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  • 51. Cuéllar-Zuquin, Juliana
    et al.
    Pepino, Ana Julieta
    Fernández Galván, Ignacio
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Rivalta, Ivan
    Aquilante, Francesco
    Garavelli, Marco
    Lindh, Roland
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Segarra-Martí, Javier
    Characterizing Conical Intersections in DNA/RNA Nucleobases with Multiconfigurational Wave Functions of Varying Active Space Size2023Inngår i: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 19, nr 22, s. 8258-8272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We characterize the photochemically relevant conical intersections between the lowest-lying accessible electronic excited states of the different DNA/RNA nucleobases using Cholesky decomposition-based complete active space self-consistent field (CASSCF) algorithms. We benchmark two different basis set contractions and several active spaces for each nucleobase and conical intersection type, measuring for the first time how active space size affects conical intersection topographies in these systems and the potential implications these may have toward their description of photoinduced phenomena. Our results show that conical intersection topographies are highly sensitive to the electron correlation included in the model: by changing the amount (and type) of correlated orbitals, conical intersection topographies vastly change, and the changes observed do not follow any converging pattern toward the topographies obtained with the largest and most correlated active spaces. Comparison across systems shows analogous topographies for almost all intersections mediating population transfer to the dark 1nO/Nπ* states, while no similarities are observed for the "ethylene-like" conical intersection ascribed to mediate the ultrafast decay component to the ground state in all DNA/RNA nucleobases. Basis set size seems to have a minor effect, appearing to be relevant only for purine-based derivatives. We rule out structural changes as a key factor in classifying the different conical intersections, which display almost identical geometries across active space and basis set change, and we highlight instead the importance of correctly describing the electronic states involved at these crossing points. Our work shows that careful active space selection is essential to accurately describe conical intersection topographies and therefore to adequately account for their active role in molecular photochemistry.

  • 52.
    Danelius, Emma
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Andersson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Solution ensemble analysis of macrocycles2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Macrocycles are key drug leads for protein targets with large, flat and featureless binding sites, including protein-protein interfaces.  Due to their conformational flexibility macrocycles typically exist as a mixture of interconverting geometries in solution, and hence cannot be represented by a single, averaged conformation.  This flexibility is a result of continuously forming and breaking a number of weak intramolecular interactions.  The yielded conformations in solution vastly impact the bioactivity, solubility and membrane permeability of the macrocycles.  Therefore, describing their conformational ensembles, as well as the impact of conformation stabilizing weak interactions, is of fundamental importance, and the knowledge gained is directly applicable to medicinal chemistry.

    In order to describe macrocycle structure and dynamics, time-averaged solution spectroscopic data has to be deconvoluted into the present conformations along with their respective probability.  We have studied the solution ensembles of a series of macrocycles using the NAMFIS (NMR analysis of molecular flexibility in solution) algorithm.  This combined computational and spectroscopic ensembles analysis deconvolutes time averaged NMR data by identifying the real conformations and assigning them with their molar fractions.  Theoretical ensembles were predicted using Monte Carlo conformational searches with molecular mechanics minimization.  The generated ensembles, typically containing 40-150 conformers, were then used together with experimental NOE-based distances and J-coupling-based dihedral angles to identify the molar fractions of the conformations present in solution.

    We applied this technique to gain understanding of weak chemical interactions in a biologically relevant environment, by analyzing macrocyclic β-hairpin peptides.  The stabilizing effect provided by an interstrand weak interaction, as compared to a reference peptide lacking this interaction, was quantified through ensemble analysis.  We have shown that a single interstrand hydrogen [1,2,3] or halogen bond (Figure 1) [4], can significantly influence the folding, and increase the population of the folded conformation by up to 40%.  The NMR results were corroborated by CD-spectroscopy and MD-calculations.

  • 53.
    Danelius, Emma
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Andersson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Jarvoll, Patrik
    Lood, Kajsa
    Gräfenstein, Jürgen
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Halogen bond promoted peptide folding2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We have developed a β-hairpin peptide model system that permits quantitative evaluation of weak interactions in a biologically relevant environment. The influence of a single weak force was measured by detection of the extent to which it modulates peptide folding. Initially we have optimized a β-hairpin model system, using the simpler to synthesize hydrogen bonding analogues of our target system encompassing halogen bond donor and acceptor sites [1,2,3]. Using a combined computational and NMR spectroscopic ensemble analysis, we have quantified the stabilizing effect of a single secondary interaction on the folded β-hairpin conformation. We have demonstrated that a chlorine centered halogen bond, formed between two amino acid side chains in an interstrand manner (Figure 1), provides a conformational stabilization comparable to the analogous hydrogen bond [4]. The negative control, i.e. the peptide containing a noninteracting aliphatic side chain, was ~30% less folded than the hydrogen and halogen bonding analogues, revealing the high impact of the interstrand interaction on folding. The experimental results are corroborated by computation on the DFT level. This is the first report of quantification of a conformation-stabilizing chlorine centered halogen bond in a peptide system.  

  • 54.
    Danelius, Emma
    et al.
    University of Gothenburg, SE-41296 Gothenburg, Sweden.
    Andersson, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. University of Gothenburg, SE-41296 Gothenburg, Sweden.
    Jarvoll, Patrik
    University of Gothenburg, SE-41296 Gothenburg, Sweden.
    Lood, Kajsa
    University of Gothenburg, SE-41296 Gothenburg, Sweden.
    Gräfenstein, Jürgen
    University of Gothenburg, SE-41296 Gothenburg, Sweden.
    Erdélyi, Máté
    University of Gothenburg, SE-41296 Gothenburg, Sweden.
    Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation2017Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Biochemistry, ISSN 0006-2960, Vol. 56, nr 25, s. 3265-3272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Halogen bonding is a weak chemical force that has so far mostly found applications in crystal engineering. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a β-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.

  • 55.
    Danelius, Emma
    et al.
    Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.;Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA..
    Bu, Guanhong
    Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA..
    Wieske, Lianne H. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gonen, Tamir
    Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.;Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.;Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA..
    MicroED as a Powerful Tool for Structure Determination of Macrocyclic Drug Compounds Directly from Their Powder Formulations2023Inngår i: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 18, nr 12, s. 2582-2589Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Macrocycles are important drug leads with many advantages including the ability to target flat and featureless binding sites as well as to act as molecular chameleons and thereby reach intracellular targets. However, due to their complex structures and inherent flexibility, macrocycles are difficult to study structurally, and there are limited structural data available. Herein, we use the cryo-EM method MicroED to determine the novel atomic structures of several macrocycles that have previously resisted structural determination. We show that structures of similar complexity can now be obtained rapidly from nanograms of material and that different conformations of flexible compounds can be derived from the same experiment. These results will have an impact on contemporary drug discovery as well as natural product exploration.

    Fulltekst (pdf)
    fulltext
  • 56.
    Danelius, Emma
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Poongavanam, Vasanthanathan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Peintner, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Wieske, Lianne H. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Solution Conformations Explain the Chameleonic Behaviour of Macrocyclic Drugs2020Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 26, nr 23, s. 5231-5244Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It has been hypothesised that drugs in the chemical space "beyond the rule of 5" (bRo5) must behave as molecular chameleons to combine otherwise conflicting properties, including aqueous solubility, cell permeability and target binding. Evidence for this has, however, been limited to the cyclic peptide cyclosporine A. Herein, we show that the non-peptidic and macrocyclic drugs roxithromycin, telithromycin and spiramycin behave as molecular chameleons, with rifampicin showing a less pronounced behaviour. In particular roxithromycin, telithromycin and spiramycin display a marked, yet limited flexibility and populate significantly less polar and more compact conformational ensembles in an apolar than in a polar environment. In addition to balancing of membrane permeability and aqueous solubility, this flexibility also allows binding to targets that vary in structure between species. The drugs' passive cell permeability correlates to their 3D polar surface area and corroborate two theoretical models for permeability, developed for cyclic peptides. We conclude that molecular chameleonicity should be incorporated in the design of orally administered drugs in the bRo5 space.

  • 57.
    Daniel, Umereweneza
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Yoseph, Atilaw
    Stefan, Peintner
    Anastasia, Rudenko
    Catarina, Bourgard
    Ruisheng, Xiong
    Théoneste, Muhizi
    Per, Sunnerhagen
    Gogoll, A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Macrocyclic pyrrolizidine alkaloids and silphiperfolanol angelate esters from Senecio mannii.Manuskript (preprint) (Annet vitenskapelig)
  • 58.
    Delcey, Mickael G
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi.
    Couto, Rafael Carvalho
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi. Uppsala Univ, KTH Royal Inst Technol, Dept Theoret Chem & Biol, Sch Chem Biotechnol & Hlth, SE-10691 Stockholm, Sweden..
    Sorensen, Lasse Kragh
    KTH Royal Inst Technol, Dept Theoret Chem & Biol, Sch Chem Biotechnol & Hlth, SE-10691 Stockholm, Sweden..
    Fernández Galván, Ignacio
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Guo, Meiyuan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi.
    Lindh, Roland
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Uppsala Univ, Uppsala Ctr Computat Chem UC3, POB 576, SE-75123 Uppsala, Sweden..
    Lundberg, Marcus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Teoretisk kemi.
    Exact semi-classical light-matter interaction operator applied to two-photon processes with strong relativistic effects2020Inngår i: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 153, nr 2, artikkel-id 024114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    X-ray processes involve interactions with high-energy photons. For these short wavelengths, the perturbing field cannot be treated as constant, and there is a need to go beyond the electric-dipole approximation. The exact semi-classical light-matter interaction operator offers several advantages compared to the multipole expansion such as improved stability and ease of implementation. Here, the exact operator is used to model x-ray scattering in metal K pre-edges. This is a relativistic two-photon process where absorption is dominated by electric-dipole forbidden transitions. With the restricted active space state-interaction approach, spectra can be calculated even for the multiconfigurational wavefunctions including second-order perturbation. However, as the operator itself depends on the transition energy, the cost for evaluating integrals for hundreds of thousands unique transitions becomes a bottleneck. Here, this is solved by calculating the integrals in a molecular-orbital basis that only runs over the active space, combined with a grouping scheme where the operator is the same for close-lying transitions. This speeds up the calculations of single-photon processes and is critical for the modeling of two-photon scattering processes. The new scheme is used to model K alpha resonant inelastic x-ray scattering of iron-porphyrin complexes with relevance to studies of heme enzymes, for which the total computational time is reduced by several orders of magnitude with an effect on transition intensities of 0.1% or less. d (c) 2020 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

    Fulltekst (pdf)
    FULLTEXT01
  • 59.
    Delgado, Alexis A. A.
    et al.
    Southern Methodist Univ, Dept Chem, Computat & Theoret Chem Grp CATCO, 3215 Daniel Ave, Dallas, TX 75275 USA..
    Sethio, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Munar, Ipek
    Bogazici Univ, Dept Chem, TR-34342 Istanbul, Turkey..
    Aviyente, Viktorya
    Bogazici Univ, Dept Chem, TR-34342 Istanbul, Turkey..
    Kraka, Elfi
    Southern Methodist Univ, Dept Chem, Computat & Theoret Chem Grp CATCO, 3215 Daniel Ave, Dallas, TX 75275 USA..
    Local vibrational mode analysis of ion-solvent and solvent-solvent interactions for hydrated Ca2+ clusters2020Inngår i: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 153, nr 22, artikkel-id 224303Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hydrated calcium ion clusters have received considerable attention due to their essential role in biological processes such as bone development, hormone regulation, blood coagulation, and neuronal signaling. To better understand the biological role of the cation, the interactions between the Ca2+ ions and water molecules have been frequently investigated. However, a quantitative measure for the intrinsic Ca-O (ion-solvent) and intermolecular hydrogen bond (solvent-solvent) interactions has been missing so far. Here, we report a topological electron density analysis and a natural population analysis to analyze the nature of these interactions for a set of 14 hydrated calcium clusters via local mode stretching force constants obtained at the omega B97X-D/6-311++G(d,p) level of theory. The results revealed that the strength of inner Ca-O interactions for <mml:mfenced close="]" open="["Ca(H2O)n2+ (n = 1-8) clusters correlates with the electron density. The application of a second hydration shell to ["Ca(H2O)n2+ (n = 6-8) clusters resulted in stronger Ca-O interactions where a larger electron charge transfer between lp(O) of the first hydration shell and the lower valence of Ca prevailed. The strength of the intermolecular hydrogen bonds, formed between the first and second hydration shells, became stronger when the charge transfers between hydrogen bond (HB) donors and HB acceptors were enhanced. From the local mode stretching force constants of implicitly and explicitly solvated Ca2+, we found the six-coordinated cluster to possess the strongest stabilizations, and these results prove that the intrinsic bond strength measures for Ca-O and hydrogen bond interactions form new effective tools to predict the coordination number for the hydrated calcium ion clusters.

  • 60.
    Delgado, Alexis Antoinette Ann
    et al.
    Southern Methodist Univ, Dept Chem, Computat & Theoret Chem Grp, 3215 Daniel Ave, Dallas, TX 75275 USA..
    Sethio, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kraka, Elfi
    Southern Methodist Univ, Dept Chem, Computat & Theoret Chem Grp, 3215 Daniel Ave, Dallas, TX 75275 USA..
    Assessing the Intrinsic Strengths of Ion-Solvent and Solvent-Solvent Interactions for Hydrated Mg2+ Clusters2021Inngår i: INORGANICS, ISSN 2304-6740, Vol. 9, nr 5, artikkel-id 31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Information resulting from a comprehensive investigation into the intrinsic strengths of hydrated divalent magnesium clusters is useful for elucidating the role of aqueous solvents on the Mg2+ ion, which can be related to those in bulk aqueous solution. However, the intrinsic Mg-O and intermolecular hydrogen bond interactions of hydrated magnesium ion clusters have yet to be quantitatively measured. In this work, we investigated a set of 17 hydrated divalent magnesium clusters by means of local vibrational mode force constants calculated at the omega B97X-D/6-311++G(d,p) level of theory, where the nature of the ion-solvent and solvent-solvent interactions were interpreted from topological electron density analysis and natural population analysis. We found the intrinsic strength of inner shell Mg-O interactions for [Mg(H2O)(n)](2+) (n = 1-6) clusters to relate to the electron density at the bond critical point in Mg-O bonds. From the application of a secondary hydration shell to [Mg(H2O)(n)](2+) (n = 5-6) clusters, stronger Mg-O interactions were observed to correspond to larger instances of charge transfer between the lp(O) orbitals of the inner hydration shell and the unfilled valence shell of Mg. As the charge transfer between water molecules of the first and second solvent shell increased, so did the strength of their intermolecular hydrogen bonds (HBs). Cumulative local vibrational mode force constants of explicitly solvated Mg2+, having an outer hydration shell, reveal a CN of 5, rather than a CN of 6, to yield slightly more stable configurations in some instances. However, the cumulative local mode stretching force constants of implicitly solvated Mg2+ show the six-coordinated cluster to be the most stable. These results show that such intrinsic bond strength measures for Mg-O and HBs offer an effective way for determining the coordination number of hydrated magnesium ion clusters.

    Fulltekst (pdf)
    FULLTEXT01
  • 61.
    Devaraj, Karthik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ruthenium-catalyzed C-H Functionalization of (Hetero)arenes2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis concerned about the Ru-catalyzed C-H functionalizations on the synthesis of 2-arylindole unit, silylation of heteroarenes and preparation of aryne precursor.

    In the first project, we developed the Ru-catalyzed C2-H arylation of N-(2-pyrimidyl) indoles and pyrroles with nucleophilic arylboronic acids under oxidative conditions. Wide variety of arylboronic acids afforded the desired product in excellent yield regardless of the substituents or functional group electronic nature. Electron-rich heteroarenes are well suited for this method than electron-poor heteroarenes. Halides such as bromide and iodide also survived, further derivatisation of the halide is shown by Heck alkenylation. In order to find catalytic on-cycle intermediate extensive mechanistic experiments have been carried out by preparing presumed ruthenacyclic complexes and C-H/D exchange reactions. It suggested that para-cymene ligand is not present in the catalytic on-cycle intermediate and we suspect that metalation occurs with electrophilic ruthenium center via SEAr mechanism.

    In the second project, we developed the Ru-catalyzed silylation of gramine, tryptamine and their congeners using silanes as coupling partner. The transformation worked well with many different silanes. Regarding directing group, nitrogen atom containing directing groups are more favoured than the oxygen containing directing groups. Wide range of gramines and tryptamines also yielded the desired product in poor to excellent yield. At higher temperature, albeit in low yield, undirected silylation occurred. In order to get some insights about the reaction pathway of the silylation C-H/D exchange experiments were performed, and it revealed the possibility of C4-H activation of gramines by an electron rich metal- Si-H/D experiments showed Si-H activation by Ru is easy.

    In the final project, we presented the closely related aryne precursors from arylboronic acids via Ru-catalyzed C-H silylation of arylboronates and their selective oxidation. Worthy of note, the aryne capture products obtained from arylboronic acids in a single purification.

    Delarbeid
    1. Ru-Catalysed C-H Arylation of Indoles and Pyrroles with Boronic Acids: Scope and Mechanistic Studies
    Åpne denne publikasjonen i ny fane eller vindu >>Ru-Catalysed C-H Arylation of Indoles and Pyrroles with Boronic Acids: Scope and Mechanistic Studies
    Vise andre…
    2015 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, nr 14, s. 5380-5386Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The Ru-catalysed C2-H arylation of indoles and pyrroles by using boronic acids under oxidative conditions is reported. This reaction can be applied to tryptophan derivatives and tolerates a wide range of functional groups on both coupling partners, including bromides and iodides, which can be further derivatised selectively. New indole based ruthenacyclic complexes are described and investigated as possible intermediates in the reaction. Mechanistic studies suggest the on-cycle intermediates do not possess a para-cymene ligand and that the on-cycle metalation occurs through an electrophilic attack by the Ru centre.

    Emneord
    catalysis, C-H activation, heterocycles, reaction mechanisms, ruthenium
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-252711 (URN)10.1002/chem.201405931 (DOI)000352504500017 ()25689052 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council
    Tilgjengelig fra: 2015-05-18 Laget: 2015-05-11 Sist oppdatert: 2017-12-04bibliografisk kontrollert
    2. Ru-Catalysed C-H Silylation of Gramines, Tryptamines and their Congeners
    Åpne denne publikasjonen i ny fane eller vindu >>Ru-Catalysed C-H Silylation of Gramines, Tryptamines and their Congeners
    2016 (engelsk)Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, nr 34, s. 5868-5871Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Selective Ru-catalysed C2–H silylation of heteroarenes is presented. The transformation works with or without directing group assistance and requires no protecting groups. Gramines and tryptamines may be converted efficiently whilst avoiding deleterious elimination side-reactions. Mechanistic studies reveal an unusual activation of the indole C4–H bond by an electron-rich metal.

    sted, utgiver, år, opplag, sider
    Royal Society of Chemistry, 2016
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-286545 (URN)10.1039/C6CC00803H (DOI)000374396500022 ()27050747 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council
    Tilgjengelig fra: 2016-04-20 Laget: 2016-04-20 Sist oppdatert: 2017-11-30bibliografisk kontrollert
    3. Synthesis of aryne precursors via transition metal-catalyzed C-H silylation
    Åpne denne publikasjonen i ny fane eller vindu >>Synthesis of aryne precursors via transition metal-catalyzed C-H silylation
    2014 (engelsk)Inngår i: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 248Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-247860 (URN)000349167403600 ()
    Konferanse
    248th National Meeting of the American-Chemical-Society (ACS), AUG 10-14, 2014, San Francisco, CA
    Tilgjengelig fra: 2015-03-26 Laget: 2015-03-24 Sist oppdatert: 2020-06-05bibliografisk kontrollert
    Fulltekst (pdf)
    fulltext
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  • 62.
    Devaraj, Karthik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ingner, Fredric
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Sollert, Carina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gates, Paul J.
    Univ Bristol, Sch Chem, Cantocks Close, Bristol BS8 1TS, Avon, England.
    Orthaber, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Syntetisk molekylär kemi.
    Pilarski, Lukasz T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Arynes and Their Precursors from Arylboronic Acids via Catalytic C-H Silylation2019Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 84, nr 9, s. 5863-5871Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new, operationally simple approach is presented to access arynes and their fluoride-activated precursors based on Ru-catalyzed C-H silylation of arylboronates. Chromatographic purification may be deferred until after aryne capture, rendering the arylboronates de facto precursors. Access to various new arynes and their derivatives is demonstrated, including, for the first time, those based on a 2,3-carbazolyne and 2,3-fluorenyne core, which pave the way for novel derivatizations of motifs relevant to materials chemistry.

  • 63.
    Devaraj, Karthik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Sollert, Carina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gates, P. J.
    Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England.
    Pilarski, Lukasz
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ru-Catalysed C-H Silylation of Gramines, Tryptamines and their Congeners2016Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, nr 34, s. 5868-5871Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Selective Ru-catalysed C2–H silylation of heteroarenes is presented. The transformation works with or without directing group assistance and requires no protecting groups. Gramines and tryptamines may be converted efficiently whilst avoiding deleterious elimination side-reactions. Mechanistic studies reveal an unusual activation of the indole C4–H bond by an electron-rich metal.

  • 64.
    Dickman, Rachael
    et al.
    UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England.
    Danelius, Emma
    Swedish NMR Ctr, Medicinaregatan 5, S-40530 Gothenburg, Sweden.
    Mitchell, Serena A.
    UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England.
    Hansen, D. Flemming
    UCL, Div Biosci, Inst Struct & Mol Biol, Gower St, London WC1E 6BT, England.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Swedish NMR Ctr, Medicinaregatan 5, S-40530 Gothenburg, Sweden.
    Tabor, Alethea B.
    UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England.
    A Chemical Biology Approach to Understanding Molecular Recognition of Lipid II by Nisin(1-12): Synthesis and NMR Ensemble Analysis of Nisin(1-12) and Analogues2019Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 25, nr 64, s. 14572-14582Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Natural products that target lipid II, such as the lantibiotic nisin, are strategically important in the development of new antibacterial agents to combat the rise of antimicrobial resistance. Understanding the structural factors that govern the highly selective molecular recognition of lipid II by the N-terminal region of nisin, nisin(1-12), is a crucial step in exploiting the potential of such compounds. In order to elucidate the relationships between amino acid sequence and conformation of this bicyclic peptide fragment, we have used solid-phase peptide synthesis to prepare two novel analogues of nisin(1-12) in which the dehydro residues have been replaced. We have carried out an NMR ensemble analysis of one of these analogues and of the wild-type nisin(1-12) peptide in order to compare the conformations of these two bicyclic peptides. Our analysis has shown the effects of residue mutation on ring conformation. We have also demonstrated that the individual rings of nisin(1-12) are pre-organised to an extent for binding to the pyrophosphate group of lipid II, with a high degree of flexibility exhibited in the central amide bond joining the two rings.

    Fulltekst (pdf)
    fulltext
  • 65.
    Diwakarla, Shanti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nylander, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Grönbladh, Alfhild
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Reddy Vanga, Sudarsana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Shamsudin Khan, Yasmin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Gutierrez-de-Teran, Hugo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Ng, Leelee
    Pham, Vi
    Sävmarker, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Lundback, Thomas
    Jenmalm-Jensen, Annika
    Andersson, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Engen, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Rosenström, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Åqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Yeen Chai, Siew
    Hallberg, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Binding to and Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Macrocyclic Disulfides Enhances Spine Density2016Inngår i: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, Vol. 89, nr 4, s. 413-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Angiotensin IV (Ang IV) and related peptide analogues, as well as non-peptide inhibitors of insulin-regulated aminopeptidase (IRAP), have previously been shown to enhance memory and cognition in animal models. Furthermore, the endogenous IRAP substrates oxytocin and vasopressin are known to facilitate learning and memory. In this study, the two recently synthesized 13-membered macrocylic competitive IRAP inhibitors HA08 and HA09, which were designed to mimic the N-terminal of oxytocin and vasopressin, were assessed and compared based on their ability to bind to the IRAP active site, and alter dendritic spine density in rat hippocampal primary cultures. The binding modes of the IRAP inhibitors HA08, HA09 and of Ang IV in either the extended or γ-turn conformation at the C-terminal to human IRAP were predicted by docking and molecular dynamics (MD) simulations. The binding free energies calculated with the linear interaction energy (LIE) method, which are in excellent agreement with experimental data and simulations, have been used to explain the differences in activities of the IRAP inhibitors, both of which are structurally very similar, but differ only with regard to one stereogenic center. In addition, we show that HA08, which is 100-fold more potent than the epimer HA09, can enhance dendritic spine number and alter morphology, a process associated with memory facilitation. Therefore, HA08, one of the most potent IRAP inhibitors known today, may serve as a suitable starting point for medicinal chemistry programs aided by MD simulations aimed at discovering more drug-like cognitive enhancers acting via augmenting synaptic plasticity.

  • 66.
    Doak, Bradley C.
    et al.
    Monash Univ, Dept Med Chem, MIPS, 381 Royal Parade, Parkville, Vic 3052, Australia.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Cyclophilin Succumbs to a Macrocyclic Chameleon2018Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, nr 21, s. 9469-9472Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Targets that have large and groove-shaped binding sites, such as cyclophilin, are difficult to drug with small molecules. Macrocycles of natural product origin can be ideal starting points for such targets as illustrated by the transformation of sanglifehrin A into an orally bioavailable potential candidate drug. Optimization benefits from development of convergent, modular synthetic routes in combination with structure and property based methods for lead optimization.

  • 67.
    Doak, Bradley C.
    et al.
    Monash Univ, MIPS, Dept Med Chem, Parkville, Vic, Australia..
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Drug discovery beyond the rule of 5-Opportunities and challenges2017Inngår i: Expert Opinion on Drug Discovery, ISSN 1746-0441, E-ISSN 1746-045X, Vol. 12, nr 2, s. 115-119Artikkel i tidsskrift (Fagfellevurdert)
  • 68.
    Dollevoet, Kim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    C-H activation of indoles catalyzed by a ruthenium-complex: Synthesis of 2-3-hexene-1-(pyrimidin-2-yl)1H-indole2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Fulltekst (pdf)
    fulltext
  • 69.
    Doloczki, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Development of fluorescent probes based on the benzothiadiazole scaffold2021Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Fluorescent probes are valuable imaging tools for studying biological processes on a cellular level. While antibody-based fluorescence imaging typically requires fixation of cells, small-molecule fluorophores have the advantage that they can often be used for live-cell imaging. In the last decade, the electron-poor 2,1,3-benzothiadiazole scaffold has impressively emerged as a useful acceptor fragment in fluorescent probes for bioimaging (and for applications in organic electronics). Some of the reported benzothiadiazole-based fluorophores allow for specific imaging of intracellular lipid droplets, which are lipid-rich organelles that can be found in various types of cells. Dysregulated lipid metabolism and the accumulation of lipid droplets are strongly associated with diseases such as obesity, diabetes, and cancer. For instance, lipid droplets play an important role in the energy metabolism of cancer cells. Fluorescence imaging of lipid droplets can therefore be used for studying various types of cancer and is considered as a biomarker for cancer diagnosis and prognosis.

    In this work, various donor-acceptor fluorophores based on the benzothiadiazole scaffold were synthesized. Extensive photophysical characterization in different solvents shed light on the structure-property relationships of these compounds. For instance, dual emission from the locally excited state and the intramolecular charge transfer state was observed for many compounds – the equilibrium of which was strongly dependent on the electronic nature of the substituent and the polarity of the solvent. Cell studies revealed five promising new compounds for fluorescence imaging of lipid droplets in cancer cells. One of these molecules featured an off-on fluorescence behavior in hypoxic (i.e., oxygen deficient) cancer cells. Calculation of octanol/water partition coefficients (logP) revealed that only the most lipophilic compounds in this study (logP ≥ 4) reliably accumulated in, and stained, lipid droplets.

  • 70.
    Doloczki, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Shining Light on Benzothiadiazoles and Indolines: Photophysical Properties and Cancer Cell Imaging2023Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Fluorescent molecules, also called fluorophores, play an important role in life sciences. As crucial tools in fluorescence microscopy, they can be used to study biological processes on a cellular level, which is a fundamental aspect of cancer research. Depending on the specific research question, the requirements for fluorophores can be very diverse. Expanding the toolbox of fluorescent probes can therefore contribute to the possibilities of fluorescence imaging in general, especially since no single fluorophore is perfect for all applications.

    In this thesis, donor-acceptor fluorophores based on two different core structures, 2,1,3-benzothiadiazole and indoline, were investigated. The compounds were photophysically studied by steady-state absorption and fluorescence spectroscopy and examined in fluorescence cell microscopy.

    Monosubstituted benzothiadiazole derivatives with nitrogen-based substituents were synthesized and photophysically studied in various solvents. Fluorescence microscopy experiments revealed three promising new compounds that specifically stain lipid droplets in cancer cells. Lipid droplets are interesting cellular targets for imaging because of their high relevance in the energy metabolism of cancer cells. 

    Furthermore, two fluorescent indoline derivatives, which differ only by one functional group (imine vs ketone) were compared for their photophysical properties and cell imaging behavior. The indolin-3-imine derivative showed pH sensitivity due to protonation of the imine moiety, which was significantly enhanced in the excited state because of photobasicity. Fluorescence microscopy experiments showed ubiquitous cell staining with a tendency towards lysosomes, which are acidic cell organelles. In contrast, the indolin-3-one analogue featured lipid droplet-specific staining, although with rapid photobleaching. Spectroscopic studies in solution revealed photoisomerization through ring-opening upon irradiation, which explained the emission bleaching during microscopy. While this behavior is not beneficial for imaging applications, it was found that the indolin-3-one exhibited photoactivated cytotoxicity, which likely arises from singlet oxygen generation.

    Delarbeid
    1. Photophysical characterization and fluorescence cell imaging applications of 4-N-substituted benzothiadiazoles
    Åpne denne publikasjonen i ny fane eller vindu >>Photophysical characterization and fluorescence cell imaging applications of 4-N-substituted benzothiadiazoles
    Vise andre…
    2022 (engelsk)Inngår i: RSC Advances, E-ISSN 2046-2069, Vol. 12, nr 23, s. 14544-14550Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    In this work, a series of fluorescent 2,1,3-benzothiadiazole derivatives with various N-substituents in the 4- position was synthesized and photophysically characterized in various solvents. Three compounds emerged as excellent fluorescent probes for imaging lipid droplets in cancer cells. A correlation between their high lipophilicity and lipid droplet specificity could be found, with log P ≥ 4 being characteristic for lipid droplet accumulation.

    sted, utgiver, år, opplag, sider
    Royal Society of Chemistry, 2022
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-474469 (URN)10.1039/d2ra01404a (DOI)000794328700001 ()
    Forskningsfinansiär
    Swedish Research Council, 2018-03524
    Tilgjengelig fra: 2022-05-16 Laget: 2022-05-16 Sist oppdatert: 2023-08-08bibliografisk kontrollert
    2. An Indolin-3-imine Photobase and pH Sensitive Fluorophore
    Åpne denne publikasjonen i ny fane eller vindu >>An Indolin-3-imine Photobase and pH Sensitive Fluorophore
    Vise andre…
    2023 (engelsk)Inngår i: ChemPhotoChem, E-ISSN 2367-0932, artikkel-id e202300171Artikkel i tidsskrift (Fagfellevurdert) Epub ahead of print
    Abstract [en]

    This work presents the pH sensing ability of a fluorescent indolin-3-imine derivative. Protonation of the weakly basic imine (pKa = 8.3 of its conjugate acid) results in a significant redshift of the absorption band. The fluorophore acts as a photobase, with a basicity increase of approximately 6 units upon photoexcitation. This behavior promotes excited state proton transfer from weak acids such as protic solvents. The characteristics of the fluorophore enable sensing of water fractions in organic solvents and differentiation between methanol, ethanol, and longer chain alcohols. Initial cell studies indicated the future potential of indolin-3-imines as fluorophores for bioimaging applications.

    sted, utgiver, år, opplag, sider
    John Wiley & Sons, 2023
    Emneord
    Indolin-3-imine, fluorophore, pHsensor, excited state proton transfer, photobase
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-508682 (URN)10.1002/cptc.202300171 (DOI)
    Forskningsfinansiär
    Swedish Research Council, 2018-03524
    Tilgjengelig fra: 2023-08-07 Laget: 2023-08-07 Sist oppdatert: 2023-09-27
    3. Photoinduced ring‐opening and phototoxicity of an indolin‐3‐one derivative
    Åpne denne publikasjonen i ny fane eller vindu >>Photoinduced ring‐opening and phototoxicity of an indolin‐3‐one derivative
    Vise andre…
    2023 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 29, nr 51, artikkel-id e202300864Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The study of a fluorescent indolin-3-one derivative is reported that, as opposed to its previously described congeners, selectively undergoes photoactivated ring-opening in apolar solvents. The excited state involved in this photoisomerization was partially deactivated by the formation of singlet oxygen. Cell studies revealed lipid droplet accumulation and efficient light-induced cytotoxicity.

    sted, utgiver, år, opplag, sider
    John Wiley & Sons, 2023
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-507596 (URN)10.1002/chem.202300864 (DOI)001044603700001 ()
    Tilgjengelig fra: 2023-07-09 Laget: 2023-07-09 Sist oppdatert: 2024-01-23bibliografisk kontrollert
    Fulltekst (pdf)
    UUThesis_Doloczki,S-2023
    Download (jpg)
    presentationsbild
  • 71.
    Doloczki, Susanne
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Holmberg, Karl O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Galván, Ignacio Fdez.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Swartling, Fredrik J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Dyrager, Christine
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Photophysical characterization and fluorescence cell imaging applications of 4-N-substituted benzothiadiazoles2022Inngår i: RSC Advances, E-ISSN 2046-2069, Vol. 12, nr 23, s. 14544-14550Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this work, a series of fluorescent 2,1,3-benzothiadiazole derivatives with various N-substituents in the 4- position was synthesized and photophysically characterized in various solvents. Three compounds emerged as excellent fluorescent probes for imaging lipid droplets in cancer cells. A correlation between their high lipophilicity and lipid droplet specificity could be found, with log P ≥ 4 being characteristic for lipid droplet accumulation.

    Fulltekst (pdf)
    fulltext
  • 72.
    Doloczki, Susanne
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kern, Christoph
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Holmberg, Karl O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi och neurodegeneration.
    Zhao, Miao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi och neurodegeneration.
    Swartling, Fredrik J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi och neurodegeneration.
    Streuff, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Dyrager, Christine
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    An Indolin-3-imine Photobase and pH Sensitive Fluorophore2023Inngår i: ChemPhotoChem, E-ISSN 2367-0932, artikkel-id e202300171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This work presents the pH sensing ability of a fluorescent indolin-3-imine derivative. Protonation of the weakly basic imine (pKa = 8.3 of its conjugate acid) results in a significant redshift of the absorption band. The fluorophore acts as a photobase, with a basicity increase of approximately 6 units upon photoexcitation. This behavior promotes excited state proton transfer from weak acids such as protic solvents. The characteristics of the fluorophore enable sensing of water fractions in organic solvents and differentiation between methanol, ethanol, and longer chain alcohols. Initial cell studies indicated the future potential of indolin-3-imines as fluorophores for bioimaging applications.

  • 73.
    Doloczki, Susanne
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kern, Christoph
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Holmberg Olausson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Swartling, Fredrik J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Streuff, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Dyrager, Christine
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Photoinduced ring‐opening and phototoxicity of an indolin‐3‐one derivative2023Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 29, nr 51, artikkel-id e202300864Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The study of a fluorescent indolin-3-one derivative is reported that, as opposed to its previously described congeners, selectively undergoes photoactivated ring-opening in apolar solvents. The excited state involved in this photoisomerization was partially deactivated by the formation of singlet oxygen. Cell studies revealed lipid droplet accumulation and efficient light-induced cytotoxicity.

    Fulltekst (pdf)
    fulltext
  • 74.
    Drugge, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Development of halogen-bonded organic frameworks2022Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Metal-organic frameworks (MOFs) are highly porous crystalline materials that have a wide range of applicability, catalysis being one of large interest. In this project we attempted to form Halogen-bonded frameworks (XOFs) as they could be highly useful as catalysts in the synthesis of halogen containing molecules. The applicability of these frameworks was also tested. A positive iodonium ion was first stored in a bispyridine-iodonium complex which was then transferred to the organic linkers. One framework was also formed using a diiodtetrafluorobenzene as the node, i.e. using a neutral halogen. 

    Powder X-ray diffraction showed that all frameworks formed had some level of crystallinity indicating that a larger structure had been formed. Infrared spectroscopy showed that N-I-N bonds were present in the frameworks. These results suggests that XOFs had in fact been formed. When attempting to use one of the frameworks for a iodocyclisation it showed the ability to absorb iodine, giving further reasons for working on the subject in the future.

    Fulltekst tilgjengelig fra 2024-08-22 16:59
  • 75.
    Elabd, Ahmed
    et al.
    Univ Fribourg, Dept Chem, CH-1700 Fribourg, Switzerland..
    Kim, Jiheon
    Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea.;Seoul Natl Univ, Inst Chem Proc, Seoul 08826, South Korea..
    Sethio, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Kang, Sangho
    Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea.;Seoul Natl Univ, Inst Chem Proc, Seoul 08826, South Korea..
    Kang, Taemin
    Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 08826, South Korea.;Seoul Natl Univ, Inst Chem Proc, Seoul 08826, South Korea..
    Choi, Jang Wook
    Seoul Natl Univ, Inst Chem Proc, Seoul 08826, South Korea.;Sch Chem & Biol Engn, Seoul Natl Univ, Dept Mat Sci & Engn, Seoul 08826, South Korea..
    Coskun, Ali
    Univ Fribourg, Dept Chem, CH-1700 Fribourg, Switzerland..
    Dual Functional High Donor Electrolytes for Lithium-Sulfur Batteries under Lithium Nitrate Free and Lean Electrolyte Conditions2022Inngår i: ACS Energy Letters, E-ISSN 2380-8195, Vol. 7, nr 8, s. 2459-2468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Electrolyte engineering is a highly promising strategy in lithium-sulfur batteries to increase the sulfur utilization and maintain a stable interface at the lithium metal anode for long-term cycling. Whereas high donor electrolytes can increase the solubility of polysulfides to promote the sulfur utilization and therefore operate under lean electrolyte conditions, their poor thermodynamic stability toward lithium metal anode causes uncontrolled decomposition at its interface and impair the cycle life severely. Here, we introduce a dual functional high donor electrolyte, 3-fluoropyridine (3-FPN), to simultaneously achieve high polysulfide solubility up to 1.5 M and compatibility with lithium metal. These features result in a high specific capacity of 1087.9 mAh g(sulfur)(-1) and robust cycling under a lean electrolyte condition of 7 mu Lelectrolyte mgsulfur-1in the absence of LiNO3. Remarkably, 3-FPN preserves stable cyclability even at a high areal sulfur loading of 8 mgsulfur cm-2, which opens a new avenue in advancing the electrolytes for lithium-sulfur batteries toward their high volumetric energy density and long cycle life.

  • 76.
    Emanuelsson, Rikard
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Enthalpic versus Entropic Contribution to the Quinone Formal Potential in a Polypyrrole-Based Conducting Redox Polymer2016Inngår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 120, nr 38, s. 21178-21183Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A conducting redox polymer (CPR) based on pyrrole with a hydroquinone pendant group was synthesized through electropolymerization of the corresponding monomer. The formal potential (E-0') in aqueous solution at different pH as well as in MeCN containing equal amounts of pyridiniumtriflates and the corresponding free pyridine with different pK(a) was investigated. E-0' could be completely recovered in MeCN, and by utilizing pyridine bases with different donor acceptor strengths, a decrease of 61 meV/pK(a) was found that corresponded exactly to the pH dependence of E-0' in aqueous electrolyte. To separate the entropic and enthalpic contributions to E-0', temperature-dependent electrochemistry was performed. Two different modes of operation with changing pH/pK(a) between the two media were revealed. In MeCN, E-0' varies only because of the enthalpic contribution as the entropic contribution is unaffected by change in pKa. In water, there is primarily an entropic contribution to E-0' with changing pH due to solvation of the proton. The presented results are expected to open up for new design possibilities of CRPs based on ion coordinating redox groups for electrical energy storage.

  • 77. Endale, Milkyas
    et al.
    Alao, John Patrick
    Akala, Hoseah M
    Rono, Nelson K
    Eyase, Fredrick L
    Derese, Solomon
    Ndakala, Albert
    Mbugua, Martin
    Walsh, Douglas S
    Sunnerhagen, Per
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yenesew, Abiy
    Antiplasmodial quinones from Pentas longiflora and Pentas lanceolata.2012Inngår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 78, nr 1, s. 31-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50) = 0.9-3 µg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50) = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three--nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.

  • 78. Endale, Milkyas
    et al.
    Ekberg, Annabel
    Akala, Hoseah M
    Alao, John Patrick
    Sunnerhagen, Per
    Yenesew, Abiy
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Busseihydroquinones A-D from the roots of Pentas bussei2012Inngår i: Journal of Natural Products, ISSN 0163-3864, E-ISSN 1520-6025, Vol. 75, nr 7, s. 1299-1304Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Four new naphthohydroquinones, named busseihydroquinones A-D (1-4), along with a known homoprenylated dihydronaphthoquinone (5), were isolated from the CH(2)Cl(2)/MeOH (1:1) extract of the roots of Pentas bussei. Although the genus Pentas is frequently used by traditional healers for the treatment of malaria, only marginal activities against the chloroquine-sensitive (D6) and the chloroquine-resistant (W2) strains of Plasmodium falciparum were observed for the crude root extract and the isolated constituents of this plant.

  • 79.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    15N NMR chemical shift in the characterisation of halogen bonding in solution2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    15N NMR chemical shift in the characterisation of halogen bonding in solution  

    Sebastiaan B. Hakkert, Jürgen Gräfenstein and Mate Erdelyi*   

    NMR chemical shift changes induced upon formation of non-covalent interactions have been used as sensitive and specific observables in the evaluation of weak chemical forces in solutions, among others of halogen bonding.1 1H NMR has high sensitivity yet a narrow chemical shift range, ca 10 ppm, resulting in small and thus difficult to measure chemical shift changes upon binding. In contrast, 13C NMR offers a wider shift range, ca 200 ppm, providing larger chemical shift changes upon weak binding to be detected; however, its low sensitivity limits its applicability. 19F NMR provides high sensitivity and a wide chemical shift range, ca 500 ppm, and hence is straightforwardly applicable on substances that possess a fluorine close to the halogen bond donor site,2 but is unfortunately often unavailable for real-life substances applied in medicinal chemistry, for example, typically missing fluorine substitution. 15N NMR despite its low sensitivity, which can be overcome by indirect detection experiments (HMBC), provides several advantages, such as an unusually wide chemical shift range, ca 900 ppm, and most importantly the detectability of halogen and hydrogen bonds directly at the Lewis base involved in the interaction. Accordingly, upon formation of a halogen bond with a nitrogen donor ligand typically 10-20 ppm,3 and for very strong interactions up to 100 ppm,4 15N chemical shift changes have been reported.  

    In this project we have evaluated the capability of 15N NMR to describe halogen bonding interactions with respect to solvent and electronic effects, and the alteration of N-X bond lengths. The observations made for halogen bonds were compared to those obtained for analogous hydrogen bonding systems using the same nitrogen donor halogen/hydrogen bond acceptor. The experimental data obtained on an 800 MHz spectrometer was compared to and interpreted with the help of computational data (DFT).The observed chemical shift changes upon formation of halogen bonds were correlated to various descriptors to understand their origin. Based on the above data the scope and limitations of 15N NMR for detection and understanding of halogen bonding in solution will be discussed.

    References

    1. Bertrán, J. F.; Rodríguez, M. Org. Magn. Reson. 1979, 12, 92, 1980, 14, 244; 1981, 16, 79.

    2. Metrangolo, P.; Panzeri, W.; Recupero F; Resnati, G. J. Fluorine Chem. 2002, 114, 27.

    3. Castro-Fernandez, S.; Lahoz, I. R.; Llamas-Saiz, A. L.; Alonso-Gomez, J. L.; Cid, M. M.; Navarro-Vazquez, A. Org. Lett. 2014, 16, 1136; Puttreddy, R.; Jurcek, O.; Bhowmik, S.; Makela, T.; Rissanen, K. Chem. Commun. 2016, 52, 2338.

    4. Carlsson, A.-C. C.; Grafenstein, J.; Budnjo, A.; Laurila, J. L.; Bergquist, J.; Karim, A.; Kleinmaier, R.; Brath, U.; Erdelyi, M. J. Am. Chem. Soc. 2012, 134, 5706

  • 80.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Halogen and hydrogen bonding -: computationally supported NMR spectroscopy2017Konferansepaper (Fagfellevurdert)
  • 81.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Halogen Bonding:: An Alternative Tool to Modulate Peptide Conformation2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Halogen bonding: an alternative tool to modulate peptide conformation

    Emma Danelius(1), Hanna Andersson(1), Patrik Jarvoll(1), Kajsa Lood(1), Jürgen Gräfenstein(1) and  Mate Erdelyi(1,2)

    1) Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden

    2) Department of Chemistry – BMC, Uppsala University, Sweden   

    Halogen bonding is a weak chemical force that resembles hydrogen bonding in many aspects. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has so far rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. 

    The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. 

    A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a β-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.  

  • 82.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    ParLig:: Paramagnetic Ligand Tagging to Identify Protein Binding Sites2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    ParLig: Paramagnetic Ligand Tagging to  Identify Protein Binding Sites

    Ulrika Brath,1 Shashikala I. Swamy,1 Alberte X. Veiga,1 Ching-Chieh Tung,2 Filip Van Petegem,2 Mate Erdelyi1*

    Department of Chemistry & Molecular Biology and the Swedish NMR Centre, University of Gothenburg,Sweden

    Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, Canada  

    Abstract: Identification of the binding site and binding mode of low affinity ligands, such as screening hits, is essential for the development of pharmaceutical leads using rational drug design strategies. We introduce ParLig, a paramagnetic ligand tagging approach that enables localization of protein – ligand binding clefts by detection and analysis of intermolecular protein NMR pseudocontact shifts, invoked by the covalent attachment of a paramagnetic lanthanoid chelating tag to the ligand of interest. Its scope is demonstrated by identification of the low mM volatile anesthetic interaction site of calmodulin. The technique provides an efficient route to rapid screening of protein – ligand systems, and to the identification of the binding site and mode of low affinity complexes.

    References: 

    1. Brath, U., Swami, S.I., Veiga, A.X., Tung, C.-C., Van Petegem, F., Erdelyi, M., J. Am. Chem Soc. 137, 11391-11398 (2015) .

  • 83.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pentacoordinate carbonium ions in solution2018Konferansepaper (Fagfellevurdert)
  • 84.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Solid-phase methods for the synthesis of heterocycles2006Inngår i: Microwave-Assisted  Synthesis of Heterocycles, Topics in Heterocyclic Chemistry, Berlin/Heidelberg, Germany: Springer GmbH & Co KB, Berlin/Heidelberg, Germany , 2006, s. 79-128Kapittel i bok, del av antologi (Fagfellevurdert)
  • 85.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    The three-center halogen bond2019Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Halonium ions, X+, play important roles in chemistry. In halogenation reactions, they are transferred from a halogen donor, D, to an acceptor, A, in the formally stepwise process D+- X + A →[D-X∙∙∙A]+ → [D∙∙∙X∙∙∙A]+→ [D∙∙∙X-A]  → D + X-A+. The same process takes place when a halogen moves from a halogen bond [1] acceptor to another one within a complex, that has so far mostly been studied in model systems with the two donor sites possessing comparable Lewis basicities (A ~ D) [2-5]. Throughout these processes the halonium ion simultaneously forms bonds to two Lewis bases, with the bonds having varying degrees of covalency and secondary character [2].  Halonium ions are strong halogen bond donors that prefer to form a three-center geometry, [D∙∙∙X∙∙∙D]+, in which both D-X halogen bonds have partial covalent and partial secondary characters [2-6].

    In this talk, the influence of electronic and steric factors, solvent polarity and counterions, and of the type of the halogen on the geometry and reactivity of [D∙∙∙X∙∙∙D]+ halogen bond complexes will be discussed. The symmetric state, [D∙∙∙X∙∙∙D]+, is demonstrated to be strongly preferred over the alternative asymmetric arrangements [D∙∙∙X-D]+. Understanding the three-center halogen bonds provides insights into the fundamentals of the halogen bonding phenomenon and of halonium transfer reactions. The studied complexes are isoelectronic to the transition state of SN2 reactions, and thus may provide model systems for the exploration of fundamental reaction mechanisms.

    The synthesis, and the NMR spectroscopic and computational (DFT) studies of a variety of three-center halogen bond systems [2-6] will be presented focusing on the influence of steric and electronic factors on the geometry and electronic character of the three-center-fourelectron halogen bond.

    References 1. Halogen bonding is the noncovalent interaction of halogen in which they act as electron acceptors. 2. Karim, A.; Reitti, M.; Carlsson, A.-C.C.; Gräfenstein, J.; Erdelyi, M. Chem. Sci. 2014, 5, 3226. 3. Carlsson, A.-C.C.; Mehmeti, K.; Uhrbom, M.; Karim, A.; Bedin, M.; Puttreddy, R.; Kleinmaier, R.; Neverov, A.; Nekoueishahraki, B.; Gräfenstein, J.; Rissanen, K.; Erdelyi, M., J. Am. Chem. Soc. 2016, 138, 9853. 4. Carlsson, A.-C.C.; Gräfenstein,J.; Budnjo, A.; Bergquist, J.; Karim, A.; Kleinmaier, R.; Brath, U.; Erdelyi, M. J. Am. Chem. Soc. 2012, 134, 5706.  5. Hakkert, S.B.; Erdelyi, M. J. Phys. Org. Chem. 2015, 28, 226. 6.Lindblad, S.; Mehmeti, K.; Veiga, A.; Nekoueishahraki, B.; Gräfenstein, J.; Erdelyi, M. J. Am. Chem. Soc.2018, 140, 13503.

  • 86.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    The three-centered halogen bond2018Konferansepaper (Fagfellevurdert)
  • 87.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    d’Auvergne, E.
    Navarro-Vazquez, A.
    Griesinger, C.
    Dynamics of the glycosidic linkage: conformational space of lactose2011Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 17, nr 34, s. 9368-9376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dynamics of the glycosidic bond of lactose was studied by a paramagnetic tagging‐based NMR technique, which allowed the collection of an unusually large series of NMR data for a single compound. By the use of distance‐ and orientation‐dependent residual dipolar couplings and pseudocontact shifts, the simultaneous fitting of the probabilities of computed conformations and the orientation of the magnetic susceptibility tensor of a series of lanthanide complexes of lactose show that its glycosidic bond samples syn/syn, anti/syn and syn/anti ϕ/ψ regions of the conformational space in water. The analysis indicates a higher reliability of pseudocontact shift data as compared to residual dipolar couplings with the presently available weakly orienting paramagnetic tagging technique. The method presented herein allows for an improved understanding of the dynamic behaviour of oligosaccharides.

    Fulltekst (pdf)
    fulltext
  • 88.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Esterhuysen, Catharine
    Department of Chemistry, Stellenbosch University, Matieland 7602 South Africa.
    Zhu, Weiliang
    Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China.
    Halogen Bonding: From Fundamentals to Applications2021Inngår i: ChemPlusChem, E-ISSN 2192-6506, Vol. 86, nr 9, s. 1229-1230Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Guest Editors Maté Erdélyi, Catharine Esterhuysen, and Weilang Zhu introduce the joint Special Collection on Halogen Bonding published by ChemPlusChem and The Chemical Record. This collection is organized in association with the 4th International Symposium on Halogen Bonding (ISXB4) and features top multidisciplinary contributions where halogen bonding plays a pivotal role, including computational, synthetic and catalytic, supramolecular and crystal engineering, and biological investigations and applications. 

  • 89.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, Adolf
    Rapid Microwave-assisted solid-phase peptide synthesis2003Konferansepaper (Fagfellevurdert)
  • 90.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, Aldof
    Development of a stilbene-type photoswitchable β-hairpin mimetic2005Konferansepaper (Fagfellevurdert)
  • 91.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Karlén, A.
    Gogoll, Aldolf
    Studies of Photoswitchable β-Hairpin Mimetics2003Konferansepaper (Fagfellevurdert)
  • 92.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Langer, V.
    Karlén, A.
    Gogoll, Adolf
    Structural Studies of Diastereomeric β-Hairpin Mimetics2002Konferansepaper (Fagfellevurdert)
  • 93.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Lindblad, Sofia
    Mehmeti, Krenare
    Veiga, Alberte X
    Nekoueishahraki, Bijan
    Gräfenstein, Jurgen
    The Halogen Bond of Halonium Ions2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Halonium ions, X+ , play important roles in chemistry. In halogenation reactions, they are transferred from a donor, D, to an acceptor, A, in the formally stepwise process D-X + A

    → [D-X∙∙∙A]+ → [D∙∙∙X∙∙∙A][D∙∙∙X - A]+ → D + X - A+. The same process takes place when a halogen moves from a halogen bond donor to an acceptor within a complex, which has been studied so far mostly in model systems in which the donor and the acceptor possess comparable Lewis basicities (A ~ D) [1-4].  Throughout these processes the halonium ion simultaneously forms bonds to two Lewis bases that may possess varying degrees of covalency and secondary character [1]. Halonium ions are strong halogen bond donors that prefer to form a symmetric geometry, [D∙∙∙X∙∙∙D]+, with two D-X bonds of partial covalent and partial secondary character. This symmetric state is much preferred over the asymmetric alternative arrangement, [D∙∙∙X - D]+[1-4].

    We have explored how electronic and steric factors influence the electron density distribution and the geometry of [D∙∙∙X∙∙∙D]+-type complexes. Understanding this provides insights into the fundamental details of halonium transfer reactions, halogen transfer processes within halogen bonded systems as well as into important reaction mechanisms, such as SN2.

    In this talk the synthesis, NMR spectroscopic and computational (DFT) studies of so far undiscussed systems [5] will be presented, and the influence of steric and electronic factors on the geometry and electronic character of the three-center-four-electron halogen bond will be discussed.

  • 94.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Navarro-Vázquez, Armando
    Pfeiffer, Bernhard
    Kuzniewski, Christian N
    Felser, Andrea
    Widmer, Toni
    Gertsch, Jürg
    Pera, Benet
    Díaz, José Fernando
    Altmann, Karl-Heinz
    Carlomagno, Teresa
    The binding mode of side chain- and C3-modified epothilones to tubulin2010Inngår i: ChemMedChem, ISSN 1860-7179, E-ISSN 1860-7187, Vol. 5, nr 6, s. 911-920Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of beta-His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.

    Fulltekst (pdf)
    fulltext
  • 95.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pfeiffer, Bernhard
    Hauenstein, Kurt
    Fohrer, Jörg
    Gertsch, Jürg
    Altmann, Karl-Heinz
    Carlomagno, Teresa
    Conformational preferences of natural and C3-modified epothilones in aqueous solution.2008Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 51, nr 5, s. 1469-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

  • 96.
    Ergun Dönmez, Merve
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Hydroarylation of Fullerene C60 Using Arylboronic Acids via Rhodium Catalysis: Improving the Outcomes and Simplifying the Conditions2022Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Hydroarylation with arylboronic acids is one of the functionalization methods for synthesis of modified fullerenes. In this work, we provide a fast and reproducible one-phase method for hydroarylation of fullerene using boronic acids and an analytical HPLC method that efficiently separates unreacted C60 and product from a hydroarylation reaction mixture as well as a fulleropyrrolidine reaction mixture. This analytical method was not only successively applied to preparative scale to isolate the functionalized fullerenes but also validated for quantification of unreacted C60 in the reaction mixtures together with 1H NMR quantification used for the hydroarylated product. Reaction conditions screening was done by investigating the effects of solvents, time and temperature, protic additive, catalyst amount and different substituents on arylboronic acid. It was found that the reaction gives the best outcome when it is done at 110 °C for 4h, using anhydrous methanol or tert-butanol:water mixture as protic additives and 10 mol % [Rh(cod)(MeCN)2]BF4 as catalyst. Both the conversion and the product yield were found higher than the reported values. 

    Delarbeid
    1. Analytical and preparative separation and isolation of functionalized fullerenes by conventional HPLC stationary phases: method development and column screening
    Åpne denne publikasjonen i ny fane eller vindu >>Analytical and preparative separation and isolation of functionalized fullerenes by conventional HPLC stationary phases: method development and column screening
    2020 (engelsk)Inngår i: RSC Advances, E-ISSN 2046-2069, Vol. 10, nr 33, s. 19211-19218Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Isolation and purification of functionalized fullerenes from often complex reaction mixtures is challenging due to the hydrophobic nature and low solubility in regular organic solvents. We have developed an HPLC method that efficiently, employing regular reversed phase stationary phases, separates not only C-60 from C-70 in a model mixture, but also C-60 monoadducts from polyadducts and unreacted C-60 from fulleropyrrolidine and hydroarylation example reaction mixtures. Six HPLC columns with regular reversed phase stationary phases were evaluated using varying proportions of acetonitrile in toluene as eluent; with C18 and C12 stationary phases with high surface area (450-400 m(2) g(-1)) being the most efficient regarding separation efficiency and analysis time for all mixtures. The analytical method is effectively transferrable to a preparative scale to isolate the monoaddition products from complex fullerene reaction mixtures.

    sted, utgiver, år, opplag, sider
    ROYAL SOC CHEMISTRY, 2020
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-420044 (URN)10.1039/d0ra02814b (DOI)000537781700009 ()
    Tilgjengelig fra: 2020-09-21 Laget: 2020-09-21 Sist oppdatert: 2024-03-26bibliografisk kontrollert
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  • 97.
    Ergun Dönmez, Merve
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Eriksson, Måns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Hulu, Gustav
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Nordström, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Playing with Protic Additives to Improve the Outcome of Rhodium‐Catalyzed Hydroarylation of Fullerene C60 with Arylboronic Acids2024Inngår i: Helvetica Chimica Acta, ISSN 0018-019X, E-ISSN 1522-2675, Vol. 107, artikkel-id e202300206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new one-phase process for hydroarylation of C60 fullerene using arylboronic acids and a rhodium catalyst in an aromatic solvent containing soluble protic additives is described. Yields of monohydroarylated product with tert-butanol and water as the protic additive range from 14 to 50% depending on which arylboronic acid is used after reaction times of 4 hours or less which is a significant improvement from the outcome of reactions carried out using conditions from the literature. Accurate monitoring of reaction outcomes was achieved by a combination of UV-Vis spectroscopy and 1H-NMR spectroscopy: C60 conversion was determined using an analytical HPLC-UV-vis method employing commonly available columns for the separation, while product formation was quantified by 1H-NMR spectroscopy with an internal standard. Moreover, two new arylboronic acids carrying 4-alkynyl aryl substituents, synthesized using Sonogashira couplings, are reported, as well as the use of these in the hydroarylation of C60.

    Fulltekst (pdf)
    fulltext
  • 98.
    Ergun Dönmez, Merve
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Eriksson, Måns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Xiong, Ruisheng
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Studying rhodium-catalyzed alkene/alkyne and C60 hydroarylaton using 19F NMR spectroscopy: Towards mechanistic understandingManuskript (preprint) (Annet vitenskapelig)
  • 99.
    Ergun Dönmez, Merve
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Analytical and preparative separation and isolation of functionalized fullerenes by conventional HPLC stationary phases: method development and column screening2020Inngår i: RSC Advances, E-ISSN 2046-2069, Vol. 10, nr 33, s. 19211-19218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Isolation and purification of functionalized fullerenes from often complex reaction mixtures is challenging due to the hydrophobic nature and low solubility in regular organic solvents. We have developed an HPLC method that efficiently, employing regular reversed phase stationary phases, separates not only C-60 from C-70 in a model mixture, but also C-60 monoadducts from polyadducts and unreacted C-60 from fulleropyrrolidine and hydroarylation example reaction mixtures. Six HPLC columns with regular reversed phase stationary phases were evaluated using varying proportions of acetonitrile in toluene as eluent; with C18 and C12 stationary phases with high surface area (450-400 m(2) g(-1)) being the most efficient regarding separation efficiency and analysis time for all mixtures. The analytical method is effectively transferrable to a preparative scale to isolate the monoaddition products from complex fullerene reaction mixtures.

    Fulltekst (pdf)
    fulltext
  • 100.
    Ergun Dönmez, Merve
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Surprisingly complex: Identification of arylboronic acid species in non-polar solvents containing protic and non-protic Lewis base additives by NMR spectroscopyManuskript (preprint) (Annet vitenskapelig)
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