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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
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    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.
    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.

  • 6.
    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.

  • 7.
    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
    Show others...
    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
    Show others...
    (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.
    Show others...
    (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
  • 8.
    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.

  • 9.
    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
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    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
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    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
  • 10.
    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.

  • 11. 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.

  • 12. Lindgren, Cecilia
    et al.
    Andersson, Ida E.
    Berg, Lotta
    Dobritzsch, Doreen
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Ge, Changrong
    Haag, Sabrina
    Uciechowska, Urszula
    Holmdahl, Rikard
    Kihlberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Linusson, Anna
    Hydroxyethylene isosteres introduced in type II collagen fragments substantially alter the structure and dynamics of class II MHC A(q)/glycopeptide complexes2015In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, no 22, p. 6203-6216Article in journal (Refereed)
    Abstract [en]

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

  • 13.
    Löfås, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Jahn, B. O.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Wärnå, John
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Emanuelsson, Rikard
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    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.
    A computational study of potential molecular switches that exploit Baird's rule on excited-state aromaticity and antiaromaticity2014In: Faraday discussions (Online), ISSN 1359-6640, E-ISSN 1364-5498, Vol. 174, p. 105-124Article in journal (Refereed)
    Abstract [en]

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

  • 14.
    Miller, Philip W.
    et al.
    Department of Chemistry, Imperial College London, London, UK.
    Kato, Koichi
    Department of Molecular Imaging, National Centre of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
    Långstrom, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Carbon-11, Nitrogen-13, and Oxygen-15 Chemistry: An Introduction to Chemistry with Short-Lived Radioisotopes2015In: The Chemistry of Molecular Imaging / [ed] Nicholas Long and Wing-Tak Wong, Wiley-Blackwell, 2015, p. 79-103Chapter in book (Refereed)
    Abstract [en]

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

  • 15.
    Norrehed, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Johansson, Henrik
    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.
    Improved stereochemical analysis of conformationally flexible diamines by binding to a bisporphyrin molecular clip2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 43, p. 14631-14638Article in journal (Refereed)
    Abstract [en]

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

  • 16.
    Norrehed, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Synthetical Organic Chemistry.
    Polavarapu, Prasad
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Yang, Wenzhi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Gogoll, Adolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Conformational restriction of flexible molecules in solution by a semirigid bis-porphyrin molecular tweezer2013In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 69, no 34, p. 7131-7138Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Pershagen, Elias
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Development and Multicolor Imaging Applications of Lanthanide-Based Luminescent Probes2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

     

    List of papers
    1. A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes
    Open this publication in new window or tab >>A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes
    2013 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 9, p. 3099-3109Article, review/survey (Refereed) Published
    Abstract [en]

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

    Keywords
    coumarins, cyclen, europium, fluorescent probes, lanthanides, reactive oxygen species
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-197616 (URN)10.1002/chem.201203957 (DOI)000315142300022 ()
    Available from: 2013-04-01 Created: 2013-04-01 Last updated: 2017-12-06Bibliographically approved
    2. Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation
    Open this publication in new window or tab >>Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation
    2012 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 24, p. 9832-9835Article in journal (Refereed) Published
    Abstract [en]

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

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-177592 (URN)10.1021/ja3004045 (DOI)000305358900002 ()
    Available from: 2012-07-16 Created: 2012-07-16 Last updated: 2017-12-07Bibliographically approved
    3. Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes
    Open this publication in new window or tab >>Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes
    2015 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 54, no 6, p. 1787-1790Article in journal (Refereed) Published
    National Category
    Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-236755 (URN)10.1002/anie.201408560R1 (DOI)000349209200016 ()25504579 (PubMedID)
    Available from: 2014-11-22 Created: 2014-11-22 Last updated: 2017-12-05Bibliographically approved
    4. Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition
    Open this publication in new window or tab >>Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition
    2012 (English)In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 41, no 25, p. 7660-7669Article in journal (Refereed) Published
    Abstract [en]

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

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-178965 (URN)10.1039/c2dt30569k (DOI)000304912000025 ()
    Available from: 2012-08-03 Created: 2012-08-02 Last updated: 2017-12-07Bibliographically approved
  • 18.
    Pershagen, Elias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Borbas, K. Eszter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes2015In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 54, no 6, p. 1787-1790Article in journal (Refereed)
  • 19. Ramapanicker, Ramesh
    et al.
    Sun, Xiaojiao
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Viljanen, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Baltzer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Powerful binders for the D-dimer by conjugation of the GPRP peptide to polypeptides from a designed set: illustrating a general route to new binders for proteins2013In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 24, no 1, p. 17-25Article in journal (Refereed)
    Abstract [en]

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

  • 20.
    Rosenberg, Martin
    et al.
    Department of Chemistry, University of Copenhagen.
    Dahlstrand, Christian
    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.
    Kilså, Kristine
    Department of Chemistry, University of Copenhagen.
    Manipulation of Excited State Energies in Fulvenic MoleculesManuscript (preprint) (Other academic)
  • 21.
    Sun, Xiaojiao
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    High Affinity Synthetic Molecular Binders for Proteins: Design, Synthesis and Evaluation2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

     

    List of papers
    1. Powerful binders for the D-dimer by conjugation of the GPRP peptide to polypeptides from a designed set: illustrating a general route to new binders for proteins
    Open this publication in new window or tab >>Powerful binders for the D-dimer by conjugation of the GPRP peptide to polypeptides from a designed set: illustrating a general route to new binders for proteins
    2013 (English)In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 24, no 1, p. 17-25Article in journal (Refereed) Published
    Abstract [en]

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

    National Category
    Organic Chemistry Other Chemistry Topics
    Identifiers
    urn:nbn:se:uu:diva-183200 (URN)10.1021/bc300186z (DOI)000313933700003 ()
    Available from: 2012-10-23 Created: 2012-10-23 Last updated: 2017-12-07Bibliographically approved
    2. A synthetic polypeptide conjugate from a 42-residue polypeptide and salicylhydroxamic acid binds human myeloperoxidase with high affinity
    Open this publication in new window or tab >>A synthetic polypeptide conjugate from a 42-residue polypeptide and salicylhydroxamic acid binds human myeloperoxidase with high affinity
    2012 (English)In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 18, no 12, p. 731-739Article in journal (Refereed) Published
    Abstract [en]

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

    National Category
    Organic Chemistry Other Chemistry Topics
    Identifiers
    urn:nbn:se:uu:diva-183195 (URN)10.1002/psc.2459 (DOI)000311053700003 ()
    Available from: 2012-10-23 Created: 2012-10-23 Last updated: 2017-12-07Bibliographically approved
    3. Polypeptide conjugates that bind chitinases
    Open this publication in new window or tab >>Polypeptide conjugates that bind chitinases
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

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

    National Category
    Organic Chemistry Other Chemistry Topics Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-183201 (URN)
    Available from: 2012-10-23 Created: 2012-10-23 Last updated: 2012-11-23
  • 22.
    Sun, Xiaojiao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Winander, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Karlsson, Magnus
    Department of forest mycology and pathology, swedish university of agricultural sciences, sweden.
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Stenlid, Jan
    Department of forest mycology and pathology, swedish university of agricultural sciences, sweden.
    Baltzer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Polypeptide conjugates that bind chitinasesManuscript (preprint) (Other academic)
    Abstract [en]

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

  • 23.
    Sun, Xiaojiao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Yang, Jie
    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, Physical Organic Chemistry.
    Baltzer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    A synthetic polypeptide conjugate from a 42-residue polypeptide and salicylhydroxamic acid binds human myeloperoxidase with high affinity2012In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 18, no 12, p. 731-739Article in journal (Refereed)
    Abstract [en]

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

  • 24.
    Tong, Hui
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Dahlstrand, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Villaume, Sebastien
    Jun, Zhu
    Piqueras, Mari Carmen
    University of Valencia.
    Crespo, Raül
    University of Valencia.
    Ottosson, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Fulvenes: Compounds for which the Singlet-Triplet Energy Gaps are Closely Linked to Aromaticity and  Aromaticity DifferencesManuscript (preprint) (Other academic)
  • 25.
    Tundup, Smanla
    et al.
    Univ Georgia, Dept Infect Dis, Coll Vet Med, Athens, GA 30602 USA.;Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA..
    Srivastava, Leena
    Univ Georgia, Dept Infect Dis, Coll Vet Med, Athens, GA 30602 USA..
    Norberg, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Watford, Wendy
    Univ Georgia, Dept Infect Dis, Coll Vet Med, Athens, GA 30602 USA..
    Harn, Donald
    Univ Georgia, Dept Infect Dis, Coll Vet Med, Athens, GA 30602 USA.;Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA..
    A Neoglycoconjugate Containing the Human Milk Sugar LNFPIII Drives Anti-Inflammatory Activation of Antigen Presenting Cells in a CD14 Dependent Pathway2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0137495Article in journal (Refereed)
    Abstract [en]

    The milk pentasaccharide LNFPIII has therapeutic action for metabolic and autoimmune diseases and prolongs transplant survival in mice when presented as a neoglycoconjugate. Within LNFPIII is the Lewis(x) trisaccharide, expressed by many helminth parasites. In humans, LNFPIII is found in human milk and also known as stage-specific embryonic antigen-1. LNFPIII-NGC drives alternative activation of macrophages and dendritic cells via NF kappa B activation in a TLR4 dependent mechanism. However, the connection between LNFPIII-NGC activation of APCs, TLR4 signaling and subsequent MAP kinase signaling leading to anti-inflammatory activation of APCs remains unknown. In this study we determined that the innate receptor CD14 was essential for LNFPIII-NGC induction of both ERK and NFkB activation in APCs. Induction of ERK activation by LNFPIII-NGC was completely dependent on CD14/TLR4-Ras-Raf1/TPL2-MEK axis in bone marrow derived dendritic cells (BMDCs). In addition, LNFPIII-NGC preferentially induced the production of Th2 "favoring" chemokines CCL22 and matrix metalloprotease protein-9 in a CD14 dependent manner in BMDCs. In contrast, LNFPIII-NGC induces significantly lower levels of Th1 "favoring" chemokines, MIP1 alpha, MIP1 beta and MIP-2 compared to levels in LPS stimulated cells. Interestingly, NGC of the identical human milk sugar LNnT, minus the alpha 1-3 linked fucose, failed to activate APCs via TLR4/MD2/CD14 receptor complex, suggesting that the alpha 1-3 linked fucose in LNFPIII and not on LNnT, is required for this process. Using specific chemical inhibitors of the MAPK pathway, we found that LNFPIII-NGC induction of CCL22, MMP9 and IL-10 production was dependent on ERK activation. Over all, this study suggests that LNFPIII-NGC utilizes CD14/TLR4-MAPK (ERK) axis in modulating APC activation to produce anti-inflammatory chemokines and cytokines in a manner distinct from that seen for the pro-inflammatory PAMP LPS. These pathways may explain the in vivo therapeutic effect of LNFPIII-NGC treatment for inflammation based diseases.

  • 26.
    Åberg, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Combinatorial synthesis of labelled drugs and PET tracers: synthesis of a focused library of 11C-carbonyl-labelled acrylamides as potential biomarkers of EGFR expression2012In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 55, no 14, p. 477-483Article in journal (Refereed)
    Abstract [en]

    Combinatorial synthesis is extensively used in drug development and lead optimisation. However, this approach has rarely been used for positron emission tomography because of limitations in available technologies. [11C]Carbon monoxide is amenable to combinatorial synthesis in transition-metal-catalysed reactions because it can react with a wide variety of electrophiles and nucleophiles, which opens up the possibilities for combinatorial radiochemistry. Herein, we exemplify the combinatorial approach by 11C-labelling a library of epidermal growth factor receptor inhibitors. The selection of candidates was guided by molecular docking. Epidermal growth factor receptor is overexpressed in a variety of tumours, and it has become an important drug target. The 11C-labelling reactions were performed using four substituted vinyl iodides and three different 4-anilino-6-aminoquinazolines using a palladium-mediated reaction with [11C]carbon monoxide using a single set of reaction conditions. In total, 12 labelled acrylamide derivatives were radiolabelled and obtained in 24–61% decay-corrected radiochemical yield (from [11C]carbon monoxide). Starting from 5.6 GBq [11C]carbon monoxide, 0.85 GBq of formulated N-[4-(3-bromo-phenylamino)-quinazolin-6-yl]-acryl[11C]amide [11C]12da was obtained within 47 min from end of bombardment (specific activity of 60 GBq µmol−1). This strategy is an example of how [11C]carbon monoxide can be utilised in the labelling of libraries of drug candidates and positron emission tomography tracers for in vitro and in vivo testing.

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