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  • 51.
    Frick, Andreas
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Åhs, Fredrik
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Appel, Lieuwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Jonasson, My
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wahlstedt, Kurt
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Bani, Massimo
    GlaxoSmithKline, Verona, Italy.
    Pich, Emilio Merlo
    GlaxoSmithKline, Verona, Italy.
    Bettica, Paolo
    GlaxoSmithKline, Verona, Italy.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Fredriksson, Mats
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Furmark, Tomas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder2016Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 26, nr 11, s. 1775-1783Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Abstract Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40 mg), the NK1R antagonist GR205171 (n=6; 5 mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [11C]5-hydroxytryptophan and [15O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala.

  • 52.
    Furmark, Tomas
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Marteinsdottir, Ina
    Linkoping Univ, Dept Clin & Expt Med, Ctr Social & Affect Neurosci, Linkoping, Sweden.
    Frick, Andreas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Heurling, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tillfors, Maria
    Univ Orebro, Ctr Hlth & Med Psychol, Orebro, Sweden.
    Appel, Lieuwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Hartvig, Per
    Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Fischer, Håkan
    Stockholm Univ, Dept Psychol, Stockholm, Sweden.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Southern Denmark Univ, Odense Univ Hosp, Odense, Denmark.
    Eriksson, Elias
    Gothenburg Univ, Dept Pharmacol, Gothenburg, Sweden.
    Fredrikson, Mats
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder.2016Inngår i: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 30, nr 10, s. 1028-1035Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[β -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.

  • 53.
    Ge, Changrong P
    et al.
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Tong, Dongmei R
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden.;Southern Med Univ, Dept Pathophysiol, Key Lab Shock & Microcirculat Res Guangdong, Guangzhou, Guangdong, Peoples R China..
    Liang, Bibo T
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden.;Southern Med Univ, Dept Pathophysiol, Key Lab Shock & Microcirculat Res Guangdong, Guangzhou, Guangdong, Peoples R China..
    Lönnblom, Erik S
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden..
    Schneider, Nadine K
    Goethe Univ, Fraunhofer Inst Mol Biol & Appl Ecol IME, Project Grp Translat Med & Pharmacol, Frankfurt, Germany.;Goethe Univ, Div Rheumatol, Univ Hosp Frankfurt, Frankfurt, Germany..
    Hagert, Cecilia U
    Univ Turku, Medicity Res Lab, Turku, Finland.;Natl Doctoral Programme Informat & Struct Biol, Turku, Finland..
    Viljanen, Johan V.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ayoglu, Burcu R
    KTH Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Affin Prote, Stockholm, Sweden..
    Stawikowska, Roma T
    Florida Atlantic Univ, Dept Chem & Biochem, Jupiter, FL USA..
    Nilsson, Peter C
    KTH Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Affin Prote, Stockholm, Sweden..
    Fields, Gregg B
    Florida Atlantic Univ, Dept Chem & Biochem, Jupiter, FL USA..
    Skogh, Thomas A
    Linkoping Univ, Dept Rheumatol, Dept Clin & Expt Med, Linkoping, Sweden..
    Kastbom, Alf R
    Linkoping Univ, Dept Rheumatol, Dept Clin & Expt Med, Linkoping, Sweden..
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Burkhardt, Harald T
    Goethe Univ, Fraunhofer Inst Mol Biol & Appl Ecol IME, Project Grp Translat Med & Pharmacol, Frankfurt, Germany.;Goethe Univ, Div Rheumatol, Univ Hosp Frankfurt, Frankfurt, Germany..
    Dobritzsch, Doreen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Holmdahl, Rikard K
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden.;Univ Turku, Medicity Res Lab, Turku, Finland.;Natl Doctoral Programme Informat & Struct Biol, Turku, Finland.;Southern Med Univ, Ctr Med Immunopharmacol Res, Guangzhou, Guangdong, Peoples R China..
    Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage2017Inngår i: JCI INSIGHT, ISSN 2379-3708, Vol. 2, nr 13, artikkel-id e93688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.

  • 54. Giordanetto, Fabrizio
    et al.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties?2014Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 57, nr 2, s. 278-95Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Macrocycles are ideal in efforts to tackle "difficult" targets, but our understanding of what makes them cell permeable and orally bioavailable is limited. Analysis of approximately 100 macrocyclic drugs and clinical candidates revealed that macrocycles are predominantly used for infectious disease and in oncology and that most belong to the macrolide or cyclic peptide class. A significant number (N = 34) of these macrocycles are administered orally, revealing that oral bioavailability can be obtained at molecular weights up to and above 1 kDa and polar surface areas ranging toward 250 Å(2). Moreover, insight from a group of "de novo designed" oral macrocycles in clinical studies and understanding of how cyclosporin A and model cyclic hexapeptides cross cell membranes may unlock wider opportunities in drug discovery. However, the number of oral macrocycles is still low and it remains to be seen if they are outliers or if macrocycles will open up novel oral druggable space.

  • 55.
    Golker, Kerstin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Olsson, Gustaf D.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Nicholls, Ian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    The influence of a methyl substituent on molecularly imprinted polymer morphology and recognition - Acrylic acid versus methacrylic acid2017Inngår i: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 92, s. 137-149Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this report, we have investigated factors contributing to the morphology and template recognition of bupivacaine-imprinted copolymers of methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA). To this end, MAA, the most commonly used functional monomer in non-covalent molecular imprinting protocols, was compared and contrasted with the closely related acrylic acid (AA) in terms of polymer morphologies, recognition characteristics, and molecular level events in the corresponding pre-polymerization mixtures. Two series of analogous bupivacaine-imprinted EGDMA-copolymers containing increasing fractions of either AA or MAA were studied through all-component MD simulations in the pre-polymerization phase, equilibrium binding experiments on corresponding synthesized polymers and morphology characterization by N-2-sorption measurements. A higher degree of hydrogen bonding frequency between respective functional monomer and bupivacaine was recorded for the mixtures containing AA compared to those containing MAA. In contrast, results from binding experiments demonstrated higher binding capacities for the polymers prepared with MAA than for those prepared with AA, which is explained by differences in polymer morphology. The surface areas and pore volumes of the AA-polymers were higher than for the MAA-polymers and the overall pore structure in the AA-polymers was ink-bottle shaped while the pores in the MAA-polymers were slit-shaped. We suggest that the methyl substituent of MAA contributes to differences in the reaction kinetics for AA and MAA during polymerization and resulted in different morphologies, in particular pore shape, which affected mass-transfer and consequently the binding qualities of the materials.

  • 56.
    Gustav, Hulu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Improved Reaction Conditions for Rhodium-catalyzed Hydroarylation of C60 Fullerenes with Tolylboronic acid: Towards bis[60] fullerene dumbbells2018Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Fulltekst tilgjengelig fra 2020-06-08 16:25
  • 57.
    Hribersek, Matic
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Control of Aryne Capture Regioselectivity via Fluoroboronate-induced Distortion2019Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Arynes are valued as extremely versatile electrophilic intermediates. Control over the regioselectivity with which arynes react is typically achieved using comparatively simple and/or chemically inutile substituents close to the reactive triple bond. This poses a challenge for the broad acceptance of arynes as the basis of genuinely useful synthetic building blocks.

    The work in this thesis attempts to overcome this limitation by developing a strategy in which the boronate ester functional group that drives the regioselectivity of an aryne capture is installed at a remote location of the molecule and offers ample opportunity for further derivatisation. This has been achieved via a catalytic C-H borylation strategy.

    Using experimental, mechanistic and computational studies, we show that remote, boron-based functional group is temporarily activated in-situ into a form able to furnish unprecedented levels of aryne capture regioselectivity. After the aryne capture, the boronate may be used in myriad further manipulations to provide compounds that are difficult or impossible otherwise to synthesize.

  • 58.
    Huang, Hao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Karlsson, Christoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Mamedov, Fikret
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. Waseda Univ, Dept Appl Chem, Tokyo 1698555, Japan..
    Polaron Disproportionation Charge Transport in a Conducting Redox Polymer2017Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 121, nr 24, s. 13078-13083Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Herein we report a mechanistic study of the charge transport in poly-3-((2,5-hydroquinone)vinyl)-1H-pyrrole by conductance measurements at various temperatures performed in situ during doping of the polypyrrole backbone in contact with an aqueous electrolyte. Charge transport was found to occur by electron hopping with associated electron transfer activation energies in the range of 0.08-0.2 eV. In situ electron paramagnetic resonance experiments indicated polarons as the dominant charge carriers and the charge transport was found to follow a second-order dependence with respect to the number of accumulated charges. Based on the findings, we present a polaron comproportionation/disproportionation model for electron conduction in poly-3-((2,5-hydroquinone)vinyl)-1H-pyrrole, thus, providing a complement to existing models for charge propagation in conducting polymers.

  • 59.
    Huang, Hao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Karlsson, Christoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Synthesis and Characterization of Poly-3-((2,5-hydroquinone)vinyl)-1H-pyrrole: investigation on Backbone/Pendant Interactions in a Conducting Redox Polymer2017Inngår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, nr 16, s. 10427-10435Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We herein report the synthesis and electrochemical characterization of poly-3-((2,5-hydroquinone)vinyl)-1H-pyrrole, consisting of a polypyrrole backbone derivatized at the beta position by a vinyl-hydroquinone pendant group. The structure of the polymer was characterized by solid state NMR spectroscopy. The interactions between the polypyrrole backbone and the oxidized quinone or reduced hydroquinone pendant groups are probed by several in situ methods. In situ attenuated total reflectance-Fourier transform infrared spectroscopy shows spectroscopic response from both the doping of the polymer backbone and the redox activity of the pendant groups. Using an in situ Electrochemical Quartz Crystal Microbalance we reveal that the polymer doping is unaffected by the pendant group redox chemistry, as opposed to previous reports. Despite the continuous doping the electrochemical conversion from the hydroquinone state to the quinone state results in a significant conductance drop, as observed by in situ conductivity measurements using an InterDigitated Array electrode set-up. Twisting of the conducting polymer backbone as a result of a decreased separation between pendant groups due to π-π stacking in the oxidized state is suggested as the cause of this conductance drop.

  • 60.
    Huang, Xiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Conducting Redox Polymers for Electrode Materials: Synthetic Strategies and Electrochemical Properties2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Organic electrode materials represent an intriguing alternative to their inorganic counterparts due to their sustainable and environmental-friendly properties. Their plastic character allows for the realization of light-weight, versatile and disposable devices for energy storage. Conducting redox polymers (CRPs) are one type of the organic electrode materials involved, which consist of a π-conjugated polymer backbone and covalently attached redox units, the so-called pendant. The polymer backbone can provide conductivity while it is oxidized or reduced (i. e., p- or n-doped) and the concurrent redox chemistry of the pendant provides charge capacity. The combination of these two components enables CRPs to provide both high charge capacity and high power capability. This dyad polymeric framework provides a solution to the two main problems associated with organic electrode materials based on small molecules: the dissolution of the active material in the electrolyte, and the sluggish charge transport within the material. This thesis introduces a general synthetic strategy to obtain the monomeric CRPs building blocks, followed by electrochemical polymerization to afford the active CRPs material. The choice of pendant and of polymer backbone depends on the potential match between these two components, i.e. the redox reaction of the pendant and the doping of backbone occurring within the same potential region. In the thesis, terephthalate and polythiophene were selected as the pendant and polymer backbone respectively, to get access to low potential CRPs. It was found that the presence of a non-conjugated linker between polymer backbone and pendant is essential for the polymerizability of the monomers as well as for the preservation of individual redox activities. The resulting CRPs exhibited fast charge transport within the polymer film and low activation barriers for charge propagation. These low potential CRPs were designed as the anode materials for energy storage applications. The combination of redox active pendant as charge carrier and a conductive polymer backbone reveals new insights into the requirements of organic matter based electrical energy storage materials.

    Delarbeid
    1. Matching Diethyl Terephthalate with n-Doped Conducting Polymers
    Åpne denne publikasjonen i ny fane eller vindu >>Matching Diethyl Terephthalate with n-Doped Conducting Polymers
    Vise andre…
    2015 (engelsk)Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, nr 33, s. 18956-18963Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The combination of small, high charge capacity molecules as pendant groups with a conducting polymer backbone having good electronic conductivity upon doping, gives the possibility to design a high capacity conducting redox polymer material for electric energy storage applications. The desired synergetic effect of the two components requires energy matching as well as chemical compatibility of the pendant group and the polymer backbone. Here we investigate the matching of diethyl terephthalate (DeT) with the thiophene-based conducting polymers polythiophene (PT), poly(3,4-ethylenedioxythiophene) (PEDOT), and polyphenylthiophene. We show that a stable and well-defined electrochemical response of DeT is achieved, together with all conducting polymers except for PT in tetrabutylammonium hexafluorophosphate electrolyte, indicating good energy match as well as chemical compatibility between DeT and polymers. By varying the size of ammonium cations in the electrolytes, we further show how this size affects the conductivity and the cycling stability of the polymers and also that the n-doping performance of all conducting polymers can be improved by the use of smaller alkyl ammonium cations. On the basis of these results, we suggest that PEDOT and PT are suitable candidates for a polymer backbone in conducting redox polymers with DeT pendant groups.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-262423 (URN)10.1021/acs.jpcc.5b05067 (DOI)000360026200015 ()
    Forskningsfinansiär
    Swedish Foundation for Strategic Research Swedish Research CouncilCarl Tryggers foundation Swedish Energy Agency
    Tilgjengelig fra: 2015-09-17 Laget: 2015-09-15 Sist oppdatert: 2017-12-04bibliografisk kontrollert
    2. Synthesis and Redox Properties of Thiophene Terephthalate Building Blocks for Low-Potential Conducting Redox Polymers
    Åpne denne publikasjonen i ny fane eller vindu >>Synthesis and Redox Properties of Thiophene Terephthalate Building Blocks for Low-Potential Conducting Redox Polymers
    Vise andre…
    2015 (engelsk)Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, nr 49, s. 27247-27254Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Terephthalate-substituted thiophene derivatives are promising redox-active components for anode materials in lithium-ion batteries. In this study, we present the synthesis of substituted 2-(thiophen-3-yl)terephthalate derivatives (TTDs) as suitable monomers for thiophene-based conducting redox polymers, along with their characterization by electrochemical and spectroscopic techniques. Density functional theory (DFT) calculations, utilizing the universal solvation model based on solute electron density (SMD), were used to predict both the first and the second reduction potentials of these TTDs. The computational results showed good agreement with the experimental data in nonaqueous acetonitrile solvent, with mean absolute errors of 30 and 40 mV for the first and second reduction steps, respectively. Time-dependent (TD) DFT calculations on TTDs indicated terephthalate local transitions at both 200 and 240 nm and charge-transfer transitions above 300 nm by examination of the involved molecular orbitals.

    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-268481 (URN)10.1021/acs.jpcc.5b08518 (DOI)000366339000008 ()
    Forskningsfinansiär
    Swedish Research Council, VR 621-2011-4423Swedish Foundation for Strategic Research Swedish Energy Agency
    Tilgjengelig fra: 2015-12-05 Laget: 2015-12-05 Sist oppdatert: 2017-12-01bibliografisk kontrollert
    3. Conducting Redox Polymer Based Anode Materials for High Power Electrical Energy Storage
    Åpne denne publikasjonen i ny fane eller vindu >>Conducting Redox Polymer Based Anode Materials for High Power Electrical Energy Storage
    Vise andre…
    2016 (engelsk)Inngår i: Electrochimica Acta, ISSN 0013-4686, E-ISSN 1873-3859, Vol. 204, s. 270-275Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    In this report we present the synthesis and characterization of two conducting redox polymers (CRPs) with polythiophene backbone and diethyl terephthalate pendant groups for the use as anode materials in secondary batteries. The materials show excellent rate capability allowing 301,Lm layers to be fully converted within seconds without the use of conductive additives. The high rate capability is traced to the open morphology of the materials that allows for fast ion transport, and to the mediation of electrons through the conducting polymer (CP) backbone. The requirements for the latter are i) that the redox chemistry of the pendant groups and the CP backbone overlaps and ii) that the CP conductivity is not compromised by the presence of the pendant groups. In the CRPs presented herein both these requirements are met and this is thus the first report on successful combination of the redox chemistry of organic redox molecules with the n-doping of conducting polymers.

    Emneord
    conducting redox polymers, terephthalates, polythiophene, n-doping
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-298055 (URN)10.1016/j.electacta.2016.03.163 (DOI)000376136700031 ()
    Forskningsfinansiär
    Swedish Foundation for Strategic Research Swedish Research CouncilCarl Tryggers foundation Stiftelsen Olle Engkvist ByggmästareSwedish Energy AgencyEU, Horizon 2020, 644631
    Tilgjengelig fra: 2016-07-05 Laget: 2016-06-29 Sist oppdatert: 2017-11-28bibliografisk kontrollert
    4. Effect of the Linker in Terephthalate-Functionalized Conducting Redox Polymers
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of the Linker in Terephthalate-Functionalized Conducting Redox Polymers
    Vise andre…
    2016 (engelsk)Inngår i: Electrochimica Acta, ISSN 0013-4686, E-ISSN 1873-3859, Vol. 222, s. 149-155Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Abstract The combination of high capacity redox active pendent groups and conducting polymers, realized in conducting redox polymers (CRPs), provides materials with high charge storage capacity that are electronically conducting which makes CRPs attractive for electrical energy storage applications. In this report, six polythiophene and poly(3,4-ethylenedioxythiophene)(PEDOT)-based CRPs with a diethyl terephthalate unit covalently bound to the polymer chain by various linkers have been synthesized and characterized electrochemically. The effects of the choice of polymer backbone and of the nature of the link on the electrochemistry, and in particular the cycling stability of these polymers, are discussed. All CRPs show both the doping of the polymer backbone as well as the redox behavior of the pendent groups and the redox potential of the pendent groups in the CRPs is close to that of corresponding monomer, indicating insignificant interaction between the pendant and the polymer backbone. While all CRPs show various degrees of charge decay upon electrochemical redox conversion, the PEDOT-based CRPs show significantly improved stability compared to the polythiophene counterparts. Moreover, we show that by the right choice of link the cycling stability of diethyl terephthalate substituted PEDOT-based CRPs can be significantly improved.

    Emneord
    conducting redox polymers, PEDOT, polythiophene, terephthalate
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-310464 (URN)10.1016/j.electacta.2016.10.183 (DOI)000392566200018 ()
    Forskningsfinansiär
    Swedish Foundation for Strategic Research Swedish Research CouncilCarl Tryggers foundation Stiftelsen Olle Engkvist ByggmästareSwedish Energy AgencyEU, European Research Council, 644631
    Tilgjengelig fra: 2016-12-16 Laget: 2016-12-16 Sist oppdatert: 2017-11-29bibliografisk kontrollert
    5. A versatile route to polythiophenes with functional pendant groups using alkyne chemistry
    Åpne denne publikasjonen i ny fane eller vindu >>A versatile route to polythiophenes with functional pendant groups using alkyne chemistry
    Vise andre…
    2016 (engelsk)Inngår i: Beilstein Journal of Organic Chemistry, ISSN 2195-951X, E-ISSN 1860-5397, Vol. 12, s. 2682-2688Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A new versatile polythiophene building block, 3-(3,4-ethylenedioxythiophene)prop-1-yne (pyEDOT) (3), is prepared from glycidol in four steps in 28% overall yield. pyEDOT features an ethynyl group on its ethylenedioxy bridge, allowing further functionalization by alkyne chemistry. Its usefulness is demonstrated by a series of functionalized polythiophene derivatives that were obtained by pre- and post-electropolymerization transformations, provided by the synthetic ease of the Sonogashira coupling and click chemistry.

    Emneord
    electropolymerization, functional polymers, polythiophene, Sonogashira coupling, thiophene
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-310098 (URN)10.3762/bjoc.12.265 (DOI)000391506600001 ()
    Forskningsfinansiär
    Swedish Research Council, VR 621-2011-4423 2015-4870Swedish Foundation for Strategic Research Swedish Energy Agency
    Tilgjengelig fra: 2016-12-09 Laget: 2016-12-09 Sist oppdatert: 2017-11-29bibliografisk kontrollert
    6. Conducting redox polymers with non-activated charge transport properties
    Åpne denne publikasjonen i ny fane eller vindu >>Conducting redox polymers with non-activated charge transport properties
    Vise andre…
    2017 (engelsk)Inngår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, nr 36, s. 25052-25058Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Non-activated charge transport has been demonstrated in terephthalate-functionalized conducting redox polymers. The transition from a temperature-activated conduction mechanism to a residual scattering mechanism was dependent on the doping level. The latter mechanism is associated with apparent negative activation barriers to charge transport and is generally found in polymer materials with a high degree of order. Crystallographic data, however, suggested a low degree of order in this polymer, indicating the existence of interconnected crystal domains in the predominantly amorphous polymer matrix through which the charge was transported. We have thus shown that the addition of bulky pendant groups to conducting polymers does not prevent efficient charge transport via the residual scattering mechanism with low barriers to charge transport.

    sted, utgiver, år, opplag, sider
    Royal Society of Chemistry, 2017
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-304625 (URN)10.1039/c7cp03939e (DOI)000411606200067 ()28879367 (PubMedID)
    Forskningsfinansiär
    Swedish Research CouncilSwedish Foundation for Strategic Research Stiftelsen Olle Engkvist ByggmästareEU, Horizon 2020, 64431Swedish Energy Agency
    Tilgjengelig fra: 2016-10-06 Laget: 2016-10-06 Sist oppdatert: 2018-06-04bibliografisk kontrollert
  • 61.
    Huang, Xiao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yang, Li
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    A versatile route to polythiophenes with functional pendant groups using alkyne chemistry2016Inngår i: Beilstein Journal of Organic Chemistry, ISSN 2195-951X, E-ISSN 1860-5397, Vol. 12, s. 2682-2688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new versatile polythiophene building block, 3-(3,4-ethylenedioxythiophene)prop-1-yne (pyEDOT) (3), is prepared from glycidol in four steps in 28% overall yield. pyEDOT features an ethynyl group on its ethylenedioxy bridge, allowing further functionalization by alkyne chemistry. Its usefulness is demonstrated by a series of functionalized polythiophene derivatives that were obtained by pre- and post-electropolymerization transformations, provided by the synthetic ease of the Sonogashira coupling and click chemistry.

  • 62.
    Huang, Xiao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yang, Li
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    3-(3,4-ethylenedioxythiophene)prop-1-yne (pyEDOT): A new versatile building block for functionalized PEDOTs2016Inngår i: 25th Organikerdagarna, 2016Konferansepaper (Fagfellevurdert)
  • 63.
    Ingner, Fredric
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Preparation of carbazolyne precursors through catalytic C-H functionalization2016Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 64.
    Ingner, Fredric
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Sustainable methods for the preparation of diverse Au(I) complexes2019Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Over the last three decades, the role of Au(I) complexes has become increasingly important within medicinal chemistry, material applications and synthesis. Alas, their preparation remains reliant on harsh reaction conditions, hazardous solvents, exogenous additives and, often, high reaction temperatures. Within this thesis we develop mild, sustainable, methods for the preparation of Au(I) complexes, that takes place in ambient conditions and omits the use of hazardous solvents. These goals are realized in two different manuscripts. The first manuscript utilizes a nucleophilic borate to afford Au(I) aryl complexes in green solvents without the requirement for exogenous additives. Purification consists of a simple filtration and washing step and affords products in very good to excellent yields for most examples. The second manuscript employs a mechanochemical protocol for expedient preparation of Au(I) aryl complexes from a number of parent aryl sources such as borates, arenes and heteroarenes. This includes the first mechanochemical preparation of Au(I) aryl complexes from borate or hetroarene sources. The developed mechanochemical C-H auration protocols allow for significantly less acidic C-H bonds than previously reported.

  • 65.
    Jiang, Xiangyi
    et al.
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
    Yu, Ji
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
    Zhou, Zhongxia
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
    Kongsted, Jacob
    Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark.
    Song, Yuning
    Shandong Univ, Dept Clin Pharm, Qilu Hosp, Jinan, Shandong, Peoples R China.
    Pannecouque, Christophe
    Rega Inst Med Res, Lab Virol & Chemotherapy, Leuven, Belgium.
    De Clercq, Erik
    Rega Inst Med Res, Lab Virol & Chemotherapy, Leuven, Belgium.
    Kang, Dongwei
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
    Poongavanam, Vasanthanathan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark.
    Liu, Xinyong
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
    Zhan, Peng
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
    Molecular design opportunities presented by solvent-exposed regions of target proteins2019Inngår i: Medicinal research reviews (Print), ISSN 0198-6325, E-ISSN 1098-1128, Vol. 39, nr 6, s. 2194-2238Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Solvent-exposed regions, or solvent-filled pockets, within or adjacent to the ligand-binding sites of drug-target proteins provide opportunities for substantial modifications of existing small-molecular drug molecules without serious loss of activity. In this review, we present recent selected examples of exploitation of solvent-exposed regions of proteins in drug design and development from the recent medicinal-chemistry literature.

  • 66.
    Kalepu, Jagadeesh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gandeepan, Parthasarathy
    Georg August Univ Gottingen, Inst Organ & Biomol Chem, Tammannstr 2, D-37077 Gottingen, Germany.
    Ackermann, Lutz
    Georg August Univ Gottingen, Inst Organ & Biomol Chem, Tammannstr 2, D-37077 Gottingen, Germany.
    Pilarski, Lukasz T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    C4-H indole functionalisation: precedent and prospects2018Inngår i: Chemical Science, ISSN 2041-6520, E-ISSN 2041-6539, Vol. 9, nr 18, s. 4203-4216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    C4-decorated indoles feature in a plethora of bioactive and functional compounds of importance to natural product synthesis, material sciences, as well as crop protection and pharmaceutical industries. Traditionally, their syntheses largely involved harsh stoichiometric metalations and radical reactions. However, transition metal catalysed C-H activation has recently evolved into a powerful strategy for the late-stage diversification of indoles at the C4-H position. Modern photoredox, enzymatic and precious transition metal catalysis represent the key stimuli for developing challenging C-C and C-Het bond forming transformations under mild reaction conditions. Herein, we discuss the evolution and application of these methods for the step-economical transformations of otherwise inert C4-H bonds up to December 2017.

  • 67.
    Kalepu, Jagadeesh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pilarski, Lukasz T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Weinreb Amides as Directing Groups for Transition Metal-Catalyzed C-H Functionalizations2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 5, artikkel-id 830Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Weinreb amides are a privileged, multi-functional group with well-established utility in classical synthesis. Recently, several studies have demonstrated the use of Weinreb amides as interesting substrates in transition metal-catalyzed C-H functionalization reactions. Herein, we review this part of the literature, including the metal catalysts, transformations explored so far and specific insights from mechanistic studies.

  • 68. Karim, A.
    et al.
    Schulz, N.
    Andersson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Nekoueishahraki, B.
    Carlsson, A-C
    Sarabi, D.
    Valkonen, A.
    Rissanen, K.
    Gräfenstein, Jürgen
    Keller, S.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    The three-center-four-electron tetrel bond2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We present a thermodynamically stable complex that possesses a three-center-four-electron (3c4e) tetrel bond [1,2], formed by capturing a reactive carbenium ion with a bidentate Lewis base. We report NMR spectroscopic, titration calorimetric and reaction kinetic evidences for the structure of this pentacoordinate species and discuss the properties of its tetrel bond, [N˜˜˜∙∙∙C∙∙∙˜˜˜N]+, in comparison with the analogous halogen, [N˜˜˜∙∙∙X∙∙∙˜˜˜N]+ and hydrogen, [N∙∙∙˜˜˜H∙∙∙˜˜˜N]+, bonds [3]. The necessity of the involvement of a bidentate Lewis base for the formation of a stable 3c4e tetrel bond is demonstrated by providing spectroscopic and crystallographic evidence, that a monodentate Lewis base induces a reaction rather than stabilizing the reactive species. A vastly decreased Lewis basicity of the bidentate ligand or reduced Lewis acidity of the carbenium ion weakens — or even prohibits — the formation of the pentacoordinate species, whereas synthetic modifications facilitating attractive orbital overlaps promote it. As the geometry of the pentacoordinate complex resembles the SN2 transition state, it may provide a model system for the investigation of fundamental reaction mechanisms and chemical bonding theories [4].

    References

    1. G.C. Pimentel J. Chem. Phys. 1951, 19, 446-448

    2. R.H. Crabtree Chem. Soc. Rev. 2017, 46, 1720-1729.

    3. S.B. Hakkert, M. Erdelyi J. Phys. Org. Chem. 2015, 95, 2572-2578

    4. Karim, N. Schultz, H. Andersson, B. Nekoueishahraki et al, 2018, submitted.

  • 69.
    Karim, Alavi
    et al.
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Schulz, Nils
    Ruhr Univ Bochum, Fac Chem & Biochem, Organ Chem 1, Univ Str 150, D-44801 Bochum, Germany.
    Andersson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Nekoueishahraki, Bijan
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Carlsson, Anna-Carin C.
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden;AstraZeneca R&D, Pepparedsleden 1, Molndal, Sweden.
    Sarabi, Daniel
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Valkonen, Arto
    Univ Jyvaskyla, Dept Chem, POB 35, FI-40014 Jyvaskyla, Finland.
    Rissanen, Kari
    Univ Jyvaskyla, Dept Chem, POB 35, FI-40014 Jyvaskyla, Finland.
    Grafenstein, Juergen
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Keller, Sandro
    TUK, Mol Biophys, D-67663 Kaiserslautern, Germany.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden;Swedish NMR Ctr, Med Gatan, SE-41390 Gothenburg, Sweden.
    Carbon's Three-Center, Four-Electron Tetrel Bond, Treated Experimentally2018Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 140, nr 50, s. 17571-17579Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tetrel bonding is the noncovalent interaction of group IV elements with electron donors. It is a weak, directional interaction that resembles hydrogen and halogen bonding yet remains barely explored. Herein, we present an experimental investigation of the carbon-centered, three-center, four-electron tetrel bond, [N-C-N](+), formed by capturing a carbenium ion with a bidentate Lewis base. NMR-spectroscopic, titration-calorimetric, and reaction-kinetic evidence for the existence and structure of this species is reported. The studied interaction is by far the strongest tetrel bond reported so far and is discussed in comparison with the analogous halogen bond. The necessity of the involvement of a bidentate Lewis base in its formation is demonstrated by providing spectroscopic and crystallographic evidence that a monodentate Lewis base induces a reaction rather than stabilizing the tetrel bond complex. A vastly decreased Lewis basicity of the bidentate ligand or reduced Lewis acidity of the carbenium ion weakens or even prohibits the formation of the tetrel bond complex, whereas synthetic modifications facilitating attractive orbital overlaps promote it. As the geometry of the complex resembles the S(N)2 transition state, it provides a model system for the investigation of fundamental reaction mechanisms and chemical bonding theories.

  • 70.
    Kathiravan, Subban
    et al.
    Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, S-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, S-39182 Kalmar, Sweden..
    Monoprotected L-Amino Acid (L-MPAA), Accelerated Bromination, Chlorination, and Iodination of C(sp²)-H Bonds by Iridium(III) Catalysis2017Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, nr 29, s. 7031-7036Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Halogenated arenes are important structural motifs commonly found in biologically active molecules and used for a variety of transformations in organic synthesis. Herein, we report the mono-protected L-amino acid (L-MPAA) accelerated iridium(III)-catalyzed halogenation of (hetero)anilides at room temperature. This reaction constitutes the first example of an iridium(III)/L-MPAA-catalyzed general halogenation of (hetero)arenes through C(sp²)-H activation. Furthermore, we demonstrate the potential utility of our method through its use in the synthesis of a quinolone derivative.

  • 71.
    Kathiravan, Subban
    et al.
    Linnaeus Univ, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.;Linnaeus Univ, Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Linnaeus Univ, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.;Linnaeus Univ, Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Rhodium(III)-catalysed, redox-neutral C(sp(2))-H alkenylation using pivalimide as a directing group with internal alkynes2017Inngår i: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 58, nr 1, s. 1-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the presence of [RhCp*Cl(2)l(2), N-pivaloyl anilines react with internal alkynes to give the corresponding 2-alkenylpivalimides under redox neutral conditions through C-H activation. This redox neutral hydroarylation, which does not require an external organic acid, unlocks a regioselective synthetic route to 2-alkenyl anilines and is generally applicable to diversely substituted electron rich and electron poor pivalimides.

  • 72.
    Khamesian, Marjan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Fernández Galván, Ignacio
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Delcey, Mickael G
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi.
    Sørensen, Lasse Kragh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology, Stockholm, Sweden.
    Lindh, Roland
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Uppsala Center of Computational Chemistry–UC3, Uppsala University, Uppsala, Sweden.
    Spectroscopy of linear and circular polarized ligth with the exact semiclassical light–matter interaction2019Inngår i: Annual Reports in Computational Chemistry: Volume 15 / [ed] David A. Dixon, Elsevier, 2019, s. 39-76Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    We present the theory and the analytical and numerical solution for the calculation of the oscillator and rotatory strengths of molecular systems using a state-specific formalism. For a start, this is done in the context of the exact semiclassical light–matter interaction in association with electronic wave functions expanded in a Gaussian basis. The reader is guided through the standard approximations of the field, e.g., the use of commutators, truncation of Taylor expansions, and the implications of these are discussed in parallel. Expressions for the isotropically averaged values are derived, recovering the isotropic oscillator strength in terms of the transition electric-dipole moment, and the isotropic rotatory strength in terms of the transition electric-dipole and magnetic-dipole moments. This chapter gives a detailed description of the computation of the integrals over the plane wave in association with Gaussian one-particle basis sets. Finally, a brief description is given of how the computed oscillator and rotatory strengths are related to the quantities commonly used and discussed in experimental studies.

  • 73.
    Kuang, Guanglin
    et al.
    AlbaNova Univ Ctr, Sch Biotechnol, Royal Inst Technol KTH, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Wang, Xu
    AlbaNova Univ Ctr, Sch Biotechnol, Royal Inst Technol KTH, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Halldin, Christer
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, S-17176 Stockholm, Sweden..
    Nordberg, Agneta
    Karolinska Univ Hosp, Ctr Alzheimer Res Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, S-14186 Stockholm, Sweden..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ågren, Hans
    AlbaNova Univ Ctr, Sch Biotechnol, Royal Inst Technol KTH, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Tu, Yaoquan
    AlbaNova Univ Ctr, Sch Biotechnol, Royal Inst Technol KTH, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Theoretical study of the binding profile of an allosteric modulator NS-1738 with a chimera structure of the alpha 7 nicotinic acetylcholine receptor2016Inngår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 18, nr 40, s. 28003-28009Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Potentiation of the function of the alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) is believed to provide a possible way for the treatment of cholinergic system dysfunctions such as Alzheimer's disease and schizophrenia. Positive allosteric modulators (PAMs) are able to augment the peak current response of the endogenous agonist of alpha 7-nAChR by binding to some allosteric sites. In this study, the binding profile of a potent type I PAM, NS-1738, with a chimera structure (termed alpha 7-AChBP) constructed from the extracellular domain of alpha 7-nAChR and an acetylcholine binding protein was investigated with molecular docking, molecular dynamics simulation, and free energy calculation methods. We found that NS-1738 could bind to three allosteric sites of alpha 7-AChBP, namely, the top pocket, the vestibule pocket and the agonist sub-pocket. NS-1738 has moderate binding affinities (-6.76 to -9.15 kcal mol(-1)) at each allosteric site. The urea group is critical for binding and can form hydrogen-bond interactions with the protein. The bulky trifluoromethyl group also has a great impact on the binding modes and binding affinities. We believe that our study provides valuable insight into the binding profiles of type I PAMs with alpha 7-nAChR and is helpful for the development of novel PAMs.

  • 74.
    Kuang, Guanglin
    et al.
    Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Zhou, Yang
    Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Zou, Rongfeng
    Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Halldin, Christer
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, S-17176 Stockholm, Sweden..
    Nordberg, Agneta
    Karolinska Univ Hosp, Ctr Alzheimer Res Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, S-14186 Huddinge, Sweden..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ågren, Hans
    Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.;Siberian Fed Univ, Inst Nanotechnol Spect & Quantum Chem, Svobodny Pr 79, Krasnoyarsk 660041, Russia..
    Tu, Yaoquan
    Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Characterization of the binding mode of the PET tracer [F-18] ASEM to a chimera structure of the alpha 7 nicotinic acetylcholine receptor2017Inngår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, nr 32, s. 19787-19793Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) is assumed to be implicated in a variety of neurological disorders, such as schizophrenia and Alzheimer's disease (AD). The progress of these disorders can be studied through imaging alpha 7-nAChR with positron emission tomography (PET). [F-18]ASEM is a novel and potent alpha 7-nAChR PET radioligand showing great promise in recent tests. However, the mechanism of the molecular interaction between [F-18] ASEM and alpha 7-nAChR is still unclear. In this paper, the binding profile of [F-18] ASEM to a chimera structure of alpha 7-nAChR was investigated with molecular docking, molecular dynamics, and metadynamics simulation methods. We found that [F-18] ASEM binds at the same site as the crystallized agonist epibatidine but with a different binding mode. The dibenzo[b, d] thiophene ring has a different orientation compared to the pyridine ring of epibatidine and has van der Waals interactions with residues from loop C on one side and p-p stacking interaction with Trp53 on the other side. The conformation of Trp53 was found to have a great impact on the binding of [F-18] ASEM. Six binding modes in terms of the side chain dihedral angles chi(1) and chi(2) of Trp53 were discovered by metadynamics simulation. In the most stable binding mode, Trp53 adopts a different conformation from that in the crystalline structure and has a rather favorable pi-pi stacking interaction with [F-18] ASEM. We believe that these discoveries can be valuable for the development of novel PET radioligands.

  • 75.
    Kumar, Rajnish
    et al.
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,NOVUM, 4th Floor, S-14186 Stockholm, Sweden.
    Kumar, Amit
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,NOVUM, 4th Floor, S-14186 Stockholm, Sweden.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Darreh-Shori, Taher
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,NOVUM, 4th Floor, S-14186 Stockholm, Sweden.
    Discovery of novel choline acetyltransferase inhibitors using structure-based virtual screening2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 16287Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer disease and related dementias are major challenges, demanding urgent needs for earliest possible diagnosis to optimize the success rate in finding effective therapeutic interventions. Mounting solid scientific premises point at the core acetylcholine-biosynthesizing cholinergic enzyme, ChAT as a legitimate in vivo target for developing positron emission tomography biomarker for early diagnosis and/or monitoring therapeutic responses in the neurodegenerative dementias. Up-to-date, no PET tracer ligands for ChAT are available. Here we report for the first time a novel hierarchical virtual screening approach on a commercial library of similar to 300,000 compounds, followed by in vitro screening of the hits by a new High-Throughput ChAT assay. We report detailed pharmacodynamic data for three identified selective novel ChAT ligands with IC50 and K-i values ranging from similar to 7 to 26 mu M. In addition, several novel selective inhibitors of the acetylcholine-degrading enzymes, AChE and BuChE were identified, with one of the compounds showing an IC50-value of similar to 6 mu M for AChE. In conclusion, this report provides an excellent starting platform for designing and optimizing potent and selective ChAT ligands, with high potential as PET-imaging probe for early diagnosis of AD, and related dementias, such as Down's syndrome and Lewy body disorders.

  • 76.
    Kumar, Rajnish
    et al.
    Karolinska Inst, Ctr Alzheimer Res, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Dept Neurobiol Care Sci & Soc, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Div Translat Alzheimer Neurobiol, 4th Floor, S-14186 Huddinge, Sweden..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Darreh-Shori, Taher
    Karolinska Inst, Ctr Alzheimer Res, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Dept Neurobiol Care Sci & Soc, 4th Floor, S-14186 Huddinge, Sweden.;Novum, Div Translat Alzheimer Neurobiol, 4th Floor, S-14186 Huddinge, Sweden..
    Novel ligands of Choline Acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 31247Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent reports have brought back the acetylcholine synthesizing enzyme, choline acetyltransferase in the mainstream research in dementia and the cholinergic anti-inflammatory pathway. Here we report, a specific strategy for the design of novel ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity Relationship (HQSAR) and lead optimization. Molecular docking was performed on a series of ChAT inhibitors to decipher the molecular fingerprint of their interaction with the active site of ChAT. Then robust statistical fragment HQSAR models were developed. A library of novel ligands was generated based on the pharmacophoric and shape similarity scoring function, and evaluated in silico for their molecular interactions with ChAT. Ten of the top scoring invented compounds are reported here. We confirmed the activity of alpha-NETA, the only commercially available ChAT inhibitor, and one of the seed compounds in our model, using a new simple colorimetric ChAT assay (IC50 similar to 88 nM). In contrast, alpha-NETA exhibited an IC50 of -30 mu M for the ACh-degrading cholinesterases. In conclusion, the overall results may provide useful insight for discovering novel ChAT ligands and potential positron emission tomography tracers as in vivo functional biomarkers of the health of central cholinergic system in neurodegenerative disorders, such as Alzheimer's disease.

  • 77.
    Larsson, Johanna
    et al.
    OnTarget Chem, Virdings Alle 32B, S-75450 Uppsala, Sweden..
    Demory, Emilien
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Devaraj, Karthik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Sollert, Carina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pilarski, Lukasz T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Selective Activation of Arylboronate or Aryne Reactivity as a Versatile Postfunctionalization Strategy2016Inngår i: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 27, nr 7, s. 969-976Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This review discusses the preparation and orthogonal reactivity of boryl ortho-silyl(hetero)aryl triflates as precursors for arynes. These triflates undergo a wide variety of selective reactions of either the boronate or aryne component. Activation of the boronate group affords diverse (hetero)aryne precursors, whereas aryne activation and capture gives previously difficult-to-access arylboronates, all starting from the same set of common starting materials. Thus, the boronate and aryne functionality can be used for their mutual postfunctionalization with unprecedented flexibility.

  • 78.
    Lindblad, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Investigating the Formation of [D-X-D]+ Halogen and [N-P-N]2+ Pnictogen Bonds in Solution2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Fulltekst tilgjengelig fra 2020-06-24 22:35
  • 79.
    Lindblad, Sofia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Mehmeti, Krenare
    University of Gothenburg.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Asymmetric [N-X-N]+ Halogen Bonds in Solution2018Konferansepaper (Annet vitenskapelig)
  • 80.
    Lindblad, Sofia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Mehmeti, Krenare
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Veiga, Alberte X.
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden;Concept Life Sci, Discovery Pk,Ramsgate Rd, Sandwich CT13 9ND, Kent, England.
    Nekoueishahraki, Bijan
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Grafenstein, Jurgen
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden; Swedish NMR Ctr, Medicinaregatan 5C, SE-41390 Gothenburg, Sweden.
    Halogen Bond Asymmetry in Solution2018Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 140, nr 41, s. 13503-13513Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Halogen bonding is the noncovalent interaction of halogen atoms in which they act as electron acceptors. Whereas three-center hydrogen bond complexes, [D center dot center dot center dot H center dot center dot center dot D](+) where D is an electron donor, exist in solution as rapidly equilibrating asymmetric species, the analogous halogen bonds, [D center dot center dot center dot X center dot center dot center dot D](+), have been observed so far only to adopt static and symmetric geometries. Herein, we investigate whether halogen bond asymmetry, i.e., a [D-X center dot center dot center dot D](+) bond geometry, in which one of the D-X bonds is shorter and stronger, could be induced by modulation of electronic or steric factors. We have also attempted to convert a static three-center halogen bond complex into a mixture of rapidly exchanging asymmetric isomers, [D center dot center dot center dot X-D](+) (sic) [D-X center dot center dot center dot D](+), corresponding to the preferred form of the analogous hydrogen bonded complexes. Using N-15 NMR, IPE NMR, and DFT, we prove that a static, asymmetric geometry, [D-X center dot center dot center dot D](+), is obtained upon desymmetrization of the electron density of a complex. We demonstrate computationally that conversion into a dynamic mixture of asymmetric geometries, [D center dot center dot center dot X-D](+) (sic) [D-X center dot center dot center dot D](+), is achievable upon increasing the donor-donor distance. However, due to the high energetic gain upon formation of the three-center-four electron halogen bond, the assessed complex strongly prefers to form a dimer with two static and symmetric three-center halogen bonds over a dynamic and asymmetric halogen bonded form. Our observations indicate a vastly different preference in the secondary bonding of H+ and X+. Understanding the consequences of electronic and steric influences on the strength and geometry of the three-center halogen bond provides useful knowledge on chemical bonding and for the development of improved halonium transfer agents.

  • 81.
    Lindgren, Cecilia
    et al.
    Umea Univ, Dept Chem, SE-90187 Umea, Sweden.
    Tyagi, Mohit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Viljanen, Johan V.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Toms, Johannes
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ge, Changrong
    Karolinska Inst, Med Inflammat Res, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
    Zhang, Naru
    Karolinska Inst, Med Inflammat Res, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden;Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China.
    Holmdahl, Rikard
    Karolinska Inst, Med Inflammat Res, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden;Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Linusson, Anna
    Umea Univ, Dept Chem, SE-90187 Umea, Sweden.
    Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis2018Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, nr 11, s. 4774-4790Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CI1259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CI1259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CI1259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CI1259-273, together with the positioning of the galactose moiety of CI1259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CI1259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.

  • 82.
    Linnman, Clas
    et al.
    Harvard Med Sch, Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Pain & Brain, Boston, MA USA..
    Catana, Ciprian
    Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA USA..
    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 kirurgiska vetenskaper, Radiologi.
    Engler, Henry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Univ Republica, Uruguayan Ctr Mol Imaging CUDIM, Fac Med, Montevideo, Uruguay.;Univ Republica, Fac Sci, Montevideo, Uruguay..
    Långström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Imperial Coll, Fac Med, Neuropsychopharmacol Sect, London, England..
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Furmark, Tomas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Fredrikson, Mats
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Borsook, David
    Harvard Med Sch, Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Pain & Brain, Boston, MA USA..
    Peterson, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 9, artikkel-id e0161563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

  • 83.
    Lu, Xi
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Mestres, Gemma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Singh, Vijay Pal
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Effati, Pedram
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Poon, Jia-Fei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Marjam, Karlsson Ott
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity2017Inngår i: Antioxidants, E-ISSN 2076-3921, Vol. 6, nr 13, s. 1-13Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2 -induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.

  • 84.
    Lundstedt, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Webb, Matthew J
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ozonolysis of polycyclic aromatic hydrocarbons in participating solvents2017Inngår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, nr 10, s. 6152-6159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Seven polycyclic aromatic hydrocarbon (PAH) compounds that can be considered small models for graphene edges have been treated with ozone in solution. The presence of participating solvents such as water or methanol had a pronounced influence on conversion and identity of the functional groups formed, whereas the regioselectivity of the ozonation remained unaffected. Six previously unreported compounds have been isolated from the ozonolysis of pyrene 1, perylene 2 and benzo[e] pyrene 4. Comparison of the experimental data with calculated local ionization energy surfaces (IES) shows a good correlation, and indicates that this computational tool would be useful to predict the regioselectivity of ozone also for larger PAHs, including graphene and graphene nanoribbons.

  • 85.
    Ma, Huan
    et al.