirus type 11p GFP-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by >/= 80% but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.

  • 112. Andersson, Erik
    et al.
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tornberg, Karin
    Schnürer, Ylva
    Öberg, Lars G.
    Mattiasson, Bo
    Incomplete degradation of polycyclic aromatic hydrocarbons in soil inoculated with wood-rotting fungi and their effect on the indigenious soil bacteria2003In: Environmental toxicology and chemistry, Vol. 22, no 6, p. 1238-1243Article in journal (Refereed)
  • 113.
    Andersson, Hans
    Umeå University, Faculty of Science and Technology, Chemistry.
    Reaction Between Grignard reagents and Heterocyclic N-oxides: Synthesis of Substituted Pyridines, Piperidines and Piperazines2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes the development of new synthetic methodologies for preparation of bioactive interesting compounds, e.g. substituted pyridines, piperidines or piparazines. Thesecompounds are synthesized from commercially available, cheap and easily prepared reagents, videlicet the reaction between Grignard reagents and heterocyclic N-oxides.

     The first part of this thesis deals with an improvement for synthesis of dienal-oximes and substituted pyridines. This was accomplished by a rapid addition of Grignard reagents to pyridine N-oxides at rt. yielding a diverse set of substituted dienal-oximes. During these studies, it was observed that the obtained dienal-oxmies are prone to ring-close upon heating. By taking advantage of this, a practical synthesis of substituted pyridines was developed.

    In the second part, an ortho-metalation of pyridine N-oxides using Grignard reagents is discussed. The method can be used for incorporation of a range of different electrophiles, including aldehydes, ketones and halogens. Furthermore, the importance for incorporation of halogens are exemplified through a Suzuki–Miyaura coupling reaction of 2-iodo pyridine N-oxides and different boronic acids. Later it was discovered that if the reaction temperature is kept below -20 °C, the undesired ringopening can be avoided. Thus, the synthesis of 2,3-dihydropyridine N-oxide, by reacting Grignard reagents with pyridine N-oxides at -40 °C followed by sequential addition of aldehyde or ketone, was accomplished. The reaction provides complete regio- and stereoselectivity yielding trans-2,3-dihydropyridine N-oxides in good yields. These intermediate products could then be used for synthesis of either substituted piperidines, by reduction, or reacted in a Diels–Alder cycloaddtion to give the aza-bicyclo compound.

    In the last part of this thesis, the discovered reactivity for pyridine N-oxides, is applied on pyrazine N-oxides in effort to synthesize substituted piperazines. These substances are obtained by the reaction of Grignard reagents and pyrazine N-oxides at -78 °C followed by reduction and protection, using a one-pot procedure. The product, a protected piperazine, that easily can be orthogonally deprotected, allowing synthetic modifications at either nitrogens in a fast and step efficient manner. Finally, an enantioselective procedure using a combination of PhMgCl and (-)-sparteine is discussed, giving opportunity for a stereoselective synthesis of substituted piperazines.

  • 114.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Olsson, Roger
    Synthesis of 2-Substituted Pyridines via a Regiospecific Alkylation, Alkynylation, and Arylation of Pyridine N-Oxides2007In: Organic Letters, Vol. 9, no 7, p. 1335-7Article in journal (Refereed)
    Abstract [en]

    Sequential addition of Grignard reagents to pyridine N-oxides in THF at room temperature followed by treatment with acetic anhydride at 120 C afforded 2-substituted pyridines in good to high yields. Furthermore, by exchanging acetic anhydride for DMF in the second step, 2-substituted pyridine N-oxides were obtained, as intermediates suitable for addition of a second Grignard reagent for the synthesis of 2,6-disubstituted pyridines.

  • 115.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Banchelin, Thomas Sainte-Luce
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Das, Pralay
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gustafsson, Magnus
    Acadia Pharmaceuticals AB, Medeon Science Park S-20512, Malmö, Sweden.
    Olsson, Roger
    Acadia Pharmaceuticals AB, Medeon Science Park S-20512, Malmö, Sweden.
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines2010In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 12, no 2, p. 284-6Article in journal (Refereed)
    Abstract [en]

    A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.

  • 116.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Das, Sajal
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gustafsson, Magnus
    Olsson, Roger
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Synthesis of substituted 4-pyridones and 4-aminopyridinium salts via a one-pot pyridine synthesis2010In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 51, no 32, p. 4218-4220Article in journal (Refereed)
    Abstract [en]

    Synthesis of substituted 4-benzyloxypyridinium salts by the addition of Grignard reagents to pyridine N-oxides provides an efficient route for obtaining substituted 4-pyridones or 4-aminopyridinium salts.

  • 117.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gustafsson, Magnus
    Boström, Dan
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Olsson, Roger
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    The Regio- and Stereoselective Synthesis of trans-2,3-Dihydropyridine N-oxides and Piperidines2009In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 48, no 18, p. 3288-3291Article in journal (Refereed)
    Abstract [en]

    No Abstract

  • 118.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gustafsson, Magnus
    Olsson, Roger
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Selective synthesis of 2-substituted pyridine N-oxides via directed ortho-metallation using Grignard reagents2008In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 49, no 48, p. 6901-3Article in journal (Refereed)
    Abstract [en]

    Addition of i-PrMgCl to pyridine N-oxides in THF at −78 °C generates selectively an ortho-metallated species, which can be trapped with various electrophiles to generate 2-substituted pyridine N-oxides. Furthermore, by applying a double metal-catalyzed cross-coupling, direct arylation of the pyridine N-oxides is achieved.

  • 119.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Olsson, Roger
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Reactions between Grignard reagents and heterocyclic N-oxides: stereoselective synthesis of substituted pyridines, piperidines, and piperazines2011In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, p. 337-346Article in journal (Refereed)
    Abstract [en]

    In this perspective we discuss the recent developments of stereoselective synthesis of substituted pyridines, piperidines, and piperazines from cheap and commercially readily available starting materials. Pyridine N-oxides and pyrazine N-oxides are reacted with alkyl, aryl, alkynyl and vinyl Grignard reagents to give a diverse set of heterocycles in high yields. Optically active substituted piperazines are obtained by an asymmetric reaction from pyrazine N-oxides using sparteine as chiral ligand. In addition, a stereoselective synthesis of dienal-oximes from the reaction between pyridine N-oxides and Grignard reagents is presented, which results in a useful intermediate for the synthesis of a diverse set of compounds.

  • 120.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sainte-Luce Banchelin, Thomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Das, Sajal
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Olsson, Roger
    Institutionen för kemi och molekylärbiologi, Göteborgs universitet, Göteborg, Sverige .
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Efficient, mild and completely regioselective synthesis of substituted pyridines2010In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 46, no 19, p. 3384-3386Article in journal (Refereed)
    Abstract [en]

    Addition of Grignard reagents to pyridine N-oxides in THF at low temperature (-78 to -20 °C) and treatment with TFAA provides an efficient general procedure for synthesis of substituted pyridines. The method is compatible with a range of functional groups such as esters, halogens and nitriles.

  • 121.
    Andersson, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Wang, Xiaoyang
    Umeå University, Faculty of Science and Technology, Chemistry.
    Björklund, Mikael
    Umeå University, Faculty of Science and Technology, Chemistry.
    Olsson, Roger
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Reaction of pyridine N-oxides with Grignard reagents: a stereodefined synthesis of substituted dienal oximes2007In: Tetrahedron Letters, Vol. 48, p. 6941-4Article in journal (Refereed)
    Abstract [en]

    Rapid addition of Grignard reagents to pyridine N-oxides under mild conditions gave stereodefined dienal oximes in good to excellent yields. This reaction provides an efficient access to substituted olefins with defined stereochemistry that are potentially of interest as bioactives themselves or as versatile synthetic intermediates.

  • 122.
    Andersson, Ida E.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Modified Glycopeptides Targeting Rheumatoid Arthritis: Exploring molecular interactions in class II MHC/glycopeptide/T-cell receptor complexes2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that leads to degradation of cartilage and bone mainly in peripheral joints. In collagen-induced arthritis (CIA), a mouse model for RA, activation of autoimmune CD4+ T cells depends on a molecular recognition system where T-cell receptors (TCRs) recognize a complex between the class II MHC Aq protein and CII259-273, a glycopeptide epitope from type II collagen (CII). Interestingly, vaccination with the Aq/CII259-273 complex can relieve symptoms and cause disease regression in mice. This thesis describes the use of modified glycopeptides to explore interactions important for binding to the Aq protein and recognition by autoimmune T-cell hybridomas obtained from mice with CIA.

    The CII259-273 glycopeptide was modified by replacement of backbone amides with different amide bond isosteres, as well as substitution of two residues that anchor the glycopeptide in prominent pockets in the Aq binding site. A three-dimensional structure of the Aq/glycopeptide complex was modeled to provide a structural basis for interpretation of the modified glycopeptide’s immunological activities. Overall, it was found that the amide bond isosteres affected Aq binding more than could be explained by the static model of the Aq/glycopeptide complex. Molecular dynamics (MD) simulations, however, revealed that the introduced amide bond isosteres substantially altered the hydrogen-bonding network formed between the N-terminal 259-265 backbone sequence of CII259-273 and Aq. These results indicated that the N-terminal hydrogen-bonding interactions follow a cooperative model, where the strength and presence of individual hydrogen bonds depended on the neighboring interactions.

    The two important anchor residues Ile260 and Phe263 were investigated using a designed library of CII259-273 based glycopeptides with substitutions by different (non-)natural amino acids at positions 260 and 263. Evaluation of binding to the Aq protein showed that there was scope for improvement in position 263 while Ile was preferred in position 260. The obtained SAR understanding provided a valuable basis for future development of modified glycopeptides with improved Aq binding. Furthermore, the modified glycopeptides elicited varying T-cell responses that generally could be correlated to their ability to bind to Aq. However, in several cases, there was a lack of correlation between Aq binding and T-cell recognition, which indicated that the interactions with the TCRs were determined by other factors, such as presentation of altered epitopes and changes in the kinetics of the TCR’s interaction with the Aq/glycopeptide complex.

    Several of the modified glycopeptides were also found to bind well to the human RA-associated DR4 protein and elicit strong responses with T-cell hybridomas obtained from transgenic mice expressing DR4 and the human CD4 co-receptor. This encourages future investigations of modified glycopeptides that can be used to further probe the MHC/glycopeptide/TCR recognition system and that also constitute potential therapeutic vaccines for treatment of RA. As a step towards this goal, three modified glycopeptides presented in this thesis have been identified as candidates for vaccination studies using the CIA mouse model.

  • 123.
    Andersson, Ida E
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, C David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Batsalova, Tsvetelina
    Medicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Dzhambazov, Balik
    Medicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Holmdahl, Rikard
    Medicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Kihlberg, Jan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Linusson, Anna
    AstraZeneca R&D Mölndal, Mölndal.
    Design of glycopeptides used to investigate class II MHC binding and T-Cell responses associated with autoimmune arthritis2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 3, p. e17881-Article in journal (Refereed)
    Abstract [en]

    The glycopeptide fragment CII259–273 from type II collagen (CII) binds to the murine Aq and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259–273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259–273 glycopeptide library in which two anchor positions crucial for binding in pockets of Aq and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR) understanding of binding to Aq and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.

  • 124.
    Andersson, Ida E.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Batsalova, Tsvetelina
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Dzhambazov, Balik
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Edvinsson, Lotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holmdahl, Rikard
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Kihlberg, Jan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Oxazole-modified glycopeptides that target arthritis-associated class II MHC Aq and DR4 proteins2010In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 8, no 13, p. 2931-2940Article in journal (Refereed)
    Abstract [en]

    The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA). Here, we describe the design and synthesis of a small series of modified CII259-273 glycopeptides with oxazole heterocycles replacing three potentially labile peptide bonds. These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins. The oxazole modifications drastically reduced or completely abolished binding to A(q). Two of the glycopeptidomimetics were, however, well tolerated in binding to DR4 and they also induced strong responses by one or two DR4-restricted T-cell hybridomas. This work contributes to the development of an altered glycopeptide for inducing immunological tolerance in CIA, with the long-term goal of developing a therapeutic vaccine for treatment of RA.

  • 125.
    Andersson, Ida E.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Batsalova, Tsvetelina
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Haag, Sabrina
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Dzhambazov, Balik
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Holmdahl, Rikard
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Kihlberg, Jan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    (E)-Alkene and Ethylene Isosteres Substantially Alter the Hydrogen-Bonding Network in Class II MHC Aq/Glycopeptide Complexes and Affect T-Cell Recognition2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 36, p. 14368-14378Article in journal (Refereed)
    Abstract [en]

    The structural basis for antigen presentation by class II major histocompatibility complex (MHC) proteins to CD4(+) T-cells is important for understanding and possibly treating autoimmune diseases. In the work described in this paper, (E)-alkene and ethylene amide-bond isosteres were used to investigate the effect of removing hydrogen-bonding possibilities from the CII259-270 glycopeptide, which is bound by the arthritis-associated murine A(q) class II MHC protein. The isostere-modified glycopeptides showed varying and unexpectedly large losses of A(q) binding that could be linked to the dynamics of the system. Molecular dynamics (MD) simulations revealed that the backbone of CII259-270 and the A(q) protein are able to form up to 11 hydrogen bonds, but fewer than this number are present at any one time. Most of the strong hydrogen-bond interactions were formed by the N-terminal part of the glycopeptide, i.e., in the region where the isosteric replacements were made. The structural dynamics also revealed that hydrogen bonds were strongly coupled to each other; the loss of one hydrogen-bond interaction had a profound effect on the entire hydrogen-bonding network. The A(q) binding data revealed that an ethylene isostere glycopeptide unexpectedly bound more strongly to A(q) than the corresponding (E)-alkene, which is in contrast to the trend observed for the other isosteres. Analysis of the MD trajectories revealed that the complex conformation of this ethylene isostere was structurally different and had an altered molecular interaction pattern compared to the other A(q)/glycopeptide complexes. The introduced amide-bond isosteres also affected the interactions of the glycopeptide/A(q) complexes with T-cell receptors. The dynamic variation of the patterns and strengths of the hydrogen-bond interactions in the class II MHC system is of critical importance for the class II MHC/peptide/TCR signaling system.

  • 126.
    Andersson, Ida E.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Dzhambazov, Balik
    Medical Inflammation Research, BMC I11, Lund University, SE-221 84 Lund, Sweden.
    Holmdahl, Rikard
    Medical Inflammation Research, BMC I11, Lund University, SE-221 84 Lund, Sweden.
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kihlberg, Jan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Probing molecular interactions within Class II MHC Aq/Glycopeptide/T-Cell Receptor Complexes associated with Collagen-Induced Arthritis2007In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 50, no 23, p. 5627-5643Article in journal (Refereed)
    Abstract [en]

    T cells obtained in a mouse model for rheumatoid arthritis are activated by a glycopeptide fragment from rat type II collagen (CII) bound to the class II major histocompatibility complex Aq molecule. We report a comparative model of Aq in complex with the glycopeptide CII260-267. This model was used in a structure-based design approach where the amide bond between Ala261 and Gly262 in the glycopeptide was selected for replacement with [COCH2], [CH2NH2+], and [(E)-CH=CH] isosteres. Ala-Gly isostere building blocks were then synthesized and introduced in CII260-267 and CII259-273 glycopeptides. The modified glycopeptides were evaluated for binding to the Aq molecule, and the results were interpreted in view of the Aq/glycopeptide model. Moreover, recognition by a panel of T-cell hybridomas revealed high sensitivity for the backbone modifications. These studies contribute to the understanding of the interactions in the ternary Aq/glycopeptide/T-cell receptor complexes that activate T cells in autoimmune arthritis and suggest possibilities for new vaccination approaches.

  • 127.
    Andersson, Ingegärd
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Angus-Dunne, Sarah
    Umeå University, Faculty of Science and Technology, Chemistry.
    Howarth, Oliver
    Pettersson, Lage
    Umeå University, Faculty of Science and Technology, Chemistry.
    Speciation in vanadium bioinorganic systems 6. Speciation study of aqueous peroxovanadates, including complexes with imidazole2000In: Journal of Inorganic Biochemistry, Vol. 80, no 1-2, p. 51-8Article in journal (Refereed)
    Abstract [en]

    Using a combination of potentiometry (glass electrode) and quantitative 51V NMR spectroscopy, the full speciation in the vanadate–peroxide and vanadate–peroxide–imidazole systems was determined in the pH range 1–10 (0.150 M Na(Cl) medium, 25 °C). Using the computer program LAKE, the pKa value of imidazole and the formation constants for 10 peroxovanadate species and also for three more species where a single imidazole moiety is also bound, have been calculated. The experimental data show a good fit to the calculated speciation model, even for the less abundant species. The species are either monomeric or dimeric in vanadium, and four resonances of the dimeric species have been unambiguously assigned via 2D 51V NMR. Diperoxovanadates are the favoured species at pH 2–10, when sufficient peroxide is present. Imidazole is found to bind strongly to them at pH 6–9. The equilibrium conditions are illustrated in distribution diagrams.

  • 128.
    Andersson, Ingegärd
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gorzsás, András
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kerezsi, Csaba
    Tóth, Imre
    Pettersson, Lage
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Speciation in the aqueous H+/H2VO4–/H2O2/phosphate systemManuscript (Other academic)
  • 129.
    Andersson, Ingegärd
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gorzsás, András
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kerezsi, Csaba
    Tóth, Imre
    Pettersson, Lage
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Speciation in the aqueous H+/H2VO4–/H2O2/phosphate system2005In: DALTON TRANSACTIONS, ISSN 1477-9226, Vol. 22, p. 3658-66Article in journal (Refereed)
    Abstract [en]

    The speciation in the aqueous H+/H2VO4- /phosphate (dihydrogen phosphate, P) and H+/H2VO4/H2O2/P systems has been determined in the physiological medium of 0.150 M Na(Cl) at 25 degrees C. A combination of multinuclear NMR integral and chemical shift (Bruker AMX500) as well as potentiometric data (glass electrode) have been collected and treated simultaneously by the computer program LAKE. The pK(a)-values for phosphoric acid have been determined by potentiometric and P-31 NMR chemical shift data, and have been found to be 1.85 +/- 0.02, 6.69 +/- 0.02 and 11.58 +/- 0.07. The errors given are 3 sigma. Altogether nine vanadate phosphate species have been found in the ternary H+/H2VO4-/P- system in the PH region 1-11, with the following compositions: VP, VP2 and V14P. Equilibrium is very slow in acidic solutions, requiring more than 3 months for the formation of V14P species. On the other hand, less than 15 min are needed for equilibration at neutral and alkaline pH. In the H+/H2VO4-/H2O2/P- system, four new species have been found in addition to all binary and ternary complexes. They are of VXP and VX2P compositions, where X denotes the peroxo ligand. V-51 and P-31 NMR chemical shifts, compositions and formation constants are given, and equilibrium conditions are illustrated in distribution diagrams as well as the fit of the model to the experimental data. Biological and medical relevance of the species is also discussed and physiological conditions are modelled.

  • 130.
    Andersson, Ingegärd
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gorzsás, András
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Pettersson, Lage
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Speciation in the aqueous H+/H2VO4–/H2O2/picolinate system relevant to diabetes research2004In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    A detailed study of the quaternary aqueous H+/H2VO4/H2O2/picolinate (Pi) system has been performed at 25 °C in 0.150 M Na(Cl) medium using quantitative 51V NMR (500 MHz) and potentiometric data (glass electrode). In the ternary H+/H2VO4/Pi system, six complexes have been found in the pH region 1–10. In the quaternary H+/H2VO4/H2O2/Pisystem, eight additional complexes have been found. Generally, equilibria are fast in both systems. The rate of peroxide decomposition depends on the species in solution. Chemical shifts, compositions and formation constants for the species are given. Equilibrium conditions and the fit of the model to the experimental data are illustrated in distribution diagrams. Possible formation of mixed ligand species with imidazole, lactic acid and citric acid have been investigated and ruled out under the same experimental conditions. Structural proposals are given, based on 13C NMR data and available crystal structures.

  • 131.
    Andersson, Kristoffer
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Selective detection of TNT withmodified SERS-surfaces: Investigation of TNT adsorption and detection using goldand silver nano structured surfaces modified by cysteineand cysteamine2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In the search for trace amounts of explosives in various environmental samples, the

    analytical procedure is in need of improvements. If it is for national security or for

    environmental purposes the detection of trace amounts of for example 2,4,6-

    trinitrotoluene (TNT) is a costly and time consuming procedure. The use of Raman

    spectrometry for trace amounts detection is one of the research areas that are in the

    advancement and mainly because of the discovery of Surface-Enhanced Raman

    spectroscopy (SERS). Raman spectrometry detects the inelastically scattered light

    from molecules giving a fingerprint spectrum that can be interpreted and species can

    be detected. The inelastically scattering of light only occurs in a small amount of the

    molecules making the signal low and sensitive for interferences. SERS enhances the

    signal from the molecules making it possible to detect very low concentrations. The

    surfaces used in SERS need to be selective for the wanted species to be useful for the

    analysis of environmental samples that often contains a wide variety of compounds.

    This project’s aim was to investigate the possibility of modifying gold- and silvercoated

    SERS surfaces (provided by DTU Nanotech) to get a selective detection of

    trace amounts of TNT in water and air samples.

    The results from the modification indicated some problems with the surfaces. The

    modification molecules were cysteine or cysteamine. The hypothesis was that both of

    them should bind to the surface by sulphur bond. But for cysteine this was not the

    case. The results indicated a binding of the carboxyl group making the use of the

    modification for the selective detection of TNT impossible. The modification by

    cysteamine was more successful but the detection of TNT in water samples was hard

    to get clear results from. The detection of TNT in air samples was carried out by a

    method never tested before using a so-called Linkam cell in conjunction with a TNT

    treated GC-column which together create a controlled environment. The results from

    this experiment were very positive where a clear SERS-signal from TNT could be

    detected.

  • 132.
    Andersson, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Axner, Ove
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Fällman, Erik
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Physical Properties of Biopolymers Assessed by Optical Tweezers: Analysis of folding and refolding of bacterial pili2008In: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 9, no 2, p. 221-235Article in journal (Refereed)
    Abstract [en]

    Bacterial adhesion to surfaces mediated by specific adhesion organelles that promote infections, as exemplified by the pili of uropathogenic E. coli, is studied mostly at the level of cell-cell interactions and thereby reflects the averaged behavior of multiple pili. The role of pilus rod structure has therefore only been estimated from the outcome of experiments involving large numbers of organelles at the same time. It has, however, lately become clear that the biomechanical behavior of the pilus shafts play an important, albeit hitherto rather unrecognized, role in the adhesion process. For example, it has been observed that shafts from two different strains, even though they are similar in structure, result in large differences in the ability of the bacteria to adhere to their host tissue. However, in order to identify all properties of pilus structures that are of importance in the adhesion process, the biomechanical properties of pili must be assessed at the single-molecule level. Due to the low range of forces of these structures, until recently it was not possible to obtain such information. However, with the development of force-measuring optical tweezers (FMOT) with force resolution in the low piconewton range, it has lately become possible to assess forces mediated by individual pili on single living bacteria in real time. FMOT allows for a more or less detailed mapping of the biomechanical properties of individual pilus shafts, in particular those that are associated with their elongation and contraction under stress. This Mi- nireview presents the FMOT technique, the biological model system, and results from assessment of the biomechanical properties of bacterial pili. The information retrieved is also compared with that obtained by atomic force microscopy.

  • 133.
    Andersson, Mathilda
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Biochar removal of micropollutants in wastewater effluentsfrom Morocco and South Africa2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 134.
    Andersson, Ola
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Adsorption modeling of heavy metals to Sawdust, bark of Pine and Absol2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 135. Andersson, PA
    et al.
    Takaichi, S
    Cogdell, RJ
    Gillbro, Tomas
    Umeå University, Faculty of Science and Technology, Chemistry.
    Photophysical characterization of natural cis-carotenoids2001In: PHOTOCHEMISTRY AND PHOTOBIOLOGY, ISSN 0031-8655, Vol. 74, no 4, p. 549-57Article in journal (Refereed)
    Abstract [en]

    By means of steady-state fluorescence spectroscopy we explore the photophysics of two lowest lying singlet excited states in two natural 15-cis-carotenoids, namely phytoene and phytofluene, possessing three and five conjugated double bonds (N), respectively. The results are interpreted in relation to the photophysics of all-trans-carotenoids with varying N. The fluorescence of phytofluene is more Stokes-shifted relative to that of phytoene, and is ascribed to the forbidden S-1 --> S-0 transition, with its first excited singlet state (S-1) lying 3340 cm(-1) below the dipole allowed second excited singlet state (S-2), at 77 K. For phytoene the S-2 and S-1 potential surfaces are closer in energy, probably giving rise to the mixed S-2 and S-1 fluorescence characteristics. The origin of phytoene fluorescence is discussed and is suggested to be due to the S-1 --> S-0 transition; with the S-1 state located 1100 cm(-1) below S-2 at 77 K. The dependence of the fluorescence quantum yield on temperature and viscosity shows that large amplitude molecular motions are involved in the radiationless relaxation process of phytoene. The transition dipole moment of absorption and emission are parallel in phytoene and nonparallel in phytofluene.

  • 136.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Physico-chemical characteristics and quantitative structure-activity relationships of PCBs2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The polychlorinated biphenyls (PCBs) comprise a group of 209 congeners varying in the number of chlorine atoms and substitution patterns. These compounds tend to be biomagnified in foodwebs and have been shown to induce an array of effects in exposed organisms. The structural characteristics of the PCBs influence their potency as well as mechanism of action. In order to assess the biological potency of these compounds a multi-step quantitative structure-activity relationship (QSAR) procedure was used in the project described in this thesis.

    The ultraviolet absorption (UV) spectra were measured for all 209 PCBs, and digitised for use as physico-chemical descriptors. Interpretations of the spectra using principal component analysis (PCA) showed the number of ortho chlorine atoms and para-para substitution patterns to be significant. Additional physico-chemical descriptors were derived from semi-empirical calculations. These included various molecular energies, the ionisation potential, electron affinity, dipole moments, and the internal barrier of rotation. The internal barrier of rotation was especially useful for describing the conformation of the PCBs on a continuous scale.

    In total 52 physico-chemical descriptors were compiled and analysed by PCA for the tetra- to hepta-chlorinated congeners. The structural variation within these compounds was condensed into four principal properties derived from a PCA for use as design variables in a statistical design to select congeners representative for these homologue-groups. The 20 selected PCBs have been applied to study structure-specific biochemical responses in a number of bioassays, and to study the biomagnification of the PCBs in various fish species.

    QSARs were established using partial least squares projections to latent structures (PLS) for the PCBs potency to inhibit intercellular communication, activate respiratory burst, inhibit dopamine uptake in synaptic vesicles, compete with estradiol for binding to estrogen receptors, and induce cytochrome P4501A (CYP1A) related activities. By the systematic use of the designed set of PCBs the biological potency was screened over the chemical domain of the class of compounds. Further, sub-regions of highly potent PCBs were identified for each response measured. For risk assessment of the PCBs potency to induce dioxin-like activities the predicted induction potencies (PIPs) were calculated. In addition, two sets of PCBs were presented that specifically represent congeners of environmental relevance in combination with predicted potency to induce estrogenic and CYP1A related activities.

  • 137.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Berg, A. H.
    Bjerselius, R.
    Norrgren, L.
    Olsson, P.-E.
    Örn, S.
    Tysklind, Mats
    Uptake and elimination of selected PCBs in zebra fish, three-spined stickleback and arctic char after three different routes of exposure2001In: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341, E-ISSN 1432-0703, Vol. 40, no 4, p. 519-530Article in journal (Refereed)
    Abstract [en]

    The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

  • 138.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Berg, A H
    Bjerselius, R
    Norrgren, L
    Olsén, H
    Olsson, P-E
    Örn, S
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Bioaccumulation of Selected PCBs in Zebrafish, Three-Spined Stickleback, and Arctic Char After Three Different Routes of Exposure2001In: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341 (Print) 1432-0703 (Online), Vol. 40, no 4, p. 519-30Article in journal (Refereed)
    Abstract [en]

    The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

  • 139.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rappe, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ultraviolet absorption characteristics and calculated semi-empirical parameters as chemical descriptors in multivariate modelling of polychlorinated biphenyls1996In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 10, no 2, p. 171-185Article in journal (Refereed)
    Abstract [en]

    The structural variation within the polychlorinated biphenyls (PCBs) was characterized by using principal component analysis (PCA). A multivariate model was evolved from 52 physicochemical descriptors including measured ultraviolet (UV) absorption spectra, calculated semiempirical parameters (AM1) and properties captured from the literature. Parameters calculated by using the AM1-Hamiltonian were e.g. heat of formation, dipole moments, ionization potential and the barrier of internal rotation. The UV spectra were measured and digitized in the range 200-300 nm. The multivariate model revealed that most of the information within the set of physicochemical parameters was related to molecular size. Descriptors depending on size were e.g. GC retention times, partition coefficients and a subset of semiempirically derived energy terms. Important also were parameters reflecting differences in substitution patterns and related to electronic and steric properties, such as UV absorption in the wavelength region 245-300 nm, the barrier of internal rotation and the ionization potential. The developed model describes the large variation in physicochemical characteristics within the PCBs. The importance of a broad chemical characterization is illustrated by a quantitative structure-activity relationship (QSAR) for the potency of inhibition of intercellular communication for 27 structurally diverse tetra- to heptachlorinated PCBs.

  • 140.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Tysklind, Mats
    The internal barriers of rotation for the 209 polychlorinated biphenyls1997In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 4, no 2, p. 75-81Article in journal (Refereed)
    Abstract [en]

    The internal barrier of rotation (Erot) was calculated for all 209 polychlorinated biphenyls (PCBs) by using a semi-empirical method, viz. the Austin Model 1 (AM1) Hamiltonian. The difference in total energy between a forced planar state and an optimised twisted structure was defined as Erot. The Erot values were in the range of 8.33 to 483 kJ/mol, and were significantly influenced by the number of chlorine atoms in ortho position. An additional structural characteristic of the PCBs influencing Erot of ortho substituted congeners was substitution by chlorine atoms in vicinal meta positions, which is assumed to prevent outward bending of ortho substituents. This so-called buttressing effect contributed with 4 to 31 kJ/mol per added chlorine atom. In conclusion, the internal barrier of rotation, calculated for all 209 PCBs, provides an important structure dependent physico-chemical parameter for multivariate modelling of future quantitative structure-activity and structure-property relationships (QSARs/QSPRs).

  • 141.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ultraviolet absorption spectra of all 209 polychlorinated biphenyls evaluated by principal component analysis1997In: Fresenius' Journal of Analytical Chemistry, ISSN 0937-0633, E-ISSN 1432-1130, Vol. 357, no 8, p. 1088-1092Article in journal (Refereed)
    Abstract [en]

    The ultraviolet absorption spectra of all 209 polychlorinated biphenyls (PCBs) were recorded in the range 200-300 nm and displayed two important absorption maxima, viz., the main-band, lambda(max) 200-225 nm, and the kappa-band, lambda(max) 245-265 nm. By utilising principal component analysis, substitution related spectral characteristics of the PCBs, underlying the main patterns of the spectra, were examined. Captured in the multivariate evaluation were e.g., the importance of chlorine atoms in ortho positions, determining the intensity and existence of the kappa-band, chlorine substitution in para-para position, and the total number of chlorine atoms. The measured UV-spectra of all 209 polychlorinated biphenyls provide important physico-chemical descriptors for use in future quantitative structure-activity and structure-property relationship (QSAR/QSPR) studies.

  • 142.
    Andersson, Patrik L
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fick, Jerker
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rännar, Stefan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    A Multivariate Chemical Similarity Approach to Search for Drugs of Potential Environmental Concern2011In: Journal of chemical information and modeling, ISSN 1549-960X, Vol. 51, no 8, p. 1788-1794Article in journal (Refereed)
    Abstract [en]

    A structural similarity tool was developed and aimed to search for environmentally persistent drugs. The basis for the tool was a selection of so-called anchor molecules and a multidimensional chemical map of drugs. The map was constructed using principal component analysis covering 899 drugs described by 67 diverse calculated chemical descriptors. The anchor molecules (diclofenac, trimethoprim, and carbamazepine) were selected to represent drugs of known environmental concern. In addition 12 chemicals listed by the Stockholm Convention on persistent organic pollutants were used representing typical environmental pollutants. Chemical similarity was quantified by measuring relative Euclidean distances in the five-dimensional chemical map, and more than 100 nearest neighbors (kNNs) were found within a relative distance of less than 10% from each drug anchor. The developed chemical similarity approach not only identified persistent or semipersistent drugs but also a large number of potentially persistent drugs lacking environmental fate data.

  • 143.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Maran, Uko
    Fara, Dan
    Karelson, Mati
    Hermens, Joop L M
    General and Class Specific Models for Prediction of Soil Sorption Using Various Physicochemical Descriptors2002In: Journal of Chemical Information and Modeling, Vol. 42, no 6, p. 1450-9Article in journal (Refereed)
    Abstract [en]

    Diverse chemical descriptors were explored for use in QSAR models aimed to screen the soil sorption potential of organic compounds. The descriptors included logP, HyperChem QSARProperties descriptors, a combination of connectivity indices, geometrical, and quantum chemical measures, and two sets from the DRAGON and CODESSA program packages, respectively. Generally, the univariate logP models were capable of capturing most of the variation and give an indication of the sorption potential. The multivariate models required refined variable selection procedures but were shown to include crucial descriptors for modeling compound classes with specific chemical characteristics.

  • 144.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Stenberg, Maria
    Umeå University, Faculty of Science and Technology, Chemistry.
    Mariussen, E
    Fonnum, F
    Structure-Activity Relationships of PCBS Potency as neurotoxicants2006In: Organohalogen Compounds, Vol. 68, p. 117-20Article in journal (Refereed)
  • 145.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    An introduction to QSARs2006In: Using chemistry in environmental and health risk assessment, US-AB Universitetsservice, Stockholm , 2006, p. 51-74Chapter in book (Refereed)
  • 146.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    van der Burght, Aafje S.A.M.
    van den Berg, Martin
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species: ranking scales and species differences2000In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 19, no 5, p. 1454-1463Article in journal (Refereed)
    Abstract [en]

    Cytochrome P4501A–induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure-activity relationships have been established, including 52 physi-cochemical parameters and different measures of the dose-response curves. Relative effect potencies are predicted for the 154 tetra-to hepta-PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol-water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure-activity relationship, with high activity for the non-ortho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.

  • 147.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    van der Burght, ASAM
    van den Berg, M
    Tysklind, Mats
    Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences2000In: ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, ISSN 0730-7268, Vol. 19, no 5, p. 1454-63Article in journal (Refereed)
    Abstract [en]

    Cytochrome P4501A-induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure-activity relationships have been established, including 52 physicochemical parameters and different measures of the dose-response curves. Relative effect potencies are predicted for the 154 tetra-to hepta-PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol-water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure-activity relationship, with high activity for the non-or rho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.

  • 148.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Öberg, Kjell
    Örn, U
    Chemical characterization of brominated flame retardants and identification2006In: Environmental Toxicology and Chemistry, ISSN 0730-7268, Vol. 25, no 5, p. 1275-82Article in journal (Refereed)
    Abstract [en]

    Three training sets were selected, each consisting of 10 structurally diverse compounds representative of brominated flame retardants (BFRs) that are either in use or have been used. Just three compounds account for nearly all the total production volume of BFRs. In the present study, however, the physicochemical characteristics of a far more structurally diverse set of 65 BFRs was explored using 15 molecular descriptors (including log P, constitutional counts, and semiempirical quantum mechanical parameters) and principal component analysis (PCA). The PCA generated an overview of the structural variation among BFRs, and certain compounds with unique physicochemical properties and specific clusters of compounds with distinct properties were identified. The training-set compounds were selected by applying the condensed information obtained from the PCA and statistical experimental design. The three training sets, which were designated as optimal, practical, and alternative, were selected either to maximize the structural variation (optimal) or to combine structural variation with practical advantages, such as ease of experimental handling and commercial availability (practical and alternative). Inclusion of the suggested compounds in assessments of the persistence, bioaccumulation, and toxicity properties of BFRs and related programs should help to increase our understanding of the effects and environmental fate of these compounds.

  • 149.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Örn, U
    Öberg, Kjell
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Chemical characterization and strategic selection of BFRs for PBT assessment2004In: Abstract BFR2004 Toronto, 2004Conference paper (Other academic)
  • 150.
    Andersson, Per M
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wold, Svante
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lundstedt, Torbjörn
    Comparison between physicochemical and calculated molecular descriptors2000In: Journal of Chemometrics: Special Issue: Proceedings of the SSC6, August 1999, HiT/TF, Norway . Issue Edited by Kim Esbensen, Vol. 14, no 5-6, p. 629-42Article in journal (Refereed)
    Abstract [en]

    It has earlier been proven that measured physicochemical properties are useful in the selection of building blocks for combinatorial chemistry as well as for investigation of the scope and limitations of organic reactions. However, measured physicochemical properties are only available for small subsets of reagents, starting materials or building blocks; therefore it is necessary to use calculated descriptors and it is essential that the descriptors are relevant. The objective was to investigate whether three different descriptor data sets contained similar information about the chemical structure, with the major aim to investigate whether calculated descriptors contain similar information as experimental data. A total of 205 heterogeneous primary amines were characterized using three different data sets of molecular descriptor variables. The first set consisted of four physicochemical variables compiled from the literature and commercially available chemicals in chemical catalogues. From these four descriptors together with molecular weight, three additional descriptors could be calculated, resulting in a total of eight descriptor variables in the first data set. The second data set consisted of 81 calculated molecular descriptor variables relating to size, connectivity, atom count, topology and electrotopology indices. The third data set consisted of 10 semi-empirical variables (AM1). All the calculated variables were generated using the software Tsar 3.11. The descriptor variable sets were compared using principal component analysis (PCA) and partial least squares projections to latent structures (PLS). The following result shows that the different descriptor sets do contain similar latent information and that the different types of calculated variables do correlate well with the experimental data, making them suitable to use for e.g. combinatorial library design.

1234567 101 - 150 of 4437
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf