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  • 51.
    Jahn, Burkhard O.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Galperin, Michael
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, United States.
    Fransson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi.
    Organic Single Molecular Structures for Light Induced Spin-Pump Devices2013Ingår i: ACS Nano, ISSN 1936-0851, E-ISSN 1936-086X, Vol. 7, nr 2, s. 1064-1071Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present theoretical results on molecular structures for realistic spin-pump applications. Taking advantage of the electron spin resonance concept, we find that interesting candidates constitute triplet biradicals with two strongly spatially and energetically separated singly occupied molecular orbitals (SOMOs). Building on earlier reported stable biradicals, particularly bis(nitronyl nitroxide) based biradicals, we employ density functional theory to design a selection of potential molecular spin-pumps which should be persistent at ambient conditions. We estimate that our proposed molecular structures will operate as spin-pumps using harmonic magnetic fields in the MHz regime and optical fields in the infrared to visible light regime.

  • 52.
    Jorner, Kjell
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ayub, Rabia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Denisova, Aleksandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Siloles and cyclopentadienes as "aromatic chameleons" influenced by aromaticity in both the ground state and lowest electronically excited states2014Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 247, artikel-id 560-ORGNArtikel i tidskrift (Övrigt vetenskapligt)
  • 53.
    Jorner, Kjell
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Tong, Hui
    Denisova, Aleksandra V.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Impact of Ground- and Excited-State Aromaticity on Cyclopentadiene and Silole Excitation Energies and Excited-State Polarities2014Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, nr 30, s. 9295-9303Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A new qualitative model for estimating the properties of substituted cyclopentadienes and siloles in their lowest pi pi* excited states is introduced and confirmed through quantum chemical calculations, and then applied to explain earlier reported experimental excitation energies. According to our model, which is based on excited-state aromaticity and antiaromaticity, siloles and cyclopentadienes are cross-hyperconjugated "aromatic chameleons" that adapt their electronic structures to conform to the various aromaticity rules in different electronic states (Huckel's rule in the pi(2) electronic ground state (S-0) and Baird's rule in the lowest pi pi* excited singlet and triplet states (S-1 and T-1)). By using pen-and-paper arguments, one can explain polarity changes upon excitation of substituted cyclopentadienes and siloles, and one can tune their lowest excitation energies by combined considerations of ground-and excited-state aromaticity/antiaromaticity effects. Finally, the "aromatic chameleon" model can be extended to other monocyclic compound classes of potential use in organic electronics, thereby providing a unified view of the S-0, T-1, and S-1 states of a range of different cyclic cross-pi-conjugated and cross-hyperconjugated compound classes.

  • 54.
    Jorner, Kjell
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Tong, Hui
    State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences.
    Densiova, Aleksandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Using Ground and Excited State Aromaticity to Understand Cyclopentadiene and Silole Excitation Energies and Excited State PolaritiesArtikel i tidskrift (Övrigt vetenskapligt)
  • 55.
    Jorner, Kjell
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Feixas, Ferran
    Univ Girona, IQCC, Campus Montilivi S-N, Girona 17071, Catalonia, Spain.;Univ Girona, Dept Quim, Campus Montilivi S-N, Girona 17071, Catalonia, Spain..
    Ayub, Rabia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Lindh, Roland
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi. Uppsala Univ, Uppsala Ctr Computat Chem UC3, Box 518, S-75120 Uppsala, Sweden..
    Sola, Miquel
    Univ Girona, IQCC, Campus Montilivi S-N, Girona 17071, Catalonia, Spain.;Univ Girona, Dept Quim, Campus Montilivi S-N, Girona 17071, Catalonia, Spain..
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Analysis of a Compound Class with Triplet States Stabilized by Potentially Baird Aromatic [10]Annulenyl Dicationic Rings2016Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 22, nr 8, s. 2793-2800Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The low-lying triplet state of a recently published compound (TMTQ) was analyzed quantum chemically in light of suggestions that it is influenced by Baird aromaticity. Two mesomeric structures describe this state: 1)a zwitterionic Baird aromatic structure with a triplet diradical 8-electron methano[10]annulene (M10A) dicationic ring and 2)a Huckel aromatic with a neutral closed-shell 10-electron ring. According to charge and spin density distributions, the Huckel aromatic structure dominates the triplet state (the Baird aromatic contributes at most 12%), and separation of the aromatic fluctuation index (FLU) into and electron contributions emphasizes this finding. The small singlet-triplet energy gap is due to Huckel aromaticity of the M10A ring, clarified by comparison to the smaller analogues of TMTQ. Yet, TMTQ and its analogues are Huckel-Baird hybrids allowing for tuning between closed-shell 4n+2 Huckel aromaticity and open-shell 4n Baird aromaticity.

  • 56. Kepe, Vladimir
    et al.
    Moghbel, Mateen C.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Zaidi, Habib
    Vinters, Harry V.
    Huang, Sung-Cheng
    Satyamurthy, Nagichettiar
    Doudet, Doris
    Mishani, Eyal
    Cohen, Robert M.
    Hoilund-Carlsen, Poul F.
    Alavi, Abass
    Barrio, Jorge R.
    Amyloid-beta Positron Emission Tomography Imaging Probes: A Critical Review2013Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 36, nr 4, s. 613-631Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The rapidly rising prevalence and cost of Alzheimer's disease in recent decades has made the imaging of amyloid-beta deposits the focus of intense research. Several amyloid imaging probes with purported specificity for amyloid-beta plaques are currently at various stages of FDA approval. However, a number of factors appear to preclude these probes from clinical utilization. As the available "amyloid specific" positron emission tomography imaging probes have failed to demonstrate diagnostic value and have shown limited utility for monitoring therapeutic interventions in humans, a debate on their significance has emerged. The aim of this review is to identify and discuss critically the scientific issues contributing to the extensive inconsistencies reported in the literature on their purported in vivo amyloid specificity and potential utilization in patients.

  • 57. Kivimaeki, A.
    et al.
    Norman, P.
    Coreno, M.
    de Simone, M.
    Grazioli, C.
    Totani, R.
    Ressel, B.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Puglia, Carla
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Molekyl- och kondenserade materiens fysik.
    Use of two-dimensional photoelectron spectroscopy in the decomposition of an inner-shell excitation spectrum broadened by super-Coster-Kronig decay2013Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics, ISSN 1050-2947, E-ISSN 1094-1622, Vol. 88, nr 6, s. 062502-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Ge 3p core excitation spectrum of the n-butylgermane molecule only reveals two peaks, whereas the rest of the fine structure is obscured due to the large lifetime broadenings of core-excited states. A two-dimensional presentation of resonant photoemission spectra allows us to observe some other resonances. The interpretation of experimental results is supported by ab initio calculations conducted at the four-component relativistic level of theory with full account made for spin-orbit interactions already in the zeroth-order Hamiltonian.

  • 58. Laakso, Johanna
    et al.
    Rosser, Geraldine A.
    Szijjarto, Csongor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Beeby, Andrew
    Borbas, Eszter K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Synthesis of Chlorin-Sensitized Near Infrared-Emitting Lanthanide Complexes2012Ingår i: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 51, nr 19, s. 10366-10374Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lanthanide (Yb3+, Nd3+) complexes equipped with red-absorbing hydroporphyrin (chlorin) antennae were synthesized and characterized. The syntheses are scalable, highly modular, and enable the introduction of different chlorins functionalized with a single reactive group (COOH or NH2). Absorption maxima were dependent on chlorin substitution pattern (monomeso aryl or dimeso aryl) and metalation state (free base or zinc chelate). The complexes benefit from dual chlorin (610-639 nm) and lanthanide (980 or 1065 nm for Yb- or Nd-complexes, respectively) emission in the biologically relevant red and near IR region of the spectrum.

  • 59.
    Langstrom, Bengt
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Karimi, Farhad
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Watanabe, Y.
    Endogenous compounds labeled with radionuclides of short half-life - some perspectives2013Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 56, nr 3-4, s. 251-262Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In the article, the strategy and synthesis of some endogenous compounds labeled mainly with 11C are presented. There are some examples illustrating how endogenous labeled compounds in connection with positron emission tomography have unique properties to describe various biological processes, and a few examples of the use of tracers labeled with 13N and 15O are also discussed. Labeled endogenous compounds may be an important asset to describe the conditions and the status of biological systems and might therefore be a key for the future search of individualized medicine.

  • 60. Lindgren, Cecilia
    et al.
    Andersson, Ida E.
    Berg, Lotta
    Dobritzsch, Doreen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Ge, Changrong
    Haag, Sabrina
    Uciechowska, Urszula
    Holmdahl, Rikard
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Linusson, Anna
    Hydroxyethylene isosteres introduced in type II collagen fragments substantially alter the structure and dynamics of class II MHC A(q)/glycopeptide complexes2015Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, nr 22, s. 6203-6216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Class II major histocompatibility complex (MHC) proteins are involved in initiation of immune responses to foreign antigens via presentation of peptides to receptors of CD4(+) T-cells. An analogous presentation of self-peptides may lead to autoimmune diseases, such as rheumatoid arthritis (RA). The glycopeptide fragment CII259-273, derived from type II collagen, is presented by A(q) MHCII molecules in the mouse and has a key role in development of collagen induced arthritis (CIA), a validated model for RA. We have introduced hydroxyethylene amide bond isosteres at the Ala(261)-Gly(262) position of CII259-273. Biological evaluation showed that A(q) binding and T cell recognition were dramatically reduced for the modified glycopeptides, although static models predicted similar binding modes as the native type II collagen fragment. Molecular dynamics (MD) simulations demonstrated that introduction of the hydroxyethylene isosteres disturbed the entire hydrogen bond network between the glycopeptides and A(q). As a consequence the hydroxyethylene isosteric glycopeptides were prone to dissociation from A(q) and unfolding of the beta(1)-helix. Thus, the isostere induced adjustment of the hydrogen bond network altered the structure and dynamics of A(q)/glycopeptide complexes leading to the loss of A(q) affinity and subsequent T cell response.

  • 61.
    Löfås, Henrik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Grigoriev, Anton
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Conductance through Carbosilane Cage Compounds: A Computational Investigation2013Ingår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 117, nr 42, s. 21692-21699Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Silicon is still the dominating material in microelectronics, yet primarily π-conjugated hydrocarbons are investigated in the field of single-molecule electronics even though linear oligosilanes are σ-conjugated. A drawback with the latter is their high conformational flexibility which strongly affects conductance. Here we report on a first principles density functional theory investigation of a series of rigid [2.2.2]bicyclic carbosilanes with 3, 2, 1, or 0 disilanylene bridges, providing all-silicon paths for charge transport. It is explored if these paths can be seen as independent and equivalent current paths acting as parallel resistors. For high conductance through the carbosilanes they need to be anchored to the gold electrodes via groups that are matched with the σ-conjugated paths of the oligosilane cage segment, and we find that silyl (SiH3) groups are better matched than thiophenol groups. Even for the carbosilane with three disilanylene bridges we find that the most transmitting conductance channel is not equally distributed on the three parallel bridges. In addition, there is significant communication between the various pathways, which results in destructive interference lowering the conductance. Taken together, the different disilanylene bridges in the cage compounds do not act as parallel resistors.

  • 62.
    Löfås, Henrik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Grigoriev, Anton
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Molecular Conductance Switches Exploiting Baird's Rule on Excited State Aromaticity and AntiaromaticityManuskript (preprint) (Övrigt vetenskapligt)
  • 63.
    Löfås, Henrik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Jahn, B. O.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Wärnå, John
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ahuja, Rajeev
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Grigoriev, Anton
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    A computational study of potential molecular switches that exploit Baird's rule on excited-state aromaticity and antiaromaticity2014Ingår i: Faraday discussions (Online), ISSN 1359-6640, E-ISSN 1364-5498, Vol. 174, s. 105-124Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of tentative single-molecule conductance switches which could be triggered by light were examined by computational means using density functional theory (DFT) with non-equilibrium Green's functions (NEGF). The switches exploit the reversal in electron counting rules for aromaticity and antiaromaticity upon excitation from the electronic ground state (S0) to the lowest [small pi][small pi]* excited singlet and triplet states (S1 or T1), as described by Huckel's and Baird's rules, respectively. Four different switches and one antifuse were designed which rely on various photoreactions that either lead from the OFF to the ON states (switches 1, 2 and 4, and antifuse 5) or from the ON to the OFF state (switch 3). The highest and lowest ideal calculated switching ratios are 1175 and 5, respectively, observed for switches 1 and 4. Increased thermal stability of the 1-ON isomer is achieved by benzannulation (switch 1B-OFF/ON). The effects of constrained electrode-electrode distances on activation energies for thermal hydrogen back-transfer from 1-ON to 1-OFF and the relative energies of 1-ON and 1-OFF at constrained geometries were also studied. The switching ratio is strongly distance-dependent as revealed for 1B-ON/OFF where it equals 711 and 148 when the ON and OFF isomers are calculated in electrode gaps with distances confined to either that of the OFF isomer or to that of the ON isomer, respectively.

  • 64.
    Miller, Philip W.
    et al.
    Department of Chemistry, Imperial College London, London, UK.
    Kato, Koichi
    Department of Molecular Imaging, National Centre of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
    Långstrom, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Carbon-11, Nitrogen-13, and Oxygen-15 Chemistry: An Introduction to Chemistry with Short-Lived Radioisotopes2015Ingår i: The Chemistry of Molecular Imaging / [ed] Nicholas Long and Wing-Tak Wong, Wiley-Blackwell, 2015, s. 79-103Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    This chapter first introduces the field of carbon-11, nitrogen-13, and oxygen-15 chemistry, and then provides an up-to-date account of their chemistry. The carbon-11 isotope is most widely produced by the proton bombardment of nitrogen-14 in a gas phase cyclotron target. 11CO2 is the most widely produced in target C-11 primary precursor. Methylation reactions are commonly used for the production of many of the key 11C-tracers. Palladium-mediated C-11 carbonylation reactions are most widely exploited and used to effectively label imides, ketones, carboxylic acids, esters, amides, and acrylamides. N-13 labelled amines are of interest for improving positron emission tomography (PET) myocardial perfusion imaging and representing their metabolism. Oxygen-15 is generally produced in target via the bombardment of nitrogen gas with deuterons. The majority of O-15 chemistry is therefore based on the production of small molecules either directly within the cyclotron target or via one chemical transformation using high temperature gas phase methods.

  • 65.
    Nachtigall, Olaf
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Lomoth, Reiner
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Lundstedt, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Webb, Matthew J
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Pyrene–Azobenzene Dyads and Their Photochemistry2014Ingår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2014, nr 5, s. 966-972Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The facile synthesis of three new folding azobenzene-pyrene systems 13, connected together by a serendipitously obtained and unpredicted ester linkage, is reported. Additional characterization of the photochemistry of these systems revealed variations in azobenzene photoisomerization (trans-cis and cis-trans) and quenching of pyrene fluorescence, as a result of intra-excitation energy transfer from the pyrene chromophore to an azobenzene. Through the use of aryl substituent electronic effects to tune the absorption properties of the azobenzene relative to the pyrene, we show that efficient photo-switching can be achieved when the trans-azobenzene absorbance band is well separated from that of the pyrene (compound 1), whereas overlap of the corresponding absorbance bands in the cases of 2 and 3 significantly compromises trans-cis isomerization by enhancing cis-trans interconversion.

  • 66. Nordberg, Agneta
    et al.
    Carter, Stephen F.
    Rinne, Juha
    Drzezga, Alexander
    Brooks, David J.
    Vandenberghe, Rik
    Perani, Daniela
    Forsberg, Anton
    Langstrom, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Scheinin, Noora
    Karrasch, Mira
    Nagren, Kjell
    Grimmer, Timo
    Miederer, Isabelle
    Edison, Paul
    Okello, Aren
    Van Laere, Koen
    Nelissen, Natalie
    Vandenbulcke, Mathieu
    Garibotto, Valentina
    Almkvist, Ove
    Kalbe, Elke
    Hinz, Rainer
    Herholz, Karl
    A European multicentre PET study of fibrillar amyloid in Alzheimer's disease2013Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, nr 1, s. 104-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. In this study 238 [C-11]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [C-11]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 +/- 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 +/- 8 years) and 51 healthy controls (mean age 67.4 +/- 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 +/- 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. [C-11]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [C-11]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [C-11]PIB retention was observed in MCI ApoE epsilon 4 carriers compared to non-ApoE epsilon 4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. This study demonstrated the robustness of [C-11]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.

  • 67.
    Norrehed, Sara
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Johansson, Henrik
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Improved stereochemical analysis of conformationally flexible diamines by binding to a bisporphyrin molecular clip2013Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 43, s. 14631-14638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The relative stereochemistry of acyclic diamines with several stereogenic centers has been analyzed by NMR spectroscopy in combination with conformational deconvolution. Binding to a bisporphyrin molecular clip improves the stereochemical assignment significantly. The diamines were synthesized from inexpensive sugar alcohols, and their stable hydrochlorides were quantitatively converted into free bases by treatment with ion-exchange resin.

  • 68.
    Norrehed, Sara
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Polavarapu, Prasad
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Yang, Wenzhi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Conformational restriction of flexible molecules in solution by a semirigid bis-porphyrin molecular tweezer2013Ingår i: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 69, nr 34, s. 7131-7138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A semirigid bis-porphyrin molecular clip with a glycoluril backbone has been synthesized. The clip provides an adaptable molecular cavity for binding of diamines. Binding constants for diamines of 104–107 M−1 are orders of magnitude higher than those for monoamines of 103 M−1, indicating a preference to bidentate binding. NMR studies confirmed that binding of bidentate guests occurs inside the clip. Short- and medium-size acyclic molecular guests are locked into a single, extended conformation, and also guests with longer flexible chains exhibit considerably less conformational mobility than when free in solution. The size of the cavity adapts to the guest size, as indicated by modelling studies and self diffusion constants of the complexes.

  • 69. Olsson, Gustaf D.
    et al.
    Karlsson, Bjorn C. G.
    Shoravi, Siamak
    Wiklander, Jesper G.
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Mechanisms underlying molecularly imprinted polymer molecular memory and the role of crosslinker: resolving debate on the nature of template recognition in phenylalanine anilide imprinted polymers2012Ingår i: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 25, nr 2, s. 69-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of molecular dynamics simulations of prepolymerization mixtures for phenylalanine anilide imprinted co-(ethylene glycol dimethacrylate-methacrylic acid) molecularly imprinted polymers have been employed to investigate the mechanistic basis for template selective recognition in these systems. This has provided new insights on the mechanisms underlying template recognition, in particular the significant role played by the crosslinking agent. Importantly, the study supports the occurrence of template self-association events that allows us to resolve debate between the two previously proposed models used to explain this system's underlying recognition mechanisms. Moreover, the complexity of the molecular level events underlying template complexation is highlighted by this study, a factor that should be considered in rational molecularly imprinted polymer design, especially with respect to recognition site heterogeneity.

  • 70.
    Olsson, Gustaf D.
    et al.
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, S-39182 Kalmar, Sweden..
    Niedergall, Klaus
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany..
    Bach, Monika
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany.;Univ Stuttgart, Inst Interfacial Engn & Plasmatechnol IGVT, D-70174 Stuttgart, Germany..
    Karlsson, Björn C. G.
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, S-39182 Kalmar, Sweden..
    Tovar, Guenter
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany.;Univ Stuttgart, Inst Interfacial Engn & Plasmatechnol IGVT, D-70174 Stuttgart, Germany..
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, S-39182 Kalmar, Sweden..
    Simulation of imprinted emulsion prepolymerization mixtures2015Ingår i: Polymer journal, ISSN 0032-3896, E-ISSN 1349-0540, Vol. 47, nr 12, s. 827-830Artikel i tidskrift (Refereegranskat)
  • 71.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    ORGANIC PHOTOCHEMISTRY Exciting excited-state aromaticity2012Ingår i: Nature Chemistry, ISSN 1755-4330, E-ISSN 1755-4349, Vol. 4, nr 12, s. 969-971Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 72.
    Ottosson, Henrik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Borbas, K. Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    AROMATICITY A light-switched yin and yang pair2015Ingår i: Nature Chemistry, ISSN 1755-4330, E-ISSN 1755-4349, Vol. 7, nr 5, s. 373-375Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 73.
    Over, Bjorn
    et al.
    AstraZeneca R&D Gothenburg, Innovat Med & Early Dev Biotech Unit, Cardiovasc & Metab Dis, Molndal, Sweden..
    Matsson, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tyrchan, Christian
    AstraZeneca R&D Gothenburg, Innovat Med & Early Dev Biotech Unit, Resp Inflammat & Autoimmun Dis, Molndal, Sweden..
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Doak, Bradley C.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Foley, Michael A.
    Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.;Triinst Therapeut Discovery Inst, New York, NY USA..
    Hilgendorf, Constanze
    AstraZeneca R&D Gothenburg, Safety & ADME Translat Sci, Drug Safety & Metab, Molndal, Sweden..
    Johnston, Stephen E.
    Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA..
    Lee, Maurice D.
    Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.;Ensemble Therapeut, Cambridge, MA 02139 USA..
    Lewis, Richard J.
    AstraZeneca R&D Gothenburg, Innovat Med & Early Dev Biotech Unit, Resp Inflammat & Autoimmun Dis, Molndal, Sweden..
    McCarren, Patrick
    Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA..
    Muncipinto, Giovanni
    Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.;Ensemble Therapeut, Cambridge, MA 02139 USA..
    Norinder, Ulf
    Swedish Toxicol Sci Res Ctr, Sodertalje, Sweden..
    Perry, Matthew W. D.
    Duvall, Jeremy R.
    Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.;Ensemble Therapeut, Cambridge, MA 02139 USA..
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Structural and conformational determinants of macrocycle cell permeability2016Ingår i: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 12, nr 12, s. 1065-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 nonpeptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.

  • 74. Over, Bjorn
    et al.
    McCarren, Patrick
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Foley, Michael
    Giordanetto, Fabrizio
    Gronberg, Gunnar
    Hilgendorf, Constanze
    Lee, Maurice D.
    Matsson, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Muncipinto, Giovanni
    Pellisson, Melanie
    Perry, Matthew W. D.
    Svensson, Richard
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Duvall, Jeremy R.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Impact of Stereospecific Intramolecular Hydrogen Bonding on Cell Permeability and Physicochemical Properties2014Ingår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 57, nr 6, s. 2746-2754Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Profiling of eight stereoisomeric T. cruzi growth inhibitors revealed vastly different in vitro properties such as solubility, lipophilicity, pK(a), and cell permeability for two sets of four stereoisomers. Using computational chemistry and NMR spectroscopy, we identified the formation of an intramolecular NH -> NR3 hydrogen bond in the set of stereoisomers displaying lower solubility, higher lipophilicity, and higher cell permeability. The intramolecular hydrogen bond resulted in a significant pKa difference that accounts for the other structure property relationships. Application of this knowledge could be of particular value to maintain the delicate balance of size, solubility, and lipophilicity required for cell penetration and oral administration for chemical probes or therapeutics with properties at, or beyond, Lipinski's rule of 5.

  • 75.
    Papadakis, Raffaello
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    The excited state antiaromatic benzene ring: a molecular Mr Hyde?2015Ingår i: Chemical Society Reviews, ISSN 0306-0012, E-ISSN 1460-4744, Vol. 44, nr 18, s. 6472-6493Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The antiaromatic character of benzene in its first pi pi(star) excited triplet state (T-1) was deduced more than four decades ago by Baird using perturbation molecular orbital (PMO) theory [J. Am. Chem. Soc. 1972, 94, 4941], and since then it has been confirmed through a range of high-level quantum chemical calculations. With focus on benzene we now first review theoretical and computational studies that examine and confirm Baird's rule on reversal in the electron count for aromaticity and antiaromaticity of annulenes in their lowest triplet states as compared to Huckel's rule for the ground state (S-0). We also note that the rule according to quantum chemical calculations can be extended to the lowest singlet excited state (S-1) of benzene. Importantly, Baird, as well as Aihara [Bull. Chem. Soc. Jpn. 1978, 51, 1788], early put forth that the destabilization and excited state antiaromaticity of the benzene ring should be reflected in its photochemical reactivity, yet, today these conclusions are often overlooked. Thus, in the second part of the article we review photochemical reactions of a series of benzene derivatives that to various extents should stem from the excited state antiaromatic character of the benzene ring. We argue that benzene can be viewed as a molecular "Dr Jekyll and Mr Hyde" with its largely unknown excited state antiaromaticity representing its "Mr Hyde" character. The recognition of the "Jekyll and Hyde" split personality feature of the benzene ring can likely be useful in a range of different areas.

  • 76.
    Pershagen, Elias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Development and Multicolor Imaging Applications of Lanthanide-Based Luminescent Probes2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The study of biological analytes in their native environment is a major challenge for biochemistry and molecular biology.  Luminesce spectroscopy is well suited for this task due to its non-invasiveness, high spatial and temporal resolution, and high signal to noise ratio. This thesis describes the development and applications of Ln-based luminescent probes for detecting small molecules and enzymes.  Specifically the probes presented are based on coumarin sensitizers coupled to a DO3A chelated LnIII center. The 1st generation of these probes employ 7-OH coumarins, caged at the 7-O position (Chapter 2). By use of p-pinacolatoboron benzyl or p-methoxybenzyl cages, this design allowed the construction of ratiometric EuIII-based probes capable of detecting the reactive oxygen species H2O2, NO and ONOO.

    The second and third part of the thesis describes a further improvement of the design (Chapters 3 and 4). By employing caged coumarin precursors EuIII and TbIII-based probes were developed for a variety of different analytes (F, Pd0, H2O2, β-galactosidase, β-glucosidase, α-mannosidase and phosphatase). Most of these probes displayed excellent turn-on responses when treated with their respective analytes. Furthermore they could be used for detecting multiple analytes simultaneously (Chapter 4). By use of one Eu-based and another Tb-based probe, the simultaneous detection of two analytes was possible. This could further be extended to simultaneous three analyte detection by the additional employment of an organic coumarin-based probe.

    The last part of the thesis (Chapter 5) describes protocols for the rapid and efficient access to triazole-linked lanthanide-antenna complexes by use of the copper-catalyzed azide-alkyne cycloaddition reaction. For robust substrates, microwave heating at 100 °C enabled rapid (15-60 min) access to various lanthanide complexes, which could be isolated via simple precipitation. Using these conditions pure bi- and tri-homometallic lanthanide complexes could be prepared. A second protocol, for substrates carrying sensitive functionalities was also developed. The application of catalytic amounts of CuOAc, BimPy2 ligand, and a large excess of NaAsc afforded a variety of lanthanide complexes, among them caged responsive probes, in moderate to good yields.

     

    Delarbeten
    1. A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes
    Öppna denna publikation i ny flik eller fönster >>A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes
    2013 (Engelska)Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 9, s. 3099-3109Artikel, forskningsöversikt (Refereegranskat) Published
    Abstract [en]

    Coumarin-sensitized, long-wavelength-absorbing luminescent EuIII-complexes have been synthesized and characterized. The lanthanide binding site consists of a cyclen-based chelating framework that is attached through a short linker to a 7-hydroxycoumarin, a 7-B(OH)2-coumarin, a 7-O-(4-pinacolatoboronbenzyl)-coumarin or a 7-O-(4-methoxybenzyl)-coumarin. The syntheses are straightforward, use readily available building blocks, and proceed through a small number of high-yielding steps. The sensitivity of coumarin photophysics to the 7-substituent enables modulation of the antenna-absorption properties, and thus the lanthanide excitation spectrum. Reactions of the boronate-based functionalities (cages) with H2O2 yielded the corresponding 7-hydroxycoumarin species. The same species was produced with peroxynitrite in a x106107-fold faster reaction. Both reactions resulted in the emergence of a strong approximate to 407nm excitation band, with concomitant decrease of the 366nm band of the caged probe. In aqueous solution the methoxybenzyl caged Eu-complex was quenched by ONOO. We have shown that preliminary screening of simple coumarin-based antennae through UV/Vis absorption spectroscopy is possible as the changes in absorption profile translate with good fidelity to changes in EuIII-excitation profile in the fully elaborated complex. Taken together, our results show that the 7-hydroxycoumarin antenna is a viable scaffold for the construction of turn-on and ratiometric luminescent probes.

    Nyckelord
    coumarins, cyclen, europium, fluorescent probes, lanthanides, reactive oxygen species
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-197616 (URN)10.1002/chem.201203957 (DOI)000315142300022 ()
    Tillgänglig från: 2013-04-01 Skapad: 2013-04-01 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    2. Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation
    Öppna denna publikation i ny flik eller fönster >>Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation
    2012 (Engelska)Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, nr 24, s. 9832-9835Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A new strategy for accessing analyte-responsive luminescent probes is presented. The lanthanide luminescence of Eu and Tb centers is switched on by the analyte-triggered formation of a sensitizing antenna from a nonsensitizing caged precursor. As the cage can be freely varied, an array of probes for different analytes (pd(0/2+), H2O2, F-, beta-galactosidase) can be created from the same core structure. The probe design affords nanomolar to micromolar detection limits, provides the capability to detect two analytes in parallel, and can be utilized to monitor enzymatic activity in live cells.

    Nationell ämneskategori
    Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-177592 (URN)10.1021/ja3004045 (DOI)000305358900002 ()
    Tillgänglig från: 2012-07-16 Skapad: 2012-07-16 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes
    Öppna denna publikation i ny flik eller fönster >>Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes
    2015 (Engelska)Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 54, nr 6, s. 1787-1790Artikel i tidskrift (Refereegranskat) Published
    Nationell ämneskategori
    Organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-236755 (URN)10.1002/anie.201408560R1 (DOI)000349209200016 ()25504579 (PubMedID)
    Tillgänglig från: 2014-11-22 Skapad: 2014-11-22 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    4. Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition
    Öppna denna publikation i ny flik eller fönster >>Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition
    2012 (Engelska)Ingår i: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 41, nr 25, s. 7660-7669Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cu-I-catalysed azide-alkyne cycloaddition reactions were used to functionalise lanthanide(III)-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly accelerated the reactions, enabling full conversion to the triazole products in some cases in 5 min. Alkyl and aryl azides and alkyl and aryl alkynes could all serve as coupling partners. These reaction conditions proved efficient for cyclen-tricarboxylates and previously unreactive cyclen-tris-primary amide chelates. The synthesis of heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic (Eu/La/Eu) complexes was achieved in up to 60% isolated yield starting from coumarin 2-appended alkynyl complexes Tb16 or La16 and an azido-Eu complex Eu4, and bis-alkynyl La-complex La5 and Eu4, respectively. EuTb17 displayed dual Eu-III and Tb-III-emission upon antenna-centred excitation.

    Nationell ämneskategori
    Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-178965 (URN)10.1039/c2dt30569k (DOI)000304912000025 ()
    Tillgänglig från: 2012-08-03 Skapad: 2012-08-02 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
  • 77. Pershagen, Elias
    et al.
    Borbas, Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Analyte-switchable singlet oxygen generating lanthanide complexes2013Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 245, s. 186-INOR-Artikel i tidskrift (Övrigt vetenskapligt)
  • 78. Pershagen, Elias
    et al.
    Borbas, Eszter K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Lanthanide-based luminescent probes for the detection of enzymatic activity2014Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 247Artikel i tidskrift (Övrigt vetenskapligt)
  • 79.
    Pershagen, Elias
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Borbas, K. Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Designing reactivity-based responsive lanthanide probes for multicolor detection in biological systems2014Ingår i: Coordination chemistry reviews, ISSN 0010-8545, E-ISSN 1873-3840, Vol. 273, s. 30-46Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Strategies for the design and synthesis of responsive luminescent probes based on lanthanide complexes are surveyed. The sensitive detection of analytes ranging from ions to small molecules to large biomolecules such as enzymes in complex biological milieu drives the quest for even more selective probes with improved photophysical properties and broad availability for non-specialists. Here, reactivity-based probes, i.e. those in which the sensing event is accompanied by the breaking of a covalent bond are reviewed, with an emphasis on the strategies that could be generalized to the detection of additional analytes. Syntheses providing advanced cyclen-based ligands with minimum effort, as well as those that enable post-complexation modification of lanthanide-bound structures are presented. (C) 2013 Elsevier B.V. All rights reserved.

  • 80.
    Pershagen, Elias
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Borbas, K. Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes2015Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 54, nr 6, s. 1787-1790Artikel i tidskrift (Refereegranskat)
  • 81. Pershagen, Elias
    et al.
    Nordholm, Johan
    Borbas, K. Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation2012Ingår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, nr 24, s. 9832-9835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A new strategy for accessing analyte-responsive luminescent probes is presented. The lanthanide luminescence of Eu and Tb centers is switched on by the analyte-triggered formation of a sensitizing antenna from a nonsensitizing caged precursor. As the cage can be freely varied, an array of probes for different analytes (pd(0/2+), H2O2, F-, beta-galactosidase) can be created from the same core structure. The probe design affords nanomolar to micromolar detection limits, provides the capability to detect two analytes in parallel, and can be utilized to monitor enzymatic activity in live cells.

  • 82.
    Pershagen, Elias
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Szijjarto, Csongor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Borbas, Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Biological tools based on trivalent lanthanides2013Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 246, s. 350-INOR-Artikel i tidskrift (Övrigt vetenskapligt)
  • 83.
    Peterson, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Svärdsudd, Kurt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Appel, Lieuwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Engler, Henry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Aarnio, Mikko
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Langström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    PET-Scan Shows Peripherally Increased Neurokinin 1 Receptor Availability in Chronic Tennis Elbow: Visualizing Neurogenic Inflammation?2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, s. e75859-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET) with the NK1 specific radioligand [C-11]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.

  • 84. Ramapanicker, Ramesh
    et al.
    Sun, Xiaojiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Viljanen, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Powerful binders for the D-dimer by conjugation of the GPRP peptide to polypeptides from a designed set: illustrating a general route to new binders for proteins2013Ingår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 24, nr 1, s. 17-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The synthetic tetrapeptide GPRP based on the amino-terminal GPR sequence of the fibrin α-chain, binds the D-dimer protein with a dissociation constant KD of 25 μM. The D-dimer protein, a well-known biomarker for thrombosis, contains two cross-linked D fragments from the fibrinogen protein formed upon degradation of the fibrin gel, the core component of blood clots. In order to develop a specific high-affinity binder for the D-dimer protein, GPRP was conjugated via an aliphatic spacer to each member of a set of sixteen polypeptides designed for the development of binder molecules for proteins in general. The binders were individually characterised and ranked using surface plasmon resonance (SPR) analysis. The dissociation constant of the complex formed from the D-dimer and 4-D15L8-GPRP labelled with fluorescein was determined by fluorescense titration and found to be 3 nM, an affinity four orders of magnitude higher than that of free GPRP. According to SPR analysis binding was completely inhibited by free GPRP at mM concentrations and the polypeptide conjugate was therefore shown to bind specifically to the binding site of GPRP. Affinities were further enhanced by dimerisation of the polypeptide conjugates via a bifunctional linker resulting in dissociation constants that were further decreased (affinities increased) by factors of 2-4. The results suggest an efficient route to specific binders for proteins based on short peptides with affinites that need only to be modest, thus shortening the time of binder development dramatically.

  • 85. Rosenberg, Martin
    et al.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Kilsa, Kristine
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Excited State Aromaticity and Antiaromaticity: Opportunities for Photophysical and Photochemical Rationalizations2014Ingår i: Chemical Reviews, ISSN 0009-2665, E-ISSN 1520-6890, Vol. 114, nr 10, s. 5379-5425Artikel, forskningsöversikt (Refereegranskat)
  • 86.
    Rosenberg, Martin
    et al.
    Department of Chemistry, University of Copenhagen.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Kilså, Kristine
    Department of Chemistry, University of Copenhagen.
    Manipulation of Excited State Energies in Fulvenic MoleculesManuskript (preprint) (Övrigt vetenskapligt)
  • 87. Rosengren, Annika M.
    et al.
    Karlsson, Bjorn C. G.
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Monitoring the Distribution of Warfarin in Blood Plasma2012Ingår i: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 3, nr 8, s. 650-652Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Warfarin is an anticoagulant drug extensively used in the treatment and prevention of thrombotic disorders. Previous studies have shown that warfarin binds extensively to blood plasma proteins and that only a small fraction of the drug is unbound and thus available for therapeutic function. Both warfarin's narrow therapeutic window and the susceptibility of anticoagulant function to patient-dependent factors necessitate regular monitoring. In this study, we have shown that the lifetimes for each of the various bound and free forms of the drug in blood plasma can be quantified in situ by time-correlated single-photon counting fluorescence spectroscopy over the clinically significant concentration range. A relationship between the blood coagulation and the distribution of fluorescence lifetimes was observed. The in situ detection of clinically relevant concentrations of warfarin in its respective bound and unbound forms could provide a prognostic tool for use in patient treatment.

  • 88.
    Rouf, Alvi M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Tibbelin, Julius
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Jahn, Burkhard O.
    Anas, Saithalavi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Lozinski, Kaitlin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Efficient and convenient acid catalyzed hypersilyl protection of alcohols and thiols by tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide2013Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 245, s. 312-ORGN-Artikel i tidskrift (Övrigt vetenskapligt)
  • 89. Ruibal, A.
    et al.
    Benlloch, J. M.
    Olmos, R. V.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Molecular imaging in breast cancer2012Ingår i: Journal of Oncology, ISSN 1687-8450, Vol. 2012, s. 426260-Artikel, forskningsöversikt (Refereegranskat)
  • 90. Rydberg, Johan
    et al.
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Sarojini, Vijayalekshmi
    Intrinsically unstructured proteins by designelectrostatic interactions can control binding, folding, and function of a helix-loop-helix heterodimer2013Ingår i: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 19, nr 8, s. 461-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intrinsically disordered proteins that exist as unordered monomeric structures in aqueous solution at pH7 but fold into four-helix bundles upon binding to recognized polypeptide targets have been designed. NMR and CD spectra of the monomeric polypeptides show the hallmarks of unordered structures, whereas in the bound state they are highly helical. Analytical ultracentrifugation data shows that the polypeptides bind to their targets to form exclusively heterodimers at neutral pH. To demonstrate the relationship between binding, folding, and function, a catalytic site for ester hydrolysis was introduced into an unordered and largely inactive monomer, but that was structured and catalytically active in the presence of a specific polypeptide target. Electrostatic interactions between surface-exposed residues inhibited the binding and folding of the monomers at pH7. Charge-charge repulsion between ionizable amino acids was thus found to be sufficient to disrupt binding between polypeptide chains despite their inherent propensities for structure formation and may be involved in the folding and function of inherently disordered proteins in biology. 

  • 91.
    Sawadjoon, Supaporn
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Lundstedt, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Samec, Joseph
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Pd-Catalyzed Transfer Hydrogenolysis of Primary, Secondary, and Tertiary Benzylic Alcohols by Formic Acid: A Mechanistic Study2013Ingår i: ACS Catalysis, ISSN 2155-5435, Vol. 3, nr 4, s. 635-642Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A palladium-catalyzed transfer hydrogenolysis of primary, secondary, and tertiary benzylic alcohols by formic acid has been developed and studied. The product hydrocarbons were obtained in excellent yields from bothsecondary and tertiary benzylic alcohols and in good yields for primary benzylicalcohols. The rate of disappearance of 1-phenylethanol (1) follows zero-order dependence in 1 and first-order dependence in formic acid and palladium. Catalytic amounts of base inhibit a competing disproportionation reaction ofalcohol to alkane and ketone, and an optimum was obtained when 5 equiv ofbase to palladium was used Deuterium kinetic isotope studies for the transferhydrogenolysis reveal individual isotope effects for the hydridic position (k(CHOH)/k(CDOH) = 2.26 +/- 0.24) and the protic position (k(CHOH)/k(CHOD) = 0.62 +/- 0.06) of the formic acid. Simultaneous deuteration in both positions offormic acid gave a combined isotope effect of (k(CHOH)/k(CDOD) = 1.41 +/- 0.11). We propose a mechanism involving the following steps: a competitive inhibition of the open palladium site by adsorption of the formate anion to generate formato-palladium species, followed by a reversible protonation and arate-limiting hydride transfer to obtain the active palladium with chemisorbed hydrogen that performs the hydrogenolysis of the alcohol in a fast reaction step.

  • 92.
    Sawadjoon, Supaporn
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Sjöberg, Per J R
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Orthaber, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Matsson, Olle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Samec, Joseph S M
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Mechanistic Insights into the Pd-Catalyzed Direct Amination of Allyl Alcohols: Evidence for an Outer-sphere Mechanism Involving a Palladium Hydride Intermediate2014Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, nr 6, s. 1520-1524Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mechanism of direct amination of allyl alcohol by a palladium triphenylphosphite complex has been explored. Labelling studies show that the reaction proceeds through a π-allylpalladium intermediate. A second-order dependence of reaction rate on allyl alcohol concentration was observed. Kinetic isotope effect studies and ESI-MS studies are in agreement with a reaction proceeding through a palladium hydride intermediate in which both O-H bond and C-O bond cleavages are involved in rate-determining steps. A stereochemical study supports an outer-sphere nucleophilic attack of the π-allylpalladium intermediate giving complete chiral transfer from starting material to product.

  • 93. Schillinger, E.
    et al.
    Möder, M.
    Olsson, G. D.
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Sellergren, B.
    An artificial estrogen receptor through combinatorial imprinting2012Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, nr 46, s. 14773-14783Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Polymeric sorbents targeting endocrine-disrupting estrogen active compounds (EAC) were prepared by terpolymer imprinting using 17β-estradiol (E2) as template. From a group of eight functional monomers representing Brønsted acids, bases, hydrogen-bond donors and acceptors, as well as π-interacting monomers, a terpolymer library that comprises all possible binary combinations of the functional monomers was prepared. Binding tests revealed that imprinted polymers exhibit a markedly higher affinity for E2 compared to nonimprinted polymers (NIPs) or polymers prepared by using single functional monomers. A combination of methacrylic acid (MAA) and p-vinylbenzoic acid offered a particularly promising lead polymer, displaying an imprinting factor of 17 versus 2.4 for a benchmark polymer prepared by using only MAA as functional monomer. The saturation capacities ascribed to imprinted sites were four to five times higher for this polymer compared to previously reported imprinted polymers. NMR titrations and molecular dynamics simulations corroborated these results, indicating an orthogonal preference of the two functional monomers with respect to the E2 3-OH and 17-OH groups. The optimized polymer exhibited a retentivity for EACs that correlates with their inhibitory effect on the natural receptor. By using the optimized molecularly imprinted polymers (MIPs) in a model water-purification system, they were capable of completely removing ppb levels of a small group of EACs from water. This is in contrast to the performance of nonimprinted polymers and well-established sorbents for water purification (e.g., active carbon), which still contained detectable amounts of the compounds after treatment. Receptor mimics: Combinatorially optimized imprinted polymers (MIPs, see figure) targeting endocrine disruptors exhibited a retentivity for estrogen active compounds (EACs), correlating with their inhibitory effect on the natural receptor. By using the optimized MIPs in a model system for water purification, they were capable of near-complete removal of ppb levels of a small group of EACs from water.

  • 94.
    Scholl, Michael
    et al.
    Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.;Univ Gothenburg, MedTech West, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Dept Clin Neurosci & Rehabil, S-41345 Gothenburg, Sweden..
    Carter, Stephen F.
    Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.;Univ Manchester, Wolfson Mol Imaging Ctr, Manchester M20 3LJ, Lancs, England..
    Westman, Eric
    Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Clin Geriatr, S-14157 Huddinge, Sweden..
    Rodriguez-Vieitez, Elena
    Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden..
    Almkvist, Ove
    Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.;Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, S-14186 Stockholm, Sweden.;Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden..
    Thordardottir, Steinunn
    Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, S-14186 Stockholm, Sweden.;Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Neurogeriatr, S-14157 Huddinge, Sweden..
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Graff, Caroline
    Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, S-14186 Stockholm, Sweden.;Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Neurogeriatr, S-14157 Huddinge, Sweden..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Nordberg, Agneta
    Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.;Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, S-14186 Stockholm, Sweden..
    Early astrocytosis in autosomal dominant Alzheimer's disease measured in vivo by multi-tracer positron emission tomography2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 16404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studying autosomal dominant Alzheimer's disease (ADAD), caused by gene mutations yielding nearly complete penetrance and a distinct age of symptom onset, allows investigation of presymptomatic pathological processes that can identify a therapeutic window for disease-modifying therapies. Astrocyte activation may occur in presymptomatic Alzheimer's disease (AD) because reactive astrocytes surround beta-amyloid (A beta) plaques in autopsy brain tissue. Positron emission tomography was performed to investigate fibrillar A beta, astrocytosis and cerebral glucose metabolism with the radiotracers C-11-Pittsburgh compound-B (PIB), C-11-deuterium-L-deprenyl (DED) and F-18-fluorodeoxyglucose (FDG) respectively in presymptomatic and symptomatic ADAD participants (n = 21), patients with mild cognitive impairment (n = 11) and sporadic AD (n = 7). Multivariate analysis using the combined data from all radiotracers clearly separated the different groups along the first and second principal components according to increased PIB retention/decreased FDG uptake (component 1) and increased DED binding (component 2). Presymptomatic ADAD mutation carriers showed significantly higher PIB retention than non-carriers in all brain regions except the hippocampus. DED binding was highest in presymptomatic ADAD mutation carriers. This suggests that non-fibrillar A beta or early stage plaque depostion might interact with inflammatory responses indicating astrocytosis as an early contributory driving force in AD pathology. The novelty of this finding will be investigated in longitudinal follow-up studies.

  • 95. Schöll, Michael
    et al.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Thordardottir, Steinunn
    Ferreira, Daniel
    Bogdanovic, Nenad
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Almkvist, Ove
    Graff, Caroline
    Nordberg, Agneta
    Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers2012Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, nr 3, s. 229-236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate the particular pathology of the Arctic APP (APParc) early-onset familial Alzheimer disease (eoFAD) mutation for the first time in vivo with PET in comparison with other eoFAD mutations and sporadic Alzheimer disease (sAD).

    Methods: We examined 2 APParc mutation carriers together with 5 noncarrier siblings cross-sectionally with C-11-labeled Pittsburgh compound B (PiB) and F-18-fluorodeoxyglucose (FDG) PET, as well as MRI, CSF biomarkers, and neuropsychological tests. Likewise, we examined 7 patients with sAD, 1 carrier of a presenilin 1 (PSEN1) mutation, 1 carrier of the Swedish APP (APPswe) mutation, and 7 healthy controls (HCs).

    Results: Cortical PiB retention was very low in the APParc mutation carriers while cerebral glucose metabolism and CSF levels of A beta(1-42), total and phosphorylated tau were clearly pathologic. This was in contrast to the PSEN1 and APPswe mutation carriers revealing high PiB retention in the cortex and the striatum in combination with abnormal glucose metabolism and CSF biomarkers, and the patients with sAD who showed typically high cortical PiB retention and pathologic CSF levels as well as decreased glucose metabolism when compared with HCs.

    Conclusions: The lack of fibrillar beta-amyloid (A beta) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of A beta(1-42) in CSF, that other forms of A beta such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.

  • 96.
    Sun, Xiaojiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    High Affinity Synthetic Molecular Binders for Proteins: Design, Synthesis and Evaluation2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis describes the design and synthesis of small molecule derivatives and their polypeptide conjugates as high affinity binders for proteins: the D-dimer protein (D-dimer), a biomarker for diagnosis of thromboembolic diseases; human myeloperoxidase (MPO), a biomarker for cardiovascular diseases; and chitinases, potential targets for asthma therapy. The interactions between the synthetic binder molecules and those proteins were evaluated by surface plasmon resonance (SPR) biosensor analysis and fluorescence spectroscopy. Competition SPR experiments or other methods proved that the small molecule components of the binder molecules were critical for binding and specifically bound to the original binding site of small molecules. The binder molecules consisted of a 42-residue helix-loop-helix polypeptide conjugated to a small molecule via aliphatic spacers of suitable length. The small molecules could be any type of moderately binding structure. In the binder development for the D-dimer, the tetrapeptide GPRP with a dissociation constant Kd of 25 μM was used and the affinity of 4C15L8GPRP obtained was estimated to be approximately 3 nM. In the binder development for MPO, salicylhydroxamic acid (SHA) with Kd of 2 μM was used and the affinity of 4C37L34C11SHA obtained was estimated to be approximately 0.4 nM. In the binder development for chitinases, a theobromine derivative (pentoxifylline) with a Kd of 43±10 μM was used and the affinity of 4C37L34-P obtained was estimated to be considerably higher than that of pentoxifylline. The binder molecules were identified from a 16-membered pool of candidates obtained by conjugating the small molecules to each member of a set of 16 designed polypeptides. The affinities were greatly enhanced by 2-3 orders of magnitude, compared to the small molecule. The polypeptides did not bind to the proteins with measurable affinities. The discovery of these new synthetic binders for protein targets can pave the way to diagnostic tests in vivo or in vitro, independent of antibodies.

     

    Delarbeten
    1. Powerful binders for the D-dimer by conjugation of the GPRP peptide to polypeptides from a designed set: illustrating a general route to new binders for proteins
    Öppna denna publikation i ny flik eller fönster >>Powerful binders for the D-dimer by conjugation of the GPRP peptide to polypeptides from a designed set: illustrating a general route to new binders for proteins
    2013 (Engelska)Ingår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 24, nr 1, s. 17-25Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The synthetic tetrapeptide GPRP based on the amino-terminal GPR sequence of the fibrin α-chain, binds the D-dimer protein with a dissociation constant KD of 25 μM. The D-dimer protein, a well-known biomarker for thrombosis, contains two cross-linked D fragments from the fibrinogen protein formed upon degradation of the fibrin gel, the core component of blood clots. In order to develop a specific high-affinity binder for the D-dimer protein, GPRP was conjugated via an aliphatic spacer to each member of a set of sixteen polypeptides designed for the development of binder molecules for proteins in general. The binders were individually characterised and ranked using surface plasmon resonance (SPR) analysis. The dissociation constant of the complex formed from the D-dimer and 4-D15L8-GPRP labelled with fluorescein was determined by fluorescense titration and found to be 3 nM, an affinity four orders of magnitude higher than that of free GPRP. According to SPR analysis binding was completely inhibited by free GPRP at mM concentrations and the polypeptide conjugate was therefore shown to bind specifically to the binding site of GPRP. Affinities were further enhanced by dimerisation of the polypeptide conjugates via a bifunctional linker resulting in dissociation constants that were further decreased (affinities increased) by factors of 2-4. The results suggest an efficient route to specific binders for proteins based on short peptides with affinites that need only to be modest, thus shortening the time of binder development dramatically.

    Nationell ämneskategori
    Organisk kemi Annan kemi
    Identifikatorer
    urn:nbn:se:uu:diva-183200 (URN)10.1021/bc300186z (DOI)000313933700003 ()
    Tillgänglig från: 2012-10-23 Skapad: 2012-10-23 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. A synthetic polypeptide conjugate from a 42-residue polypeptide and salicylhydroxamic acid binds human myeloperoxidase with high affinity
    Öppna denna publikation i ny flik eller fönster >>A synthetic polypeptide conjugate from a 42-residue polypeptide and salicylhydroxamic acid binds human myeloperoxidase with high affinity
    2012 (Engelska)Ingår i: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 18, nr 12, s. 731-739Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Myeloperoxidase (MPO) is a 150 kD tetrameric heme protein consisting of two heavy chains and two light chains, which ispresent in neutrophils, white blood cells, at concentrations between 2% and 5% and plays an important role in the innateimmune system. The MPO concentration in serum or plasma has been shown to be linked to the risk for cardiovasculardiseases, and MPO is considered to be a high potential diagnostic biomarker. To develop a molecule that binds MPO,salicylhydroxamic acid (SHA), a substrate analog inhibitor of MPO with a KD=2uM, was conjugated to a designed set of42-residue polypeptide scaffolds via 9- and 11-carbon atom aliphatic spacers to form 20 different protein binder candidates,and their interactions with MPO were evaluated by surface plasmon resonance analysis. The polypeptide conjugate4C37L34C11SHA was found to bind to MPO with an affinity that could be estimated to have a dissociation constant of around400 pM, nearly four orders of magnitude higher than that of SHA. Inhibition of binding to MPO by free SHA was observed incompetition experiments demonstrating that the binding of the polypeptide conjugate is dominated by the interactions ofSHA with the heme cavity. Although still in the future, the discovery of these new synthetic binders for MPO suggests aroute to clinical diagnostic tests in vivo or in vitro, independent of antibodies.

    Nationell ämneskategori
    Organisk kemi Annan kemi
    Identifikatorer
    urn:nbn:se:uu:diva-183195 (URN)10.1002/psc.2459 (DOI)000311053700003 ()
    Tillgänglig från: 2012-10-23 Skapad: 2012-10-23 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. Polypeptide conjugates that bind chitinases
    Öppna denna publikation i ny flik eller fönster >>Polypeptide conjugates that bind chitinases
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Polypeptide conjugates formed from members of a designed set of polypeptides and the chitinase inhibitors pentoxifylline, C4B3 and C5B1 were evaluated for affinity and selectivity towards chitinases. The polypeptide conjugate 4C37L34-P was found to recognize and bind chitinases from the fungal species Aspergillus nidulans and Neurospora crassa, as well as from the fungus Trichoderma viride and the bacterial strain Streptomyces griseus. The small organic molecule pentoxifylline and the polypeptide 4C37L34 both contributed to binding of the chitinases and the affinity of the polypeptide conjugate was significantly enhanced in comparison with that of pentoxifylline with an affinity that was on the order of 2-3 orders of magnitude higher than that of pentoxyfylline. In view of the large numbers of chitinases present in nature the recognition and detection of groups of chitinases using one binder molecule for many enzymes may be an advantageous approach.

    Nationell ämneskategori
    Organisk kemi Annan kemi Biologiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-183201 (URN)
    Tillgänglig från: 2012-10-23 Skapad: 2012-10-23 Senast uppdaterad: 2012-11-23
  • 97.
    Sun, Xiaojiao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Winander, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Karlsson, Magnus
    Department of forest mycology and pathology, swedish university of agricultural sciences, sweden.
    Fromell, Karin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Johansson, Gunnar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Stenlid, Jan
    Department of forest mycology and pathology, swedish university of agricultural sciences, sweden.
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Polypeptide conjugates that bind chitinasesManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Polypeptide conjugates formed from members of a designed set of polypeptides and the chitinase inhibitors pentoxifylline, C4B3 and C5B1 were evaluated for affinity and selectivity towards chitinases. The polypeptide conjugate 4C37L34-P was found to recognize and bind chitinases from the fungal species Aspergillus nidulans and Neurospora crassa, as well as from the fungus Trichoderma viride and the bacterial strain Streptomyces griseus. The small organic molecule pentoxifylline and the polypeptide 4C37L34 both contributed to binding of the chitinases and the affinity of the polypeptide conjugate was significantly enhanced in comparison with that of pentoxifylline with an affinity that was on the order of 2-3 orders of magnitude higher than that of pentoxyfylline. In view of the large numbers of chitinases present in nature the recognition and detection of groups of chitinases using one binder molecule for many enzymes may be an advantageous approach.

  • 98.
    Sun, Xiaojiao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Yang, Jie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Norberg, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    A synthetic polypeptide conjugate from a 42-residue polypeptide and salicylhydroxamic acid binds human myeloperoxidase with high affinity2012Ingår i: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 18, nr 12, s. 731-739Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Myeloperoxidase (MPO) is a 150 kD tetrameric heme protein consisting of two heavy chains and two light chains, which ispresent in neutrophils, white blood cells, at concentrations between 2% and 5% and plays an important role in the innateimmune system. The MPO concentration in serum or plasma has been shown to be linked to the risk for cardiovasculardiseases, and MPO is considered to be a high potential diagnostic biomarker. To develop a molecule that binds MPO,salicylhydroxamic acid (SHA), a substrate analog inhibitor of MPO with a KD=2uM, was conjugated to a designed set of42-residue polypeptide scaffolds via 9- and 11-carbon atom aliphatic spacers to form 20 different protein binder candidates,and their interactions with MPO were evaluated by surface plasmon resonance analysis. The polypeptide conjugate4C37L34C11SHA was found to bind to MPO with an affinity that could be estimated to have a dissociation constant of around400 pM, nearly four orders of magnitude higher than that of SHA. Inhibition of binding to MPO by free SHA was observed incompetition experiments demonstrating that the binding of the polypeptide conjugate is dominated by the interactions ofSHA with the heme cavity. Although still in the future, the discovery of these new synthetic binders for MPO suggests aroute to clinical diagnostic tests in vivo or in vitro, independent of antibodies.

  • 99.
    Szijjarto, Csongor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Pershagen, Elias
    Borbas, K. Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition2012Ingår i: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 41, nr 25, s. 7660-7669Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cu-I-catalysed azide-alkyne cycloaddition reactions were used to functionalise lanthanide(III)-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly accelerated the reactions, enabling full conversion to the triazole products in some cases in 5 min. Alkyl and aryl azides and alkyl and aryl alkynes could all serve as coupling partners. These reaction conditions proved efficient for cyclen-tricarboxylates and previously unreactive cyclen-tris-primary amide chelates. The synthesis of heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic (Eu/La/Eu) complexes was achieved in up to 60% isolated yield starting from coumarin 2-appended alkynyl complexes Tb16 or La16 and an azido-Eu complex Eu4, and bis-alkynyl La-complex La5 and Eu4, respectively. EuTb17 displayed dual Eu-III and Tb-III-emission upon antenna-centred excitation.

  • 100.
    Szijjarto, Csongor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Pershagen, Elias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Ilchenko, Nadia O.
    Borbas, K. Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes2013Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 9, s. 3099-3109Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Coumarin-sensitized, long-wavelength-absorbing luminescent EuIII-complexes have been synthesized and characterized. The lanthanide binding site consists of a cyclen-based chelating framework that is attached through a short linker to a 7-hydroxycoumarin, a 7-B(OH)2-coumarin, a 7-O-(4-pinacolatoboronbenzyl)-coumarin or a 7-O-(4-methoxybenzyl)-coumarin. The syntheses are straightforward, use readily available building blocks, and proceed through a small number of high-yielding steps. The sensitivity of coumarin photophysics to the 7-substituent enables modulation of the antenna-absorption properties, and thus the lanthanide excitation spectrum. Reactions of the boronate-based functionalities (cages) with H2O2 yielded the corresponding 7-hydroxycoumarin species. The same species was produced with peroxynitrite in a x106107-fold faster reaction. Both reactions resulted in the emergence of a strong approximate to 407nm excitation band, with concomitant decrease of the 366nm band of the caged probe. In aqueous solution the methoxybenzyl caged Eu-complex was quenched by ONOO. We have shown that preliminary screening of simple coumarin-based antennae through UV/Vis absorption spectroscopy is possible as the changes in absorption profile translate with good fidelity to changes in EuIII-excitation profile in the fully elaborated complex. Taken together, our results show that the 7-hydroxycoumarin antenna is a viable scaffold for the construction of turn-on and ratiometric luminescent probes.

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