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  • 101.
    Papadakis, Raffaello
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Li, Hu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Bergman, Joakim
    AstraZeneca R&D, Med Chem KH471, S-43183 Molndal, Sweden.
    Lundstedt, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Jorner, Kjell
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Ayub, Rabia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Haldar, Soumyajyoti
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Jahn, Burkhard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Denisova, Aleksandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Zietz, Burkhard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Lindh, Roland
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi.
    Sanyal, Biplab
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Leifer, Klaus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Metal-free photochemical silylations and transfer hydrogenations of benzenoid hydrocarbons and graphene2016Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first hydrogenation step of benzene, which is endergonic in the electronic ground state (S0), becomes exergonic in the first triplet state (T1). This is in line with Baird’s rule, which tells that benzene is antiaromatic and destabilized in its T1 state and also in its first singlet excited state (S1), opposite to S0, where it is aromatic and remarkably unreactive. Here we utilized this feature to show that benzene and several polycyclic aromatic hydrocarbons (PAHs) to various extents undergo metal-free photochemical (hydro)silylations and transfer-hydrogenations at mild conditions, with the highest yield for naphthalene (photosilylation: 21%). Quantum chemical computations reveal that T1-state benzene is excellent at H-atom abstraction, while COT, aromatic in the T1 and S1 states according to Baird’s rule, is unreactive. Remarkably, also CVD-graphene on SiO2 is efficiently transfer-photohydrogenated using formic acid/water mixtures together with white light or solar irradiation under metal-free conditions.

  • 102.
    Peintner, Stefan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Danelius, Emma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Poongavanam, Vasanthanathan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Erdelyi, Mate
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. The Swedish NMR Centre.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    The Solvent Polarity Dependence of Macrocycles’ Conformations2018Konferansepaper (Fagfellevurdert)
  • 103. Perrin, Charles L
    et al.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    One-bond C-C coupling constants in ethers are not primarily determined by N-sigma delocalization.2005Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 127, nr 17, s. 6168-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One-bond carbon-carbon coupling constants, 1JCC, were measured for a series of cyclic and acyclic ethers. Surprisingly, the dependence on COCC dihedral angle, tau, parallels cos(tau), rather than the cos(2tau) characteristic of n-sigma* delocalization. These results complement recently calculated 1JCH values in three ethers. The variations in 1J are not primarily determined by delocalization but instead are attributed to a dipolar interaction that affects electron density, perhaps via the hybridization.

  • 104. Perrin, Charles L
    et al.
    Ohta, Brian K
    Kuperman, Joshua
    Liberman, Jordan
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Stereochemistry of beta-deuterium isotope effects on amine basicity.2005Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 127, nr 26, s. 9641-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Secondary beta-deuterium isotope effects on amine basicities are measured using a remarkably precise NMR titration method. Deuteration is found to increase the basicity of methylamine, dimethylamine, benzylamine, N,N-dimethylaniline, 2-methyl-2-azanorbornane, and pyrrolizidine. The increase in dimethylamine arises entirely from enthalpy, contrary to a previous report. The method permits a determination of intramolecular isotope effects in 1-benzyl-4-methylpiperidine and 2-benzyl-2-azanorbornane. It is found that deuteration has a larger isotope effect when either antiperiplanar or synperiplanar to a lone pair, but the synperiplanar effect is smaller, as confirmed by computations. The isotope effect is attributed to a lowered zero-point energy of a C-H bond adjacent to an amine nitrogen, arising from delocalization of either a syn or an anti lone pair, and with no detectable angle-independent inductive effect.

  • 105.
    Peuker, Sebastian
    et al.
    University of Gothenburg, Gothenburg, Sweden.
    Andersson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gustavsson, Emil
    University of Gothenburg, Gothenburg, Sweden.
    Maiti, Kiran Sankar
    University of Gothenburg, Gothenburg, Sweden.
    Kania, Rafal
    University of Gothenburg, Gothenburg, Sweden.
    Karim, Alavi
    University of Gothenburg, Gothenburg, Sweden.
    Niebling, Stephan
    University of Gothenburg, Gothenburg, Sweden.
    Pedersen, Anders
    Swedish NMR Centre at the University of Gothenburg, Gothenburg, Sweden.
    Erdelyi, Mate
    University of Gothenburg, Gothenburg, Sweden.
    Westenhoff, Sebastian
    University of Gothenburg, Gothenburg, Sweden.
    Efficient Isotope Editing of Proteins for Site-Directed Vibrational Spectroscopy2016Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 138, nr 7, s. 2312-2318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vibrational spectra contain unique information on protein structure and dynamics. However, this information is often obscured by spectral congestion, and site-selective information is not available. In principle, sites of interest can be spectrally identified by isotope shifts, but site-specific isotope labeling of proteins is today possible only for favorable amino acids or with prohibitively low yields. Here we present an efficient cell-free expression system for the site-specific incorporation of any isotope-labeled amino acid into proteins. We synthesized 1.6 mg of green fluorescent protein with an isotope-labeled tyrosine from 100 mL of cell-free reaction extract. We unambiguously identified spectral features of the tyrosine in the fingerprint region of the time-resolved infrared absorption spectra. Kinetic analysis confirmed the existence of an intermediate state between photoexcitation and proton transfer that lives for 3 ps. Our method lifts vibrational spectroscopy of proteins to a higher level of structural specificity.

  • 106.
    Pilarski, Lukasz T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Young Career Focus: Dr. Lukasz T. Pilarski (Uppsala University, Sweden)2017Inngår i: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 28, nr 8, s. A83-A85Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background and Purpose. SYNFORM regularly meets young up-and-coming researchers who are performing exceptionally well in the arena of organic chemistry and related fields of research, in order to introduce them to the readership. This Young Career Focus presents Dr. Lukasz T. Pilarski (Uppsala University, Sweden).

  • 107.
    Poon, Jia-fei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Exploring Catalytic Tellurium-Based Antioxidants: Synthesis and Evaluation2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis is concerned with the synthesis and evaluation of various tellurium-based chain-breaking antioxidants. The purpose is to find novel regenerable compounds with improved radical-trapping capacity.

    In the first part of this work, we explore the possibilities to incorporate tellurium into tocopherols and aromatic amines. Overall, tocopherols carrying alkyltelluro groups are better radical-trapping agents than the corresponding sulfur- and selenium analogues. Among them, 7-octyltelluro δ-tocopherol showed a ca. 17-fold higher reactivity than recorded for α-tocopherol and much better regenerability. Even longer inhibition times were recorded for the corresponding bis(tocopheryl) tellurides. In the aromatic amine series, diphenyl amines carrying alkyltelluro groups were shown to function as efficient radical-quenchers capable of inhibiting peroxidation for 460 min in the presence of N-acetylcysteine. Thiol-consumption experiments suggested that the long inhibition times are due to efficient quenching of in-situ formed alkoxyl radicals in a solvent cage.

    In the second part of the thesis, we study how the antioxidant properties are affected by variations in the electron density at tellurium and the number of alkyltelluro substituents in the molecule. Evaluation of a series of aryltelluro phenols carrying electron donating and electron withdrawing groups in the para-position of the aryl moiety suggested that a high electron density at the heteroatom prolonged the inhibition time. Among alkyltelluro phenols, alkyltelluro resorcinols and bis(alkyltelluro) phenols, phenols carrying alkyltelluro groups in both ortho positions were superior when it comes to radical-trapping activity and regenerability.

    Delarbeid
    1. Catalytic Antioxidants: Regenerable Tellurium Analogues of Vitamin E
    Åpne denne publikasjonen i ny fane eller vindu >>Catalytic Antioxidants: Regenerable Tellurium Analogues of Vitamin E
    2013 (engelsk)Inngår i: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, nr 24, s. 6274-6277Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    In an effort to improve the chain-breaking capacity of the natural antioxidants, an octyltelluro group was introduced next to the phenolic moiety in β- and δ-tocopherol. The new vitamin E analogues quenched peroxyl radicals more efficiently than α-tocopherol and were readily regenerable by aqueous N-acetylcysteine in a simple membrane model composed of a stirring chlorobenzene/water two-phase system. The novel tocopherol analogues could also mimic the action of the glutathione peroxidase enzymes.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-213569 (URN)10.1021/ol403131t (DOI)000329077700042 ()
    Tilgjengelig fra: 2013-12-28 Laget: 2013-12-28 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    2. Regenerable Antioxidants - Introduction of Chalcogen Substituents into Tocopherols
    Åpne denne publikasjonen i ny fane eller vindu >>Regenerable Antioxidants - Introduction of Chalcogen Substituents into Tocopherols
    2015 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, nr 6, s. 2447-2457Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    To improve the radical-trapping capacity of the natural antioxidants, alkylthio-, alkylseleno-, and alkyltelluro groups were introduced into all vacant aromatic positions in β-, γ- and δ-tocopherol. Reaction of the tocopherols with electrophilic chalcogen reagents generated by persulfate oxidation of dialkyl dichalcogenides provided convenient but low-yielding access to many sulfur and selenium derivatives, but failed in the case of tellurium. An approach based on lithiation of the appropriate bromo-tocopherol, insertion of chalcogen into the carbon-lithium bond, air-oxidation to a dichalcogenide, and final borohydride reduction/alkylation turned out to be generally applicable to the synthesis of all chalcogen derivatives. Whereas alkylthio- and alkylseleno analogues were generally poorer quenchers of lipid peroxyl radicals than the corresponding parents, all tellurium compounds showed a substantially improved radical-trapping activity. Introduction of alkyltelluro groups into the tocopherol scaffold also caused a dramatic increase in the regenerability of the antioxidant. In a two-phase lipid peroxidation system containing N-acetylcysteine as a water-soluble co-antioxidant the inhibition time was up to six-fold higher than that recorded for the natural antioxidants.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-243231 (URN)10.1002/chem.201405895 (DOI)000348510400023 ()
    Merknad

    De två första författarna delar förstaförfattarskapet.

    Tilgjengelig fra: 2015-02-05 Laget: 2015-02-05 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. Regenerable Radical-Trapping Tellurobistocopherol Antioxidants
    Åpne denne publikasjonen i ny fane eller vindu >>Regenerable Radical-Trapping Tellurobistocopherol Antioxidants
    Vise andre…
    2016 (engelsk)Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 81, nr 24, s. 12540-12544Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Tellurobistocopherols 911 were prepared by lithiation of the corresponding bromotocopherols, reaction with tellurium tetrachloride and reductive workup. Compounds 911 quenched linoleic-acid-derived peroxyl radicals much more efficiently than α-tocopherol in a chlorobenzene/water two-phase system. N-Acetylcysteine or tris(2-carboxylethyl)phosphine as co-antioxidants in the aqueous phase could regenerate the tellurobistocopherols and increase their inhibition times. Antioxidant 11 inhibited peroxidation for 7-fold longer than that recorded with α-tocopherol. Thiol consumption in the aqueous phase was monitored and found to be inversely related to the inhibition time.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-302464 (URN)10.1021/acs.joc.6b02450 (DOI)000390180100051 ()
    Merknad

    Authors in list of papers in thesis: Poon, J.; Yan, J.; Gates, P.; Engman, L.

    Tilgjengelig fra: 2016-09-04 Laget: 2016-09-04 Sist oppdatert: 2017-11-21bibliografisk kontrollert
    4. Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic Amines
    Åpne denne publikasjonen i ny fane eller vindu >>Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic Amines
    Vise andre…
    2016 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 22, nr 36, s. 12891-12903Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The synthesis of a variety of aromatic amines carrying an ortho-alkyltelluro group is described. The new antioxidants quenched lipidperoxyl radicals much more efficiently than α-tocopherol and were regenerable by aqueous-phase N-acetylcysteine in a two-phase peroxidation system. The inhibition time for diaryl amine 9 b was four-fold longer than recorded with α-tocopherol. Thiol consumption in the aqueous phase was found to correlate inversely to the inhibition time and the availability of thiol is the limiting factor for the duration of antioxidant protection. The proposed mechanism for quenching of peroxyl radicals involves O-atom transfer from peroxyl to Te followed by H-atom transfer from amine to alkoxyl radical in a solvent cage.

    Emneord
    antioxidants; amines; chain-breaking activity; organotellurium; regenerable
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-302460 (URN)10.1002/chem.201602377 (DOI)000383758200044 ()27484352 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 621-2011-4006
    Tilgjengelig fra: 2016-09-04 Laget: 2016-09-04 Sist oppdatert: 2017-11-21bibliografisk kontrollert
    5. In Search of Catalytic Antioxidants-(Alkyltelluro)phenols, (Alkyltelluro)resorcinols, and Bis(alkyltelluro)phenols
    Åpne denne publikasjonen i ny fane eller vindu >>In Search of Catalytic Antioxidants-(Alkyltelluro)phenols, (Alkyltelluro)resorcinols, and Bis(alkyltelluro)phenols
    2013 (engelsk)Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, nr 12, s. 6008-6015Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The quenching of peroxyl radicals by ortho-(alkyltelluro)phenols occurs by a more complex mechanism than formal H-atom transfer. In an effort to improve on this concept, we have prepared (alkyltelluro)resorcinols and bis(alkyltelluro)phenols and evaluated their catalytic chain breaking and preventive antioxidative properties. The in situ formed trianion produced from 2-bromophenol and 3 equiv of tert-butyllithiutn was allowed to react with dialkyl ditellurides to provide ortho-(alkyltelluro)phenols in low yields. 2-Bromoresorcinols after treatment with 4 equiv of tert-butyllithium similarly afforded 2-(alkyltelluro)resorcinols. Bis(alkyltelluro)phenols were accessed by allowing the trianion produced from the reaction of 2,6-dibromophenol with 5 equiv of tert-butyllithium to react with dialkyl ditellurides. The novel phenolic compounds were found to inhibit azo-initiated peroxidation of linoleic acid much more efficiently than alpha-tocopherol in a two-phase peroxidation system containing excess N-acetylcysteine as a stoichiometric thiol reducing agent in the aqueous phase. Whereas most of the (alkyltelluro)phenols and resorcinols could inhibit peroxidation for only 89-228 min, some of the bis(alkyltelluro)phenols were more regenerable and offered protection for >410 min. The novel (alkyltelluro)phenols were also evaluated for their capacity to catalyze reduction of hydrogen peroxide in the presence of thiophenol (glutathione peroxidase-like activity). (Alkyltelluro)resorcinols 7a-c were the most efficient catalysts with activities circa 65 times higher than those recorded for diphenyl diselenide.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-205014 (URN)10.1021/jo400703w (DOI)000320979500020 ()
    Tilgjengelig fra: 2013-08-13 Laget: 2013-08-13 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 108.
    Poon, Jia-fei
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yan, Jiajie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Jorner, Kjell
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Donau, Carsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Singh, Vijay P.
    Department of Chemistry & Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh, India.
    Gates, Paul J.
    School of Chemistry, University of Bristol, United Kingdom.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Substituent Effects in Chain-Breaking Aryltellurophenol Antioxidants2018Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, nr 14, s. 3520-3527Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    2-Aryltellurophenols substituted in the aryltelluro or phenolic part of the molecule were prepared by lithiation of the corresponding O-THP-protected 2-bromophenol, followed by reaction with a suitable diaryl ditelluride and deprotection. In a two-phase system containing N-acetylcysteine as a co-antioxidant in the aqueous phase, all compounds quenched lipid peroxyl radicals more efficiently than α-tocopherol with 3 to 5-fold longer inhibition times. Compounds carrying electron donating para-substituents in the phenolic or aryltelluro part of the molecule showed the best results. The mechanism for quenching of peroxyl radicals was discussed in the light of calculated OH bond dissociation energies, deuterium labeling experiments and studies of thiol-consumption in the aqueous phase. 

  • 109.
    Poon, Jia-Fei
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yan, Jiajie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Singh, Vijay P
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gates, Paul J
    Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic Amines2016Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 22, nr 36, s. 12891-12903Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The synthesis of a variety of aromatic amines carrying an ortho-alkyltelluro group is described. The new antioxidants quenched lipidperoxyl radicals much more efficiently than α-tocopherol and were regenerable by aqueous-phase N-acetylcysteine in a two-phase peroxidation system. The inhibition time for diaryl amine 9 b was four-fold longer than recorded with α-tocopherol. Thiol consumption in the aqueous phase was found to correlate inversely to the inhibition time and the availability of thiol is the limiting factor for the duration of antioxidant protection. The proposed mechanism for quenching of peroxyl radicals involves O-atom transfer from peroxyl to Te followed by H-atom transfer from amine to alkoxyl radical in a solvent cage.

  • 110.
    Poon, Jia-fei
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yan, Jiajie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Singh, Vijay P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gates, Paul J.
    School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Regenerable Radical-Trapping Tellurobistocopherol Antioxidants2016Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 81, nr 24, s. 12540-12544Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tellurobistocopherols 911 were prepared by lithiation of the corresponding bromotocopherols, reaction with tellurium tetrachloride and reductive workup. Compounds 911 quenched linoleic-acid-derived peroxyl radicals much more efficiently than α-tocopherol in a chlorobenzene/water two-phase system. N-Acetylcysteine or tris(2-carboxylethyl)phosphine as co-antioxidants in the aqueous phase could regenerate the tellurobistocopherols and increase their inhibition times. Antioxidant 11 inhibited peroxidation for 7-fold longer than that recorded with α-tocopherol. Thiol consumption in the aqueous phase was monitored and found to be inversely related to the inhibition time.

  • 111.
    Poongavanam, Vasanthanathan
    et al.
    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.
    Corona, Angela
    Univ Cagliari, Dept Life & Environm Sci, Cagliari, Italy..
    Steinmann, Casper
    Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark.;Aalborg Univ, Dept Chem & Biosci, Aalborg, Denmark..
    Scipione, Luigi
    Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, Rome, Italy..
    Grandi, Nicole
    Univ Cagliari, Dept Life & Environm Sci, Cagliari, Italy..
    Pandolfi, Fabiana
    Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, Rome, Italy..
    Di Santo, Roberto
    Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, Rome, Italy..
    Costi, Roberta
    Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, Rome, Italy..
    Esposito, Francesca
    Univ Cagliari, Dept Life & Environm Sci, Cagliari, Italy..
    Tramontano, Enzo
    Univ Cagliari, Dept Life & Environm Sci, Cagliari, Italy.;CNR, Ist Ric Genet & Biomed, Monserrato, CA, Italy..
    Kongsted, Jacob
    Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark..
    Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies2018Inngår i: MedChemComm, ISSN 2040-2503, E-ISSN 2040-2511, Vol. 9, nr 3, s. 562-575Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Persistent HIV infection requires lifelong treatment and among the 2.1 million new HIV infections that occur every year there is an increased rate of transmitted drug-resistant mutations. This fact requires a constant and timely effort in order to identify and develop new HIV inhibitors with innovative mechanisms. The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only viral encoded enzyme that still lacks an efficient inhibitor despite the fact that it is a well-validated target whose functional abrogation compromises viral infectivity. Identification of new drugs is a long and expensive process that can be speeded up by in silico methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15 inhibited the RNase H function below 100 mu M with three hits exhibiting IC50 values < 10 mu M. The most active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 mu M and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly identified compounds; for instance, compound AA involves extensive interactions with a lipophilic pocket formed by Ala502, Lys503, and Trp (406, 426 and 535) and polar interactions with Arg557 and the highly conserved RNase H primer-grip residue Asn474. The structural insights obtained from this work provide the bases for further lead optimization.

  • 112.
    Poongavanam, Vasanthanathan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Danelius, Emma
    Univ Gothenburg, Dept Chem & Mol Biol, Kemivagen 10, SE-41296 Gothenburg, Sweden.
    Peintner, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Alcaraz, Lilian
    Johnson & Johnson Innovat, Med Chem, One Chapel Pl, London W1G 0BG, England.
    Caron, Giulia
    Univ Torino, Dept Mol Biotechnol & Hlth Sci, Quarello 15, I-10135 Turin, Italy.
    Cummings, Maxwell D.
    Janssen Res & Dev, 1400 McKean Rd, Spring House, PA 19477 USA.
    Wlodek, Stanislaw
    OpenEye Sci Software, 9 Bisbee Court, Santa Fe, NM 87508 USA.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Swedish NMR Ctr, Medicinaregatan 5, SE-40530 Gothenburg, Sweden.
    Hawkins, Paul C. D.
    OpenEye Sci Software, 9 Bisbee Court, Santa Fe, NM 87508 USA.
    Ermondi, Giuseppe
    Univ Torino, Dept Mol Biotechnol & Hlth Sci, Quarello 15, I-10135 Turin, Italy.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Conformational Sampling of Macrocyclic Drugs in Different Environments: Can We Find the Relevant Conformations?2018Inngår i: ACS OMEGA, ISSN 2470-1343, Vol. 3, nr 9, s. 11742-11757Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conformational flexibility is a major determinant of the properties of macrocycles and other drugs in beyond rule of 5 (bRo5) space. Prediction of conforrriations is essential for design of drugs in this space, and we have evaluated three tools for conformational sampling of la set of 10 bRo5 drugs and clinical candidates in polar and apolar environments. The distance-geometry based OMEGA was found to yield ensembles spanning larger structure and property spaces than the ensembles obtained by MOE LowModeMD (MOE) and MacroModel (MC). Both MC and OMEGA but not MOE generated different ensembles for polar and apolar environments. All three conforinational search methods generated conformers similar to the crystal structure conformers for 9 of the 10 compounds, with OMEGA performing somewhat better than MOE and MC. MOE and OMEGA found all six conformers of roxithromycin that were identified by NMR in aqueous solutions, whereas only OMEGA sampled the three conformers observed in chloroform. We suggest that characterization of conformers using molecular descriptors, e.g., the radius of gyration and polar surface area, is preferred to energy- or root-mean-square deviation-based methods for selection of biologically relevant conformers in drug discovery in bRo5 space.

  • 113.
    Poongavanam, Vasanthanathan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Doak, Bradley Croy
    Department of Medicinal Chemistry, MIPS, Monash University, Victoria, Australia.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Opportunities and guidelines for discovery of orally absorbed drugs in beyond rule of 5 space2018Inngår i: Current Opinion in Chemical Biology, ISSN 1367-5931, Vol. 44, s. 23-29Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Recent years have seen a dramatic increase in the number of drugs approved in chemical space outside of Lipinski’s rule of 5, that is in what has been termed beyond rule of 5 (bRo5) space. The development of three major classes of oral drugs that treat HIV and HCV infections and the growing evidence that novel, difficult targets can be accessed has prompted research into understanding design of drugs displaying cell permeability, solubility and ultimately oral bioavailability in bRo5 space. Studies have found a consistent outer property limit for a reasonable chance of de novo designing oral bioavailability. In addition, several property-based guidelines, along with incorporation of chameleonic features, have emerged as strategies to aid design in bRo5 space. A more detailed understanding of the complex and environment dependent conformational landscape will likely be the focus of the next generation of guidelines allowing property predictions of ever more complex compounds. By pushing the boundaries of current orally designable chemical space we hope that discoveries will be made for fundamental science and also for discovery of novel therapeutics.

  • 114.
    Poongavanam, Vasanthanathan
    et al.
    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..
    Kongsted, Jacob
    Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark..
    Wustner, Daniel
    Univ Southern Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark..
    Computational Analysis of Sterol Ligand Specificity of the Niemann Pick C2 Protein2016Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 55, nr 36, s. 5165-5179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transport of cholesterol derived from hydrolysis of lipoprotein associated cholesteryl esters out of late endosomes depends critically on the function of the Niemann Pick Cl (NPC1) and C2 (NPC2) proteins. Both proteins bind cholesterol but also various other sterols and both-With strongly varying affinity: The molecular mechanisms under lying this multiligand specificity are not known. On the basis:Of the crystal structure of NPC2, we have here investigated structural details of NPC2 sterol interactions using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA): calculations. We found that an aliphatic side chain in the sterol ligand results in strong binding to NPC2, while side chain oxidized sterols gave weaker binding. Estradiol and the hydrophobic amine U18666A had the lowest affinity of all lested ligands and at the same time showed the highest flexibility within the NPC2 binding pocket. The binding affinity of all ligands correlated highly with their calculated partitioning coefficient (logP) between octanol/water phases and with the potential of sterols to stabilize the protein backbone. prom molecular dynamics simulations, we suggest a general mechanism for NPC2 mediated sterol transfer, in which Phe66, Val96, and Tyr100 act as reversible gate keepers. These residues stabilize the sterol in the binding pose via pi-pi stacking but move transiently. apart during sterol release. A computational mutation analysis revealed that the binding of various ligands depends critically on the same specific amino acid residues within the binding pocket providing shape complementary to sterols, but also on residues in distal regions of the protein.

  • 115.
    Poongavanam, Vasanthanathan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Vigneshwaran, Namashivayam
    Univ Bonn, Pharmaceut Inst, Pharmaceut Chem 2, Bonn, Germany.
    Vanagamudi, Murugesan
    Sree Vidyanikethan Coll Pharm, Dept Med & Pharmaceut Chem, Tirupati, Andhra Prades, India.
    Hadi Al, Shamaileh
    Murdoch Univ, Ctr Comparat Genom, Perth, WA, Australia.
    Rakesh, Veedu
    Murdoch Univ, Ctr Comparat Genom, Perth, WA, Australia.; Perron Inst Neurol & Translat Sci, Perth, WA, Australia..
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Murugan, N. Arul
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, Stockholm, Sweden.
    Integrative approaches in HIV-1 non-nucleoside reverse transcriptase inhibitor design2018Inngår i: WIREs Comput Mol Sci, Vol. 8, nr 1, artikkel-id e1328Artikkel i tidsskrift (Fagfellevurdert)
  • 116.
    Pujari-Palmer, Shiuli
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Lu, Xi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Singh, Vijay P.
    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.
    Pujari-Palmer, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Karlsson Ott, Marjam
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Incorporation and delivery of an organoselenium antioxidant from a brushite cement2017Inngår i: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 197, s. 115-119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An inflammatory reaction occurs following biomaterial implantation in the body, which produce toxic byproducts such as reactive oxygen species (ROS). Although ROS is required to clear the wound, excessive ROS can damage the tissue around the implant site, eventually leading to implant failure. One approach to control the inflammatory response is to incorporate an antioxidant into the biomaterial in order to scavenge ROS produced by activated phagocytes. In the present study, an organoselenium antioxidative compound was incorporated into a brushite cement, with the goal of scavenging ROS generated from activated primary human mononuclear leukocytes (MNCs), in vitro. The effect of the antioxidant on the physical properties of brushite cement, and its release from the cement were investigated via compressive strength, setting time, phase composition, and UV spectroscopy analysis. The physical properties of brushite remained unchanged following incorporation of the antioxidant. The antioxidant was slowly released from the cement, following a non-Fickian transport mechanism, with approximately 60% of the loaded antioxidant released over five days. The released antioxidant was then tested for its ability to scavenge ROS released by MNCs using the luminol amplified chemiluminescence assay. The results show that antioxidative released at both early stages (24 h) and late stages (120 h) retained its scavenging capacity and effectively reduced ROS production. These results indicate that brushite cements loaded with organoselenium compounds can modulate ROS production after implantation and potentially modulate the inflammatory response to improve device integration.

  • 117. Pupier, Marion
    et al.
    Nuzillard, Jean-Marc
    Wist, Julien
    Schlörer, Nils E
    Kuhn, Stefan
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Steinbeck, Christoph
    Williams, Antony J
    Butts, Craig
    Claridge, Tim D W
    Mikhova, Bozhana
    Robien, Wolfgang
    Dashti, Hesam
    Eghbalnia, Hamid R
    Farès, Christophe
    Adam, Christian
    Kessler, Pavel
    Moriaud, Fabrice
    Elyashberg, Mikhail
    Argyropoulos, Dimitris
    Pérez, Manuel
    Giraudeau, Patrick
    Gil, Roberto R
    Trevorrow, Paul
    Jeannerat, Damien
    NMReDATA, a standard to report the NMR assignment and parameters of organic compounds2018Inngår i: Magnetic Resonance in Chemistry, ISSN 0749-1581, E-ISSN 1097-458X, Vol. 56, nr 8, s. 703-715Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Even though NMR has found countless applications in the field of small molecule characterization, there is no standard file format available for the NMR data relevant to structure characterization of small molecules. A new format is therefore introduced to associate the NMR parameters extracted from 1D and 2D spectra of organic compounds to the proposed chemical structure. These NMR parameters, which we shall call NMReDATA (for nuclear magnetic resonance extracted data), include chemical shift values, signal integrals, intensities, multiplicities, scalar coupling constants, lists of 2D correlations, relaxation times, and diffusion rates. The file format is an extension of the existing Structure Data Format, which is compatible with the commonly used MOL format. The association of an NMReDATA file with the raw and spectral data from which it originates constitutes an NMR record. This format is easily readable by humans and computers and provides a simple and efficient way for disseminating results of structural chemistry investigations, allowing automatic verification of published results, and for assisting the constitution of highly needed open-source structural databases.

  • 118.
    Rahman, Obaidur
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, S-17176 Stockholm, Sweden.;Bencar AB, Dag Hammarsjoldsvag 34B, S-57237 Uppsala, Sweden..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Bencar AB, Dag Hammarsjoldsvag 34B, S-57237 Uppsala, Sweden.
    Halldin, Christer
    Karolinska Univ Hosp, Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, S-17176 Stockholm, Sweden..
    Alkyl Iodides and [C-11]CO in Nickel-Mediated Cross-Coupling Reactions: Successful Use of Alkyl Electrophiles containing a beta Hydrogen Atom in Metal-Mediated [C-11]Carbonylation2016Inngår i: CHEMISTRYSELECT, ISSN 2365-6549, Vol. 1, nr 10, s. 2498-2501Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transition metal-mediated cross-coupling reactions of non-activated alkyl electrophiles suffer from competing b-hydride elimination and therefore have limited applications in synthetic organic chemistry. Hereby the first successful use of nickel-mediated carbonylative cross-coupling of non-activated alkyl iodides using [C-11] carbon monoxide is presented. The reaction conditions were optimised for the synthesis of N-(pyridine-2-yl) cyclohexane([C-11] carbonyl)-carboxamide. The nickel(0) complex, Ni(COD) 2, in the presence of bathophenanthroline in the non-polar protic solvent tert-butanol at 100 degrees C offered the highest trapping efficiency (TE) and radiochemical yield (RCY) of 89% and 72%, respectively. The applicability of the method was further explored in the syntheses of five additional ([C-11] carbonyl) amides (6a to 6e in Figure 2) and the TE and RCY in the latter cases were 70-90% and 33-57%, respectively. The presented method has a potential for the development of C-11-labelled PET tracers with a carbonyl group connected to an alkyl chain containing beta hydrogen.

  • 119.
    Rainoldi, Giulia
    et al.
    Univ Milan, Dipartimento Chim, Via Golgi 19, I-20133 Milan, Italy..
    Begnini, Fabio
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    de Munnik, Mariska
    Vrije Univ Amsterdam, Dept Chem & Pharmaceut Sci, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands.;Vrije Univ Amsterdam, AIMMS, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands..
    Lo Presti, Leonardo
    Univ Milan, Dipartimento Chim, Via Golgi 19, I-20133 Milan, Italy..
    Vande Velde, Christophe M. L.
    Univ Antwerp, Fac Appl Engn, Adv Reactor Technol, Groenenborgerlaan 171, B-2020 Antwerp, Belgium..
    Orru, Romano
    Vrije Univ Amsterdam, Dept Chem & Pharmaceut Sci, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands.;Vrije Univ Amsterdam, AIMMS, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands..
    Lesma, Giordano
    Univ Milan, Dipartimento Chim, Via Golgi 19, I-20133 Milan, Italy..
    Ruijter, Eelco
    Vrije Univ Amsterdam, Dept Chem & Pharmaceut Sci, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands.;Vrije Univ Amsterdam, AIMMS, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands..
    Silvani, Alessandra
    Univ Milan, Dipartimento Chim, Via Golgi 19, I-20133 Milan, Italy..
    Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines2018Inngår i: ACS COMBINATORIAL SCIENCE, ISSN 2156-8952, Vol. 20, nr 2, s. 98-105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obtained thiazolidines proved to be suitable substrates for further transformations. Notably, both the Ugi-Joullie and the azido-Ugi reactions resulted highly diastereoselective, affording predominantly the trans-configured products, as confirmed by X-ray crystallographic analysis.

  • 120.
    Raposo, Bruno
    et al.
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.;Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur,NRB 836, Boston, MA 02115 USA..
    Merky, Patrick
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    Lundqvist, Christina
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, S-41346 Gothenburg, Sweden..
    Yamada, Hisakata
    Kyushu Univ, Med Inst Bioregulat, Div Host Def, Fukuoka 8128582, Japan..
    Urbonaviciute, Vilma
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    Niaudet, Colin
    Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden..
    Viljanen, Johan V.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kyewski, Bruno
    German Canc Res Ctr, Div Dev Immunol, Tumor Immunol Program, D-69120 Heidelberg, Germany..
    Ekwall, Olov
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, S-41346 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, S-41346 Gothenburg, Sweden..
    Holmdahl, Rikard
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    Bäcklund, Johan
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    T cells specific for post-translational modifications escape intrathymic tolerance induction2018Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikkel-id 353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Establishing effective central tolerance requires the promiscuous expression of tissue-restricted antigens by medullary thymic epithelial cells. However, whether central tolerance also extends to post-translationally modified proteins is not clear. Here we show a mouse model of autoimmunity in which disease development is dependent on post-translational modification (PTM) of the tissue-restricted self-antigen collagen type II. T cells specific for the non-modified antigen undergo efficient central tolerance. By contrast, PTM-reactive T cells escape thymic selection, though the PTM variant constitutes the dominant form in the periphery. This finding implies that the PTM protein is absent in the thymus, or present at concentrations insufficient to induce negative selection of developing thymocytes and explains the lower level of tolerance induction against the PTM antigen. As the majority of self-antigens are post-translationally modified, these data raise the possibility that T cells specific for other self-antigens naturally subjected to PTM may escape central tolerance induction by a similar mechanism.

  • 121.
    Rodriguez-Vieitez, Elena
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden..
    Carter, Stephen F.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden.;Univ Manchester, Inst Brain Behav & Mental Hlth, Wolfson Mol Imaging Ctr, Manchester, Lancs, England..
    Chiotis, Konstantinos
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden..
    Saint-Aubert, Laure
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden..
    Leuzy, Antoine
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden..
    Scholl, Michael
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden..
    Almkvist, Ove
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden.;Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Nordberg, Agneta
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, SE-14157 Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
    Comparison of Early-Phase C-11-Deuterium-L-Deprenyl and C-11-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease2016Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, nr 7, s. 1071-1077Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The PET tracer C-11-deuterium-L-deprenyl (C-11-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase C-11-DED and C-11-Pittsburgh compound B (C-11-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which C-11-DED binding is influenced by brain perfusion was investigated. METHODS: C-11-DED, C-11-PiB, and F-18-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16). A modified reference Patlak model was used to quantify C-11-DED binding. A simplified reference tissue model was applied to both C-11-DED and C-11-PiB to measure brain perfusion relative to the cerebellar gray matter (R-1) and binding potentials. C-11-PiB retention and F-18-FDG uptake were also quantified as target-to-pons SUV ratios in 12 regions of interest (ROIs). RESULTS: The strongest within-subject correlations with the corresponding R-1 values (R-1,R-DED and R-1,R-PiB, respectively) and with F-18-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min after injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based intersubject Pearson correlations with R-1,R-DED/R-1,R-PiB and with F-18-FDG uptake, whereas C-11-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporoparietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporoparietal F-18-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared with controls. CONCLUSION: The 1- to 4-min early-frame intervals of C-11-DED or C-11-PiB are suitable surrogate measures for brain perfusion. C-11-DED binding is independent of brain perfusion, and thus C-11-DED PET can provide information on both functional (brain perfusion) and pathologic (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase C-11-DED and C-11-PiB perfusion appear to provide complementary rather than redundant information.

  • 122.
    Sareila, Outi
    et al.
    Univ Turku, Med Res Lab, Turku, Finland..
    Hagert, Cecilia
    Univ Turku, Med Res Lab, Turku, Finland.;Natl Doctoral Programme Informat & Struct Biol, Turku, Finland..
    Kelkka, Tiina
    Univ Turku, Med Res Lab, Turku, Finland.;Turku Doctoral Programme Biomed Sci, Turku, Finland.;Univ Helsinki, Hematol Res Unit Helsinki, Helsinki, Finland..
    Linja, Marjo
    Univ Turku, Med Res Lab, Turku, Finland..
    Xu, Bingze
    Karolinska Inst, Dept Med Biochem & Biophys, Div Med Inflammat Res, SE-7177 Stockholm, Sweden..
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Holmdahl, Rikard
    Univ Turku, Med Res Lab, Turku, Finland.;Karolinska Inst, Dept Med Biochem & Biophys, Div Med Inflammat Res, SE-7177 Stockholm, Sweden..
    Reactive Oxygen Species Regulate Both Priming and Established Arthritis, but with Different Mechanisms2017Inngår i: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 27, nr 18, s. 1473-1490Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the Ncf1 gene is associated with increased arthritis severity. In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis.

    Results: Targeted Ncf1 knock-in mice lacked NOX2-derived ROS, and in vivo allelic conversion of Ncf1 by the CreER(T2) recombinase led to full protein expression and ROS production within 10 days. Mice in which Ncf1 had been activated before immunization with type II collagen (CII) developed only mild clinical symptoms of collagen-induced arthritis (CIA), whereas the ROS-deficient littermates had severe arthritis. The functional Ncf1 restricted the expansion of IL-17A-producing T cells specific for the immunodominant CII peptide. When the Ncf1 gene was activated after the priming phase, Ncf1-dependent protection from autoimmune arthritis was still observed, together with a reduced number of splenic monocytes but it was not associated with alterations in peptide-specific T cell response. The Ncf1-deficient mice expressed pronounced interferon signature, which could be normalized by conditional expression of Ncf1 and was also present in the Ncf1-mutated mouse during arthritis.

    Innovation and Conclusion: Ncf1 deficiency has been known to predispose to autoimmunity in both humans and rodents. Our in vivo results point to a regulatory role of NOX2-derived ROS not only during priming but also during the effector phase of CIA, most likely via different mechanisms.

  • 123.
    Schulz, Nils
    et al.
    Ruhr Univ Bochum, Fac Chem & Biochem, Organ Chem 1, Univ Str 150, D-44801 Bochum, Germany.
    Schindler, Severin
    Ruhr Univ Bochum, Fac Chem & Biochem, Organ Chem 1, Univ Str 150, D-44801 Bochum, Germany.
    Huber, Stefan M.
    Ruhr Univ Bochum, Fac Chem & Biochem, Organ Chem 1, Univ Str 150, D-44801 Bochum, Germany.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    NMR Determination of the Binding Constant of Ionic Species: A Caveat2018Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 83, nr 18, s. 10881-10886Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Determination of the dissociation constant of ionic complexes with the standard NMR titration and NMR dilution techniques may yield a severely compromised result, due to the typically unconsidered chemical shift alteration induced by the gradual change of the ionic strength during the experiment. We show that the reliability of an NMR titration experiment is markedly improved upon keeping the overall ionic strength constant.

  • 124.
    Sebastiano, Matteo Rossi
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Doak, Bradley C.
    Monash Univ, MIPS, Dept Med Chem, Victoria, Australia.
    Backlund, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Poongavanam, Vasanthanathan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Over, Björn
    AstraZeneca R&D Gothenburg, Innovat Med & Early Dev Biotech Unit, Cardiovasc & Metab Dis, Mölndal, Sweden.
    Ermondi, Giuseppe
    Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy.
    Caron, Giulia
    Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy.
    Matsson, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Impact of Dynamically Exposed Polarity on Permeability and Solubility of Chameleonic Drugs Beyond the Rule of 52018Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, nr 9, s. 4189-4202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conformational flexibility has been proposed to significantly affect drug properties outside rule-of-5 (Ro5) chemical space. Here, we investigated the influence of dynamically exposed polarity on cell permeability and aqueous solubility for a structurally diverse set of drugs and clinical candidates far beyond the Ro5, all of which populated multiple distinct conformations as revealed by X-ray crystallography. Efflux-inhibited (passive) Caco-2 cell permeability correlated strongly with the compounds’ minimum solvent-accessible 3D polar surface areas (PSA), whereas aqueous solubility depended less on the specific 3D conformation. Inspection of the crystal structures highlighted flexibly linked aromatic side chains and dynamically forming intramolecular hydrogen bonds as particularly effective in providing “chameleonic” properties that allow compounds to display both high cell permeability and aqueous solubility. These structural features, in combination with permeability predictions based on the correlation to solvent-accessible 3D PSA, should inspire drug design in the challenging chemical space far beyond the Ro5.

  • 125.
    Shoravi, Siamak
    et al.
    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..
    Karlsson, Bjorn C. G.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Bexborn, Fredrik
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Abghoui, Younes
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Hussain, Javed
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Wiklander, Jesper G.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed Sci, SE-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    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.;Uppsala Univ, BMC, Dept Chem, SE-75123 Uppsala, Sweden..
    In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies2016Inngår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 14, nr 18, s. 4210-4219Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.

  • 126.
    Sigtryggsson, Sigtryggur Bjarki
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Design and Synthesis of Novel Small-Molecule Inhibitors of the Keap1-Nrf2 PPI2019Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 127.
    Singh, Vijay P.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Centre of Advanced Studies in Chemistry, Panjab University, India.
    Yan, Jiajie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Poon, Jia-fei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gates, Paul J.
    School of Chemistry, University of Bristol, United Kingdom.
    Butcher, Ray J.
    Department of Chemistry, Howard University, USA.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Chain-Breaking Phenolic 2,3-Dihydrobenzo[b]selenophene Antioxidants: Proximity Effects and Regeneration Studies2017Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, nr 60, s. 15080-15088Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phenolic 2,3-dihydrobenzo[b]selenophene anti-oxidants carrying the OH-group ortho (9), meta (10, 11) and para (8) to the Se were prepared by seleno-Claisen rearrangement/intramolecular hydroselenation. Meta-isomer (11) was studied by X-ray crystallography. The radical-trapping activity and regenerability of compounds 8-11 were evaluated using a two-phase system where linoleic acid was undergoing peroxidation in the lipid phase while regeneration of the antioxidant by co-antioxidants (N-acetylcysteine, glutathione, dithiothreitol, ascorbic acid, tris(carboxyethyl)phosphine hydrochloride) was ongoing in the aqueous layer. Compound 9 quenched peroxyl radicals

    more efficiently than α-tocopherol. It also provided the most long-lasting antioxidant protection. With thiol co-antioxidants it could inhibit peroxidation for more than five-fold longer than the natural product. Regeneration was more efficient when the aqueous phase pH was slightly acidic. Since calculated O-H bond dissociation energies for 8-11 were substantially larger than for α-tocopherol, an antioxidant mechanism involving O-atom transfer from peroxyl to selenium was proposed. The resulting phenolic selenoxide/alkoxyl radical would then exchange a hydrogen atom in a solvent cage before antioxidant regeneration at the aqueous lipid interphase.

  • 128.
    Sjödin, Martin
    et al.
    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.
    Sterby, Mia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Xiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Quinone-Substituted Conducting Polymers as Electrode Materials for All-Organic Proton Batteries2018Konferansepaper (Fagfellevurdert)
  • 129.
    Sjödin, Martin
    et al.
    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.
    Sterby, Mia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strietzel, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Yang, Li
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Wang, Huan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Xiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Conducting Redox Polymer Based Batteries2017Konferansepaper (Fagfellevurdert)
  • 130.
    Sjödin, Martin
    et al.
    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.
    Sterby, Mia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Åkerlund, Lisa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Xiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Organic Batteries Based on Quinone-Substituted Conducting Polymers2017Konferansepaper (Fagfellevurdert)
  • 131.
    Sjödin, Martin
    et al.
    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.
    Wang, Huan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Åkerlund, Lisa
    Sterby, Mia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Hao
    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.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Organiska batterier för hållbar och ökad energi-effektivitet i lokal energilagring2018Konferansepaper (Annet vitenskapelig)
  • 132.
    Srifa, Pemikar
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Galkin, Maxim V.
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Samec, Joseph S. M.
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Hermansson, Kersti
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Broqvist, Peter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Detecting Important Intermediates in Pd Catalyzed Depolymerization of a Lignin Model Compound by a Combination of DFT Calculations and Constrained Minima Hopping2016Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 120, nr 41, s. 23469-23479Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Density functional theory (DFT) calculations, combined with a constrained minima hopping algorithm (global minimum search while preserving the molecular identity), have been performed to investigate important reaction intermediates for the heterogeneously catalyzed beta-O-4' bond cleavage in lignin derivatives. More specifically, we have studied the adsorption properties of a keto tautomer (1-methoxypropan-2-one) and its enol form on a catalytically active Pd(111) surface. In agreement with experiments, we find that for the gas phase molecules the keto tautomer is the most stable. Interestingly, the enol tautomer has a higher affinity to the Pd catalyst than the keto form, and becomes the most stable molecular form when adsorbed on the catalyst surface. The global minimum complex found on the metal surface corresponds to an enolate structure formed when the enol tautomer chemisorbs onto the surface and donates its pi-electrons from the C=C region to two adjacent palladium atoms. The actual formation of a chemical bond to the surface in the case of the enol molecule could be the key to understanding why the enol derivative is needed for an efficient beta-O-4' bond cleavage.

  • 133.
    Stepanov, Vladimir
    et al.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Svedberg, Marie
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Jia, Zhisheng
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Krasikova, Raisa
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Lemoine, Laetitia
    Karolinska Inst, Dept Neurobiol, Ctr Alzheimer Res, Stockholm, Sweden..
    Okamura, Nobujuki
    Tohoku Univ, Dept Pharmacol, Sch Med, Sendai, Miyagi, Japan..
    Furumoto, Shozo
    Tohoku Univ, Dept Pharmacol, Sch Med, Sendai, Miyagi, Japan..
    Mitsios, Nicholas
    Karolinska Inst, Dept Neurosci, Sci Life Lab, Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, Sci Life Lab, Stockholm, Sweden..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Nordberg, Agneta
    Karolinska Inst, Dept Neurobiol, Ctr Alzheimer Res, Stockholm, Sweden..
    Halldin, Christer
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Development of [C-11]/[H-3-1]THK-5351-A potential novel carbon-11 tau imaging PET radioligand2017Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 46, s. 50-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Due to the rise in the number of patients with dementia the imperative for finding new diagnostic and treatment options becomes ever more pressing. While significant progress has been made in PET imaging of A beta aggregates both in vitro and in vivo, options for imaging tau protein aggregates selectively are still limited. Based on the work previously published by researchers from the Tohoku University, Japan, that resulted in the development of [F-18]THK-5351, we have undertaken an effort to develop a carbon-11 version of the identical structure - [C-11]THK-5351. In parallel, THK-5351 was also labeled with tritium ([H-3]THK-5351) for use in in vitro autoradiography (ARG). Methods: The carbon -11 labeling was performed starting with di-protected enantiomeric pure precursor-tertbutyl 5-(6-( (2S)-3-fluoro-2-(tetrahydro-2H-Pyran-2-yloxy)proPoxy)quinolin-2-yl)pyridin-2-yl carbamate, which was reacted with [C-11]MeI, using DMF as the solvent and NaH as base, followed by deprotection with trifluoroacetic acid/water mixture, resulting in enantiomerically pure carbon-11 radioligand,[C-11]THK-5351 (S)-1-fluoro-3-(2-(6-([C-11]methylamino)pyridin-3-yl)quinolin-6-yloxy)propan-2-ol. Tritium labeling and purification of [H-3]THK-5351 were undertaken using similar approach, resulting in [H-3]THK-5351 with RCP >99.8% and specific radioactivity of 13 GB q/mu mol. Results: [C-11]THK-5351 was produced in good yield (1900 +/- 355 MBq), specific radioactivity (SRA) (361 +/- 119 GBq/mu rnol at EOS + 20 min) and radiochemical purity (RCP) (>99.8%), with enantiomeric purity of 98.7%. [H-3]TM-5351 was evaluated for ARG of tau binding in post-mortem human brain tissue using cortical sections from one AD patient and one control subject. [H-3]THK-5351 binding density was higher in the AD patient compared to the control subject, the binding was displaced by unlabeled THK-5351 confirming specific [H-3] THK-5351 binding. (C) 2016 Elsevier Inc. All rights reserved.

  • 134.
    Sterby, Mia
    et al.
    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.
    Huang, Xiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    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.
    Characterization of PEDOT-Quinone Conducting Redox Polymers for Water Based Secondary Batteries2017Inngår i: Electrochimica Acta, ISSN 0013-4686, E-ISSN 1873-3859, Vol. 235, s. 356-364Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lithium-ion technologies show great promise to meet the demands that the transition towards renewable energy sources and the electrification of the transport sector put forward. However, concerns regarding lithium-ion batteries, including limited material resources, high energy consumption during production, and flammable electrolytes, necessitate research on alternative technologies for electrochemical energy storage. Organic materials derived from abundant building blocks and with tunable properties, together with water based electrolytes, could provide safe, inexpensive and sustainable alternatives. In this study, two conducting redox polymers based on poly(3,4-ethylenedioxythiophene) (PEDOT) and a hydroquinone pendant group have been synthesized and characterized in an acidic aqueous electrolyte. The polymers were characterized with regards to kinetics, pH dependence, and mass changes during oxidation and reduction, as well as their conductance. Both polymers show redox matching, i.e. the quinone redox reaction occurs within the potential region where the polymer is conducting, and fast redox conversion that involves proton cycling during pendant group redox conversion. These properties make the presented materials promising candidates as electrode materials for water based all-organic batteries.

  • 135.
    Sterby, Mia
    et al.
    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.
    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.
    Characterization of a PEDOT/Quinone Conducting Redox Polymer2016Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Organic materials can be used to ensure sustainable electrical energy storage, thus avoiding the use of inorganic materials that are inherently non-renewable and associated with large energy consumptions in their mining and refining. One category of organic energy storage materials consists of conducting redox polymers (CRPs). They include a conducting polymer backbone (CP), a redox active pendant group (PG), and a linker attaching the PG to the CP. The present work involves the CP poly(3,4-ethylenedioxythiophene) (PEDOT) and a quinone PG in acidic water solution. Quinones constitute an attractive class of molecules as they show reversible redox chemistry in several electrolyte systems, possess a high charge storage capacity and are naturally occurring e.g. in the electron transport chains in respiration and in photosynthesis. The CRP studied is characterized by cyclic voltammetry as well as by EQCM, in-situ conductance, and in-situ spectroscopic methods. In this work we present the formal potential of the quinone, the rate constant for electron transport in the polymer, mass changes during electrochemical redox conversion in different potential regions, and conductance data providing support for a CP-mediated electron transport through the material. Based on the results the electron and ion transport during electrochemical redox conversion will be discussed.                                                                                              

  • 136.
    Sterby, Mia
    et al.
    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.
    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.
    Linker Effect in PEDOT/Quinone Organic Battery Materials2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    One way to ensure sustainable electrical energy storage is to use organic materials. Organic materials can be made from renewable resources and thus the use of limited resources needed for inorganic materials is avoided. Conducting redox polymers (CRPs) are one type of organic material that can be used in e.g. batteries. CRPs consist of a conducting polymer backbone, a redox active pendant group, and a linker connecting the pendant group to the polymer. The present work focuses on the well-studied conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) with quinone pendant groups in water based systems. Quinones constitute a class of redox active molecules used in nature e.g. for electron transport in photosynthesis and in respiration. Although the third unit, the linker, is a passive part in the system it can greatly impact the behavior of the resulting CRP. In this report we present scan rate dependent voltammetric data as well as EQCM and in-situ conductance on two CRPs differing only by two CH2 groups in the linker. Figure 1 shows molecular structure, CV, and EQCM data of I and II indicating the significant influence that the minor difference in the linking unit has on the redox chemistry in these systems.

  • 137.
    Suriyanarayanan, Subramanian
    et al.
    Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden..
    Mandal, Sudip
    Indian Inst Technol Madras, Dept Chem, Chennai 600036, Tamil Nadu, India..
    Ramanujam, Kothandaraman
    Indian Inst Technol Madras, Dept Chem, Chennai 600036, Tamil Nadu, India..
    Nicholls, Ian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Linnaeus Univ, Ctr Biomat Chem, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, SE-39182 Kalmar, Sweden.
    Electrochemically synthesized molecularly imprinted polythiophene nanostructures as recognition elements for an aspirin-chemosensor2017Inngår i: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 253, s. 428-436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A chemosensor utilizing electro-polymerized film, as recognition element, has been devised and tested for selective determination of aspirin. The sensor consists of molecularly imprinted polymer (MIP) recognition elements electrodeposited as polymeric nanowires on gold-coated quartz resonator. A nano structures were prepared by electrochemical co-polymerization of the preformed complex between the template, aspirin, the functional monomers, 3-thienylboronic acid (3-TBA) and 3-thiopheneacetic acid (3-TAA), and thiophene, which was employed as a cross-linker. This nanostructure upon leaching aspirin serve as MIP. Polymerizations were performed in acetonitrile (MIP-org) as well as a micelle forming medium (MIP-mic). For MIP nanowire (MIP-ano) synthesis, sacrificial alumina templates were used during electro-polymerization in acetonitrile. Scanning electron microscope studies revealed compactly arranged polythiophene nanowires of uniform thickness in MIP-ano film, and MIP-mic film produced aggregated micron sized polymer structures. Density functional theoretical studies indicated a stable hydrogen bond-based complexation of aspirin by 3-TBA and 3-TAA in the pre-polymerization mixture implying that the MIP film thus prepared could selectively rebind the aspirin template. The MIP-ano-based chemosensor was sensitive towards aspirin (0.5-10 mM), over clinically relevant range (0.15-0.5 mM) under optimized FIA conditions. The sensitivity (20.62 Hz/mM) of the MIP-ano was eight and fifteen times higher than the MIP-mic (2.80 Hz/mM) and MIP-org (1.10 Hz/mM). Notably, the sensor selectively discriminates aspirin from structurally or functionally related interferants and metabolites, such as, salicylic acid, acetylsalicyloyl chloride and ibuprofen.

  • 138.
    Szałaj, Natalia