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  • 1.
    Alvi, Muhammad Rouf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Low-coordinate Organosilicon Chemistry: Fundamentals, Excursions Outside the Field, and Potential Applications2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis reports on unsaturated silicon compounds, as well as excursions from these into germanium chemistry, single molecule electronics, and silyl protective group chemistry. Both experimental and computational investigations were performed.

    Potassium germenolates were synthesized through reactions of tris(timethylsilyl) substituted acyl- and carbamylgermanes with potassium tert-butoxide. The potassium germenolates calculated by density functional theory have pyramidal structures at the Ge atoms, similar to the Si in the corresponding potassium silenolates, indicating negative charge on germanium rather than on oxygen. Germenolates also display germyl anion-like reactivity instead of germene-like reactivity as they are alkylated at Ge and initiate anionic polymerization of dienes rather than form [4+2] cycloadducts. The NMR chemical shifts reveal more negative charge at Ge in germenolates than at Si in analogous silenolates.

    Computations indicate that silabenzenes and silapyridines are reachable via [1,3]-silyl shifts from cyclic conjugated acylsilanes. Differently sized substituents were considered to prevent dimerizations, and 1-triisopropylsilyl-2-triisopropylsiloxy-6-tert-butylsilabenzene is a good synthetic target. Computations also show that silaphenolates are species with negative charge primarily localized at oxygen atom. Their planar structures, bond lengths, and NICS values reveal significant influence of aromaticity. Electrostatic repulsion should increase their stability, however, steric bulk is also important.

    Furthermore, it was found computationally that [1,3]-silyl shift from an acylsilane to a silene can function as a molecular switch reaction. Conductance calculations support this proposition.  

    Finally, tris(trimethylsilyl)silylmethaneamide (hypersilylamide) together with catalytic amounts of triflic acid were found to be efficient for protection of a range of alkyl and aryl alcohols and thiols in good to excellent yields. The protocol can be used to protect the less hindered OH group of a diol and has a broad functional group tolerance. A catalytic cycle is proposed. Hypersilyl protected alcohols and thiols are deprotected efficiently under photolytic conditions.

    List of papers
    1. Remarkably Stable Silicon Analogues of Amide Enolates: Synthesis, Structural Characterization, and Reactivity Studies
    Open this publication in new window or tab >>Remarkably Stable Silicon Analogues of Amide Enolates: Synthesis, Structural Characterization, and Reactivity Studies
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Potassium 2-N,N-dialkylamino-1,1-bis(trimethylsilyl)silen-2-olates (or amide silenolates, silicon analogues of amide enolates) were synthesized through reaction of N,N-dialkyl-tris(trimethylsilyl)silylmethaneamides with potassium tert-butoxide, and these 2-N,N-dialkylaminosilen-2-olates display remarkable thermal stabilities (e.g., merely 37% decomposition after 8 h at 90 ºC).  The crystal structure of one of the potassium 2-N,N-dialkylaminosilen-2-olates, without potassium ion chelating agent, reveals a more pyramidal configuration around the Si atom than found in previously reported silenolates, indicating a strong localization of the negative charge to this atom. The reactivities of the potassium 2-N,N-dialkylaminosilen-2-olates are in part similar to those of previous lithium and potassium silenolates as they are alkylated with MeI at Si. However, they do not react with dienes to yield [4+2] cycloadducts, the customary adducts of silenolates and reverse polarized silenes, but instead initiate anionic diene polymerization.  Consequently, they display silyl anion-like rather than silene-like reactivities. Finally, we find that potassium 2-aminosilen-2-olates with N,N-diphenylamino instead of N,N-dialkylamino substitution decompose rapidly to potassium diphenylamide, carbon monoxide, and silylenes. Clearly, if the substituent at the 2-position of a silenolate is able to accept and stabilize negative charge, such as NPh2, then this silenolate will be prone to decompose.

    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-169783 (URN)
    Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2012-04-19
    2. Formation and Fundamental Properties of Potassium Germen-2-olates
    Open this publication in new window or tab >>Formation and Fundamental Properties of Potassium Germen-2-olates
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Potassium 1,1-bis(trimethylsilyl)germen-2-olates (2a - 2d) with different substituents at the carbon atom were generated in good yields through the treatment of the correspondingly substituted tris(trimethylsilyl)acyl- and tris(trimethylsilyl)carbamyl-germanes (1a - 1d) with potassium tert-butoxide at room temperature in dry THF. Comparisons between the 29Si and 13C NMR chemical shifts of the germenolates and the analogous silenolates (4a4d) were performed. The recorded 13C and 29Si NMR chemical shifts of the potassium germenolates were also compared to those obtained from GIAO-B3LYP/6-31+G(d)//B3LYP/LANL2DZp calculations. The chemical reactivities of potassium germenolates were compared with silenolates. In this regard, the reactions of 2a - 2d were performed with methyliodide at -40 oC and the germanium methylated products (5a - 5c) were obtained in yields of 54 - 77 %. The reactions of these germenolates with 1,3-butadiene at low temperatures, however, lead to polymerization of dienes (2,3-dimethyl-1,3-butadiene, isoprene, and 1,3-pentadiene) revealing a reactivity resemblance to aminosilenolates, species which in return are comparable to silyl anions in reactivity.

    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-169795 (URN)
    Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2012-04-19
    3. Computational Investigation of Brook-Type Silabenzenes and Their Possible Formation through [1,3]-Si -> O Silyl Shifts
    Open this publication in new window or tab >>Computational Investigation of Brook-Type Silabenzenes and Their Possible Formation through [1,3]-Si -> O Silyl Shifts
    2013 (English)In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 32, no 1, p. 16-28Article in journal (Refereed) Published
    Abstract [en]

    Quantum chemical calculations with the M062X hybrid meta density functional theory method were performed in order to examine formation of Brook-type silabenzenes 4a 4l, silapyridines 6a 6d, and five-membered ring silaheteroaromatics 8a8d through [1,3]-trimethylsilyl (TMS) and [1,3]-tri(isopropyl)silyl (TIPS) shifts from a tetrahedral silicon atom to an adjacent carbonyl oxygen of cyclic conjugated acylsilane precursors. All Brook-type silabenzenes and silapyridines, having a 2-trialkylsiloxy substituent, are at lower relative energies than their precursors, whereas silaheteroaromatics 8a 8d are found at slightly higher energies. The free energies of activation for the thermal [1,3]-TMS shifts range from 29 to 44 kcal/mol, with the lowest for a Brook-type silapyridine and the highest for a silafuran. The geometries of the Brook-type silabenzenes, silapyridines, silafuran and silathiophene indicate aromatic character, but the silapyrroles are nonaromatic. At M062X/6-311+G(d)//M062X/6-31G(d) level all Brook-type silabenzene dimers studied herein are more stable than two silabenzenes, also for a silabenzene with bulky TIPS, OTIPS and tert-butyl substituents (4l). Yet, comparisons of the B3LYP/6-31G(d) dimerization energies of 4l with that of the isolable 1-Tbt-silabenzene (Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl) of Tokitoh [J. Chin. Chem. Soc. 2008, 55, 487] indicate that 4l will also be a monomeric silabenzene, and thus, a suitable synthetic target.

    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-169784 (URN)10.1021/om300023s (DOI)000313606200005 ()
    Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2017-12-07Bibliographically approved
    4. Silaphenolates and Silaphenylthiolates: Two Unexplored Unsaturated Silicon Compound Classes Influenced by Aromaticity
    Open this publication in new window or tab >>Silaphenolates and Silaphenylthiolates: Two Unexplored Unsaturated Silicon Compound Classes Influenced by Aromaticity
    2012 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 17, no 1, p. 369-389Article in journal (Refereed) Published
    Abstract [en]

    Monosilicon analogs of phenolates and phenylthiolates are studied by quantum chemical calculations. Three different silaphenolates and three different silaphenylthiolates are possible; the ortho-, meta-, and para-isomers. For the silaphenolates, the meta- isomer is the thermodynamically most stable, regardless if the substituent R at Si is H, t-Bu or SiMe3. However, with R = H and SiMe3 the energy differences between the three isomers are small, whereas with R = t-Bu the meta- isomer is similar to 5 kcal/mol more stable than the ortho- isomer. For the silaphenylthiolates the ortho- isomer is of lowest energy, although with R = H the ortho- and meta- isomers are isoenergetic. The calculated nucleus independent chemical shifts (NICS) indicate that the silaphenolates and silaphenylthiolates are influenced by aromaticity, but they are less aromatic than the parent silabenzene. The geometries and charge distributions suggest that all silaphenolates and silaphenylthiolates to substantial degrees are described by resonance structures with an exocyclic C=O double bond and a silapentadienyl anionic segment. Indeed, they resemble the all-carbon phenolate and phenylthiolate. Silaphenylthiolates are less bond alternate and have slightly more negative NICS values than analogous silaphenolates, suggesting that this compound class is a bit more aromatic. Dimerization of the silaphenolates and silaphenylthiolates is hampered due to intramolecular Coulomb repulsion in the dimers, and silaphenolates with a moderately bulky SiMe3 group as substituent at Si should prefer the monomeric form.

    Keywords
    silicon, aromaticity, quantum chemical calculations
    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-166896 (URN)10.3390/molecules17010369 (DOI)000299535700025 ()
    Available from: 2012-01-16 Created: 2012-01-16 Last updated: 2017-12-08Bibliographically approved
    5. The [1,3]-Si→O Silyl Shift from a Nonconducting Acylsilane to a Conducting Brook-Silene as Basis for a Molecular Switch
    Open this publication in new window or tab >>The [1,3]-Si→O Silyl Shift from a Nonconducting Acylsilane to a Conducting Brook-Silene as Basis for a Molecular Switch
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    By usage of density functional theory (DFT) calculations we explored if the [1,3]-silyl shift leading from an acylsilane with two p-conjugated substituents to a silene (a Si=C double bonded compound) can be used as a basis for a molecular conductance switch. In such a switch, the acylsilane, with a tetrahedral saturated silicon atom disrupting the conjugation through the molecule, acts as the OFF state, whereas the silene with a conjugated path running through the complete molecule represents the ON state. Our requirements are (i) the silenes should be slightly higher in relative energy than the acylsilane so as to promote a thermal backrearragment, (ii) the barrier for the backtransfer of the silyl group should be 25-30 kcal/mol, (iii) the ON/OFF conductance ratio should be high, and (iv) the switch should be realistic. According to our calculations using non-equilibrium Green’s function theory, a 1,2-bis(4-thiophenylethynyl)silene has a conductance which is 270 times higher than that of the corresponding acylsilane at zero bias voltage. However, at a voltage of +1 V the ON/OFF ratio decreases to ~40.

    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-169782 (URN)
    Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2012-04-19
    6. Highly Efficient and Convenient Acid Catalyzed Hypersilyl Protection of Alcohols and Thiols by Tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide
    Open this publication in new window or tab >>Highly Efficient and Convenient Acid Catalyzed Hypersilyl Protection of Alcohols and Thiols by Tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide
    Show others...
    2012 (English)Article in journal (Other academic) Submitted
    Abstract [en]

    Tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide, herein named hypersilylamide, is a convenient and efficient source of the hypersilyl group in the first widely applicable acid catalyzed protocol for silyl group protection of primary, secondary, tertiary alkyl as well as aryl alcohols and thiols in high yields. The sole by-product is N,N-dimethylformamide (DMF) and a range of solvents can be used, including DMF. A high selectivity in the protection of diols can be achieved, also for diols with very small differences in the steric demands at the two hydroxyl groups. Moreover, in the protection of equivalent alcohol and thiol sites the protection of the alcohol is faster, allowing for selective protection in high yields. Quantum chemical calculations at the M062X hybrid meta density functional theory level give insights on the mechanism for the catalytic process. Finally, the hypersilyl group is easily removed from all protected alcohols and thiols examined herein by irradiation at 254 nm.

    National Category
    Organic Chemistry Inorganic Chemistry
    Research subject
    Chemistry with specialization in Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-169781 (URN)
    Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2013-03-07Bibliographically approved
    7. Scope and Limitations of an Acid Catalyzed Protocol for Hypersilyl Protection of Alcohols
    Open this publication in new window or tab >>Scope and Limitations of an Acid Catalyzed Protocol for Hypersilyl Protection of Alcohols
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    A highly efficient and convenient triflic acid (TfOH) catalyzed protocol for the protection of various functionalized alcohols in CH2Cl2 at ambient temperature using tris(trimethylsilyl)silyl-N,N-dimethyl-methaneamide (hypersilylamide) 1 as the protecting reagent is developed. Herein, results on the scope and limitations of this protocol for a number of functionalized alcohols are presented. This method was found to be effective for the selective protection of less hindered OH groups in different classes of diols containing both pri/tert, sec/tert, or aromatic/aliphatic hydroxyl groups. In general, our protocol exhibited excellent functional group tolerance in the protection of alcohols containing alkoxy, keto, amino, as well as halo substituents in good to excellent yields.

    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-169780 (URN)
    Available from: 2012-03-06 Created: 2012-03-06 Last updated: 2012-04-19
  • 2.
    Alvi, Muhammad Rouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Burkhard O., Jahn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Computational Investigation of Brook-Type Silabenzenes and Their Possible Formation through [1,3]-Si -> O Silyl Shifts2013In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 32, no 1, p. 16-28Article in journal (Refereed)
    Abstract [en]

    Quantum chemical calculations with the M062X hybrid meta density functional theory method were performed in order to examine formation of Brook-type silabenzenes 4a 4l, silapyridines 6a 6d, and five-membered ring silaheteroaromatics 8a8d through [1,3]-trimethylsilyl (TMS) and [1,3]-tri(isopropyl)silyl (TIPS) shifts from a tetrahedral silicon atom to an adjacent carbonyl oxygen of cyclic conjugated acylsilane precursors. All Brook-type silabenzenes and silapyridines, having a 2-trialkylsiloxy substituent, are at lower relative energies than their precursors, whereas silaheteroaromatics 8a 8d are found at slightly higher energies. The free energies of activation for the thermal [1,3]-TMS shifts range from 29 to 44 kcal/mol, with the lowest for a Brook-type silapyridine and the highest for a silafuran. The geometries of the Brook-type silabenzenes, silapyridines, silafuran and silathiophene indicate aromatic character, but the silapyrroles are nonaromatic. At M062X/6-311+G(d)//M062X/6-31G(d) level all Brook-type silabenzene dimers studied herein are more stable than two silabenzenes, also for a silabenzene with bulky TIPS, OTIPS and tert-butyl substituents (4l). Yet, comparisons of the B3LYP/6-31G(d) dimerization energies of 4l with that of the isolable 1-Tbt-silabenzene (Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl) of Tokitoh [J. Chin. Chem. Soc. 2008, 55, 487] indicate that 4l will also be a monomeric silabenzene, and thus, a suitable synthetic target.

  • 3.
    Alvi, Muhammad Rouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Jahn, Burkhard O.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Tibbelin, Julius
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Baumgartner, Judith
    Institut für Anorganische Chemie, Technische Universität Graz, Stremayrgasse 9, A-8010 Graz, Austria.
    Gómez, Cesar Pay
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Highly Efficient and Convenient Acid Catalyzed Hypersilyl Protection of Alcohols and Thiols by Tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide2012Article in journal (Other academic)
    Abstract [en]

    Tris(trimethylsilyl)silyl-N,N-dimethylmethaneamide, herein named hypersilylamide, is a convenient and efficient source of the hypersilyl group in the first widely applicable acid catalyzed protocol for silyl group protection of primary, secondary, tertiary alkyl as well as aryl alcohols and thiols in high yields. The sole by-product is N,N-dimethylformamide (DMF) and a range of solvents can be used, including DMF. A high selectivity in the protection of diols can be achieved, also for diols with very small differences in the steric demands at the two hydroxyl groups. Moreover, in the protection of equivalent alcohol and thiol sites the protection of the alcohol is faster, allowing for selective protection in high yields. Quantum chemical calculations at the M062X hybrid meta density functional theory level give insights on the mechanism for the catalytic process. Finally, the hypersilyl group is easily removed from all protected alcohols and thiols examined herein by irradiation at 254 nm.

  • 4.
    Andersson, Claes-Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Synthesis and characterization of a ferrocene-linked bis-fullerene[60] dumbbell2012In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 41, no 8, p. 2374-2381Article in journal (Refereed)
    Abstract [en]

    A new [60]fullerene dumbbell consisting of two fulleropyrrolidines connected to a central ferrocene unit by amide linkages has been prepared and fully characterized by elemental analysis, 1H NMR, UV/Vis, fluorescence and mass spectrometry. The electrochemical properties as determined by cyclic voltammetry show ground state electronic communication between the ferrocene and the fullerene units. In addition, the preparaton of a ferrocene building block for an alternative linking approach is presented.

  • 5.
    Ankner, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Norberg, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Kihlberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Mild Oxidative Cleavage of 9-BBN-Protected Amino Acid Derivatives2015In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 17, p. 3767-3770Article in journal (Refereed)
    Abstract [en]

    Protection of the amino acid moiety using 9-BBN is an effective method to enable side chain manipulations in synthesis of complex amino acids. We investigated the standard, mild method for deprotection of the 9-BBN group in methanolic chloroform, and found that it relies on a slow oxidation mediated by molecular oxygen. Building on this insight, we have developed a method that allows for a fast and selective deprotection using simple peroxy acid reagents. After Fmoc protection, products were isolated in >90% yield for a series of amino acid derivatives, including a galactosylated derivative of hydroxylysine.

  • 6.
    Appel, Lieuwe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lassen, Jorgen Buus
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: Dopamine transporter occupancy as measured by PET2014In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 24, no 2, p. 251-261Article in journal (Refereed)
    Abstract [en]

    Tesofensine (TE) is a novel triple monoannine re-uptake inhibitor inducing a potent inhibition of the re-uptake process in the synaptic cleft of the neurotransmitters dopamine, norepinephrine, and serotonin. In recent preclinical and clinical evaluations TE showed a robust anti-obesity effect, but the specific mechanism of this triple monoamine re-uptake inhibitor still needs to be further elucidated. This positron emission tomography (PET) study, using [C-11]beta CIT-FE, aimed to assess the degree of the dopamine transporter (DAT) occupancy, at constant TE plasma levels, following different oral, multiple doses of TE during totally 8-12 days. In addition, the relationships between DAT occupancy and TE plasma concentrations, or doses, were investigated to enable assessment of DAT occupancies in subsequent clinical trials. The results demonstrated that TE induced a dose-dependent blockade of DAT following multiple doses of 0.125-1 mg TE at anticipated steady-state conditions. The mean striatal DAT occupancy varied dose-dependently between 18% and 77%. A signnoid E-max model well described the relationship between striatal DAT occupancy and TE plasma concentrations or doses. It was estimated that the maximum achievable DAT occupancy was about 80% and that half of this effect was accomplished by approximately 0.25 mg TE and a plasma drug concentration of 4 ng/ml. The results indicated an important mechanism of action of TE on DAT. Further, these results suggest that the previously reported dose-dependent weight loss, in TE treated subjects, was in part mediated by an up-regulation of dopaminergic pathways due to enhanced amounts of synaptic dopamine after blockade of DAT.

  • 7.
    Arkhypchuk, Anna I.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Mijangos, Edgar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Lomoth, Reiner
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Ott, Sascha
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Redox Switching in Ethenyl- Bridged Bisphospholes2014In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 49, p. 16083-16087Article in journal (Refereed)
    Abstract [en]

    A 2e(-)/2H(+) redox platform has been implemented in the ethenyl-bridged bisphosphol-3-ol 1 to afford the first phospholes that feature chemically reversible oxidations. Oxidation of the title compounds to the corresponding bisphosphol-3-one 2 leads to a change in conjugation topology and a concomitant hypsochromic shift of the lowest-energy absorption maximum by 100nm. Electrochemical oxidation proceeds without any detectable intermediates, whereas the deprotonated form of 1 can be observed in an aprotic medium during the reduction of 2. This dianionic intermediate 3 is characterized by end absorptions that are bathochromically shifted by circa 200nm compared to those of 2.

  • 8.
    Bergman, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Rahman, Rashidur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Blomgren, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Larhed, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Svedberg, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Thibblin, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Wångsell, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Synthesis and Labelling of a Piperazine-Based Library of 11C-Labeled Ligands for Imaging of the Vesicular Acetylcholine Transporter2014In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 57, no 8, p. 525-532Article in journal (Refereed)
    Abstract [en]

    The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a-f, six potential VAChT PET tracers, [C-11]-(+/-)5a-f, were C-11-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [C-11]-(+/-)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/mu mol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [C-11]-(+/-)5d and [C-11]-(+/-)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine-based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach.

  • 9.
    Bergstrand, Nill
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Bohl, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Ghaneolhosseine, Hadi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Jonsson, Markus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Silvander, Mats
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Sjöberg, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Stabilised Liposomes with Double Targeting for Use in BNCT2000In: Contemporary Boron Chemistry / [ed] Matthew Davidson, Cambridge, UK: Royal Society of Chemistry, 2000, p. 131-134Chapter in book (Other academic)
  • 10.
    Biswas, Srijit
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Dahlstrand, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Watile, Rahul A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Kalek, Marcin
    Himo, Fahmi
    Samec, Joseph S. M.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Atom-Efficient Gold(I)-Chloride-Catalyzed Synthesis of alpha-Sulfenylated Carbonyl Compounds from Propargylic Alcohols and Aryl Thiols: Substrate Scope and Experimental and Theoretical Mechanistic Investigation2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 52, p. 17939-17950Article in journal (Refereed)
    Abstract [en]

    Gold(I)-chloride-catalyzed synthesis of -sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols showed a wide substrate scope with respect to both propargylic alcohols and aryl thiols. Primary and secondary aromatic propargylic alcohols generated -sulfenylated aldehydes and ketones in 60-97% yield. Secondary aliphatic propargylic alcohols generated -sulfenylated ketones in yields of 47-71%. Different gold sources and ligand effects were studied, and it was shown that gold(I) chloride gave the highest product yields. Experimental and theoretical studies demonstrated that the reaction proceeds in two separate steps. A sulfenylated allylic alcohol, generated by initial regioselective attack of the aryl thiol on the triple bond of the propargylic alcohol, was isolated, evaluated, and found to be an intermediate in the reaction. Deuterium labeling experiments showed that the protons from the propargylic alcohol and aryl thiol were transferred to the 3-position, and that the hydride from the alcohol was transferred to the 2-position of the product. Density functional theory (DFT) calculations showed that the observed regioselectivity of the aryl thiol attack towards the 2-position of propargylic alcohol was determined by a low-energy, five-membered cyclic protodeauration transition state instead of the strained, four-membered cyclic transition state found for attack at the 3-position. Experimental data and DFT calculations supported that the second step of the reaction is initiated by protonation of the double bond of the sulfenylated allylic alcohol with a proton donor coordinated to gold(I) chloride. This in turn allows for a 1,2-hydride shift, generating the final product of the reaction.

  • 11.
    Blom, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Muhammad, Taj
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Ding, Chenmin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Nair, Manoj
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Ga-68-Labeling of RGD peptides and biodistribution2012In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, no 2, p. 165-172Article in journal (Refereed)
    Abstract [en]

    Several peptides comprising Arg-Gly-Asp (RGD) domain and macrocyclic chelator were labeled with Ga-68 for the imaging of angiogenesis. The analogues varied in peptide constitution, linker and chelator type. The labeling efficiency did not vary with the peptide constitution and linker type, but depended on the chelator type. Four of the compounds containing 2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) chelator were labeled at 90 +/- 5 degrees C using conventional or microwave heating reaching 90% of Ga-68 incorporation after 5 and 2 min respectively, when the concentration of the precursor was 2.5 mu M. The compound having 2,2', 2 ''-(1,4,7-triazonane1,4,7-triyl)triacetic acid (NOTA) as the chelator could be labeled at room temperature within 5 min using 2.5 mu M peptide precursor. Two of the compounds contained a poly (ethylene glycol) (PEG) linker to the chelator. The biodistribution of the analogues was studied in male rats.

  • 12.
    Blom, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Purification Processes for Complex Biomacromolecules2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis details various techniques and considerations for the purification of complex biomacromolecules.

     

    Initially an α-mannosidase from babaco fruit was purified using anion exchange-, lectin affinity- and size exclusion chromatography.  The enzyme was approximately 260-280 kDa in size with an apparent an unusual octagonal stoichiometry and displayed properties similar to other known plant α-mannosidases.

     

    Mucins were fractionated by ion exchange and size exclusion chromatography to assess the properties that govern the mucin surface coating interactions in biomaterial research.  Commercially available mucins, of bovine and porcine origin, as wells as crude human mucin were tested. All showed to consist of a population of molecules which differ in size, charge and composition.

     

    The third part of the thesis concerns different aspects of plasmid DNA purification processes.

    A two-step method for analysis of plasmid DNA consisting of size exclusion followed by thiophilic adsorption chromatography was evaluated. It allowed determination of the supercoiled plasmid DNA concentration in all process steps without requirement for extensive sample preparation. This method was shown to be fully comparable in terms of accuracy to capillary gel electrophoresis, considered as the industry standard.

    Purification of plasmid DNA generally involves bacterial cell alkaline lysis, which creates a solution with flocculate material which needs to be removed prior to further processing. The addition of ammonium hydrogen carbonate to the suspension was evaluated to clarify the solution. The released carbon dioxide and ammonium lifts the flocculate to the surface and allows draining of a clear solution. The method is fully scalable, does not affect the plasmid DNA quality and requires no special equipment.

    Thiophilic adsorption chromatography was evaluated for simplification of an existing commercial large scale purification process and was shown to increase both product purity and yields of several tested plasmids. Also, implementation of this step significantly reduced overall production process time.

     

     

     

    List of papers
    1. Purification and Characterization of an alpha-Mannosidase from the Tropical Fruit Babaco (Vasconcellea x Heilbornii Cv. Babaco)
    Open this publication in new window or tab >>Purification and Characterization of an alpha-Mannosidase from the Tropical Fruit Babaco (Vasconcellea x Heilbornii Cv. Babaco)
    2008 (English)In: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 56, no 22, p. 10872-10878Article in journal (Refereed) Published
    Abstract [en]

    An alpha-mannosidase (EC 3.2.1.24) present in the lyophilized latex of babaco (Vasconcellea heilbornii) has been purified to apparent homogeneity by native PAGE. The purification involves a three-step procedure with successive anion exchange with 0 Sepharose HP, lectin affinity chromatography using ConA Sepharose 4B, and gel filtration using Superdex 200 prep grade. The molecular mass was determined to be in the range of 260-280 kDa by Superdex 200 prep grade gel filtration, and isoelectric focusing showed a pI range between 5.85 and 6.55, suggesting different glycosylated isoforms. The optimal temperature for the alpha-mannosidase was determined to lie between 50 and 60 degrees C, and the optimal pH was 4.5 at 50 degrees C. The K-m value for p-nitrophenyl alpha-mannopyranoside (pNPM) was found to be 1.25 mM and the V-max, 2.4 mu kat mg(-1) at 50 degrees C and 1.94 mu kat mg(-1) at 40 degrees C. The pure alpha-mannosidase was specific for mannose and did not display activity for any other tested synthetic substrates.

    Keywords
    alpha-Mannosidase, babaco, latex, purification, characterization, subunit composition
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-107031 (URN)10.1021/jf800857k (DOI)000261056700065 ()
    Available from: 2009-07-15 Created: 2009-07-15 Last updated: 2017-12-13Bibliographically approved
    2. Potential use of mucins as biomaterial coatings. I. Fractionation, characterization, and model adsorption of bovine, porcine, and human mucins
    Open this publication in new window or tab >>Potential use of mucins as biomaterial coatings. I. Fractionation, characterization, and model adsorption of bovine, porcine, and human mucins
    2009 (English)In: Journal of Biomedical Materials Research Part A, ISSN (printed): 1549-3296. (electronic): 1552-4965., Vol. 91A, no 3, p. 762-772Article in journal (Refereed) Published
    Abstract [en]

    Previously, we presented evidence that mucins have potential as   biomaterial coatings. Here, we reveal substantial batch-to-batch   variations for a frequently used commercial bovine salivary mucin   preparation (BSM) and stress the importance of standardizing mucins   intended for comparative purposes. "Mild" fractionation strategies,   aiming at preserving natural mucin functions, were used to prepare two   more defined BSM fractions as well as three mucin fractions from   porcine gastric (PGM) and human salivary (MG1) sources. While the BSM   and PGM were highly purified and mainly adopted random coil   conformations in solution, the MG1 contained mucin-bound components   (1.6 wt% albumin) and appeared compact. Average molar masses and   root-mean-square radii for the predominant BSM, PGM, and MG1 species   spanned 0.8-4.2 MDa and 46-86 nm, respectively. An ellipsometric   evaluation, using hydrophilic and hydrophobic silica, showed the mucin   adsorption to be slow and related to mucin charge, size, conformation,   and compositional complexity. The mass uptakes on hydrophobic silica   averaged 2.6, 2.6, and 5.0 mg/m(2), for BSM, PGM, and MG1,   respectively. Finally, we find that stable mucin coatings can be formed   on polymers of different wettability. The reported mucin preparations   serve as platforms for a series of studies on the biocompatibility of  mucin coatings.

    Keywords
    mucin fractionation, mucin-associated components, size-exclusion chromatograpliy-multiangle light scattering-refractometry (SEC-MALS-RI), biomaterial coating, MUC5B
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-97899 (URN)10.1002/jbm.a.32266 (DOI)000271588800014 ()19051309 (PubMedID)
    Available from: 2008-11-28 Created: 2008-11-28 Last updated: 2012-08-01Bibliographically approved
    3. A chromatographic method for determination of supercoiled plasmid DNA concentration in complex solutions.
    Open this publication in new window or tab >>A chromatographic method for determination of supercoiled plasmid DNA concentration in complex solutions.
    2009 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, no 24, p. 2530-6Article in journal (Refereed) Published
    Abstract [en]

    A method for determination of the plasmid DNA concentration with subsequent analysis of the ratio supercoiled to open circular form is presented. The method is suitable for samples from all steps of the manufacturing process, from fermentation to final product. The analysis consists of size exclusion chromatography, followed by analytical thiophilic aromatic chromatography. In the first step, the plasmid DNA concentration is determined by group separation, including removal of RNA and other impurities, within less than 2 min. The limit of detection and quantification was 0.28 and 0.83 microg/ml, respectively. The precision of the method is high, providing a coefficient of variation as low as below 2%. In the second step, the ratio of open circular to supercoiled plasmid DNA is determined following separation of the two plasmid DNA isoforms with a linear salt gradient. The precision of the second step was evaluated using serial injections of aliquots of a sample stock solution. In comparison with the two most commonly used methods, the developed analysis was found to be significantly more accurate than agarose gel electrophoresis and equivalent to capillary gel electrophoresis. The combined methods for quantification and control of homogeneity of plasmid DNA presented here enable reliable and precise analysis at all steps of the manufacturing process.

    Keywords
    Concentration determination, Supercoiled plasmid DNA, Analytical group separation, Thiophilic aromatic chromatography
    National Category
    Chemical Sciences
    Research subject
    Chemistry with specialization in Surface Biotechnology
    Identifiers
    urn:nbn:se:uu:diva-172792 (URN)10.1016/j.jchromb.2009.06.037 (DOI)19616488 (PubMedID)
    Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2017-12-07
    4. Flocculate removal after alkaline lysis in plasmid DNA production.
    Open this publication in new window or tab >>Flocculate removal after alkaline lysis in plasmid DNA production.
    2010 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 29, no 1, p. 6-10Article in journal (Refereed) Published
    Abstract [en]

    Alkaline lysis is the most commonly used method following harvest of bacterial cells for production of plasmid DNA. The method was originally developed for laboratory scale experiments and has shown to be challenging at larger scales. A major problem prior to further downstream processing is the risk of filter clogging without efficient removal of the flocculate that occurs after neutralization. For this purpose we here present a scalable method where the clarification of alkaline lysate is greatly simplified. Through a rapid procedure, involving the addition of ammonium hydrogen carbonate to the neutralized alkaline lysate, the flocculate is lifted to the surface of the solution by the released carbon dioxide and ammonium. After this step a clarified solution can be drained from the bottom of the vessel. The procedure does not impact pH, plasmid DNA concentration or the ratio of open circular to supercoiled plasmid DNA in the solution.

    Keywords
    Alkaline lysis, Plasmid DNA, Flocculate removal
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-172791 (URN)10.1016/j.vaccine.2010.10.021 (DOI)20974301 (PubMedID)
    Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2017-12-07
    5. Scale Up of a Plasmid DNA Purification Process: Use of a Commercial Resin to Produce GMP-Grade pDNA for Clinical Studies
    Open this publication in new window or tab >>Scale Up of a Plasmid DNA Purification Process: Use of a Commercial Resin to Produce GMP-Grade pDNA for Clinical Studies
    Show others...
    2010 (English)In: BioProcess International, ISSN 1542-6319, Vol. 8, no 11, p. 46-54Article in journal (Refereed) Published
    Keywords
    Chromatography, plasmid DNA
    National Category
    Chemical Sciences
    Research subject
    Chemistry with specialization in Surface Biotechnology
    Identifiers
    urn:nbn:se:uu:diva-172889 (URN)
    Available from: 2012-04-17 Created: 2012-04-17 Last updated: 2012-08-01Bibliographically approved
  • 13.
    Blom, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Norrehed, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Andersson, Claes-Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Huang, Hao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Light, Mark E.
    Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Gogoll, Adolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis2016In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 21, no 1Article in journal (Refereed)
    Abstract [en]

    Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to  the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle  differences between these tweezers, that are discussed in terms of porphyrin dislocation  modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen  guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

  • 14.
    Blom, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Olsson, Sandra
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Norrehed, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Andersson, Claes-Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Gogoll, Adolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Photomodulable bis-porphyrin molecular tweezers as dynamic host systems for diamine guestsManuscript (preprint) (Other academic)
    Abstract [en]

    Bisporphyrin molecular tweezers with an enediyne (1) or a stiff stilbene (2) photoswitchable spacer are proposed as systems for modulation of bitopic binding to diamine guests via E/Z photoisomerization. The photoisomerization has been monitored by UV-Vis and 1H NMR spectroscopy and occurs without side reactions such as Bergman cyclization. Possible applications are rationalized in terms of competitive binding involving monoamine/diamine mixtures, and are supported by conformational analysis of the envisioned host-guest complexes. Binding dynamics for conformationally flexible guests show significantly different performance of aliphatic 1,w-diamine guests with varying N-N distance.

  • 15. Carter, Stephen F.
    et al.
    Scholl, Michael
    Almkvist, Ove
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Engler, Henry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Nordberg, Agneta
    Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by (11)C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining (11)C-Pittsburgh Compound B and (18)F-FDG2012In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, no 1, p. 37-46Article in journal (Refereed)
    Abstract [en]

    Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using (11)C-deuterium-L-deprenyl ((11)C-DED) to measure monoamine oxidase B located in astrocytes. Along with (11)C-DED PET, (11)C-Pittsburgh compound B ((11)C-PIB; fibrillar A beta deposition), (18)F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: (11)C-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the (11)C-DED data. (11)C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional (18)F-FDG uptake and (11)C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional (11)C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high (11)C-PIB retention. Increased (11)C-DED binding in most cortical and subcortical regions was observed in MCI (11)C-PIB+ patients relative to controls, MCI (11)C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased (11)C-DED binding throughout the brain of the MCI (11)C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.

  • 16. Chavan, Swapnil
    et al.
    Friedman, Ran
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy2015In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, no 5, p. 11659-11677Article in journal (Refereed)
    Abstract [en]

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity.

  • 17. Czyzewski, Michal
    et al.
    Sellars, Jonathan D.
    Guliashvili, Tamaz
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Tibbelin, Julius
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Johnstone, Lisa
    Bower, Justin
    Box, Matthew
    Davies, Robert D. M.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Steel, Patrick G.
    The first intramolecular silene Diels-Alder reactions2014In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 50, no 22, p. 2919-2921Article in journal (Refereed)
    Abstract [en]

    The synthesis of silaheterocycles through the first examples of an intramolecular silene Diels-Alder reaction is described.

  • 18.
    Dahlstrand, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Ground and Excited State Aromaticity: Design Tools for π-Conjugated Functional Molecules and Materials2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main focus of this thesis is on the aromaticity of the ground state and electronically excited states of π-conjugated molecules and polymers, as well as how aromaticity is connected to their properties.

    The electronic structures of polybenzenoid hydrocarbons (PBHs) were explored through density functional theory (DFT) calculations and the π-component of the electron localization function (ELFπ). The study revealed how the π-electronic structure is influenced by the fusion of double bonds or benzene rings to the PBHs. We also demonstrated that the π-electrons of benzene extend to accommodate as much aromaticity as possible when bond length distorted.  

    The aromatic chameleon property displayed by fulvenes, isobenzofulvenes, fulvalenes, bis(fulvene)s, and polyfulvenes were investigated using DFT calculations. The tria-, penta-, and heptafulvenes were shown to possess ionization energies and electron affinities which can be tuned extensively by substitution, some of which even outperform TTF and TCNQ, the prototypical electron donor and acceptor, respectively. The singlet-triplet energy gap of pentafulvenes can be tuned extensively by substitution to the point that the triplet state is lower than the singlet state and thus becomes the ground state. The ELFπ of isobenzofulvene shows that the benzene ring in an electronically excited state can be more aromatic than the corresponding ring in the ground state. We have shown that the 6-ring of [5.6.7]quinarene is influenced by a Hückel aromatic resonance structure with 4n+2 π-electrons in the excited quintet state. The bis(fulvene)s which are composed of a donor type heptafulvene and an acceptor type pentafulvene, retain the basic donor-acceptor properties of the two fragments and could function as compact donor-acceptor dyads. A few of the designed polyfulvenes were found to have band gaps below 1 eV at the PBC-B3LYP/6-31G(d) level.

    Various 2,7-disubstituted fluorenones and dibenzofulvenes were synthesized and their excited state properties were investigated by absorption spectroscopy and time-dependent DFT calculations. It was found that the 1A1B transition of ππ* character can be tuned by substitution in the 2,7-positions. The 2,7-bis(N,N-dimethyl) derivatives of fluorenone and dibenzofulvene displayed low energy transitions at 2.18 and 1.61 eV, respectively, in toluene.

    List of papers
    1. On the Importance of Clar Structures of Polybenzenoid Hydrocarbons as Revealed by the n-Contribution to the Electron Localization Function
    Open this publication in new window or tab >>On the Importance of Clar Structures of Polybenzenoid Hydrocarbons as Revealed by the n-Contribution to the Electron Localization Function
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    2010 (English)In: Symmetry, ISSN 2073-8994, E-ISSN 2073-8994, Vol. 2, no 3, p. 1653-1682Article in journal (Refereed) Published
    Abstract [en]

    The degree of p-electron (de)localization and aromaticity of a series of polybenzenoid hydrocarbons (PBHs) has been analyzed through the π-contribution to the electron localization function (ELFπ), calculated at the B3LYP/6-311G(d,p) hybrid density functional theory level. The extent of p-electron delocalization in the various hexagons of a PBH was determined through analysis of the bifurcation values of the ELFp basins (BV(ELFp)), the spans in the bifurcation values in each hexagon (ΔBV(ELFπ)), and the ring-closure bifurcation values of the ELFπ (RCBV(ELFπ)). These computed results were compared to the qualitative description of local aromaticities of the different hexagons in terms of Clar structures with p-sextets. Benzene, [18]annulene, and thirty two PBHs were analyzed at their equilibrium geometries, and benzene and triphenylene were also analyzed at bond length distorted structures. In general, the description of PBHs in terms of Clar valence structures is supported by the ELFp properties, although there are exceptions. For PBHs at their equilibrium geometries there is a clear sigmoidal relationship between the CC bond lengths and the amount of p-electron (de)localization at these bonds, however, this relationship is lost for bond distorted geometries. In the latter cases, we specifically examined benzene in D3h symmetric “1,3,5-cyclohexatriene” structures and triphenylene in eight different structures. From the distorted benzenes and triphenylenes it becomes clear that there is a distinct tendency for the p-electron network to retain delocalization (aromaticity). The ELFp analysis thus reveals an antidistortive rather than a distortive behavior of the p-electrons in these investigated compounds.

    Place, publisher, year, edition, pages
    Basel: MDPI, 2010
    Keywords
    Clar structures, electron localization function, polybenzenoid hydrocarbons
    National Category
    Other Basic Medicine
    Research subject
    Chemistry with specialization in Organic Chemistry; Chemistry with specialization in Quantum Chemistry
    Identifiers
    urn:nbn:se:uu:diva-140983 (URN)10.3390/sym2031653 (DOI)000208831900018 ()
    Available from: 2011-01-10 Created: 2011-01-10 Last updated: 2018-01-12Bibliographically approved
    2. Substituent Effects on the Electron Affinities and Ionization Energies of Tria-, Penta-, and Heptafulvenes: A Computational Investigation
    Open this publication in new window or tab >>Substituent Effects on the Electron Affinities and Ionization Energies of Tria-, Penta-, and Heptafulvenes: A Computational Investigation
    2010 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 75, no 23, p. 8060-8068Article in journal (Refereed) Published
    Abstract [en]

    The extent of substituent influence on the vertical electron affinities (EAs) and ionization energies (IEs) of 43 substituted tria-, penta-, and heptafulvenes was examined computationally at the OVGF/6-311G(d)//B3LYP/6-311G(d) level of theory and compared with those of tetracyanoquinodimethane (TCNQ) and tetrathiafulvalene (TTF) as representing strong electron-acceptor and -donor compounds, respectively. The substituents X at the exocyclic positions of the fulvenes were either NH2, H, or CN, while the substituents Y at the ring positions were H, CI, F, CN, or NH2. The variations of the EAs and lEs were rationalized by qualitative arguments based on frontier orbital symmetries for the different fulvene classes with either X or Y being constant. The minimum and maximum values found for the calculated EAs of the tria-, penta-, and heptafulvenes were 0.51-2.05, 0.24-3.63, and 0.53-3.14 eV, respectively, and for the IEs 5.27-9.96, 7.07-10.31, and 6.35-10.59 eV, respectively. Two of the investigated fulvenes outperform TCNQ (calcd EA = 2.63 eV) and one outperforms TTF (calcd IE = 6.25 eV) with regard to acceptor and donor abilities, respectively. We also evaluated the properties of bis(fulvene)s, i.e., compounds composed of a donor-type heptafulvene fused with an acceptor-type pentafulvene, and it was revealed that these bis(fulvene)s can be designed so that the IE and EA of the two separate fulvene segments are retained, potentially allowing for the design of compact donor-acceptor dyads.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-140156 (URN)10.1021/jo101634v (DOI)000284519900008 ()21067236 (PubMedID)
    Available from: 2011-01-04 Created: 2011-01-04 Last updated: 2017-12-11Bibliographically approved
    3. Fulvenes: Compounds for which the Singlet-Triplet Energy Gaps are Closely Linked to Aromaticity and  Aromaticity Differences
    Open this publication in new window or tab >>Fulvenes: Compounds for which the Singlet-Triplet Energy Gaps are Closely Linked to Aromaticity and  Aromaticity Differences
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-172869 (URN)
    Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2012-08-01
    4. Exploration of the π-Electronic Structure of Singlet, Triplet, and Quintet States of Fulvenes and Fulvalenes Using the Electron Localization Function
    Open this publication in new window or tab >>Exploration of the π-Electronic Structure of Singlet, Triplet, and Quintet States of Fulvenes and Fulvalenes Using the Electron Localization Function
    2012 (English)In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 116, no 20, p. 5008-5017Article in journal (Refereed) Published
    Abstract [en]

    The singlet ground states and lowest triplet states of penta- and heptafulvene, their benzannulated derivatives, as well as the lowest quintet states of pentaheptafulvalenes, either the parent compound or compounds in which the two rings are intercepted by either an alkynyl or a phenyl segment, were investigated at the (U)OLYP/6-311G(d,p) density functional theory level. The influence of (anti)-aromaticity was analyzed by the structure-based aromaticity index HOMA, the harmonic oscillator model of aromaticity. The extent of (anti)aromatic character was also evaluated in terms of the pi-electron (de)localization as measured by the pi component of the electron localization function (ELF pi). The natural atomic orbital (NAO) occupancies were calculated in order to evaluate the degree of pi-electron shift caused by the opposing electron-counting rules for aromaticity in the electronic ground state (S-0; Hiickel's rule) and the first pi pi* excited triplet state (T-1; Baird's rule). Pentaheptafulvalene (5) shows a shift of 0.5 pi electrons from the 5-ring to the 7-ring when going from the S-0 state to the lowest quintet state (Qu(1)). The pentaheptafulvalene 5 and [5.6.7]quinarene 7 were also investigated in their 90 degrees twisted conformations. From our study it is apparent that excitation localization in fulvalenes, but not in fulvenes, to a substantial degree is determined by aromaticity localization to triplet biradical 4n pi-electron cycles. Isolated benzene rings in these compounds tend to remain as closed-shell 6 pi-electron cycles.

    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-172377 (URN)10.1021/jp3032397 (DOI)000304338600021 ()
    Available from: 2012-04-09 Created: 2012-04-09 Last updated: 2017-12-07Bibliographically approved
    5. Manipulation of Excited State Energies in Fulvenic Molecules
    Open this publication in new window or tab >>Manipulation of Excited State Energies in Fulvenic Molecules
    (English)Manuscript (preprint) (Other academic)
    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-172871 (URN)
    Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2012-08-01
    6. Tuning the Band Gap of Polyfulvenes by Use of “Handles”: On the Effects of Exocyclic Substitution, Benzannulation, and Ring Methylation.
    Open this publication in new window or tab >>Tuning the Band Gap of Polyfulvenes by Use of “Handles”: On the Effects of Exocyclic Substitution, Benzannulation, and Ring Methylation.
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Polymer Chemistry Theoretical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-172872 (URN)
    Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2012-08-01
  • 19.
    Dahlstrand, Christian
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Jahn, Burkhard
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Grigoriev, Anton
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Villaume, Sebastien
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Tuning the Band Gap of Polyfulvenes by Use of “Handles”: On the Effects of Exocyclic Substitution, Benzannulation, and Ring Methylation.Manuscript (preprint) (Other academic)
  • 20.
    Dahlstrand, Christian
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Rosenberg, Martin
    Department of Chemistry, University of Copenhagen.
    Kilså, Kristine
    Department of Chemistry, University of Copenhagen.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Exploration of the π-Electronic Structure of Singlet, Triplet, and Quintet States of Fulvenes and Fulvalenes Using the Electron Localization Function2012In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 116, no 20, p. 5008-5017Article in journal (Refereed)
    Abstract [en]

    The singlet ground states and lowest triplet states of penta- and heptafulvene, their benzannulated derivatives, as well as the lowest quintet states of pentaheptafulvalenes, either the parent compound or compounds in which the two rings are intercepted by either an alkynyl or a phenyl segment, were investigated at the (U)OLYP/6-311G(d,p) density functional theory level. The influence of (anti)-aromaticity was analyzed by the structure-based aromaticity index HOMA, the harmonic oscillator model of aromaticity. The extent of (anti)aromatic character was also evaluated in terms of the pi-electron (de)localization as measured by the pi component of the electron localization function (ELF pi). The natural atomic orbital (NAO) occupancies were calculated in order to evaluate the degree of pi-electron shift caused by the opposing electron-counting rules for aromaticity in the electronic ground state (S-0; Hiickel's rule) and the first pi pi* excited triplet state (T-1; Baird's rule). Pentaheptafulvalene (5) shows a shift of 0.5 pi electrons from the 5-ring to the 7-ring when going from the S-0 state to the lowest quintet state (Qu(1)). The pentaheptafulvalene 5 and [5.6.7]quinarene 7 were also investigated in their 90 degrees twisted conformations. From our study it is apparent that excitation localization in fulvalenes, but not in fulvenes, to a substantial degree is determined by aromaticity localization to triplet biradical 4n pi-electron cycles. Isolated benzene rings in these compounds tend to remain as closed-shell 6 pi-electron cycles.

  • 21. Darreh-Shori, Taher
    et al.
    Vijayaraghavan, Swetha
    Aeinehband, Shahin
    Piehl, Fredrik
    Lindblom, Rickard P F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Almkvist, Ove
    Nordberg, Agneta
    Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 11, p. 2465-2481Article in journal (Refereed)
    Abstract [en]

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1 beta, and tumor necrosis factor (TNF)-alpha. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1b and 21%-27% higher TNF-alpha compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low beta-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-alpha and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic potential of manipulating BuChE activity or astroglial functional status.

  • 22.
    Doak, Bradley Croy
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Over, Bjorn
    Giordanetto, Fabrizio
    Kihlberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates2014In: Chemistry and Biology, ISSN 1074-5521, E-ISSN 1879-1301, Vol. 21, no 9, p. 1115-1142Article, review/survey (Refereed)
    Abstract [en]

    The rule of 5 (Ro5) is a set of in silico guidelines applied to drug discovery to prioritize compounds with an increased likelihood of high oral absorption. It has been influential in reducing attrition due to poor pharmacokinetics over the last 15 years. However, strict reliance on the Ro5 may have resulted in lost opportunities, particularly for difficult targets. To identify opportunities for oral drug discovery beyond the Ro5 (bRo5), we have comprehensively analyzed drugs and clinical candidates with molecular weight (MW) > 500 Da. We conclude that oral drugs are found far bRo5 and properties such as intramolecular hydrogen bonding, macrocyclization, dosage, and formulations can be used to improve bRo5 bioavailability. Natural products and structure-based design, often from peptidic leads, are key sources for oral bRo5 drugs. These insights should help guide the design of oral drugs in bRo5 space, which is of particular interest for difficult targets.

  • 23. Elmlund, Louise
    et al.
    Kack, Camilla
    Aastrup, Teodor
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Study of the Interaction of Trastuzumab and SKOV3 Epithelial Cancer Cells Using a Quartz Crystal Microbalance Sensor2015In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 15, no 3, p. 5884-5894Article in journal (Refereed)
    Abstract [en]

    Analytical methods founded upon whole cell-based assays are of importance in early stage drug development and in fundamental studies of biomolecular recognition. Here we have studied the binding of the monoclonal antibody trastuzumab to human epidermal growth factor receptor 2 (HER2) on human ovary adenocarcinoma epithelial cancer cells (SKOV3) using quartz crystal microbalance (QCM) technology. An optimized procedure for immobilizing the cells on the chip surface was established with respect to fixation procedure and seeding density. Trastuzumab binding to the cell decorated sensor surface was studied, revealing a mean dissociation constant, K-D, value of 7 +/- 1 nM (standard error of the mean). This study provides a new perspective on the affinity of the antibody-receptor complex presented a more natural context compared to purified receptors. These results demonstrate the potential for using whole cell-based QCM assay in drug development, the screening of HER2 selective antibody-based drug candidates, and for the study of biomolecular recognition. This real time, label free approach for studying interactions with target receptors present in their natural environment afforded sensitive and detailed kinetic information about the binding of the analyte to the target.

  • 24.
    Emanuelsson, Rikard
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Conjugation in Organic Group 14 Element Compounds: Design, Synthesis and Experimental Evaluation2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on the chemical concept of conjugation, i.e., electron delocalization, and the effect it has on electronic and optical properties of molecules. The emphasis is on electron delocalization across a saturated σ-bonded segment, and in our studies these segments are either inserted between π-conjugated moieties or joined together to form longer chains. The electronic and optical properties of these compounds are probed and compared to those of traditionally π-conjugated compounds. The investigations utilize a combination of qualitative chemical bonding theories, quantum chemical calculations, chemical syntheses and different spectroscopic methods.

    Herein, it is revealed that a saturated σ-bonded segment inserted between two π-systems can have optical and electronic properties similar to a cross-conjugated compound when substituents with heavy Group 14 elements (Si, Ge or Sn) are attached to the central atom. We coined the terminology cross-hyperconjugation for this interaction, and have shown it by both computational and spectroscopic means. This similarity is also found in cyclic compounds, for example in the 1,4-disilacyclohexa-2,5-dienes, as we reveal that there is a cyclic aspect of cross-hyperconjugation. Cross-hyperconjugation can further also be found in smaller rings such as siloles and cyclopentadienes, and we show on the similarities between these and their cross-π-conjugated analogues, the fulvenes. Here, this concept is combined with that of excited state aromaticity and the electronic properties of these systems are rationalized in terms of “aromatic chameleon” effects. We show that the optical properties of these systems can be rationally tuned and predicted through the choice of substituents and knowledge about the aromaticity rules in both ground and excited states.

    We computationally examine the relation between conjugation and conductance and reveal that oligomers of 1,4-disilacyclohexa-2,5-dienes and related analogues can display molecular cord properties. The conductance through several σ-conjugated silicon compounds were also examined and show that mixed silicon and carbon bicyclo[2.2.2]octane compounds do not provide significant benefits over the open-chain oligosilanes. However, cyclohexasilanes, a synthetic precursor to the bicyclic compounds, displayed conformer-dependent electronic structure variations that were not seen for cyclohexanes. This allowed for computational design of a mechanically activated conductance switch.

    List of papers
    1. Cross-hyperconjugation: An unexplored orbital interaction between pi-conjugated and saturated molecular segments
    Open this publication in new window or tab >>Cross-hyperconjugation: An unexplored orbital interaction between pi-conjugated and saturated molecular segments
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    2013 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 3, p. 983-987Article in journal (Refereed) Published
    Abstract [en]

    Crossing a barrier: Molecules with saturated ER2 units (E=C or Si, R=electron-releasing group) inserted between two π-conjugated segments have electronic and optical properties that resemble those of cross-conjugated molecules (see figure). This cross-hyperconjugation provides a deeper understanding of the conjugation phenomenon, and is an alternative to cross-conjugation in the design of molecules for nano and materials applications.

    Keywords
    conjugation, cross-conjugation, Group 14 elements, hyperconjugation, optical tuning
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-194990 (URN)10.1002/anie.201206030 (DOI)000313688100036 ()
    Available from: 2013-02-21 Created: 2013-02-20 Last updated: 2017-12-06Bibliographically approved
    2. Charge transfer through cross-hyperconjugated versus cross-pi-conjugated bridges: an intervalence charge transfer study
    Open this publication in new window or tab >>Charge transfer through cross-hyperconjugated versus cross-pi-conjugated bridges: an intervalence charge transfer study
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    2013 (English)In: Chemical Science, ISSN 2041-6520, Vol. 4, no 9, p. 3522-3532Article in journal (Refereed) Published
    Abstract [en]

    Recently there has been much interest in electron transfer and transport through cross-conjugated molecules as interesting test cases for the interplay between molecular and electronic structure as well as potential motifs in the design of new compounds for molecular electronics. Herein we expand on this concept and present the synthesis and characterization of a series of four organic mixed-valence dyads to probe the effect of the bridge structure on the electronic coupling. The electronic coupling between two triarylamine units could be mediated either by cross-hyperconjugation through a saturated ER2 bridge (E = C or Si, R = alkyl or silyl group), or via a cross-conjugated pi-system. The aim of the study is to compare the electron transfer through the various saturated bridges to that of a cross-pi-conjugated bridge. The electronic coupling in these mixed-valence compounds was determined by analysis of intervalence charge transfer bands, and was found to be in the range of 100-400 cm(-1). A complementary DFT and TD-DFT study indicated that the electronic coupling in the dyads with saturated ER2 segments is highly conformer dependant. Furthermore, the calculations showed that two types of interactions contribute to the electronic coupling; a through-bond cross-(hyper)conjugation mechanism and a through-space mechanism. Taken together, these findings suggest the possibility for new architectures for molecular electronics applications utilizing cross-hyperconjugation through properly selected saturated segments which have comparable electron transfer characteristics as regular cross-pi-conjugated molecules.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-208680 (URN)10.1039/c3sc50844g (DOI)000322391800021 ()
    Available from: 2013-10-07 Created: 2013-10-07 Last updated: 2014-06-30Bibliographically approved
    3. 1,4-Disilacyclohexa-2,5-diene: a molecular building block that allows for remarkably strong neutral cyclic cross-hyperconjugation
    Open this publication in new window or tab >>1,4-Disilacyclohexa-2,5-diene: a molecular building block that allows for remarkably strong neutral cyclic cross-hyperconjugation
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    2014 (English)In: Chemical Science, ISSN 2041-6520, Vol. 5, no 1, p. 360-371Article in journal (Refereed) Published
    Abstract [en]

    2,3,5,6-Tetraethyl-1,4-disilacyclohexa-2,5-dienes with either four chloro (1a), methyl (1b), or trimethylsilyl (TMS) (1c) substituents at the two silicon atoms were examined in an effort to design rigid compounds with strong neutral cross-hyperconjugation between pi- and sigma-bonded molecular segments arranged into a cycle. Remarkable variations in the lowest electronic excitation energies, lowest ionization energies, and the first oxidation potentials were observed upon change of substituents, as determined by gas phase ultraviolet (UV) absorption spectroscopy, ultraviolet photoelectron spectroscopy (UPS), and cyclic voltammetry. A particularly strong neutral cyclic cross-hyperconjugation was observed in 1c. Its lowest electron binding energy (7.1 eV) is distinctly different from that of 1b (8.5 eV). Molecular orbital analysis reveals a stronger interaction between filled pi(C=C) and pi(SiR2) group orbitals in 1c than in 1a and 1b. The energy shift in the highest occupied molecular orbital is also reflected in the first oxidation potentials as observed in the cyclic voltammograms of the respective compounds (1.47, 0.88, and 0.46 V for 1a, 1b and 1c, respectively). Furthermore, 1,4-disilacyclohexadiene 1c absorbs strongly at 273 nm (4.55 eV), whereas 1a and 1b have no symmetry allowed excitations above 215 nm (below 5.77 eV). Thus, suitably substituted 1,4-disilacyclohexa-2,5-dienes could represent novel building blocks for the design of larger cross-hyperconjugated molecules as alternatives to traditional purely cross-p-conjugated analogues, and could allow for design of molecules with properties that are not accessible to those that are exclusively pi-conjugated.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-213891 (URN)10.1039/c3sc52389f (DOI)000327601600045 ()
    Available from: 2014-01-06 Created: 2014-01-05 Last updated: 2016-03-08Bibliographically approved
    4. Optimization of the Cyclic Cross-Hyperconjugation in 1,4-Ditetrelcyclohexa-2,5-dienes
    Open this publication in new window or tab >>Optimization of the Cyclic Cross-Hyperconjugation in 1,4-Ditetrelcyclohexa-2,5-dienes
    2014 (English)In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 33, no 12, p. 2997-3004Article in journal (Refereed) Published
    Abstract [en]

    Cyclic cross-hyperconjugation can exist to variable extents in 1,4-ditetrelcyclohexa-2,5-dienes, i.e., all-carbon cyclohexa-1,4-dienes and 1,4-disila/digerma/distanna/diplumbacyclohexa-2,5-dienes. In this study we first use density functional theory (DFT) computations to optimize the conjugation strength by seeking the optimal atom E and substituent group E'Me-3 in the two saturated E(E'Me-3)(2) moieties (E and E' as the same or different tetrel (group 14) elements). We reveal that the all-carbon cyclohexadienes with gradually heavier E'Me-3 substituents at the two saturated carbon atoms display significant cross-hyperconjugation. The first electronic excitations in these compounds, which formally have two isolated C=C bonds, are calculated to reach wavelengths as long as 400 nm (excitation energies of 3.1 eV). These transitions are mostly forbidden, and the lowest allowed transitions are found at 387 nm (3.2 eV). The silicon analogues are also cross-hyperconjugated, while a decline is observed in the 1,4-digerma/distanna/diplumbacyclohexa-2,5-diene. Experiments on two substituted 1,4-disilacyclohexa-2,5-dienes confirm the effect of the E'Me3 substituents, with regard to both electronic excitations and geometries as determined by UV absorption spectroscopy and X-ray crystallography, respectively. At the end, we reveal through computations how electron-donating and electron-withdrawing substituents at the C=C double bonds influence the electronic properties of the all-carbon ring. We find that the first calculated excitation, which is forbidden, can be shifted to 440 nm (2.83 eV). This shows to what extent cyclic cross-hyperconjugation can affect the electronic and optical properties of a compound with two formally isolated C=C double bonds.

    National Category
    Organic Chemistry
    Research subject
    Chemistry with specialization in Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-221022 (URN)10.1021/om5001875 (DOI)000337936800008 ()
    Available from: 2014-03-24 Created: 2014-03-24 Last updated: 2017-12-12Bibliographically approved
    5. Using Ground and Excited State Aromaticity to Understand Cyclopentadiene and Silole Excitation Energies and Excited State Polarities
    Open this publication in new window or tab >>Using Ground and Excited State Aromaticity to Understand Cyclopentadiene and Silole Excitation Energies and Excited State Polarities
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    (English)Article in journal (Other academic) Submitted
    National Category
    Chemical Sciences
    Research subject
    Chemistry with specialization in Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-221027 (URN)
    Available from: 2014-03-24 Created: 2014-03-24 Last updated: 2014-06-30Bibliographically approved
    6. In Search of Flexible Molecular Wires with Near Conformer-Independent Conjugation and Conductance: A Computational Study
    Open this publication in new window or tab >>In Search of Flexible Molecular Wires with Near Conformer-Independent Conjugation and Conductance: A Computational Study
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    2014 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 118, no 11, p. 5637-5649Article in journal (Refereed) Published
    Abstract [en]

    Oligomers of 1,4-disila/germa/stannacyclohexa-2,5-dienes as well as all-carbon 1,4-cyclohexadienes connected via E—E single bonds (E = C, Si, Ge, or Sn) were studied through quantum chemical calculations in an effort to identify conformationally flexible molecular wires that act as molecular “electrical cords” having conformer-independent conjugative and conductive properties. Our oligomers display neutral hyperconjugative interactions (σ/π-conjugation) between adjacent σ(E—E) and π(C═C) bond orbitals, and these interactions do not change with conformation. The energies and spatial distributions of the highest occupied molecular orbitals of methyl-, silyl-, and trimethylsilyl (TMS)-substituted 1,4-disilacyclohexa-2,5-diene dimers, and stable conformers of trimers and tetramers, remain rather constant upon Si–Si bond rotation. Yet, steric congestion may be a concern in some of the oligomer types. The calculated conductances for the Si-containing tetramers are similar to that of a σ-conjugated linear all-anti oligosilane (a hexadecasilane) with equally many bonds in the conjugated paths. Moreover, the Me-substituted 1,4-disilacyclohexadiene tetramer has modest conductance fluctuations with Si–Si bond rotations when the electrode–electrode distance is locked (variation by factor 30), while the fluctuations under similar conditions are larger for the analogous TMS-substituted tetramer. When the electrode–electrode distance is changed several oligomers display small conductance variations within certain distance intervals, e.g., the mean conductance of TMS-substituted 1,4-disilacyclohexa-2,5-diene tetramer is almost unchanged over 9 Å of electrode–electrode distances.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2014
    National Category
    Physical Chemistry
    Research subject
    Chemistry with specialization in Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-209260 (URN)10.1021/jp409767r (DOI)000333381300003 ()
    Available from: 2013-10-16 Created: 2013-10-16 Last updated: 2017-12-06Bibliographically approved
    7. Coupling of Disilane and Trisilane Segments Through Zero, One, Two, and Three Disilanyl Bridges in Cyclic and Bicyclic Saturated Carbosilanes
    Open this publication in new window or tab >>Coupling of Disilane and Trisilane Segments Through Zero, One, Two, and Three Disilanyl Bridges in Cyclic and Bicyclic Saturated Carbosilanes
    Show others...
    2013 (English)In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 32, no 2, p. 396-405Article in journal (Refereed) Published
    Abstract [en]

    Several six-membered cyclic and [2.2.2]bicyclic organo-silanes with varying proportions of silicon atoms in the bridges have been prepared following a stepwise approach that exploits dianionic polysilanes. Focus in our analysis was placed on the bicyclic compounds which all have silicon atoms at the bridgehead positions. Quantum chemical calculations of these compounds revealed the possibility to enhance the coupling through a single cisoid tetrasilane cage segment by replacing one or two of the other -SiMe2SiMe2- bridges with -CH2CH2- bridges. UV absorption spectroscopy revealed a red shift in the lowest visible transitions when going from a bicyclo[2.2.2]octane with three -SiMe2SiMe2- bridges to those with two or one such bridge. However, these red shifts are deceptive, as the lowest vertically excited singlet states, which are dark according to TD-DFT calculations, do not display the same trend. Still, since these compounds have (i) excellent structural rigidity, (ii) provide potentials for functionalization through their exocyclic trimethylsilyl groups, and (iii) display electronic structure variations with the number of -SiMe2SiMe2- bridges, they could be interesting for further studies: e.g., in single-molecule electronics.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-196040 (URN)10.1021/om3006678 (DOI)000314332100007 ()
    Available from: 2013-03-04 Created: 2013-03-04 Last updated: 2017-12-06Bibliographically approved
    8. Conductance through Carbosilane Cage Compounds: A Computational Investigation
    Open this publication in new window or tab >>Conductance through Carbosilane Cage Compounds: A Computational Investigation
    Show others...
    2013 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 117, no 42, p. 21692-21699Article in journal (Refereed) Published
    Abstract [en]

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

    Keywords
    Molecular electronics, organosilicon chemistry, electronic structure, density functional theory, sigma conjugation
    National Category
    Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-209236 (URN)10.1021/jp407485n (DOI)000326260000008 ()
    Available from: 2013-10-16 Created: 2013-10-15 Last updated: 2017-12-06Bibliographically approved
    9. Configuration- and Conformation-Dependent Electronic Structure Variations in 1,4-Disubstituted Cyclohexanes Enabled by a Carbon-to-Silicon Exchange
    Open this publication in new window or tab >>Configuration- and Conformation-Dependent Electronic Structure Variations in 1,4-Disubstituted Cyclohexanes Enabled by a Carbon-to-Silicon Exchange
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    2014 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 30, p. 9304-9311Article in journal (Other academic) Published
    Abstract [en]

    Cyclohexane, with its well-defined conformers, could be an ideal force-controlled molecular switch if it were to display substantial differences in electronic and optical properties between its conformers. We utilize sigma conjugation in heavier analogues of cyclohexanes (i.e. cyclohexasilanes) and show that 1,4-disubstituted cyclohexasilanes display configuration-and conformation-dependent variations in these properties. Cis- and trans-1,4-bis(trimethylsilylethynyl)-cyclohexasilanes display a 0.11 V difference in their oxidation potentials (computed 0.11 V) and a 0.34 eV difference in their lowest UV absorption (computed difference between first excitations 0.07 eV). This is in stark contrast to differences in the corresponding properties of analogous all-carbon cyclohexanes (computed 0.02 V and 0.03 eV, respectively). Moreover, the two chair conformers of the cyclohexasilane trans isomer display large differences in electronic-structure-related properties. This enables computational design of a mechanically force-controlled conductance switch with a calculated single-molecule ON/OFF ratio of 213 at zero-bias voltage.

    National Category
    Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-209259 (URN)10.1002/chem.201402610 (DOI)000339568800023 ()
    Note

    De 2 sista författarna delar sistaförfattarskapet.

    Available from: 2013-10-16 Created: 2013-10-16 Last updated: 2017-12-06Bibliographically approved
  • 25.
    Emanuelsson, Rikard
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Denisova, Aleksandra
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Baumgartner, Judith
    Institut für Chemie, Universität Graz.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Optimization of the Cyclic Cross-Hyperconjugation in 1,4-Ditetrelcyclohexa-2,5-dienes2014In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 33, no 12, p. 2997-3004Article in journal (Refereed)
    Abstract [en]

    Cyclic cross-hyperconjugation can exist to variable extents in 1,4-ditetrelcyclohexa-2,5-dienes, i.e., all-carbon cyclohexa-1,4-dienes and 1,4-disila/digerma/distanna/diplumbacyclohexa-2,5-dienes. In this study we first use density functional theory (DFT) computations to optimize the conjugation strength by seeking the optimal atom E and substituent group E'Me-3 in the two saturated E(E'Me-3)(2) moieties (E and E' as the same or different tetrel (group 14) elements). We reveal that the all-carbon cyclohexadienes with gradually heavier E'Me-3 substituents at the two saturated carbon atoms display significant cross-hyperconjugation. The first electronic excitations in these compounds, which formally have two isolated C=C bonds, are calculated to reach wavelengths as long as 400 nm (excitation energies of 3.1 eV). These transitions are mostly forbidden, and the lowest allowed transitions are found at 387 nm (3.2 eV). The silicon analogues are also cross-hyperconjugated, while a decline is observed in the 1,4-digerma/distanna/diplumbacyclohexa-2,5-diene. Experiments on two substituted 1,4-disilacyclohexa-2,5-dienes confirm the effect of the E'Me3 substituents, with regard to both electronic excitations and geometries as determined by UV absorption spectroscopy and X-ray crystallography, respectively. At the end, we reveal through computations how electron-donating and electron-withdrawing substituents at the C=C double bonds influence the electronic properties of the all-carbon ring. We find that the first calculated excitation, which is forbidden, can be shifted to 440 nm (2.83 eV). This shows to what extent cyclic cross-hyperconjugation can affect the electronic and optical properties of a compound with two formally isolated C=C double bonds.

  • 26.
    Emanuelsson, Rikard
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Löfås, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Wallner, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry. Institut für Anorganische Chemie, Technische Universität Graz.
    Nauroozi, Djawed
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström.
    Baumgartner, Judith
    Institut für Anorganische Chemie, Technische Universität Graz.
    Marschner, Christoph
    Institut für Anorganische Chemie, Technische Universität Graz.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ott, Sascha
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Grigoriev, Anton
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Configuration- and Conformation-Dependent Electronic Structure Variations in 1,4-Disubstituted Cyclohexanes Enabled by a Carbon-to-Silicon Exchange2014In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 30, p. 9304-9311Article in journal (Other academic)
    Abstract [en]

    Cyclohexane, with its well-defined conformers, could be an ideal force-controlled molecular switch if it were to display substantial differences in electronic and optical properties between its conformers. We utilize sigma conjugation in heavier analogues of cyclohexanes (i.e. cyclohexasilanes) and show that 1,4-disubstituted cyclohexasilanes display configuration-and conformation-dependent variations in these properties. Cis- and trans-1,4-bis(trimethylsilylethynyl)-cyclohexasilanes display a 0.11 V difference in their oxidation potentials (computed 0.11 V) and a 0.34 eV difference in their lowest UV absorption (computed difference between first excitations 0.07 eV). This is in stark contrast to differences in the corresponding properties of analogous all-carbon cyclohexanes (computed 0.02 V and 0.03 eV, respectively). Moreover, the two chair conformers of the cyclohexasilane trans isomer display large differences in electronic-structure-related properties. This enables computational design of a mechanically force-controlled conductance switch with a calculated single-molecule ON/OFF ratio of 213 at zero-bias voltage.

  • 27.
    Emanuelsson, Rikard
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Löfås, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Zhu, Jun
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry. State Key Laboratory of Physical Chemistry of Solid Surfaces, Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Grigoriev, Anton
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    In Search of Flexible Molecular Wires with Near Conformer-Independent Conjugation and Conductance: A Computational Study2014In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 118, no 11, p. 5637-5649Article in journal (Refereed)
    Abstract [en]

    Oligomers of 1,4-disila/germa/stannacyclohexa-2,5-dienes as well as all-carbon 1,4-cyclohexadienes connected via E—E single bonds (E = C, Si, Ge, or Sn) were studied through quantum chemical calculations in an effort to identify conformationally flexible molecular wires that act as molecular “electrical cords” having conformer-independent conjugative and conductive properties. Our oligomers display neutral hyperconjugative interactions (σ/π-conjugation) between adjacent σ(E—E) and π(C═C) bond orbitals, and these interactions do not change with conformation. The energies and spatial distributions of the highest occupied molecular orbitals of methyl-, silyl-, and trimethylsilyl (TMS)-substituted 1,4-disilacyclohexa-2,5-diene dimers, and stable conformers of trimers and tetramers, remain rather constant upon Si–Si bond rotation. Yet, steric congestion may be a concern in some of the oligomer types. The calculated conductances for the Si-containing tetramers are similar to that of a σ-conjugated linear all-anti oligosilane (a hexadecasilane) with equally many bonds in the conjugated paths. Moreover, the Me-substituted 1,4-disilacyclohexadiene tetramer has modest conductance fluctuations with Si–Si bond rotations when the electrode–electrode distance is locked (variation by factor 30), while the fluctuations under similar conditions are larger for the analogous TMS-substituted tetramer. When the electrode–electrode distance is changed several oligomers display small conductance variations within certain distance intervals, e.g., the mean conductance of TMS-substituted 1,4-disilacyclohexa-2,5-diene tetramer is almost unchanged over 9 Å of electrode–electrode distances.

  • 28.
    Emanuelsson, Rikard
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Tibbelin, Julius
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Wallner, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Smith, Joshua R.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Strong neutral cross-hyperconjugation and linear hyperconjugation enabled by saturated Group 14 element E(E ' R-3)(2), (E ' R-3)E-E(E ' R-3), and E(E ' R-2)(2)E segments2013In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 245, p. 1246-INOR-Article in journal (Other academic)
  • 29.
    Emanuelsson, Rikard
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Wallner, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Ng, Eugene A. M.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Smith, J. R.
    Nauroozi, Djawed
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Ott, Sascha
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Cross-hyperconjugation: An unexplored orbital interaction between pi-conjugated and saturated molecular segments2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 3, p. 983-987Article in journal (Refereed)
    Abstract [en]

    Crossing a barrier: Molecules with saturated ER2 units (E=C or Si, R=electron-releasing group) inserted between two π-conjugated segments have electronic and optical properties that resemble those of cross-conjugated molecules (see figure). This cross-hyperconjugation provides a deeper understanding of the conjugation phenomenon, and is an alternative to cross-conjugation in the design of molecules for nano and materials applications.

  • 30.
    Engler, Henry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Nennesmo, Inger
    Kumlien, Eva
    Gambini, JP
    Lundberg, PO
    Savitcheva, Irina
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Imaging astrocytosis with PET in Creutzfeldt-Jakob disease: case report with histopathological findings2012In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, no 2, p. 201-207Article in journal (Refereed)
    Abstract [en]

    In a previous study, patients with suspect Creutzfeldt-Jakob's disease (CJD) have been examined with Positron Emission Tomography (PET) combining N-[11C-methyl]-L-deuterodeprenyl (DED) and [(18)F] 2- fluorodeoxyglucose (FDG) in an attempt to detect astrocytosis and neuronal dysfunction, two of the hallmarks in CJD. Increased DED uptake with pronounced hypometabolism matching the areas with high DED retention was found in the fronto-parieto-occipital areas and cerebellum of patients with confirmed CJD. However, the temporal lobes did not present such a pattern. In 6 of the 15 examined patients the autopsy was performed, but a strict comparison between the PET results and the histopathology could not be done. Recently, one patient with suspect CJD was examined with PET using DED and FDG. The results of the examinations in this patient showed a pattern similar to that found in the brain of the CJD patients from the first study. The patient died shortly after the examination and an autopsy could be performed. The autopsy showed neuronal death, astrocytosis and spongiform changes in the brain. The diagnosis of definite sporadic CJD was established by the Western blot analysis, confirming the presence of the prion resistant protein (PrPres). The PET data demonstrated high DED uptake and extreme low glucose uptake in the left brain hemisphere whereas the right side was less affected. The autopsy was performed allowing the comparison between high DED uptake and the histopathological findings of reactive astrocytosis revealed by immunostaining with antibodies against glial fibrillary acid protein (GFAP). The results confirmed the presence of a pattern with high ratio DED/FDG, similar to that found in the previous study and revealing for the first time, a good correlation between high DED uptake and high density of reactive astrocytes as demonstrated by immunostaining.

  • 31.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Age, sex and NK1 receptors in the human brain: A positron emission tomography study with [C-11]GR2051712012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no 8, p. 562-568Article in journal (Refereed)
    Abstract [en]

    The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n = 9) and women (n = 9) matched for age varying between 20 and 50 years using the highly specific NK1 receptor antagonist [11C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence.

  • 32.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Bergström, Anders
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Positron emission tomography in neuroendocrine tumors1999In: The Italian Journal of Gastroenterology and Hepatology, ISSN 1125-8055, Vol. 31, p. 167-171Article in journal (Refereed)
  • 33.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Carlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Blom, Elisabeth
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation2012In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, no 3, p. 415-421Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Islet transplantation is a promising treatment for type 1 diabetes mellitus, but the fate of the cells after intraportal infusion is unclear. It is therefore imperative to develop novel techniques for noninvasive imaging and quantification of events following islet transplantation.

    METHODS:

    Small islet-like microbeads, avidin-covered agarose resins (AARs), were used as a model system for islet transplantation. Capability for specific [(68)Ga]Ga-DOTA-(PEG)(2)-biotin uptake and retention for either AARs or human islets conjugated with avidin by means of a heparin scaffold was studied in vitro. Biodistribution of the novel positron emission tomography (PET) tracer [(68)Ga]Ga-DOTA-(PEG)(2)-biotin was evaluated in mice treated by intraportal transplantation of AARs by μPET/computed tomography and ex vivo organ distribution and compared with control mice.

    RESULTS:

    AARs had high capability to bind [(68)Ga]Ga-DOTA-(PEG)(2)-biotin, close to 50% of administrated tracer/μl in vitro (>0.25 MBq/μl). Avidin-tagged human islets could bind on average 2.2% of administered tracer/μl. Specificity (>90%) and retention (>90% after 1 h) were high for both AARs and avidin-tagged islets. Hepatic tracer uptake and retention were increased in mice transplanted with AARs [standardized uptake value (SUV)=2.6] compared to the untreated group (SUV=1.4). In vivo uptake of tracer to AARs was blocked by preadministration of unlabeled biotin.

    CONCLUSIONS:

    Avidin-tagged islet-like objects can be tracked in hepatic volume after intraportal transplantation by using [(68)Ga]Ga-DOTA-(PEG)(2)-biotin and PET.

  • 34.
    Eriksson, Susanna K
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Hahlin, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Kahk, Juhan Matthias
    Villar-Garcia, Ignacio J
    Webb, Matthew J
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Yakimova, Rositza
    Rensmo, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Edström, Kristina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Hagfeldt, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Siegbahn, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Edwards, Mårten O M
    Karlsson, Patrik G
    Backlund, Klas
    Ahlund, John
    Payne, David J
    A versatile photoelectron spectrometer for pressures up to 30 mbar2014In: Review of Scientific Instruments, ISSN 0034-6748, E-ISSN 1089-7623, Vol. 85, no 7, p. 075119-Article in journal (Refereed)
    Abstract [en]

    High-pressure photoelectron spectroscopy is a rapidly developing technique with applications in a wide range of fields ranging from fundamental surface science and catalysis to energy materials, environmental science, and biology. At present the majority of the high-pressure photoelectron spectrometers are situated at synchrotron end stations, but recently a small number of laboratory-based setups have also emerged. In this paper we discuss the design and performance of a new laboratory based high pressure photoelectron spectrometer equipped with an Al Kα X-ray anode and a hemispherical electron energy analyzer combined with a differentially pumped electrostatic lens. The instrument is demonstrated to be capable of measuring core level spectra at pressures up to 30 mbar. Moreover, valence band spectra of a silver sample as well as a carbon-coated surface (graphene) recorded under a 2 mbar nitrogen atmosphere are presented, demonstrating the versatility of this laboratory-based spectrometer.

  • 35. Finke, Aaron D.
    et al.
    Jahn, Burkhard O.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Saithalavi, Anas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Dahlstrand, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Nauroozi, Djawed
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Haberland, Sophie
    Gisselbrecht, Jean-Paul
    Boudon, Corinne
    Mijangos, Edgar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Schweizer, W. Bernd
    Ott, Sascha
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Diederich, Francois
    The 6,6-Dicyanopentafulvene Core: A Template for the Design of Electron-Acceptor Compounds2015In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, no 22, p. 8168-8176Article in journal (Refereed)
    Abstract [en]

    The electron-accepting ability of 6,6-dicyanopentafulvenes (DCFs) can be varied extensively through substitution on the five-membered ring. The reduction potentials for a set of 2,3,4,5-tetraphenyl-substituted DCFs, with varying substituents at the para-position of the phenyl rings, strongly correlate with their Hammett sigma(p)-parameters. By combining cyclic voltammetry with DFT calculations ((U)B3LYP/6-311+G(d)), using the conductor-like polarizable continuum model (CPCM) for implicit solvation, the absolute reduction potentials of a set of twenty DCFs were reproduced with a mean absolute deviation of 0.10eV and a maximum deviation of 0.19eV. Our experimentally investigated DCFs have reduction potentials within 3.67-4.41eV, however, the computations reveal that DCFs with experimental reduction potentials as high as 5.3eV could be achieved, higher than that of F-4-TCNQ (5.02eV). Thus, the DCF core is a template that allows variation in the reduction potentials by about 1.6eV.

  • 36. Forsberg, Anton
    et al.
    Engler, Henry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Blomquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Nordberg, Agneta
    The use of PIB-PET as a dual pathological and functional biomarker in AD2012In: Biochimica et Biophysica Acta - Molecular Basis of Disease, ISSN 0925-4439, E-ISSN 1879-260X, Vol. 1822, no 3, p. 380-385Article in journal (Refereed)
    Abstract [en]

    Amyloid imaging with positron emission tomography (PET) is presently used in Alzheimer's disease (AD) research. In this study we investigated the possibility to use early frames (ePIB) of the PIB scans as a rough index of CBF by comparing normalised early PIB values with cerebral glucose metabolism (rCMRglc). PIB-PET and FDG-PET were performed in 37 AD patients, 21 subjects with mild cognitive impairment (MCI) and 6 healthy controls (HC). The patients were divided based on their PIB retention (amyloid load) as either PIB positive (PIB+) or PIB negative (PIB-). Data of the unidirectional influx K-1 from a subset of the subjects including 7 AD patients and 3 HC was used for correlative analysis. Data was analysed using regions of interest (ROI) analysis. A strong, positive correlation was observed across brain regions between K-1 and ePIB (r=0.70: p <= 0.001). The ePIB values were significantly lower in the posterior cingulate (p <= 0.001) and the parietal cortices (p = 0.002) in PIB+ subjects compared to PIB-, although the group difference were stronger for rCMRglc in cortical areas (p <= 0.001). Strong positive correlations between ePIB and rCMRglc were observed in all cortical regions analysed, especially in the posterior cingulate and parietal cortices (p <= 0.001). A single dynamic PIE-PET scan may provide information about pathological and functional changes (amyloidosis and impaired blood flow). This might be important for diagnosis of AD, enrichment of patients in clinical trials and evaluation of treatment effects.

  • 37.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [(11)C]GR2051712015In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 5, article id e597Article in journal (Refereed)
    Abstract [en]

    The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [(11)C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.

  • 38.
    Fromell, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Forsberg, Pontus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Karlsson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Larsson, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Nikolajeff, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Baltzer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Designed protein binders in combination with nanocrystalline diamond for use in high-sensitivity biosensors2012In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 404, no 6-7, p. 1643-1651Article in journal (Refereed)
    Abstract [en]

    A platform for diagnostic applications showing signal-to-noise ratios that by far surpass those of traditional bioanalytical test formats has been developed. It combines the properties of modified nanocrystalline diamond (NCD) surfaces and those of polyethylene oxide and polypropylene oxide based block copolymers for surface passivation and binder conjugation with a new class of synthetic binders for proteins. The NCD surfaces were fluorine-, hydrogen-, or oxygen-terminated prior to further biofunctionalization and the surface composition was characterized by X-ray photoelectron spectroscopy. In a proof of principle demonstration targeting the C-reactive protein, an ELISA carried out using an F-terminated diamond surface showed a signal-to-noise ratio of 3,900 which compares well to the signal-to-noise of 89 obtained in an antibody-based ELISA on a polystyrene microtiter plate, a standard test format used in most life science laboratories today. The increase in signal-to-noise ratio is to a large extent the result of extremely efficient passivation of the diamond surface. The results suggest that significant improvements can be obtained in standardized test formats using new materials in combination with new types of chemical coatings and receptor molecules.

  • 39.
    Giandomenico, Valeria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Modlin, Irvin M.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Khan, Mohid S.
    Millar, Robert P.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Borlak, Jurgen
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Nielsen, Bengt
    Baltzer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Waterton, John C.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Improving the Diagnosis and Management of Neuroendocrine Tumors: Utilizing New Advances in Biomarker and Molecular Imaging Science2013In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 98, no 1, p. 16-30Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone-secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET have increased greatly in the past 3 decades. However, during this time, progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology combined with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally lacking. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow-up has the potential to enhance care. To discuss developments and issues required to improve diagnostics and management of NET patients, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Prof. Kjell Oberg at the University of Uppsala in Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This paper describes the symposium presentations and resulting discussions.

  • 40.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Carbon Nanotubes and Graphene2013In: Organic Synthesis and Molecular Engineering / [ed] Mogens Brøndsted Nielsen, John Wiley & Sons, 2013, p. 76-123Chapter in book (Other academic)
  • 41.
    Grennberg, Helena
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Jansson, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Synthesis of graphene and derivatives2012In: Advanced Functional Materials: A Perspective from Theory and Experiment / [ed] Biplab Sanyal and Olle Eriksson, Elsevier, 2012, no 1, p. 105-127Chapter in book (Refereed)
  • 42. Grigalunas, Michael
    et al.
    Ankner, Tobias
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Norrby, Per-Ola
    Wiest, Olaf
    Helquist, Paul
    Ni-Catalyzed Alkenylation of Ketone Enolates under Mild Conditions: Catalyst Identification and Optimization2015In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 137, no 22, p. 7019-7022Article in journal (Refereed)
    Abstract [en]

    A procedure for Ni-catalyzed cross-coupling of ketone enolates with alkenyl halides has been developed. Intermolecular coupling of aromatic and aliphatic ketone lithium enolates with a variety of alkenyl halides is achieved in the presence of Ni(cod)(2) catalyst (5 mol %), an N-heterocyclic carbene (NHC) ligand, and LiI (10 mol %) at 6-22 degrees C for 0.5-12 h with yields of up to 90%. During the initial development of this reaction, a misleading result with respect to the actual active catalyst was obtained using commercially available Q:Phos ligand, which was found to contain a trace of Pd metal contaminant sufficient to catalyze the reaction. However, under the final conditions optimized for Ni(cod)(2) in the presence of an NHC ligand, Pd was incompetent as a catalyst.

  • 43. Grigalunas, Michael
    et al.
    Ankner, Tobias
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Norrby, Per-Ola
    Wiest, Olaf
    Helquist, Paul
    Palladium-Catalyzed Alkenylation of Ketone Enolates under Mild Conditions2014In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 16, no 15, p. 3970-3973Article in journal (Refereed)
    Abstract [en]

    A protocol for a mild, catalytic, intermolecular alkenylation of ketone enolates has been developed using a Pd/Q-Phos catalyst. Efficient intermolecular coupling of a variety of ketones with alkenyl bromides was achieved with a slight excess of LiHMDS and temperatures down to 0 degrees C.

  • 44.
    Göransson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Emanuelsson, Rikard
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Jorner, Kjell
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Markle, Todd F.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Charge transfer through cross-hyperconjugated versus cross-pi-conjugated bridges: an intervalence charge transfer study2013In: Chemical Science, ISSN 2041-6520, Vol. 4, no 9, p. 3522-3532Article in journal (Refereed)
    Abstract [en]

    Recently there has been much interest in electron transfer and transport through cross-conjugated molecules as interesting test cases for the interplay between molecular and electronic structure as well as potential motifs in the design of new compounds for molecular electronics. Herein we expand on this concept and present the synthesis and characterization of a series of four organic mixed-valence dyads to probe the effect of the bridge structure on the electronic coupling. The electronic coupling between two triarylamine units could be mediated either by cross-hyperconjugation through a saturated ER2 bridge (E = C or Si, R = alkyl or silyl group), or via a cross-conjugated pi-system. The aim of the study is to compare the electron transfer through the various saturated bridges to that of a cross-pi-conjugated bridge. The electronic coupling in these mixed-valence compounds was determined by analysis of intervalence charge transfer bands, and was found to be in the range of 100-400 cm(-1). A complementary DFT and TD-DFT study indicated that the electronic coupling in the dyads with saturated ER2 segments is highly conformer dependant. Furthermore, the calculations showed that two types of interactions contribute to the electronic coupling; a through-bond cross-(hyper)conjugation mechanism and a through-space mechanism. Taken together, these findings suggest the possibility for new architectures for molecular electronics applications utilizing cross-hyperconjugation through properly selected saturated segments which have comparable electron transfer characteristics as regular cross-pi-conjugated molecules.

  • 45.
    Göransson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Emanuelsson, Rikard
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Jorner, Kjell
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Charge Transfer Through Cross-π-conjugated and Cross-hyperconjugated Bridges: An Intervalence Charge Transfer StudyManuscript (preprint) (Other academic)
  • 46.
    Hall, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Takahashi, Kayo
    Center for Molecular Imaging Science, Kobe, Japan.
    Erlandsson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Razifar, Pasha
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Bergström, Elisabeth
    Uppsala Imanet, Uppsala, Sweden.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Pharmacological characterization of 18F-labeled vorozole analogs2012In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 55, no 14, p. 484-490Article in journal (Refereed)
    Abstract [en]

    Two F-18-labeled analogs of vorozole ([F-18]FVOZ and [F-18]FVOO) have been developed as potential tools for the in vivo characterization of aromatase. The pharmacologicalproperties of these radioligands were evaluated using in vitro binding and in vivo distribution studies in the rat and primate. Saturation binding studies using rat ovary gave K-D and B-max values of 0.21 +/- 0.1 nM and 210 +/- 20 fmol/mg, respectively, for [F-18]FVOZ, and 7.6 +/- 1nMand 293 +/- 12fmol/mg, respectively, for [F-18]FVOO. Organ distribution studies in rats showed the highest accumulation in the adrenal glands, with standardized uptake values (SUVs) of 15 to 20, followed by ovaries and liver with SUVs of approximately 5. Ex vivo and in vitro autoradiography of the rat brain showed specific binding of both [F-18]FVOZ and [F-18]FVOO mainly in the amygdala. Positron emission tomography (PET) studies were performed in the Rhesus monkey, and these showed displaceable binding in the amygdala and the hypothalamus preoptic area. The PET images were also analyzed using masked volume-wise principal component analysis. These studies suggest that [F-18]FVOZ might be a suitable tracer for the study of aromatase in vitro and in vivo, and could be an alternative to [C-11]vorozole in human PET studies.

  • 47. Henschel, Henning
    et al.
    Kloeckner, Jan-Peter
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Prosenc, Marc H.
    Computational and structural studies on the complexation of cobalt(II) acetate by water and pyridine2012In: Journal of Molecular Structure, ISSN 0022-2860, E-ISSN 1872-8014, Vol. 1007, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Four different complexes of the cobalt(II) acetate-pyridine-water system were obtained as dominant species by crystallization from a series of dichloromethane and toluene solutions. The complexes were characterized by terms of X-ray crystal structure determination. Factors in solution properties leading to crystallization of certain complexes are discussed. Furthermore, trends in terms of structure and binding energies in a systematic series of mononuclear cobalt(II) complexes were studied using density functional calculations.

  • 48. Huang, Shan
    et al.
    Nilsson, Per H.
    Sandholm, Kerstin
    Elmlund, Louise
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Regulation of complement in whole blood by heparin molecularly imprinted polymer particles2012In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 217, no 11, p. 1199-1199Article in journal (Other academic)
  • 49.
    Jafri, Hassan M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Löfås, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Jonas, Fransson
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Blom, Tobias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Grigoriev, Anton
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Wallner, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Physical Organic Chemistry.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Leifer, Klaus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Identification of vibrational signatures from short chains of interlinked molecule-nanoparticle junctions obtained by inelastic electron tunnelling spectroscopy2013In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 5, no 11, p. 4673-4677Article in journal (Refereed)
    Abstract [en]

    Short chains containing a series of metal- molecule-nanoparticle nanojunctions are a nano-materials system with the potential to give electrical signatures close to those from single molecule experiments while enabling to build portable devices on a chip. Inelastic electron tunnelling spectroscopy (IETS) measurements provide one of the most characteristic electrical signals of single and few molecules. In interlinked molecule-nanoparticle (NP) chains containing of typically 5-7 molecules in a chain, the spectrum is expected to be a superposition of the vibrational signature of individual molecules. We have established a stable and reproducible molecule-AuNP multi-junction by placing few 1,8-octanedithiol (ODT) molecules into a versatile and portable nanoparticle-nanoelectrode platform and measured for the first time vibrational molecular signatures complex and coupled few-molecule-NP junctions. From quantum transport calculations, we model the IETS spectra and identify vibrational modes as well as the number of molecules contributing to the electron transport in the measured spectra.

  • 50.
    Jafri, Syed Hassan Mujtaba
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Blom, Tobias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Wallner, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Leifer, Klaus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Stability optimisation of molecular electronic devices based on nanoelectrode-nanoparticle bridge platform in air and different storage liquids2014In: Journal of nanoparticle research, ISSN 1388-0764, E-ISSN 1572-896X, Vol. 16, no 12, p. 2811-Article in journal (Refereed)
    Abstract [en]

    The long-term stability of metal nanoparticle-molecule junctions in molecular electronic devices based on nanoelectrodes (NEL) is a major challenge in the effort to bring related molecular electronic devices to application. To optimize the reproducibility of molecular electronic nanodevices, the time-dependent modification of such junctions as exposed to different media needs to be known. Here, we have studied (1) the stability of Au-NEL and (2) the electrical stability of molecule-Au nanoparticle (AuNP) junctions themselves with the molecule being 1,8-octanedithiol (ODT). Both the NELs only and the junctions were exposed to air and liquids such as deionized water, tetrahydrofuran, toluene and tetramethylethylenediamine (TMEDA) over a period of 1 month. The nanogaps remained stable in width when stored in either deionized water or toluene, whereas the current through 1,8-octanedithiol-NP junctions remained most stable when stored in TMEDA as compared to other solvents. Although it is difficult to follow the chemical processes in such devices in the 10-nm range with analytical methods, the behavior can be interpreted from known interactions of solvent molecules with electrodes and ODT.

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