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  • 1. Ames, William
    et al.
    Pantazis, Dimitrios A
    Krewald, Vera
    Cox, Nicholas
    Messinger, Johannes
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lubitz, Wolfgang
    Neese, Frank
    Theoretical Evaluation of Structural Models of the S(2) State in the Oxygen Evolving Complex of Photosystem II: Protonation States and Magnetic Interactions2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 49, p. 19743-19757Article in journal (Refereed)
    Abstract [en]

    Protonation states of water ligands and oxo bridges are intimately involved in tuning the electronic structures and oxidation potentials of the oxygen evolving complex (OEC) in Photosystem II, steering the mechanistic pathway, which involves at least five redox state intermediates S(n) (n = 0-4) resulting in the oxidation of water to molecular oxygen. Although protons are practically invisible in protein crystallography, their effects on the electronic structure and magnetic properties of metal active sites can be probed using spectroscopy. With the twin purpose of aiding the interpretation of the complex electron paramagnetic resonance (EPR) spectroscopic data of the OEC and of improving the view of the cluster at the atomic level, a complete set of protonation configurations for the S(2) state of the OEC were investigated, and their distinctive effects on magnetic properties of the cluster were evaluated. The most recent X-ray structure of Photosystem II at 1.9 Å resolution was used and refined to obtain the optimum structure for the Mn(4)O(5)Ca core within the protein pocket. Employing this model, a set of 26 structures was constructed that tested various protonation scenarios of the water ligands and oxo bridges. Our results suggest that one of the two water molecules that are proposed to coordinate the outer Mn ion (Mn(A)) of the cluster is deprotonated in the S(2) state, as this leads to optimal experimental agreement, reproducing the correct ground state spin multiplicity (S = 1/2), spin expectation values, and EXAFS-derived metal-metal distances. Deprotonation of Ca(2+)-bound water molecules is strongly disfavored in the S(2) state, but dissociation of one of the two water ligands appears to be facile. The computed isotropic hyperfine couplings presented here allow distinctions between models to be made and call into question the assumption that the largest coupling is always attributable to Mn(III). The present results impose limits for the total charge and the proton configuration of the OEC in the S(2) state, with implications for the cascade of events in the Kok cycle and for the water splitting mechanism.

  • 2.
    Andersson, Ida E.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Batsalova, Tsvetelina
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Haag, Sabrina
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Dzhambazov, Balik
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Holmdahl, Rikard
    Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
    Kihlberg, Jan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    (E)-Alkene and Ethylene Isosteres Substantially Alter the Hydrogen-Bonding Network in Class II MHC Aq/Glycopeptide Complexes and Affect T-Cell Recognition2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 36, p. 14368-14378Article in journal (Refereed)
    Abstract [en]

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

  • 3. Bergström, Fredrik
    et al.
    Mikhalyov, Ilya
    Hägglöf, Peter
    Wortmann, Rüdiger
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Johansson, Lennart B A
    Dimers of dipyrrometheneboron difluoride (BODIPY) with light spectroscopic applications in chemistry and biology.2002In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 124, no 2, p. 196-204Article in journal (Refereed)
    Abstract [en]

    A ground-state dimer (denoted D(I)) exhibiting a strong absorption maximum at 477 nm (epsilon = 97 000 M(-1)cm(-1)) can form between adjacent BODIPY groups attached to mutant forms of the protein, plasminogen activator inhibitor type 1 (PAI-1). No fluorescence from excited D(I) was detected. A locally high concentration of BODIPY groups was also achieved by doping lipid phases (micelles, vesicles) with BODIPY-labeled lipids. In addition to an absorption band located at about 480 nm, a new weak absorption band is also observed at ca. 570 nm. Both bands are ascribed to the formation of BODIPY dimers of different conformation (D(I) and D(II)). Contrary to D(I) in PAI-1, the D(II) aggregates absorbing at 570 nm are emitting light observed as a broad band centered at about 630 nm. The integrated absorption band of D(I) is about twice that of the monomer, which is compatible with exciton coupling within a dimer. The Förster radius of electronic energy transfer between a BODIPY excited monomer and the ground-state dimer (D(I)()) is 57 +/- 2 A. A simple model of exciton coupling suggests that in D(I) two BODIPY groups are stacked on top of each other in a sandwich-like configuration with parallel electronic transition dipoles. For D(II) the model suggests that the S(0) --> S(1) transition dipoles are colinear. An explanation for the previously reported (J. Am. Chem. Soc. 1994, 116, 7801) exceptional light spectroscopic properties of BODIPY is also presented. These are ascribed to the extraordinary electric properties of the BODIPY chromophore. First, changes of the permanent electric dipole moment (Delta(mu) approximately -0.05 D) and polarizability (-26 x 10(-40) C m(2) V(-1)) between the ground and the first excited states are small. Second, the S(0) <--> S(1) electronic transition dipole moments are perpendicular to Delta(mu).

  • 4.
    Bokvist, Marcus
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Misfolding of amyloidogenic proteins at membrane surfaces:  the impact of macromolecularcCrowding2007In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 129, no 48, p. 14848-14849Article in journal (Refereed)
    Abstract [en]

    The presence of inert macromolecular crowding agents mimics the situation in vivo where amyloidogenic proteins are released into an aqueous, congested intracellular environment. By using the amphiphatic Alzheimer A-protein as the model system, the presence of a three-dimensional macromolecular crowding environment enhanced significantly its misfolding behavior if charged membrane surfaces as two-dimensional aggregation templates were present.

  • 5.
    Brännström, Kristoffer
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nilsson, Lina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Pihl, Mathias
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sandblad, Linda
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    The N-terminal Region of Amyloid β Controls the Aggregation Rate and Fibril Stability at Low pH Through a Gain of Function Mechanism2014In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 136, no 31, p. 10956-10964Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease is linked to a pathological polymerization of the endogenous amyloid β-peptide (Aβ) that ultimately forms amyloid plaques within the human brain. We used surface plasmon resonance (SPR) to measure the kinetic properties of Aβ fibril formation under different conditions during the polymerization process. For all polymerization processes, a critical concentration of free monomers, as defined by the dissociation equilibrium constant (KD), is required for the buildup of the polymer, for example, amyloid fibrils. At concentrations below the KD, polymerization cannot occur. However, the KD for Aβ has previously been shown to be several orders of magnitude higher than the concentrations found in the cerebrospinal and interstitial fluids of the human brain, and the mechanism by which Aβ amyloid forms in vivo has been a matter of debate. Using SPR, we found that the KD of Aβ dramatically decreases as a result of lowering the pH. Importantly, this effect enables Aβ to polymerize within a picomolar concentration range that is close to the physiological Aβ concentration within the human brain. The stabilizing effect is dynamic, fully reversible, and notably pronounced within the pH range found within the endosomal and lysosomal pathways. Through sequential truncation, we show that the N-terminal region of Aβ contributes to the enhanced fibrillar stability due to a gain of function mechanism at low pH. Our results present a possible route for amyloid formation at very low Aβ concentrations and raise the question of whether amyloid formation in vivo is restricted to a low pH environment. These results have general implications for the development of therapeutic interventions.

  • 6. Cox, Nicholas
    et al.
    Rapatskiy, Leonid
    Su, Ji-Hu
    Pantazis, Dimitrios A
    Sugiura, Miwa
    Kulik, Leonid
    Dorlet, Pierre
    Rutherford, A William
    Neese, Frank
    Boussac, Alain
    Lubitz, Wolfgang
    Messinger, Johannes
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Effect of Ca(2+)/Sr(2+) substitution on the electronic structure of the oxygen-evolving complex of photosystem II: a combined multifrequency EPR, (55)Mn-ENDOR, and DFT study of the S(2) State2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 10, p. 3635-3648Article in journal (Refereed)
    Abstract [en]

    The electronic structures of the native Mn(4)O(x)Ca cluster and the biosynthetically substituted Mn(4)O(x)Sr cluster of the oxygen evolving complex (OEC) of photosystem II (PSII) core complexes isolated from Thermosynechococcus elongatus, poised in the S(2) state, were studied by X- and Q-band CW-EPR and by pulsed Q-band (55)Mn-ENDOR spectroscopy. Both wild type and tyrosine D less mutants grown photoautotrophically in either CaCl(2) or SrCl(2) containing media were measured. The obtained CW-EPR spectra of the S(2) state displayed the characteristic, clearly noticeable differences in the hyperfine pattern of the multiline EPR signal [Boussac et al. J. Biol. Chem.2004, 279, 22809-22819]. In sharp contrast, the manganese ((55)Mn) ENDOR spectra of the Ca and Sr forms of the OEC were remarkably similar. Multifrequency simulations of the X- and Q-band CW-EPR and (55)Mn-pulsed ENDOR spectra using the Spin Hamiltonian formalism were performed to investigate this surprising result. It is shown that (i) all four manganese ions contribute to the (55)Mn-ENDOR spectra; (ii) only small changes are seen in the fitted isotropic hyperfine values for the Ca(2+) and Sr(2+) containing OEC, suggesting that there is no change in the overall spin distribution (electronic coupling scheme) upon Ca(2+)/Sr(2+) substitution; (iii) the changes in the CW-EPR hyperfine pattern can be explained by a small decrease in the anisotropy of at least two hyperfine tensors. It is proposed that modifications at the Ca(2+) site may modulate the fine structure tensor of the Mn(III) ion. DFT calculations support the above conclusions. Our data analysis also provides strong support for the notion that in the S(2) state the coordination of the Mn(III) ion is square-pyramidal (5-coordinate) or octahedral (6-coordinate) with tetragonal elongation. In addition, it is shown that only one of the currently published OEC models, the Siegbahn structure [Siegbahn, P. E. M. Acc. Chem. Res.2009, 42, 1871-1880, Pantazis, D. A. et al. Phys. Chem. Chem. Phys.2009, 11, 6788-6798], is consistent with all data presented here. These results provide important information for the structure of the OEC and the water-splitting mechanism. In particular, the 5-coordinate Mn(III) is a potential site for substrate 'water' (H(2)O, OH(-)) binding. Its location within the cuboidal structural unit, as opposed to the external 'dangler' position, may have important consequences for the mechanism of O-O bond formation.

  • 7. Diaz de Grenu, Borja
    et al.
    Moreno, Daniel
    Torroba, Tomas
    Berg, Alexander
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Gunnars, Johan
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Nilsson, Tobias
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Nyman, Rasmus
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Persson, Milton
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Pettersson, Johannes
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Eklind, Ida
    Wasterby, Par
    Fluorescent Discrimination between Traces of Chemical Warfare Agents and Their Mimics2014In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 136, no 11, p. 4125-4128Article in journal (Refereed)
    Abstract [en]

    An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.

  • 8.
    Dzwilewski, Andrzej
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Wågberg, Thomas
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Photo-induced and resist-free imprint patterning of fullerene materials for use in functional electronics2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 11, p. 4006-4011Article in journal (Refereed)
    Abstract [en]

    We report a novel and potentially generic method for the efficient patterning of films of organic semiconductors and demonstrate the merit of the method on the high-solubility fullerene [6,6]-phenyl C61- butyric acid methyl ester (PCBM). The patterning technique is notably straightforward as it requires no photoresist material and encompasses only two steps: (i) exposure of select film areas to visible laser light during which the PCBM mononer is photochemically converted into a dimeric state, and (ii) development via solvent washing after which the nonexposed portions of the PCBM film are selectively removed. Importantly, the method is highly benign in that it leaves the electronic properties of the remaining patterned material intact, which is directly evidenced by the fact that we fabricate fully functional arrays of micrometersized field-effect transistors with patterned PCBM as the active material.

  • 9.
    Espaillat, Akbar
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Forsmo, Oskar
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    El Biari, Khouzaima
    Björk, Rafael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lemaitre, Bruno
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Canada, Francisco Javier
    de Pedro, Miguel A.
    Cava, Felipe
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Chemometric Analysis of Bacterial Peptidoglycan Reveals Atypical Modifications That Empower the Cell Wall against Predatory Enzymes and Fly Innate Immunity2016In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 138, no 29, p. 9193-9204Article in journal (Refereed)
    Abstract [en]

    Peptidoglycan is a fundamental structure for most bacteria. It contributes to the cell morphology and provides cell wall integrity against environmental insults. While several studies have reported a significant degree of variability in the chemical composition and organization of peptidoglycan in the domain Bacteria, the real diversity of this polymer is far from fully explored. This work exploits rapid ultraperformance liquid chromatography and multivariate data analysis to uncover peptidoglycan chemical diversity in the Class Alphaproteobacteria, a group of Gram negative bacteria that are highly heterogeneous in terms of metabolism, morphology and life-styles. Indeed, chemometric analyses revealed novel peptidoglycan structures conserved in Acetobacteria: amidation at the alpha-(L)-carboxyl of meso-diaminopimelic acid and the presence of muropeptides cross-linked by (1-3) L-Ala-D-(meso)diaminopimelate cross-links. Both structures are growth-controlled modifications that influence sensitivity to Type VI secretion system peptidoglycan endopeptidases and recognition by the Drosophila innate immune system, suggesting relevant roles in the environmental adaptability of these bacteria. Collectively our findings demonstrate the discriminative power of chemometric tools on large cell wall-chromatographic data sets to discover novel peptidoglycan structural properties in bacteria.

  • 10.
    Fang, Junfeng
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Matyba, Piotr
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Robinson, Nathaniel D.
    Department of Science and Technology, Linköping University, SE-601 74 Norrköping, Sweden.
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Identifying and alleviating electrochemical side-reactions in light-emitting electrochemical cells.2008In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 130, p. 4562-4568Article in journal (Refereed)
  • 11.
    Gracia-Espino, Eduardo
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hu, Guangzhi
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Shchukarev, Andrey
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wågberg, Thomas
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Understanding the Interface of Six-Shell Cuboctahedral and Icosahedral Palladium Clusters on Reduced Graphene Oxide: Experimental and Theoretical Study2014In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 136, no 18, p. 6626-6633Article in journal (Refereed)
    Abstract [en]

    Studies on noble-metal-decorated carbon nanostructures are reported almost on a daily basis, but detailed studies on the nanoscale interactions for well-defined systems are very rare. Here we report a study of reduced graphene oxide (rGOx) homogeneously decorated with palladium (Pd) nanoclusters with well-defined shape and size (2.3 +/- 0.3 nm). The rGOx was modified with benzyl mercaptan (BnSH) to improve the interaction with Pd clusters, and N,N-dimethylformamide was used as solvent and capping agent during the decoration process. The resulting Pd nanoparticles anchored to the rGOx-surface exhibit high crystallinity and are fully consistent with six-shell cuboctahedral and icosahedral clusters containing similar to 600 Pd atoms, where 45% of these are located at the surface. According to X-ray photoelectron spectroscopy analysis, the Pd clusters exhibit an oxidized surface forming a PdOx shell. Given the well-defined experimental system, as verified by electron microscopy data and theoretical simulations, we performed ab initio simulations using 10 functionalized graphenes (with vacancies or pyridine, amine, hydroxyl, carboxyl, or epoxy groups) to understand the adsorption process of BnSH, their further role in the Pd cluster formation, and the electronic properties of the graphene-nanoparticle hybrid system. Both the experimental and theoretical results suggest that Pd clusters interact with fiinctionalized graphene by a sulfur bridge while the remaining Pd surface is oxidized. Our study is of significant importance for all work related to anchoring of nanoparticles on nanocarbon-based supports, which are used in a variety of applications.

  • 12. Hamark, Christoffer
    et al.
    Berntsson, Ronnie Per-Arne
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of Biochemistry and Biophysics, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden.
    Masuyer, Geoffrey
    Henriksson, Linda M.
    Gustafsson, Robert
    Stenmark, Pal
    Widmalm, Goran
    Glycans Confer Specificity to the Recognition of Ganglioside Receptors by Botulinum Neurotoxin A2017In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 139, no 1, p. 218-230Article in journal (Refereed)
    Abstract [en]

    The highly poisonous botulinum neurotoxins, produced by the bacterium Clostridium botulinum, act on their hosts by a high-affinity association to two receptors on neuronal cell surfaces as the first step of invasion. The glycan motifs of gangliosides serve as initial coreceptors for these protein complexes, whereby a membrane protein receptor is bound. Herein we set out to characterize the carbohydrate minimal binding epitope of the botulinum neurotoxin serotype A. By means of ligand-based NMR spectroscopy, X-ray crystallography, computer simulations, and isothermal titration calorimetry, a screening of ganglioside analogues together with a detailed characterization of various carbohydrate ligand complexes with the toxin were accomplished. We show that the representation of the glycan epitope to the protein affects the details of binding. Notably, both branches of the oligosaccharide GD la can associate to botulinum neurotoxin serotype A when expressed as individual trisaccharides. It is, however, the terminal branch of GD1a as well as this trisaccharide motif alone, corresponding to the sialyl-Thomsen-Friedenreich antigen, that represents the active ligand epitope, and these compounds bind to the neurotoxin with a high degree of predisposition but with low affinities. This finding does not correlate with the oligosaccharide moieties having a strong contribution to the total affinity, which was expected to be the case. We here propose that the glycan part of the ganglioside receptors mainly provides abundance and specificity, whereas the interaction with the membrane itself and protein receptor brings about the strong total binding of the toxin to the neuronal membrane.

  • 13. Han, Xin-Bao
    et al.
    Tang, Xing-Yan
    Lin, Yue
    Gracia-Espino, Eduardo
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Liu, San-Gui
    Liang, Hai-Wei
    Hu, Guangzhi
    Umeå University, Faculty of Science and Technology, Department of Physics. Key Laboratory of Chemistry of Plant Resources in Arid Regions, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
    Zhao, Xin-Jing
    Liao, Hong-Gang
    Tan, Yuan-Zhi
    Wågberg, Thomas
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Xie, Su-Yuan
    Zheng, Lan-Sun
    Ultrasmall Abundant Metal-Based Clusters as Oxygen-Evolving Catalysts2019In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 141, no 1, p. 232-239Article in journal (Refereed)
    Abstract [en]

    The oxygen evolution reaction is a crucial step in water electrolysis to develop clean and renewable energy. Although noble metal-based catalysts have demonstrated high activity for the oxygen evolution reaction, their application is limited by their high cost and low availability. Here we report the use of a molecule-to-cluster strategy for preparing ultrasmall trimetallic clusters by using the polyoxometalate molecule as a precursor. Ultrafine (0.8 nm) transition-metal clusters with controllable chemical composition are obtained. The transition-metal clusters enable highly efficient oxygen evolution through water electrolysis in alkaline media, manifested by an overpotential of 192 mV at 10 mA cm–2, a low Tafel slope of 36 mV dec–1, and long-term stability for 30 h of electrolysis. We note, however, that besides the excellent performance as an oxygen evolution catalyst, our molecule-to-cluster strategy provides a means to achieve well-defined transition-metal clusters in the subnanometer regime, which potentially can have an impact on several other applications.

  • 14.
    Horvath, Istvan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Weise, Christoph F
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Emma K
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Chorell, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sellstedt, Magnus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bengtsson, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Hultgren, Scott J
    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
    Chapman, Matthew
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Wolf-Watz, Magnus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wittung-Stafshede, Pernilla
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mechanisms of Protein Oligomerization: Inhibitor of Functional Amyloids Templates α-Synuclein Fibrillation2012In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 7, p. 3439-3444Article in journal (Refereed)
    Abstract [en]

    Small organic molecules that inhibit functional bacterial amyloid fibers, curli, are promising new antibiotics. Here we investigated the mechanism by which the ring-fused 2-pyridone FN075 inhibits fibrillation of the curli protein CsgA. Using a variety of biophysical techniques, we found that FN075 promotes CsgA to form off-pathway, non-amyloidogenic oligomeric species. In light of the generic properties of amyloids, we tested whether FN075 would also affect the fibrillation reaction of human α-synuclein, an amyloid-forming protein involved in Parkinson's disease. Surprisingly, FN075 stimulates α-synuclein amyloid fiber formation as measured by thioflavin T emission, electron microscopy (EM), and atomic force microscopy (AFM). NMR data on (15)N-labeled α-synuclein show that upon FN075 addition, α-synuclein oligomers with 7 nm radius form in which the C-terminal 40 residues remain disordered and solvent exposed. The polypeptides in these oligomers contain β-like secondary structure, and the oligomers are detectable by AFM, EM, and size-exclusion chromatography (SEC). Taken together, FN075 triggers oligomer formation of both proteins: in the case of CsgA, the oligomers do not proceed to fibers, whereas for α-synuclein, the oligomers are poised to rapidly form fibers. We conclude that there is a fine balance between small-molecule inhibition and templation that depends on protein chemistry.

  • 15. Hussain, Faiza
    et al.
    Rodriguez-Granillo, Agustina
    Wittung-Stafshede, Pernilla
    Umeå University, Faculty of Science and Technology, Chemistry.
    Lysine-60 in Copper Chaperone Atox1 Plays an Essential Role in Adduct Formation with a Target Wilson Disease Domain2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 45, p. 16371-3Article in journal (Refereed)
    Abstract [en]

    The mechanism by which the human copper (Cu) chaperone Atox1 delivers Cu to metal-binding domains of Wilson disease (WD) protein for insertion into cuproenzymes is unclear. Using near-UV circular dichroism as a new tool to probe chaperone-target interactions, in combination with gel filtration and molecular dynamics simulations, we here demonstrate that Atox1 forms a stable Cu-dependent adduct with the fourth metal-binding domain of WD (WD4). Using point-mutated Atox1 variants, we show that the adduct forms in the absence of conserved residues M10 or T11 but K60 is essential for heterocomplex formation and Cu transfer. Dissection of heterocomplex energetic components reveals a crucial role for K60-mediated electrostatic interaction.

  • 16. Lundberg, Helena
    et al.
    Tinnis, Fredrik
    Zhang, Jiji
    Algarra, Andres G.
    Himo, Fahmi
    Adolfsson, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
    Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation2017In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 139, no 6, p. 2286-2295Article in journal (Refereed)
    Abstract [en]

    The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal eta(2)-carboxylate ligand of the zirconium catalyst, followed by a C-O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid.

  • 17. McAlpin, J. Gregory
    et al.
    Stich, Troy A.
    Ohlin, C. Andre
    Surendranath, Yogesh
    Nocera, Daniel G.
    Casey, William H.
    Britt, R. David
    Electronic Structure Description of a [Co(III)(3)Co(IV)O-4] Cluster: A Model for the Paramagnetic Intermediate in Cobalt-Catalyzed Water Oxidation2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 39, p. 15444-15452Article in journal (Refereed)
    Abstract [en]

    Multifrequency electron paramagnetic resonace (EPR) spectroscopy and electronic structure calculations were performed on [Co4O4(C5H5N)(4)(CH3CO2)(4)](+) (1(+)), a cobalt tetramer with total electron spin S = 1/2 and formal cobalt oxidation states III, III, III, and IV. The cuboidal arrangement of its cobalt and oxygen atoms is similar to that of proposed structures for the molecular cobaltate clusters of the cobalt-phosphate (Co-Pi) water-oxidizing catalyst. The Davies electron-nuclear double resonance (ENDOR) spectrum is well-modeled using a single class of hyperfine-coupled Co-59 nuclei with a modestly strong interaction (principal elements of the hyperfine tensor are equal to [-20(+/- 2), 77(+/- 1), -5(+/- 15)] MHz). Mims H-1 ENDOR spectra of 1(+) with selectively deuterated pyridine ligands confirm that the amount of unpaired spin on the cobalt-bonding partner is significantly reduced from unity. Multifrequency N-14 ESEEM spectra (acquired at 9.5 and 34.0 GHz) indicate that four nearly equivalent nitrogen nuclei are coupled to the electron spin. Cumulatively, our EPR spectroscopic findings indicate that the unpaired spin is delocalized almost equally across the eight core atoms, a finding corroborated by results from DFT calculations. Each octahedrally coordinated cobalt ion is forced into a low-spin electron configuration by the anionic oxo and carboxylato ligands, and a fractional electron hole is localized on each metal center in a Co 3d(xz,yz)-based molecular orbital for this essentially [Co4+3.125O4] system. Comparing the EPR spectrum of 1(+) with that of the catalyst film allows us to draw conclusions about the electronic structure of this water-oxidation catalyst.

  • 18.
    Ojeda-May, Pedro
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational Life Science Cluster (CLiC).
    Li, Yaozong
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational Life Science Cluster (CLiC).
    Ovchinnikov, Victor
    Nam, Kwangho
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Computational Life Science Cluster (CLiC).
    Role of Protein Dynamics in Allosteric Control of the Catalytic Phosphoryl Transfer of Insulin Receptor Kinase2015In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 137, no 39, p. 12454-12457Article in journal (Refereed)
    Abstract [en]

    The catalytic and allosteric mechanisms of insulin receptor kinase (IRK) are investigated by a combination of ab initio and semiempirical quantum mechanical and molecular mechanical (QM/MM) methods and classical molecular dynamics (MD) simulations. The simulations reveal that the catalytic reaction proceeds in two steps, starting with the transfer of a proton from substrate Tyr to the catalytic Asp1132, followed by the phosphoryl transfer from ATP to substrate Tyr. The enhancement of the catalytic rate of IRK upon phosphorylations in the enzyme's activation loop is found to occur mainly via changes to the free energy landscape of the proton transfer step, favoring the proton transfer in the fully phosphorylated enzyme. In contrast, the effects of the phosphorylations on the phosphoryl transfer are smaller. Equilibrium MD simulations show that IRK phosphorylations affect the protein dynamics of the enzyme before the proton transfer to Asp1132 with only a minor effect after the proton transfer. This finding is consistent with the large change in the proton transfer free energy and the smaller change in the free energy barrier of phosphoryl transfer found by QM/MM simulations. Taken together, the present results provide details on how IRK phosphorylation exerts allosteric control of the catalytic activity via modifications of protein dynamics and free energy landscape of catalytic reaction. The results also highlight the importance of protein dynamics in connecting protein allostery and catalysis to control catalytic activity of enzymes.

  • 19.
    Petzold, Katja
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Annelie
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jürgen, Schleucher
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Semiconstant-Time P,H-COSY NMR: Analysis of Complex Mixtures of Phospholipids Originating from Helicobacter pylori2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 40, p. 14150-1Article in journal (Refereed)
    Abstract [en]

    Lipids play a central role in numerous biological events, ranging from normal physiological processes to host−pathogen interactions. The proposed semiconstant-time 31P,1H−COSY NMR experiment provides identification of known and structural characterization of unknown phospholipids in complex membrane extracts with high sensitivity, based on the combination of their 1H and 31P chemical shifts and coupling patterns. Furthermore, the spectra allow quantification of phospholipid composition. Analysis of the phospholipid composition of Helicobacter pylori, the causative agent of peptic ulcer disease, showed the presence of uncommon phospholipids. This novel NMR approach allows the study of changes in membrane composition in response to biological stimuli and opens up the possibility of identifying soluble phosphorus species in a number of research fields.

  • 20. Rapatskiy, Leonid
    et al.
    Cox, Nicholas
    Savitsky, Anton
    Ames, William M
    Sander, Julia
    Nowaczyk, Marc M
    Rögner, Matthias
    Boussac, Alain
    Neese, Frank
    Messinger, Johannes
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lubitz, Wolfgang
    Detection of the Water-Binding Sites of the Oxygen-Evolving Complex of Photosystem II Using W-Band 17O Electron–Electron Double Resonance-Detected NMR Spectroscopy2012In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 40, p. 16619-16634Article in journal (Refereed)
    Abstract [en]

    Water binding to the Mn4O5Ca cluster of the oxygen-evolving complex (OEC) of Photosystem II (PSII) poised in the S2 state was studied via H217O- and 2H2O-labeling and high-field electron paramagnetic resonance (EPR) spectroscopy. Hyperfine couplings of coordinating 17O (I = 5/2) nuclei were detected using W-band (94 GHz) electron–electron double resonance (ELDOR) detected NMR and Davies/Mims electron–nuclear double resonance (ENDOR) techniques. Universal 15N (I = 1/2) labeling was employed to clearly discriminate the 17O hyperfine couplings that overlap with 14N (I = 1) signals from the D1-His332 ligand of the OEC (Stich Biochemistry 2011, 50 (34), 7390−7404). Three classes of 17O nuclei were identified: (i) one μ-oxo bridge; (ii) a terminal Mn–OH/OH2 ligand; and (iii) Mn/Ca–H2O ligand(s). These assignments are based on 17O model complex data, on comparison to the recent 1.9 Å resolution PSII crystal structure (Umena Nature 2011, 473, 55−60), on NH3 perturbation of the 17O signal envelope and density functional theory calculations. The relative orientation of the putative 17O μ-oxo bridge hyperfine tensor to the 14N(15N) hyperfine tensor of the D1-His332 ligand suggests that the exchangeable μ-oxo bridge links the outer Mn to the Mn3O3Ca open-cuboidal unit (O4 and O5 in the Umena et al. structure). Comparison to literature data favors the Ca-linked O5 oxygen over the alternative assignment to O4. All 17O signals were seen even after very short (≤15 s) incubations in H217O suggesting that all exchange sites identified could represent bound substrate in the S1 state including the μ-oxo bridge. 1H/2H (I = 1/2, 1) ENDOR data performed at Q- (34 GHz) and W-bands complement the above findings. The relatively small 1H/2H couplings observed require that all the μ-oxo bridges of the Mn4O5Ca cluster are deprotonated in the S2 state. Together, these results further limit the possible substrate water-binding sites and modes within the OEC. This information restricts the number of possible reaction pathways for O–O bond formation, supporting an oxo/oxyl coupling mechanism in S4.

  • 21.
    Sandström, Andreas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Matyba, Piotr
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Inganäs, Olle
    Linköpings universitet.
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Separating ion and and electron transport: the bi-layer light-emitting electrochemical cell2010In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 132, no 19, p. 6646-6647Article in journal (Refereed)
    Abstract [en]

    The current generation of polymer light-emitting electrochemical cells (LECs) suffers from insufficient stability during operation. One identified culprit is the active material, which comprises an intimate blend between an ion-conducting electrolyte and an electron-transporting conjugated polymer, as it tends to undergo phase separation during long-term operation and the intimate contact between the ion- and electron-transporting components provokes side reactions. To address these stability issues, we present here a bilayer LEC structure in which the electrolyte is spatially separated from the conjugated polymer. We demonstrate that employing this novel device structure, with its clearly separated ion- and electron-transport paths, leads to distinctly improved LEC performance in the form of decreased turn-on time and improved light emission. We also point out that it will allow for the utilization of combinations of active materials having mutually incompatible solubilities.

  • 22. Smolentsev, Grigory
    et al.
    Soldatov, Alexander V
    Messinger, Johannes
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Merz, Kathrin
    Weyhermller, Thomas
    Bergmann, Uwe
    Pushkar, Yulia
    Yano, Junko
    Yachandra, Vittal K
    Glatzel, Pieter
    X-ray emission spectroscopy to study Ligand Valence Orbitals in Mn coordination complexes2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 36, p. 13161-13167Article in journal (Refereed)
    Abstract [en]

    We discuss a spectroscopic method to determine the character of chemical bonding and for the identification of metal ligands in coordination and bioinorganic chemistry. It is based on the analysis of satellite lines in X-ray emission spectra that arise from transitions between valence orbitals and the metal ion 1s level (valence-to-core XES). The spectra, in connection with calculations based on density functional theory (DFT), provide information that is complementary to other spectroscopic techniques, in particular X-ray absorption (XANES and EXAFS). The spectral shape is sensitive to protonation of ligands and allows ligands, which differ only slightly in atomic number (e.g., C, N, O...), to be distinguished. A theoretical discussion of the main spectral features is presented in terms of molecular orbitals for a series of Mn model systems: [Mn(H2O)6]2+, [Mn(H2O)5OH]+, and [Mn(H2O)5NH3]2+. An application of the method, with comparison between theory and experiment, is presented for the solvated Mn2+ ion in water and three Mn coordination complexes, namely [LMn(acac)N3]BPh4, [LMn(B2O3Ph2)(ClO4)], and [LMn(acac)N]BPh4, where L represents 1,4,7-trimethyl-1,4,7-triazacyclononane, acac stands for the 2,4-pentanedionate anion, and B2O3Ph2 represents the 1,3-diphenyl-1,3-dibora-2-oxapropane-1,3-diolato dianion.

  • 23.
    Stagg, Loren
    et al.
    University of Texas MD Anderson, Houston and Rice University, Houston, Texas United States .
    Christiansen, Alexander
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wittung-Stafshede, Pernilla
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States.
    Macromolecular crowding tunes folding landscape of parallel α/β protein, apoflavodoxin2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 4, p. 646-648Article in journal (Refereed)
    Abstract [en]

    Proteins normally fold in crowded cellular environments. Here we use a set of Desulfovibrio desulfuricans apoflavodoxin variants to assess-with residue-specific resolution-how apoflavodoxin's folding landscape is tuned by macromolecular crowding. We find that, under crowded conditions, initial topological frustration is reduced, subsequent folding requires less ordering in the transition state, and β-strand 1 becomes more important in guiding the process. We propose that conditions more closely mimicking the cellular environment make the ensemble of unfolded conformations less expanded, resulting in a folding funnel that is smoother and narrower.

  • 24. Su, Ji-Hu
    et al.
    Lubitz, Wolfgang
    Messinger, Johannes
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Probing Mode and Site of Substrate Water Binding to the Oxygen-Evolving Complex in the S(2) State of Photosystem II by (17)O-HYSCORE Spectroscopy2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 31, p. 12317-Article in journal (Refereed)
  • 25.
    Talyzin, Alexandr V.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Sundqvist, Bertil
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Szabó, Tamás
    Dékány, Imre
    Dmitriev, Vladimir
    Pressure-induced insertion of liquid alcohols into graphite oxide structure2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 51, p. 18445-18449Article in journal (Refereed)
    Abstract [en]

    Graphite oxide (GO) immersed in an excess of methanol and ethanol media is found to undergo a phase transformation at about 0.2−0.8 GPa, with an expansion of the unit cell volume by 40%, due to pressure-induced insertion of solvent into interlayer space. The pressure at which the structural expansion occurs does not correlate with the solidification pressure of the alcohol, in contrast to the graphite oxide/water system. The expanded high-pressure phase of GO/ethanol could be quenched back to ambient pressure. Compression of graphite oxide with a 2:1 water/methanol medium revealed a complex anomaly with two steps attributed to insertion of methanol and water at different pressure points.

  • 26.
    Tang, Shi
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Pan, Junyou
    Buchholz, Herwig A.
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    White Light from a Single-Emitter Light-Emitting Electrochemical Cell2013In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 135, no 9, p. 3647-3652Article in journal (Refereed)
    Abstract [en]

    We report a novel and generic approach for attaining white light from a single-emitter light-emitting electrochemical cell (LEC). With an active-layer comprising a multifluorophoric conjugated copolymer (MCP) and an electrolyte designed to inhibit MCP energy-transfer interactions during LEC operation, we are able to demonstrate LECs that emit broad-band white light with a color rendering index of 82, a correlated-color temperature of 4000 K, and a current conversion efficacy of 3.8 cd/A. It is notable that this single-emitter LEC configuration eliminates color-drift problems stemming from phase separation, which are commonly observed in conventional blended multiemitter devices. Moreover, the key role of the electrolyte in limiting undesired energy-transfer reactions is highlighted by the observation that an electrolyte-free organic light-emitting diode comprising the same MCP emits red light.

  • 27.
    Tang, Shi
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Sandström, Andreas
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Fang, Junfeng
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    A Solution-Processed Trilayer Electrochemical Device: Localizing the Light Emission for Optimized Performance2012In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 34, p. 14050-14055Article in journal (Refereed)
    Abstract [en]

    We present a solution-processed trilayer light-emitting device architecture, comprising two hydrophobic and mobile-ion-containing "transport layers" sandwiching a hydrophilic and ion-free "intermediate layer", which allows for lowered self-absorption, minimized electrode quenching, and tunable light emission. Our results reveal that the transport layers can be doped in situ when a voltage is applied, that the intermediate layer as desired can contribute significantly to the light emission, and that the key to a successful operation is the employment of a porous and (similar to 5-10 nm) thin intermediate layer allowing for facile ion transport. We report that such a solution-processed device, comprising a thick trilayer material (similar to 250 nm) and air-stable electrodes, emits blue light (lambda(peak) = 450, 484 nm) with high efficiency (5.3 cd/A) at a low drive voltage of 5 V.

  • 28.
    van Reenen, Stephan
    et al.
    Eindhoven University of Technology.
    Matyba, Piotr
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Dzwilewski, Andrzej
    Eindhoven University of Technology.
    Rene A. J., Jenssen
    Eindhoven University of Technology.
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Martijn, Kemerink
    Eindhoven University of Technology.
    A unifying model for the operation of light-emitting electrochemical cells2010In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 132, no 39, p. 13776-13781Article in journal (Refereed)
    Abstract [en]

    The application of doping in semiconductors plays a major role in the high performances achieved to date in inorganic devices. In contrast, doping has yet to make such an impact in organic electronics. One organic device that does make extensive use of doping is the light-emitting electrochemical cell (LEC), where the presence of mobile ions enables dynamic doping, which enhances carrier injection and facilitates relatively large current densities. The mechanism and effects of doping in LECs are, however, still far from being fully understood, as evidenced by the existence of two competing models that seem physically distinct: the electrochemical doping model and the electrodynamic model. Both models are supported by experimental data and numerical modeling. Here, we show that these models are essentially limits of one master model, separated by different rates of carrier injection. For ohmic nonlimited injection, a dynamic p−n junction is formed, which is absent in injection-limited devices. This unification is demonstrated by both numerical calculations and measured surface potentials as well as light emission and doping profiles in operational devices. An analytical analysis yields an upper limit for the ratio of drift and diffusion currents, having major consequences on the maximum current density through this type of device.

  • 29. Villa, Eric M.
    et al.
    Ohlin, C. Andre
    Casey, William H.
    Oxygen-Isotope Exchange Rates for Three Isostructural Polyoxometalate Ions2010In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 132, no 14, p. 5264-5272Article in journal (Refereed)
    Abstract [en]

    We compare oxygen-isotope exchange rates for all structural oxygens in three polyoxoniobate ions that differ by systematic metal substitutions of Ti(IV) -> Nb(V). The [H(x)Nb(10)O(28)]((6-x)-), [H(x)TiNb(9)O(28)]((7-x)-), and [H(x)Ti(2)Nb(8)O(28)]((8 -x)-) ions are all isostructural yet have different Bronsted properties. Rates for sites within a particular molecule in the series differ by at least similar to 10(4), but the relative reactivities of the oxygen sites rank in nearly the same relative order for all ions in the series. Within a single ion, most structural oxygens exhibit rates of isotopic exchange that vary similarly with pH, indicating that each structure responds as a whole to changes in pH. Across the series of molecules, however, the pH dependencies for isotope exchanges and dissociation are distinctly different, reflecting different contributions from proton- or base-enhanced pathways. The proton-enhanced pathway for isotope exchange dominates at most pH conditions for the [H(x)Ti(2)Nb(8)O(28)]((8 -x)-) ion, but the base-enhanced pathways are increasingly important for the [H(x)TiNb(9)O(28)]((7-x)-) and [H(x)Nb(10)O(28)]((6-x)-) structures at higher pH. The local effect of Ti(IV) substitution could be assessed by comparing rates for structurally similar oxygens on each side of the [H(x)TiNb(9)O(28)]((7-x)-) ion and is surprisingly small. Interestingly, these nanometer-size structures seem to manifest the same general averaged amphoteric chemistry that is familiar for other reactions affecting oxides in water, including interface dissolution by proton- and hydroxyl-enhanced pathways.

  • 30. Villa, Eric M.
    et al.
    Ohlin, C. Andre
    Rustad, James R.
    Casey, William H.
    Isotope-Exchange Dynamics in Isostructural Decametalates with Profound Differences in Reactivity2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 45, p. 16488-16492Article in journal (Refereed)
    Abstract [en]

    Rates of oxygen-isotope exchange at all structural sites in two isostructural polyoxometalates, [H(x)Nb(10)O(28)]((6-x)-) and [H(x)Ti(2)Nb(8)O(28)]((8-x)-), show that small changes in structure have surprising and profound effects: a single-site substitution of Ti(IV) for Nb(V) inverts the pH dependencies for rates throughout the structures. Within a given structure, all oxygens exhibit similar pH dependencies although they react over a range greater than similar to 10(4), indicating that pathways involve concerted motions of the entire lattices. Profound sensitivity to changes in structure and composition suggests reaction pathways in polyoxometalate ions will be highly variable even within structural classes. The results also require new thinking about how ab initio simulations are used to understand reaction pathways involving extended structures, like the mineral-water interface. Our data indicate that reactions proceed via metastable intermediates and that the simulations must be structurally faithful or will miss the essential chemistry.

  • 31. Wu, Xuanjun
    et al.
    Yin, Zhaojun
    McKay, Craig
    Pett, Christian
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Leibniz-Institut für Analytische Wissenschaften−ISAS, Dortmund, Germany.
    Yu, Jin
    Schorlemer, Manuel
    Leibniz-Institut für Analytische Wissenschaften−ISAS, Dortmund, Germany.
    Gohl, Trevor
    Sungsuwan, Suttipun
    Ramadan, Sherif
    Baniel, Claire
    Allmon, Anthony
    Das, Rupali
    Westerlind, Ulrika
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Finn, M. G.
    Huang, Xuefei
    Protective Epitope Discovery and the Design of MUC1 Based Vaccine for Effective Tumor Protections in Immunotolerant Mice2018In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 140, no 48, p. 16596-16609Article in journal (Refereed)
    Abstract [en]

    Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUC1 antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qβ carrier with MUC1 glycopeptides containing 20-22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qβ-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qβ-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.

  • 32.
    Ådén, Jörgen
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Verma, Abhinav
    Schug, Alexander
    Wolf-Watz, Magnus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Modulation of a pre-existing conformational equilibrium tunes adenylate kinase activity2012In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 40, p. 16562-16570Article in journal (Refereed)
    Abstract [en]

    Structural plasticity is often required for distinct microscopic steps during enzymatic reaction cycles. Adenylate kinase from Escherichia coli (AKeco) populates two major conformations in solution; the open (inactive) and closed (active) state, and the overall turn-over rate is inversely proportional to the life-time of the active conformation. Therefore, structural plasticity is intimately cou-pled to enzymatic turn-over in AKeco. Here we probe the open to closed conformational equilibrium in the absence of bound substrate with NMR spectroscopy and molecular dynamics simulations. The conformational equilibrium in absence of substrate, and in turn, the turn-over number can be modulated with mutational- and osmolyte-driven perturbations. Removal of one hydrogen bond between the ATP and AMP binding sub-domains results in a population shift towards the open conformation and a resulting increase of kcat. Addition of the osmolyte TMAO to AKeco results in population shift towards the closed conformation and a significant reduction of kcat. The Michaelis constants (KM) scale with the change in kcat, which follows from the influence of the population of the closed conformation for substrate binding affinity. Hence, kcat and KM are mutually dependent and, in the case of AKeco, any perturbation that modulates kcat is mirrored with a proportional response in KM. Thus, our results demonstrate that the equilibrium constant of a pre-existing conformational equilibrium directly affect enzymatic catalysis. From an evolutionary perspective our findings suggests that, for AKeco, there exists ample flexibility to obtain a specificity constant (kcat/KM) that commensurate with the exerted cellular selective pressure.

  • 33.
    Ådén, Jörgen
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wolf-Watz, Magnus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    NMR identification of transient complexes critical to adenylate kinase catalysis2007In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 129, no 45, p. 14003-12Article in journal (Refereed)
    Abstract [en]

    A fundamental question in protein chemistry is how the native energy landscape of enzymes enables efficient catalysis of chemical reactions. Adenylate kinase is a small monomeric enzyme that catalyzes the reversible conversion of AMP and ATP into two ADP molecules. Previous structural studies have revealed that substrate binding is accompanied by large rate-limiting spatial displacements of both the ATP and AMP binding motifs. In this report a solution-state NMR approach was used to probe the native energy landscape of adenylate kinase in its free form, in complex with its natural substrates, and in the presence of a tight binding inhibitor. Binding of ATP induces a dynamic equilibrium in which the ATP binding motif populates both the open and the closed conformations with almost equal populations. A similar scenario is observed for AMP binding, which induces an equilibrium between open and closed conformations of the AMP binding motif. These ATP- and AMP-bound structural ensembles represent complexes that exist transiently during catalysis. Simultaneous binding of AMP and ATP is required to force both substrate binding motifs to close cooperatively. In addition, a previously unknown unidirectional energetic coupling between the ATP and AMP binding sites was discovered. On the basis of these and previous results, we propose that adenylate kinase belongs to a group of enzymes whose substrates act to shift pre-existing equilibria toward catalytically active states.

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