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  • 1.
    Abdelmoniem, Amr M.
    et al.
    Cairo Univ, Dept Chem, Fac Sci, Giza, Egypt.
    Elnagdi, Mohamed H.
    Cairo Univ, Giza, Egypt;Kuwait Univ, Safat, Kuwait.
    Elsehemy, Mohamed S.
    Cairo Univ, Dept Chem, Fac Pharm, Giza, Egypt.
    El-Seedi, Hesham R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.
    Abdelhamid, Ismail A.
    Cairo Univ, Dept Chem, Fac Sci, Giza, Egypt.
    Synthesis, Chemistry and Utilities of Diaminoazoles with Special Reference to 3,5-Diaminopyrazoles2018In: Current Organic Synthesis, ISSN 1570-1794, E-ISSN 1875-6271, Vol. 15, no 4, p. 487-514Article, review/survey (Refereed)
    Abstract [en]

    Background: Although the chemistry of heteroaromatic monoamino azoles has been surveyed more than once in the last decade, the chemistry of the di- and triaminoazoles has not been reviewed. In this article we will survey the synthesis, chemistry and utility of the diaminoazoles. In this review, the chemistry of the diaminoazoles as well as their most important utilities will be surveyed. Objective: The review focuses on recent progress in diaminoazoles (i.e. diaminopyrazoles, diaminoimidazoles, diaminotriazoles and diaminothiazole) with especial references to diaminopyrazoles. The synthesis as well as pharmaceutical utilities are reported. There are several methods for synthesis of diaminopyrazoles. 3,5-Diaminopyrazole and its derivatives are prepared through the reaction of malononitrile or arylhydrazononitrile with hydrazine derivatives. 3,4-Diaminopyrazoles are prepared via nitration of 3-aminopyrazole with subsequent reduction of the produced compound. The diaminopyrazoles have several applications in cosmetic and pharmaceutical industries. They also have useful utilities as a constituent in oxidative hair dyes. Conclusion: We managed to report the common methods for the synthesis of diaminoazoles with especial reference to aminopyrazoles that are prepared through the reaction of malononitrile or hydrazononitriles with hydrazine derivatives. Some important applications that include pharmaceutical utilities such as hair dye constituents are reported.

  • 2. Aguilera, Adriana Freites
    et al.
    Tolvanen, Pasi
    Heredia, Shuyana
    Muñoz, Marta González
    Samson, Tina
    Oger, Adrien
    Verove, Antoine
    Eränen, Kari
    Leveneur, Sebastien
    Mikkola, Jyri-Pekka
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Industrial Chemistry & Reaction Engineering, Department of Chemical Engineering, Johan Gadolin Process Chemistry Centre, Åbo Akademi University, Åbo-Turku, Finland.
    Salmi, Tapio
    Epoxidation of fatty acids and vegetable oils assisted by microwaves catalyzed by a cation exchange resin2018In: Industrial & Engineering Chemistry Research, ISSN 0888-5885, E-ISSN 1520-5045, Vol. 57, no 11, p. 3876-3886Article in journal (Refereed)
    Abstract [en]

    Epoxidation of oleic acid and cottonseed oil was conducted in a semibatch reactor with in-situ-formed percarboxylic acid (peracetic acid or perpropionic acid), using hydrogen peroxide as an oxidizing agent and carboxylic acid (acetic acid or propionic acid) as oxygen carriers. Amberlite IR-120 was implemented as the catalyst. The system was comprised of a loop reactor, where the mixture was pumped through a single-mode cavity in which microwave irradiation was introduced. A heat exchanger was integrated into the system to replace microwave heating, to compare the results obtained via microwave heating versus conventional heating. The catalyst loading effect was studied, as well as the influence of microwave irradiation and the implementation of the SpinChem rotating bed reactor (RBR), in hopes of decreasing the influence of the internal mass transfer. The application of microwave irradiation results in an improvement of the reaction yield in the absence of a catalyst.

  • 3.
    Akkarasamiyo, Sunisa
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sawadjoon, Supaporn
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Orthaber, Andreas
    Samec, Joseph S. M.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tsuji-Trost Reaction of Non-Derivatized Allylic Alcohols2018In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 14, p. 3488-3498Article in journal (Refereed)
    Abstract [en]

    Palladium-catalyzed allylic substitution of non-derivatized enantioenriched allylic alcohols with a variety of uncharged N-, S-, C- and O-centered nucleophiles using a bidentate BiPhePhos ligand is described. A remarkable effect of the counter ion (X) of the XPd[kappa(2)-BiPhePhos][kappa(3)-C3H5] was observed. When ClPd[kappa(2)-BiPhePhos][eta(3)-C3H5] (complexI) was used as catalyst, non-reproducible results were obtained. Study of the complex by X-ray crystallography, (PNMR)-P-31 spectroscopy, and ESI-MS showed that a decomposition occurred where one of the phosphite ligands was oxidized to the corresponding phosphate, generating ClPd[kappa(1)-BiPhePhosphite-phosphate][eta(3)-C3H5] species (complexII). When the chloride was exchanged to the weaker coordinating OTf- counter ion the more stable Pd[kappa(2)-BiPhePhos][eta(3)-C3H5](+)+[OTf] (-) (complexIII) was formed. ComplexIII performed better and gave higher enantiospecificities in the substitution reactions. ComplexIII was evaluated in Tsuji-Trost reactions of stereogenic non-derivatized allylic alcohols. The desired products were obtained in good to excellent yields (71-98%) and enantiospecificities (73-99%) for both inter- and intramolecular substitution reactions with only water generated as a by-product. The methodology was applied to key steps in total synthesis of (S)-cuspareine and (+)-lentiginosine. A reaction mechanism involving a palladium hydride as a key intermediate in the activation of the hydroxyl group is proposed in the overall transformation.

  • 4.
    Akkarasamiyo, Sunisa
    et al.
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Sawadjoon, Supaporn
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Orthaber, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Samec, Joseph S. M.
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Tsuji-Trost Reaction of Non-Derivatized Allylic Alcohols2018In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 14, p. 3488-3498Article in journal (Refereed)
    Abstract [en]

    Palladium-catalyzed allylic substitution of non-derivatized enantioenriched allylic alcohols with a variety of uncharged N-, S-, C- and O-centered nucleophiles using a bidentate BiPhePhos ligand is described. A remarkable effect of the counter ion (X) of the XPd[kappa(2)-BiPhePhos][kappa(3)-C3H5] was observed. When ClPd[kappa(2)-BiPhePhos][eta(3)-C3H5] (complexI) was used as catalyst, non-reproducible results were obtained. Study of the complex by X-ray crystallography, (PNMR)-P-31 spectroscopy, and ESI-MS showed that a decomposition occurred where one of the phosphite ligands was oxidized to the corresponding phosphate, generating ClPd[kappa(1)-BiPhePhosphite-phosphate][eta(3)-C3H5] species (complexII). When the chloride was exchanged to the weaker coordinating OTf- counter ion the more stable Pd[kappa(2)-BiPhePhos][eta(3)-C3H5](+)+[OTf] (-) (complexIII) was formed. ComplexIII performed better and gave higher enantiospecificities in the substitution reactions. ComplexIII was evaluated in Tsuji-Trost reactions of stereogenic non-derivatized allylic alcohols. The desired products were obtained in good to excellent yields (71-98%) and enantiospecificities (73-99%) for both inter- and intramolecular substitution reactions with only water generated as a by-product. The methodology was applied to key steps in total synthesis of (S)-cuspareine and (+)-lentiginosine. A reaction mechanism involving a palladium hydride as a key intermediate in the activation of the hydroxyl group is proposed in the overall transformation.

  • 5.
    Al-Smadi, Derar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Carboligation using the aldol reaction: A comparison of stereoselectivity and methods2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The research summarized in this thesis focuses on synthesizing aldehyde and aldol compounds as substrates and products for the enzyme D-fructose-6-aldolase (FSA). Aldolases are important enzymes for the formation of carbon-carbon bonds in nature. In biological systems, aldol reactions, both cleavage and formation play central roles in sugar metabolism. Aldolases exhibit high degrees of stereoselectivity and can steer the product configurations to a given enantiomeric and diastereomeric form. To become truly useful synthetic tools, the substrate scope of these enzymes needs to become broadened.

    In the first project, phenylacetaldehyde derivatives were synthesized for the use as test substrates for E. coli FSA. Different methods were discussed to prepare phenylacetaldehyde derivatives, the addition of a one carbon unit to benzaldehyde derivatives using a homologation reaction was successful and was proven efficient and non-sensitive to the moisture. The analogues were prepared through two steps with 75-80 % yields for both meta- and para-substituted compounds.

    The second project focuses on synthesizing aldol compound using FSA enzymes, both wild type and mutated variants selected from library screening, the assay has been successfully used to identify a hit with 10-fold improvement in an R134V/S166G variant. This enzyme produces one out of four possible stereoisomers.

    The third project focuses on the synthesis of a range of aldol compounds using two different approaches reductive cross-coupling of aldehydes by SmI2 or by organocatalysts using cinchonine. Phenylacetaldehydes were reacted with hydroxy-, dihydroxyacetone and hydroxyacetophenone in presence of cinchonine, the reaction was successful with hydroxyacetophenone in moderate yields and 60-99 % de ratio. On the other hand, the aldehydes reacting with methyl- and phenylglyoxal in the presence of SmI2 resulted in moderate yields and without stereoselectivity.

  • 6.
    Al-Smadi, Derar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Enugala, Thilak Reddy
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Norberg, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Kihlberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Widersten, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Synthesis of substrates for aldolase-catalyzed reactions: A comparison of methods for the synthesis of substituted phenylacetaldehydes2018In: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 29, no 9, p. 1187-1190Article in journal (Refereed)
    Abstract [en]

    Methods for the synthesis of phenylacetaldehydes (oxidation, one-carbon chain extension) were compared by using the synthesis of 4-methoxyphenylacetaldehyde as a model example. Oxidations of 4-methoxyphenylethanol with activated DMSO (Swern oxidation) or manganese dioxide gave unsatisfactory results; whereas oxidation with 2-iodoxybenzoic add (IBX) produced 4-methoxyphenylacetaldehyde in reasonable (75%) yield. However, Wittig-type one-carbon chain extension with methoxymethylene-triphenylphosphine followed by hydrolysis gave an excellent (81% overall) yield of 4-methoxyphenylacetaldehyde from 4-methoxybenzaldehyde (a cheap starting material). This approach was subsequently used to synthesise a set of 10 substituted phenylacetaldehydes in good to excellent yields.

  • 7.
    Arja, Katriann
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Multimodal Porphyrin-Based Conjugates: Synthesis and characterization for applications as amyloid ligands, photodynamic therapy agents and chiroptical materials2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Organic compounds that interact both with certain biological targets and display specific photophysical properties can be utilized as molecular tools to visualize and possibly effect disease related processes taking place in living organisms. In this regard, porphyrins are a class of naturally occurring molecules that possess intriguingly interesting photophysical properties where they can act as luminescent probes by emitting detectable light, as well as photosensitizers in the light mediated therapy called photodynamic therapy. In this thesis, the porphyrin structure has been synthetically combined with other molecule classes to achieve compounds with desirable multimodal characteristics.

    Firstly, luminescent conjugated oligothiophenes (LCOs) that have extensively, and with great success, been utilized as fluorescent ligands for amyloid formations, have been conjugated to porphyrins to render oligothiophene porphyrin hybrids (OTPHs) comprising two optically active modalities. When applied as fluorescent amyloidophilic dyes for visualization of amyloid-β (Aβ), one of the pathological hallmarks in Alzheimer’s disease, an enhanced optical assignment of distinct aggregated forms of Aβ was afforded.  Thus, properly functionalized OTPHs could give us more information about pathological processes underlying devastating disorders, such as Alzheimer’s disease. In addition, the OTPHs can be associated with synthetic peptides inducing peptide folding into certain three-dimensional helical structures giving rise to novel optically active materials.

    Secondly, this thesis also embraces porphyrins’ potential as photosensitizers in photodynamic therapy to kill cancer cells. Grounded on the prerequisites for an optimal photosensitizer, we designed porphyrin-based conjugates equipped with common carbohydrates for improved cancer cell selectivity and with a fluorinated glucose derivative, 2-fluoro 2-deoxy glucose, for advantageous metabolism in cancer cells. Furthermore, incorporation of a radioisotopic fluorine-18 atom into the glycoporphyrins could give the means for diagnostic use of the conjugates in positron emission tomography (PET).

    In order to tether together the above-mentioned molecular moieties in a controlled fashion, we developed a robust synthetic strategy for asymmetrical functionalization of porphyrin core. The method involves chlorosulfonation of this otherwise inert tetrapyrrolic structure, followed by alkynylation. Parallelly to amide coupling reactions, copper(I)-catalyzed alkyne azide cycloaddition is used for fast and high-yielding late-stage conjugations. Overall, this thesis demonstrates how combining different molecular moieties in synthetic organic chemistry yields novel molecules with combined and improved multimodal properties for biological and medicinal applications, guided by the design-by-function methodology.      

  • 8.
    Arkhypchuk, Anna I.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    D'Imperio, Nicolas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Ott, Sascha
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    One-Pot Intermolecular Reductive Cross-Coupling of Deactivated Aldehydes to Unsymmetrically 1,2-Disubstituted Alkenes2018In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 20, no 17, p. 5086-5089Article in journal (Refereed)
    Abstract [en]

    The phospha-Peterson reaction between a lithiated secondary phosphane, MesP(Li)TMS, and an aldehyde affords Mes-phosphaalkenes which, upon methanol addition and P-oxidation, react with a second carbonyl compound site specifically to produce unsymmetric alkenes. The E/Z selectivity of the one-pot cross coupling is largely determined by the electronic nature of the aryl substituent of the first aldehyde, with electron-donating groups giving rise to increased amounts of Z-alkenes.

  • 9.
    Arkhypchuk, Anna I.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Orthaber, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Kovacs, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Borbas, K. Eszter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Isolation and Characterization of a Monoprotonated Hydroporphyrin2018In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 48, p. 7051-7056Article in journal (Refereed)
    Abstract [en]

    A simple protocol for the controlled preparation of mono- and diprotonated hydroporphyrins (chlorins) is presented. The chlorins carried 10-aryl groups with electron-neutral (phenyl), electron-donating (p-OMe-C6H4) or electron-withdrawing (pentafluorophenyl) substituents. The protonation reactions were readily followed by UV/Vis absorption spectroscopy, enabling the determination of the first (4.8-5.3) and second pK(a)'s (1.7-0.5). Both mono- and diprotonated species were fully characterized by H-1 NMR spectroscopy, which, in combination with theoretical studies, showed that these macrocycles were significantly distorted in solution. A 10-phenyl-substituted monoprotonated chlorin was characterized by X-ray crystallography. This is the first structurally characterized hydroporphyrin monocation, and the first crystal structure of a sterically unencumbered singly protonated tetrapyrrole. The photostabilities of the mono- and diprotonated 10-phenylchlorins were measured upon irradiation into their Soret bands; protonation yielded increased photostabilities.

  • 10.
    Barrozo, Alexandre
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Liao, Qinghua
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Esguerra, Mauricio
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Marloie, Gael
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Florian, Jan
    Loyola Univ Chicago, Dept Chem & Biochem, Chicago, IL 60660 USA..
    Williams, Nicholas H.
    Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England..
    Kamerlin, Shina C. Lynn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Computer simulations of the catalytic mechanism of wild-type and mutant beta-phosphoglucomutase2018In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 16, no 12, p. 2060-2073Article in journal (Refereed)
    Abstract [en]

    beta-Phosphoglucomutase (beta-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of beta-glucose-1-phosphate to -glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mechanism is that both steps are concerted processes involving acid-base catalysis from a nearby aspartate (D10) side chain. This argument is supported by the observation that mutation of D10 leaves the enzyme with no detectable activity. However, computational studies have suggested that a substrate-assisted mechanism is viable for many phosphotransferases. Therefore, we carried out empirical valence bond (EVB) simulations to address the plausibility of this mechanistic alternative, including its role in the abolished catalytic activity of the D10S, D10C and D10N point mutants of beta-PGM. In addition, we considered both of these mechanisms when performing EVB calculations of the catalysis of the wild type (WT), H20A, H20Q, T16P, K76A, D170A and E169A/D170A protein variants. Our calculated activation free energies confirm that D10 is likely to serve as the general base/acid for the reaction catalyzed by the WT enzyme and all its variants, in which D10 is not chemically altered. Our calculations also suggest that D10 plays a dual role in structural organization and maintaining electrostatic balance in the active site. The correct positioning of this residue in a catalytically competent conformation is provided by a functionally important conformational change in this enzyme and by the extensive network of H-bonding interactions that appear to be exquisitely preorganized for the transition state stabilization.

  • 11. Begum, Sartaz
    et al.
    Nyandoro, Stephen
    Buriyo, Amelia
    Makangara, John
    Munissi, Joan
    Duffy, Sandra
    Avery, Vicky
    Erdelyi, Mate
    University of Gothenburg.
    Bioactivities of extracts, debromolaurintrerol and fucosterol from Macroalgae species2018In: Tanzania Journal of Science, ISSN 2507-7961, Vol. 44, no 2, p. 104-116Article in journal (Refereed)
    Abstract [en]

    Parasitic diseases including malaria, and other numerous microbial infections and physiological diseases are threatening the global population. Tanzanian coast shores are endowed with a variety of macroalgae (seaweeds), hitherto unsystematically explored to establish their biomedical potentials. Thus, antiplasmodial activity using malarial imaging assay, antimicrobial activity using microplate dilution technique, antioxidant activity using DPPH radical scavenging method and cytotoxicity using brine shrimp test were carried out on crude extracts from the selected species of algae (Acanthophora spicifera, Cystoseira myrica, Cystoseira trinodis, Laurencia filiformis, Padina boryana, Sargassum oligocystum, Turbinaria crateriformis, Ulva fasciata and Ulva reticulata) occurring along the coast of Tanzania. The extracts showed antimicrobial activities with MIC ranging from 0.3- 5.0 µg/mL against Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Cryptococcus neoformans; DPPH radical scavenging activity at EC50 1.0- 100 µg/mL and cytotoxicity on brine shrimp larvae with LC50 value ranging from20 - 1000 µg/mL. The extracts from C. myrica and P. boryana inhibited growth of Plasmodium falciparum (3D7 strain) by 80 and 71%, respectively at 40 µg/mL while a sesquiterpene debromolaurinterol (1) which was chromatographically isolated from C. myrica exhibited antiplasmodial activity with IC50 20 µM whereas a sterol fucosterol (2) from P. boryana showed weak activity at 40 µM. Bioactivities portrayed by the investigated extracts indicate their ingredients as potential sources of bioactive agents that warrant further explorations.

  • 12.
    Beiroth, Femke
    et al.
    Christiana Albertina Univ Kiel, Otto Diels Inst Organ Chem, Otto Hahn Pl 3-4, D-24118 Kiel, Germany.
    Koudelka, Tomas
    Christiana Albertina Univ Kiel, Inst Expt Med, Systemat Prote & Bioanalyt, Niemannsweg 11, D-24105 Kiel, Germany.
    Overath, Thorsten
    Christiana Albertina Univ Kiel, Inst Expt Med, Systemat Prote & Bioanalyt, Niemannsweg 11, D-24105 Kiel, Germany.
    Knight, Stefan D.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology.
    Tholey, Andreas
    Christiana Albertina Univ Kiel, Inst Expt Med, Systemat Prote & Bioanalyt, Niemannsweg 11, D-24105 Kiel, Germany.
    Lindhorst, Thisbe K.
    Christiana Albertina Univ Kiel, Otto Diels Inst Organ Chem, Otto Hahn Pl 3-4, D-24118 Kiel, Germany.
    Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH2018In: Beilstein Journal of Organic Chemistry, ISSN 2195-951X, E-ISSN 1860-5397, Vol. 14, p. 1890-1900Article in journal (Refereed)
    Abstract [en]

    Photoaffinity labeling is frequently employed for the investigation of ligand-receptor interactions in solution. We have employed an interdisciplinary methodology to achieve facile photolabeling of the lectin FimH, which is a bacterial protein, crucial for adhesion, colonization and infection. Following our earlier work, we have here designed and synthesized diazirine-functionalized mannosides as high-affinity FimH ligands and performed an extensive study on photo-crosslinking of the best ligand (mannoside 3) with a series of model peptides and FimH. Notably, we have employed high-performance mass spectrometry to be able to detect radiation results with the highest possible accuracy. We are concluding from this study that photolabeling of FimH with sugar diazirines has only very limited success and cannot be regarded a facile approach for covalent modification of FimH.

  • 13. Bhattacharjee, Snehasish
    et al.
    Chakraborty, Sandipan
    Chorell, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sengupta, Pradeep K.
    Bhowmik, Sudipta
    Importance of the hydroxyl substituents in the B-ring of plant flavonols on their preferential binding interactions with VEGF G-quadruplex DNA: Multi-spectroscopic and molecular modeling studies2018In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 118, p. 629-639Article in journal (Refereed)
    Abstract [en]

    G-quadruplex (G4) structures are known to be promising anticancer drug targets and flavonols (an important class of fiavonoids) are small molecules reported to possess several health-promoting properties including those of anticancer activities. In this work, we explored the interactions of the structurally related plant flavonols kaempferol (KAE; 3,5,7,4'-OH flavone) and morin (MOR; 3,5,7,2',4'-OH flavone) with various G4-DNA sequences along with duplex DNA using a combination of spectroscopic and molecular docking studies. Our results revealed that KAE shows preferential interaction with VEGF G4-DNA in comparison to the other G4 sequences and duplex DNA. Moreover, KAE enhances the thermal stability of VEGF G4-DNA. In contrast, MOR exhibits an appreciably weaker level of interaction with both duplex and various G4-DNAs, with no significant structural specificity. The contrasting DNA binding behaviors suggest a crucial role of the 2'-OH substituent in the Bring of flavonol moiety. While KAE is relatively planar, MOR adopts a significantly non-planar conformation attributable to steric hindrance from the additional 2'-OH substituent. This small structural difference is apparently very important for the ability of KAE and MOR to interact with VEGF G4-DNA. Thus, KAE (but not MOR) appears to be an effective ligand for VEGF G4-DNA, opening up possibilities of its application for regulation of gene expression in cancer cells. 

  • 14.
    Biswas, Dipsikha
    et al.
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Cowie, Andrew
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Tozer, Kathleen
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Perez, Lester J.
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Trivedi, Purvi
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Bartlett, Jordan J.
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Duffley, Luke
    Univ New Brunswick, St John, NB, Canada.
    Dao, Khoi Thien
    Univ New Brunswick, St John, NB, Canada.
    Paramel Varghese, Geena
    Dalhousie Med New Brunswick, St John, NB, Canada..
    Aguiar, Christie
    St Johns Hosp, St John, NB, Canada.
    Yip, Alexandra M.
    St Johns Hosp, St John, NB, Canada.
    Shea, Jennifer
    St Johns Hosp, St John, NB, Canada.
    Brunt, Keith
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Legare, Jean-Francois
    St Johns Hosp, St John, NB, Canada.
    Hassan, Ansar
    St Johns Hosp, St John, NB, Canada.
    Kienesberger, Petra
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Pulinilkunnil, Thomas
    Dalhousie Med New Brunswick, St John, NB, Canada.
    Adverse Cardiometabolic Outcomes in Obese Patients Correlates Strongly with Defective Branched-Chain Amino Acid Catabolism2018In: Journal of Molecular and Cellular Cardiology, ISSN 0022-2828, E-ISSN 1095-8584, Vol. 124, p. 121-122Article in journal (Other academic)
  • 15.
    Cairns, Andrew G.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Vazquez-Romero, Ana
    Mahdi-Moein, Mohammad
    Ådén, Jörgen
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Elmore, Charles S.
    Takano, Akihiro
    Arakawa, Ryosuke
    Varrone, Andrea
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Schou, Magnus
    Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy2018In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 9, no 11, p. 2542-2547Article in journal (Refereed)
    Abstract [en]

    Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-brain barrier permeability in nonhuman primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate α-syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analogue 14, were then radiolabeled with 11C (t1/2 = 20.4 min) at high radiochemical purity (>99%) and high specific radioactivity (>37 GBq/μmol). Following intravenous injection of each compound in NHP, a 4-fold higher radioactivity in brain was observed for [11C]14 compared to [11C]12 (0.8 vs 0.2 SUV, respectively). [11C]14 was rapidly eliminated from plasma, with [11C]12 as the major metabolic product observed by radio-HPLC. The presented prodrug approach paves the way for future development of 2-pyridones as imaging biomarkers for in vivo imaging of α-synuclein deposits in brain.

  • 16.
    Channar, Pervaiz Ali
    et al.
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Saeed, Aamer
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Larik, Fayaz Ali
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Batool, Bakhtawar
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan.
    Kalsoom, Saima
    Int Islamic Univ, SA CIRBS, Islamabad, Pakistan.
    Hasan, M. M.
    PIEAS, Islamabad, Pakistan.
    Erben, Mauricio F.
    UNLP, CONICET, Fac Ciencias Exactas, CEQUINOR,CCT La Plata,Dept Quim, CC 962, RA-1900 La Plata, Buenos Aires, Argentina.
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Ali, Musrat
    Quaid I Azam Univ, Dept Biol Sci, Islamabad 45320, Pakistan.
    Ashraf, Zaman
    Allama Iqbal Open Univ, Dept Chem, Islamabad 44000, Pakistan.
    Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid2018In: Bioorganic chemistry (Print), ISSN 0045-2068, Vol. 79, p. 293-300Article in journal (Refereed)
    Abstract [en]

    Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC50 = 1.568 +/- 0.01 mu M) showed relatively better potential compared to reference kojic acid (IC50 = 16.051 +/- 1.27 mu M). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 angstrom which might be responsible for higher activity compared to Kojic acid.

  • 17.
    Chinthakindi, Praveen K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Drug Design and Discovery.
    Arvidsson, Per I.
    Univ KwaZulu Natal, Catalysis & Peptide Res Unit, Durban, South Africa;Karolinska Inst, Sci Life Lab, Drug Discovery & Dev Platform, Stockholm, Sweden;Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Stockholm, Sweden.
    Sulfonyl Fluorides (SFs): More Than Click Reagents?2018In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 27-28, p. 3648-3666Article, review/survey (Refereed)
    Abstract [en]

    Sulfonyl fluoride (SF) containing substances are currently attracting enormous attention among practitioners of both chemical biology and synthetic organic chemistry. The groups of Jones and Liskamp have demonstrated the potential of sulfonyl fluorides as selective covalent inhibitors in studies related to drug discovery and chemical biology, respectively, in the last few years. The Sharpless group has extended the repertoire of click-reactions to those involving sulfonyl fluorides, that is, sulfur-fluoride exchange (SuFEx), a development that quickly triggered the interest in this functional group in the community of synthetic organic chemists. In this microreview, we aim to give an account of the synthetic chemistry surrounding sulfonyl fluoride containing substances from a historical perspective to present day developments.

  • 18.
    Colas, Kilian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    New C-C coupling Reactions Enabled by Main-group Organometallics2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The carbon-carbon bond has always been at the very core of chemical research. Strategies for the creation of C−C bonds are one of the keys to the construction game that organic chemists play with the building blocks provided by Nature, with the ultimate goal of producing useful molecular structures that will serve society as medicines, materials, imaging tools, catalysts, and ligands (to mention but a few). While very different in their structure, all of these molecules are often prepared by the same methods. However, efficiency could be improved with tailored chemical strategies that would serve an individual purpose. Ideally, these chemical manipulations should be efficient, selective, environmentally friendly and economic, in order to truly fulfill their final objective.

    However, despite the ever-expanding rule-book of chemical reactions, target molecules of increasing complexity often face chemists with daunting challenges, whose success rely on multi-step synthetic sequences. There is therefore a permanent need for new, specific methods and strategies that are capable of seamlessly creating C−C bonds, evading the synthesis of difficult or expensive substrates. In this regard, common organometallic reagents display a unique behavior as carbon precursors, in particular as powerful nucleophiles. Reagents based on main-group elements such as lithium or magnesium have therefore played a central role in organic synthesis ever since their discovery. The challenge often lies in controlling their high reactivity, as well as their basic character. Tuning and taming these properties provides chemists with a wide range of unique strategies for the selective synthesis of countless molecular targets.

    In the first part of this thesis, a scalable and stereoselective [3+3] homocoupling of imines in which two C−C bonds are formed in a single step is reported. This reaction relies on an unusual combination of visible-light irradiation and aluminum organometallics. This photochemical process enables the circumvention of the native [3+2] reactivity of these readily available starting materials, thus enabling rapid access to densely functionalized piperazines. Thanks to the congested environment they provide, these heterocyclic scaffolds can be used as ligands to prevent catalyst deactivation through oligomerization.

    The next chapter presents a novel Pummerer-type redox-neutral coupling of sulfoxides and Grignard reagents. This reaction is enabled by a unique turbo-magnesium amide base, and allows the use of a wide range of carbon nucleophiles in intermolecular Pummerer C−C coupling for the streamlined preparation of thioethers. Given the central character of sulfur in organic chemistry, these compounds can then be converted to a variety of unrelated functional groups for the streamlined preparation of diverse building blocks.

    In the final two chapters, the development of a method for the direct conversion of carboxylic acids to ketones with Grignard reagents is described. Using the above-mentioned combination of organometallics, a wide variety of carboxylic acids substrates and Grignard reagents can be coupled in a convenient, scalable and highly selective method that suppresses the need for activation and offers a straightforward approach to ketones from readily available starting materials.

  • 19.
    Colas, Kilian
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mendoza, Abraham
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Iterative Synthesis of Pluripotent Thioethers through Controlled Redox Fluctuation of Sulfur2018In: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 29, no 10, p. 1329-1333Article in journal (Refereed)
    Abstract [en]

    Target- and diversity-oriented syntheses are based on diverse building blocks, whose preparation requires discrete design and constructive alignment of different chemistries. To enable future automation of the synthesis of small molecules, we have devised a unified strategy that serves the divergent synthesis of unrelated scaffolds such as carbonyls, olefins, organometallics, halides, and boronic esters. It is based on iterations of a nonelectrophilic Pummerer-type C-C coupling enabled by turbo -organomagnesium amides that we have recently reported. The pluripotency of sulfur allows the central building blocks to be obtained by regulating C-C bond formation through control of its redox state.

  • 20. Daikoku, S.
    et al.
    Pendrill, Robert
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kanie, Y.
    Ito, Y.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kanie, O.
    Synthesis and structural investigation of a series of mannose-containing oligosaccharides using mass spectrometry2018In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 16, no 2, p. 228-238Article in journal (Refereed)
    Abstract [en]

    A series of compounds associated with naturally occurring and biologically relevant glycans consisting of alpha-mannosides were prepared and analyzed using collision-induced dissociation (CID), energy-resolved mass spectrometry (ERMS), and H-1 nuclear magnetic resonance spectroscopy. The CID experiments of sodiated species of disaccharides and ERMS experiments revealed that the order of stability of mannosyl linkages was as follows: 6-linked > 4-linked >= 2-linked > 3-linked mannosyl residues. Analysis of linear trisaccharides revealed that the order observed in disaccharides could be applied to higher glycans. A branched trisaccharide showed a distinct dissociation pattern with two constituting disaccharide ions. The estimation of the content of this ion mixture was possible using the disaccharide spectra. The hydrolysis of mannose linkages at 3- and 6-positions in the branched trisaccharide revealed that the 3-linkage was cleaved twice as fast as the 6-linkage. It was observed that the solution-phase hydrolysis and gas-phase dissociation have similar energetics.

  • 21.
    Danelius, Emma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Andersson, Hanna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Solution ensemble analysis of macrocycles2018Conference paper (Refereed)
    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.

  • 22.
    Danelius, Emma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Andersson, Hanna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Jarvoll, Patrik
    Lood, Kajsa
    Gräfenstein, Jürgen
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Halogen bond promoted peptide folding2018Conference paper (Refereed)
    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.  

  • 23.
    Daniel, Quentin
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Duan, Lele
    KTH, School of Chemical Science and Engineering (CHE), Centres, Centre of Molecular Devices, CMD.
    Timmer, Brian J. J.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Chen, Hong
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Luo, Xiaodan
    Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China..
    Ambre, Ram
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Wang, Ying
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Zhang, Biaobiao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Zhang, Peili
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry.
    Wang, Lei
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Li, Fusheng
    KTH, School of Chemical Science and Engineering (CHE), Centres, Centre of Molecular Devices, CMD.
    Sun, Junliang
    Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China..
    Ahlquist, Mårten S. G.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
    Sun, Licheng
    KTH, School of Chemical Science and Engineering (CHE), Centres, Centre of Molecular Devices, CMD. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry.
    Water Oxidation Initiated by In Situ Dimerization of the Molecular Ru(pdc) Catalyst2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 5, p. 4375-4382Article in journal (Refereed)
    Abstract [en]

    The mononuclear ruthenium complex [Ru(pdc)L-3] (H(2)pdc = 2,6-pyridinedicarboxylic acid, L = N-heterocycles such as 4-picoline) has previously shown promising catalytic efficiency toward water oxidation, both in homogeneous solutions and anchored on electrode surfaces. However, the detailed water oxidation mechanism catalyzed by this type of complex has remained unclear. In order to deepen understanding of this type of catalyst, in the present study, [Ru(pdc)(py)(3)] (py = pyridine) has been synthesized, and the detailed catalytic mechanism has been studied by electrochemistry, UV-vis, NMR, MS, and X-ray crystallography. Interestingly, it was found that once having reached the Ru-IV state, this complex promptly formed a stable ruthenium dimer [Ru-III(pdc)(py)(2)-O-Ru-IV(pdc)(py)(2)](+). Further investigations suggested that the present dimer, after one pyridine ligand exchange with water to form [Ru-III(pdc)(py)(2)-O-Ru-IV(pdc)(py)(H2O)](+), was the true active species to catalyze water oxidation in homogeneous solutions.

  • 24.
    Dhillon, Prakriti
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Cobalt-catalysed, regioselective C-H activation of amides with unsymmetrical 1,3-diynes using 8-aminoquinoline as a bidentate directing group2018Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    A cobalt-catalysed, ortho-directed, C-H activation of 8-aminoquinoline amides for the preparation of functionalised isoquinolones is reported. The C-H activation was performed with the amide derived from 8-aminoquinoline which acts as a bidentate directing group to facilitate the C-H activation at the ortho carbon atom of the amide towards annulation/cyclisation, with unsymmetrical 1,3-diynes. The work presented here is an exploration of the regiochemical outcome of an efficient and a novel route of synthesis that tries to gain a deeper insight into the regioselective preference for C-H activated annulations that result in the formation of a diverse range of alkynylated regioisomeric heterocycles. Of the four possible regioisomers, only one is formed as the major product depending on the stereoelectronic properties of the diyne in combination with the nature of the 8-aminoquinoline amide.

  • 25.
    Dias, Jorge T.
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Svedberg, Gustav
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nystrand, Mats
    Thermo Fisher Sci IDD, Global Res & Dev, Uppsala, Sweden..
    Svahn Andersson, Helene
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gantelius, Jesper
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Rapid signal enhancement method for nanoprobe-based biosensing (vol 7, 2017)2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 8184Article in journal (Refereed)
    Abstract [en]

    In the Methods section of this Article references 18 to 22 are incorrectly cited. The correct references were omitted from the reference list and appear below as references 1-5. References 18 to 22 are correctly cited in Introduction and Results and Discussion sections. "AuNPs of 10 nm in diameter were prepared following the protocol described by Bastus et al.18." should read: "AuNPs of 10 nm in diameter were prepared following the protocol described by Bastus et al.1." "AgNPs of 90 nm in diameter were prepared following the protocol described by Rivero et al.19." should read: "AgNPs of 90 nm in diameter were prepared following the protocol described by Rivero et al.2" "The size was determined by UV-Vis spectroscopy according to the AgNPs size theory demonstrated by Malynych20." should read: "The size was determined by UV-Vis spectroscopy according to the AgNPs size theory demonstrated by Malynych3." "The coupling of antibody to the NPs was prepared following a modified version of a protocol previously reported by Puertas et al.21." should read: "The coupling of antibody to the NPs was prepared following a modified version of a protocol previously reported by Puertas et al.4." "Microarrays were prepared as previously reported by our group22." should read: "Microarrays were prepared as previously reported by our group5.

  • 26. Dorau, Robin
    et al.
    Görbe, Tamás
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Svedendahl Humble, Maria
    Improved Enantioselectivity of Subtilisin Carlsberg Towards Secondary Alcohols by Protein Engineering2018In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 19, no 4, p. 338-346Article in journal (Refereed)
    Abstract [en]

    Generally, the catalytic activity of subtilisin Carlsberg (SC) for transacylation reactions with secondary alcohols in organic solvent is low. Enzyme immobilization and protein engineering was performed to improve the enantioselectivity of SC towards secondary alcohols. Possible amino-acid residues for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36 %), enantioselectivity (E values up to 400), substrate scope, and stability in THF.

  • 27.
    Elgland, Mathias
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Synthesis and application of β-configured [18/19F]FDGs: Novel prosthetic CuAAC click chemistry fluoroglycosylation tools for amyloid PET imaging and cancer theranostics2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Positron emission tomography (PET) is a non-invasive imaging method that renders three-dimensional images of tissue that selectively has taken up a radiolabelled organic compound, referred to as a radiotracer. This excellent technique provides clinicians with a tool to monitor disease progression and to evaluate how the patient respond to treatment. The by far most widely employed radiotracer in PET is called 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), which is often referred to as the golden standard in PET. From a molecular perspective, [18F]FDG is an analogue of glucose where a hydroxyl group has been replaced with a radioactive fluorine atom (18F). It is well known that covalent attachment of carbohydrates (i.e., glycosylation) to biomolecules tend to improve their properties in the body, in terms of; improved pharmacokinetics, increased metabolic stability and faster clearance from blood and other non-specific tissue. It is therefore natural to pursuit the development of a [18F]fluoroglycosylation method where [18F]FDG is chemically conjugated to a ligand with high affinity for a given biological target (e.g., tumors or disease-associated protein aggregates).

    This thesis describes a novel [18F]fluoroglycosylation method that in a simple and general manner facilitate the conjugation of [18F]FDG to biological ligands using click chemistry. The utility of the developed [18F]fluoroglycosylation method is demonstrated by radiolabelling of curcumin, thus forming a tracer that may be employed for diagnosis of Alzheimer’s disease. Moreover, a set of oligothiophenes were fluoroglycosylated for potential diagnosis of Alzheimer’s disease but also for other much rarer protein misfolding diseases (e.g., Creutzfeldt-Jakob disease and systemic amyloidosis). In addition, the synthesis of a series of 19F-fluoroglycosylated porphyrins is described which exhibited promising properties not only to detect but also to treat melanoma cancer. Lastly, the synthesis of a set of 19F-fluorinated E-stilbenes, structurally based on the antioxidant resveratrol is presented. The E-stilbenes were evaluated for their capacity to spectrally distinguish between native and protofibrillar transthyretin in the pursuit of finding diagnostic markers for the rare but severe disease, transthyretin amyloidosis.

  • 28.
    El-Sayed, Ashraf M.
    et al.
    New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Suckling, David M.
    New Zealand Inst Plant & Food Res Ltd, New Zealand;Univ Auckland, New Zealand.
    Honey Norisoprenoids Attract Bumble Bee, Bombus terrestris, in New Zealand Mountain Beech Forests2018In: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 66, no 50, p. 13065-13072Article in journal (Refereed)
    Abstract [en]

    Three varieties of honey of different dominant floral origin were found to attract social Hymenoptera, including the large earth bumble bee, Bombus terrestris, in a New Zealand mountain beech forest. This study was undertaken to identify volatile organic compounds that induce the attraction of bumble bees to honeybee (Apis mellifera) honey. We analyzed the chemical composition of the volatile organic compounds produced in three distinct varieties of honey (i.e., manuka, honeydew, and clover honey). The composition of the chemical profile of the three honey varieties differed in the quality and in the ratio of compounds in the headspace. o-Methoxyacetophenone was the main compound in the headspace of all three honey varieties. Among the 40 compounds identified in the headspace in the three varieties, only seven shared compounds (i.e., benzaldehyde, benzyl alcohol, phenylacetaldehyde, 2-phenylethanol, isophorone, 4-oxoisophorone, and o-methoxyacetophenone) were present in the headspace of the three honey varieties. The relative attractiveness of various blends of the seven common compounds found in the three honey varieties was tested for the attraction to bumble bees in a mountain beech forest. A binary blend of isophorone and 4-oxoisophorone at a ratio of 90:10 was the most attractive blend for both bumble bee workers and queens. A small number of honey bee workers were also attracted to the former binary blend. Our study represents the first identification of a honey-derived attractant for bumble bees and honey bees. The potential application of our finding for monitoring of bumble bees or to enhance crop pollination and help to tackle the current concern of a global pollination crisis is discussed.

  • 29.
    Erbing, Elis
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development of New Efficient Iridium-Catalyzed Methods for the Construction of Carbon-Heteroatom Bonds2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Today’s society has a large demand for biologically active chemicals that can be used for example as pharmaceuticals and in the agriculture. These are normally constructed by assembling together several smaller chemical molecules. In order to achieve this, we need that these small molecules contain certain reactive sites, or in other words, that they are functionalized with certain atoms. The work in this thesis investigates and develops new methods to create functionalities in molecules, which in turn can be used to construct larger compounds and other materials important for our society.

     The methods herein developed are based on the use of metal catalysts to construct carbon-halogen bonds. Examples of halogens include bromide and iodide. When a molecule contains one (or more) of these bonds, it can be transformed in a simple chemical step into other compounds. The number of possible chemical transformations becomes almost endless. Thus, by accessing these compounds, chemical libraries can be created easily.

    Throughout the work, sustainability has been prioritized by using, for the human health, friendly solvents whenever possible, by using versatile, stable and structurally simple but yet effective catalysts, and by minimizing the need to use unnecessary chemical activators.

    The full text will be freely available from 2019-12-10 09:00
  • 30.
    Erbing, Elis
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sanz-Marco, Amparo
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Vazquez-Romero, Ana
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Malmberg, Jesper
    Johansson, Magnus J.
    Gomez-Bengoa, Enrique
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Base- and Additive-Free Ir-Catalyzed ortho-Iodination of Benzoic Acids: Scope and Mechanistic Investigations2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 2, p. 920-925Article in journal (Refereed)
    Abstract [en]

    A protocol for the C-H activation/iodination of benzoic acids catalyzed by a simple iridium complex has been developed. The method described in this paper allows the ortho-selective iodination of a variety of benzoic acids under extraordinarily mild conditions in the absence of any additive or base in 1,1,1,3,3,3-hexafluoroisopropanol as the solvent. The iridium catalyst used tolerates air and moisture, and selectively gives ortho-iodobenzoic acids with high conversions. Mechanistic investigations revealed that an Ir(III)/Ir(V) catalytic cycle operates, and that the unique properties of HFIP enables the C-H iodination using the carboxylic moiety as a directing group.

  • 31. Erdelyi, Mate
    et al.
    Pupier, Marion
    Nuzillard, Jean-Marc
    Wist, Julien
    Schlörer, Nils
    Kuhn, Stefan
    Steinbeck, Christoph
    Williams, Antony
    Butts, Craig
    Claridge, Tim
    Mikhova, Bozhana
    Robien, Wolfgang
    Dashti, Hesam
    Eghbalnia, Hamid
    Fares, Christophe
    Adam, Christian
    Pavel, Kessler
    Moriaud, Fabrice
    Elyashberg, Mikhail
    Argyropoulos, Dimitris
    Perez, Manuel
    Giraudeau, Patrick
    Gil, Roberto
    Trevorrow, Paul
    Jeannerat, Damien
    A cross-platform format to associate NMR-extracted data (NMReDATA) to chemical structures2018Conference paper (Refereed)
  • 32.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Pentacoordinate carbonium ions in solution2018Conference paper (Refereed)
  • 33.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    The three-centered halogen bond2018Conference paper (Refereed)
  • 34.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Lindblad, Sofia
    Mehmeti, Krenare
    Veiga, Alberte X
    Nekoueishahraki, Bijan
    Gräfenstein, Jurgen
    The Halogen Bond of Halonium Ions2018Conference paper (Refereed)
    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.

  • 35.
    Forssén, Patrik
    et al.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Multia, Evgen
    University of Helsinki, Finland.
    Samuelsson, Jörgen
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Andersson, Marie
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Aastrup, Teodor
    Attana AB, Sweden.
    Altun, Samuel
    Attana AB, Sweden.
    Wallinder, Daniel
    Attana AB, Sweden.
    Wallbing, Linus
    Attana AB, Sweden.
    Liangsupree, Thanaporn
    University of Helsinki, Finland.
    Riekkola, Marja-Liisa
    University of Helsinki, Finland.
    Fornstedt, Torgny
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).
    Reliable Strategy for Analysis of Complex Biosensor Data2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 8, p. 5366-5374Article in journal (Refereed)
    Abstract [en]

    When using biosensors, analyte biomolecules of several different concentrations are percolated over a chip with immobilized ligand molecules that form complexes with analytes. However, in many cases of biological interest, e.g., in antibody interactions, complex formation steady-state is not reached. The data measured are so-called sensorgram, one for each analyte concentration, with total complex concentration vs time. Here we present a new four-step strategy for more reliable processing of this complex kinetic binding data and compare it with the standard global fitting procedure. In our strategy, we first calculate a dissociation graph to reveal if there are any heterogeneous interactions. Thereafter, a new numerical algorithm, AIDA, is used to get the number of different complex formation reactions for each analyte concentration level. This information is then used to estimate the corresponding complex formation rate constants by fitting to the measured sensorgram one by one. Finally, all estimated rate constants are plotted and clustered, where each cluster represents a complex formation. Synthetic and experimental data obtained from three different QCM biosensor experimental systems having fast (close to steady-state), moderate, and slow kinetics (far from steady-state) were evaluated using the four-step strategy and standard global fitting. The new strategy allowed us to more reliably estimate the number of different complex formations, especially for cases of complex and slow dissociation kinetics. Moreover, the new strategy proved to be more robust as it enables one to handle system drift, i.e., data from biosensor chips that deteriorate over time.

  • 36.
    Franco, Thiago A.
    et al.
    Univ Fed Rio de Janeiro, Brazil;Univ Calif Davis, USA.
    Xu, Pingxi
    Univ Calif Davis, USA.
    Brito, Nathalia F.
    Univ Fed Rio de Janeiro, Brazil.
    Oliveira, Daniele S.
    Univ Fed Rio de Janeiro, Brazil.
    Wen, Xiaolan
    Univ Calif Davis, USA.
    Moreira, Monica F.
    Univ Fed Rio de Janeiro, Brazil;Inst Nacl Ciencia & Tecnol Entomol Mol, Brazil.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Leal, Walter S.
    Univ Calif Davis, USA.
    Melo, Ana C. A.
    Univ Fed Rio de Janeiro, Brazil;Univ Calif Davis, USA;Inst Nacl Ciencia & Tecnol Entomol Mol, Brazil.
    Reverse chemical ecology-based approach leading to the accidental discovery of repellents for Rhodnius prolixus, a vector of Chagas diseases refractory to DEET2018In: Insect Biochemistry and Molecular Biology, ISSN 0965-1748, E-ISSN 1879-0240, Vol. 103, p. 46-52Article in journal (Refereed)
    Abstract [en]

    Rhodnius prolixus is one of the most important vectors of Chagas disease in Central and South America for which repellents and attractants are sorely needed. Repellents like DEET, picaridin, and IR3535 are widely used as the first line of defense against mosquitoes and other vectors, but they are ineffective against R. prolixus. Our initial goal was to identify in R. prolixus genome odorant receptors sensitive to putative sex pheromones. We compared gene expression of 21 ORs in the R. prolixus genome, identified 4 ORs enriched in male (compared with female) antennae. Attempts to de-orphanize these ORs using the Xenopus oocyte recording system showed that none of them responded to putative sex pheromone constituents. One of the them, RproOR80, was sensitive to 4 compounds in our panel of 109 odorants, namely, 2-heptanone, gamma-octalactone, acetophenone, and 4-methylcychohexanol. Interestingly, these compounds, particularly 4-methylcyclohexanol, showed strong repellency activity as indicated not only by a significant decrease in residence time close to a host, but also by a remarkable reduction in blood intake. 4-Methylcyclohexanol-elicited repellency activity was abolished in RNAi-treated insects. In summary, our search for pheromone receptors led to the discovery of repellents for R. prolixus.

  • 37.
    Giovannoli, Cristina
    et al.
    Univ Turin, Italy.
    Passini, Cinzia
    Univ Turin, Italy.
    Di Nardo, Fabio
    Univ Turin, Italy.
    Anfossi, Laura
    Univ Turin, Italy.
    Baggiani, Claudio
    Univ Turin, Italy.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Affinity Capillary Electrochromatography of Molecularly Imprinted Thin Layers Grafted onto Silica Capillaries Using a Surface-Bound Azo-Initiator and Living Polymerization2018In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 10, no 2, article id 192Article in journal (Refereed)
    Abstract [en]

    Molecularly imprinted thin layers were prepared in silica capillaries by using two different surface polymerization strategies, the first using 4,4-azobis(4-cyanovaleric acid) as a surface-coupled radical initiator, and the second, S-carboxypropyl-S'-benzyltrithiocarbonate as a reversible addition-fragmentation chain transfer (RAFT) agent in combination with 2,2-azobisisobutyronitrile as a free radical initiator. The ability to generate imprinted thin layers was tested on two different polymerization systems: (i) a 4-vinylpyridine/ethylene dimethacrylate (4VP-EDMA) in methanol-water solution with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) as a template; and (ii) methacrylic acid/ethylene dimethacrylate (MAA-EDMA) in a chloroform solution with warfarin as the template molecule. The binding properties of the imprinted capillaries were studied and compared with those of the corresponding non-imprinted polymer coated capillaries by injecting the template molecule and by measuring its migration times relative to a neutral and non-retained marker. The role of running buffer hydrophobicity on recognition was investigated by studying the influence of varying buffer acetonitrile concentration. The 2,4,5-T-imprinted capillary showed molecular recognition based on a reversed phase mechanism, with a decrease of the template recognition in the presence of higher acetonitrile content; whereas warfarin-imprinted capillaries showed a bell-shaped trend upon varying the acetonitrile percentage, illustrating different mechanisms underlying imprinted polymer-ligand recognition. Importantly, the results demonstrated the validity of affinity capillary electrochromatography (CEC) to screen the binding properties of imprinted layers.

  • 38. Gisbert, Patricia
    et al.
    Trillo, Paz
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Organic Chemistry Dpt. and Instituto de Sintesis Organica (ISO).
    Pastor, Isidro M.
    Comparative Study of Catalytic Systems Formed by Palladium and Acyl-Substituted Imidazolium Salts2018In: CHEMISTRYSELECT, ISSN 2365-6549, Vol. 3, no 3, p. 887-893Article in journal (Refereed)
    Abstract [en]

    Amino amides, which are readily accessible from amino acids, were used in the preparation of both monoamido and diamido functionalized imidazolium salts in very straightforward protocols. Different catalytic systems formed with palladium(II) acetate and acyl functionalized imidazolium salts were tested in the Matsuda-Heck reaction. The comparative study revealed that the presence of one carbamoyl moiety in the N-heterocyclic carbene precursor is more beneficial during the catalytic process. Thus, better activity was observed with the catalytic system formed using 3-benzyl-1-(N-phenylcarbamoyl-methyl)imidazolium chloride in a 1:1 metal/ligand ratio. Moreover, this fact was evidenced by means of UV/vis studies.

  • 39. GISING, Johan
    et al.
    LINDSTRÖM, Stefan
    ANTONOV, Dmitry
    BRANDT, Peter
    BELFRAGE, Anna Karin
    BREM, Jürgen
    SCHOFIELD, Christopher J
    INHIBITORS OF METALLO-BETA-LACTAMASES: WO/2018/2158002018Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The present invention relates to certain compounds that function as inhibitors of bacterial metallo-beta-lactamases. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of a bacterial infection.

  • 40.
    Gonzalez, Miguel A. Cortes
    et al.
    Stockholm Univ, Dept Organ Chem, SE-10691 Stockholm, Sweden.
    Nordeman, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Gomez, Antonio Bermejo
    Stockholm Univ, Dept Organ Chem, SE-10691 Stockholm, Sweden;Karolinska Inst, AstraZeneca PET Ctr, SE-17176 Stockholm, Sweden.
    Meyer, Denise N.
    Stockholm Univ, Dept Organ Chem, SE-10691 Stockholm, Sweden.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Schou, Magnus
    Karolinska Inst, AstraZeneca PET Ctr, SE-17176 Stockholm, Sweden.
    Szabo, Kalman J.
    Stockholm Univ, Dept Organ Chem, SE-10691 Stockholm, Sweden.
    [18F]fluoro-benziodoxole: a no-carrier-added electrophilic fluorinating reagent. Rapid, simple radiosynthesis, purification and application for fluorine-18 labelling2018In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 54, no 34, p. 4286-4289Article in journal (Refereed)
    Abstract [en]

    Operationally simple radiosynthesis and purification of [F-18]fluoro-benziodoxole was developed starting from a cyclotron produced [F-18]F- precursor, [F-18]TBAF, and tosyl-benziodoxole. The synthetic utility of [F-18]fluoro-benziodoxole was demonstrated by electrophilic fluorocyclization of o-styrilamides proceeding with high RCC (typically 50-90%) and high molar activity (up to 396 GBq mol(-1)).

  • 41.
    González Miera, Greco
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Martínez-Castro, Elisa
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Acceptorless Alcohol Dehydrogenation: OH vs NH Effect in Bifunctional NHC–Ir(III) Complexes2018In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 37, no 5, p. 636-644Article in journal (Refereed)
    Abstract [en]

    Bifunctional complexes bearing N-heterocyclic carbene (NHC) ligands functionalized with hydroxy or amine groups were synthesized to measure the beneficial effect of different modes of metal–ligand cooperation in the acceptorless dehydrogenation of alcohols. In comparison to complexes with an amine moiety, hydroxy-functionalized iridium catalysts showed superior activity. In contrast to alcohols, 1,4-diols underwent cyclization to give the corresponding tetrahydrofurans without involving dehydrogenation processes. Mechanistic investigations to rationalize the “OH effect” in these types of complexes have been undertaken.

  • 42.
    Gotfredsen, Henrik
    et al.
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Neumann, Timo
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström.
    Storm, Freja Eilso
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Munoz, Alberto Vinas
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Jevric, Martyn
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Hammerich, Ole
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Mikkelsen, Kurt V.
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Freitag, Marina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Boschloo, Gerrit
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Nielsen, Mogens Brondsted
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen O, Denmark.
    Donor-Acceptor-Functionalized Subphthalocyanines for Dye-Sensitized Solar Cells2018In: CHEMPHOTOCHEM, ISSN 2367-0932, Vol. 2, no 11, p. 976-985Article in journal (Refereed)
    Abstract [en]

    Boron subphthalocyanines (SubPcs) are attractive as light harvesting materials in photovoltaic devices. Here we present the synthesis, optical and electrochemical properties, and device performances of a series of donor-acceptor-functionalized SubPc derivatives incorporating a carboxylic acid for anchoring onto TiO2. Liquid- and solid-state dye-sensitized solar cells (DSCs) were prepared from three compounds, and a triad system consisting of two aniline donor moieties and a benzothiadiazole acceptor moiety was found to exhibit the highest power conversion efficiency (PCE) in the series (PCE=1.54 %; solid-state device). The compounds were prepared by stepwise acetylenic coupling reactions. In addition, we present the synthesis and optical properties of a SubPc derivative incorporating three anilino-substituted 1,1,4,4-tetracyanobutadiene units, prepared by the [2+2] cycloaddition between three ethynyl units at the SubPc periphery and three tetracyanoethylene molecules followed by electrocyclic ring-opening reactions.

  • 43.
    Gudmundsson, Arnar
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Yang, Bin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Efficient Formation of 2,3-Dihydrofurans via Iron-Catalyzed Cycloisomerization of alpha-Allenols2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 1, p. 12-16Article in journal (Refereed)
    Abstract [en]

    Herein, we report a highly efficient iron-catalyzed intramolecular nucleophilic cyclization of alpha-allenols to furnish substituted 2,3-dihydrofurans under mild reaction conditions. A highly diastereoselective variant of the reaction was developed as well, giving diastereomeric ratios of up to 98:2. The combination of the iron-catalyzed cycloisomerization with enzymatic resolution afforded the 2,3-dihydrofuran in high ee. A detailed DFT study provides insight into the reaction mechanism and gives a rationalization for the high chemo-and diastereoselectivity.

  • 44.
    Guo, Ming
    et al.
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Hu, Yinglu
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Wang, Lixia
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sun, Liping
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    A facile synthesis of molecularly imprinted polymers and their properties as electrochemical sensors for ethyl carbamate analysis2018In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 8, no 69, p. 39721-39730Article in journal (Refereed)
    Abstract [en]

    New molecularly imprinted polymers (MIPs), which exhibit specific recognition of ethyl carbamate (EC) have been synthesized and studied. In this process, EC was the template molecule and -cyclodextrin derivatives were employed as functional monomers in the molecular imprinting technique (MIT). An EC molecularly imprinted sensor (EC-MIS) was prepared by using MIT surface modification. The EC-MIS was characterized by cyclic voltammetry, electrochemical impedance spectroscopy and differential pulse voltammetry. EC detection performance, binding parameters and dynamics mechanism were investigated. The result showed that the synthetic route designed was appropriate and that new MIP and EC-MIS were successfully prepared. The EC-MIS exhibited a good molecular recognition of EC. A linear relationship between current and EC concentration was observed using cyclic voltammetry and the detection limit was 5.86 g L-1. The binding constant (K = 4.75 x 10(6) L mol(-1)) between EC and the EC-MIS, as well as, the number of binding sites (n = 1.48) has been determined. The EC-MIS recognition mechanism for the EC is a two-step process. The sensor was applied for the determination of EC in Chinese yellow wines, and the results were in good agreement with the gas chromatography-mass spectrometry (GC-MS) method.

  • 45.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies on Metalloenzymatic Dynamic Kinetic Resolutions and Iron-Catalyzed Reactions of Allenes2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main focus of this thesis lies in the development of new transition metal-catalyzed chemoenzymatic dynamic kinetic resolutions (DKR) of both alcohols and amines. The first part of the thesis deals with the development of new heterogeneous systems for the DKR of amines. The racemization catalysts in these different systems are all composed of palladium nanoparticles supported on either mesoporous silica or incorporated in a biocomposite that is composed of a bioactive cross-linked enzyme aggregate. 

    The second part of the thesis deals with the development of a homogeneous iron catalyst in the racemization of sec-alcohols for the implementation in a chemoenzymatic DKR. Two protocols for the racemization of sec-alcohols are reported. The first one could not be combined with a chemoenzymatic kinetic resolution, although this was overcome in the second iron based protocol. 

    Following the successful iron catalyzed chemoenzymatic DKR of sec-alcohols, the iron catalyst was used in the cyclization of α-allenic alcohols and N-protected amines to furnish 2,3-dihydrofurans and 2,3-dihydropyrroles, respectively. The cyclization is proceeding in a diastereoselective manner.

    The last part of the thesis deals with attempts to further elucidate the mechanism of activation of a known ruthenium racemization catalyst. X-ray absorption spectroscopy using synchrotron radiation was used for this purpose.

  • 46.
    Gustav, Hulu
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Improved Reaction Conditions for Rhodium-catalyzed Hydroarylation of C60 Fullerenes with Tolylboronic acid: Towards bis[60] fullerene dumbbells2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    The full text will be freely available from 2020-06-08 16:25
  • 47.
    Görbe, Tamás
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Heterogeneous catalysis in racemization and kinetic resolution along a journey in protein engineering2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part of my thesis concerns the use of heterogeneous acidic resins for racemization of tert-alcohols without any side-product formation. The focus was to develop a system which can be further extended to a DKR protocol consisting of an enzymatic KR reaction. Based on our knowledge of the resins, an unexpected migratory DKR protocol turned out to be an efficient method for the synthesis of carbocyclic allylic carbinols.

    The development of enzyme and metal catalyst hybrids was already an ongoing theme in our group. A supporter-free biohybrid catalyst was developed which can be used in several different types of reactions. The Pd(0)-CalB CLEA catalyst was applied in a two-step-cascade transformation and in the DKR of benzylic primary amines. The catalyst was characterized by different analytical techniques, to understand its composition and structure.

    The enzymes have always been the main focus of the studies and therefore wild type enzymes were initially utilized. However, these natural biocatalysts are associated with certain limitations. In contrast, protein engineering allows for enzymes to be modified and optimized. We have used the technique to create a subtilisin Carlsberg mutant, which was studied both by modeling and in vitro. The mutant was found to catalyze the (S)-selective transesterification of sec-alcohols containing long aliphatic carbon chains, and it also exhibited higher performance in organic solvent.

    The last project concerned the protein engineering of CalA enzyme towards tert-alcohols. The kinetic resolution of tert-alcohols with this enzyme is very slow but it occurs with good enantioselectivity. The aim was therefore to improve the activity of CalA via protein engineering. Seven amino acids were mutated close to the active site and a library was created based on our prediction. Throughout the screening, a few variants showed higher activity, which were sequenced and further analyzed in the transesterification of tert-alcohols.

  • 48.
    Görbe, Tamás
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lihammar, Richard
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Heterogeneous Acid-Catalyzed Racemization of Tertiary Alcohols2018In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 1, p. 77-80Article in journal (Refereed)
    Abstract [en]

    Tertiary alcohols are important structural motifs in natural products and building blocks in organic synthesis but only few methods are known for their enantioselective preparation. Chiral resolution is one of these approaches that leaves one enantiomer (50% of the material) unaffected. An attractive method to increase the efficiency of those resolutions is to racemize the unaffected enantiomer. In the present work, we have developed a practical racemization protocol for tertiary alcohols. Five different acidic resin materials were tested. The Dowex 50WX8 was the resin of choice since it was capable of racemizing tertiary alcohols without any byproduct formation. Suitable solvents and a biphasic system were investigated, and the optimized system was capable of racemizing differently substituted tertiary alcohols.

  • 49.
    Hamark, Christoffer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pendrill, Robert
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Landström, Jens
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Dotson Fagerström, Alexandra
    Sandgren, Mats
    Ståhlberg, Jerry
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Enantioselective Binding of Propranolol and Analogues Thereof to Cellobiohydrolase Cel7A2018In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 68, p. 17975-17985Article in journal (Refereed)
    Abstract [en]

    At the catalytic site for the hydrolysis of cellulose the enzyme cellobiohydrolase Cel7A binds the enantiomers of the adrenergic beta-blocker propranolol with different selectivity. Methyl-to-hydroxymethyl group modifications of propranolol, which result in higher affinity and improved selectivity, were herein studied by H-1,H-1 and H-1,C-13 scalar spin-spin coupling constants as well as utilizing the nuclear Overhauser effect (NOE) in conjunction with molecular dynamics simulations of the ligands per se, which showed the presence of all-antiperiplanar conformations, except for the one containing a vicinal oxygen-oxygen arrangement governed by the gauche effect. For the ligand-protein complexes investigated by NMR spectroscopy using, inter alia, transferred NOESY and saturation-transfer difference (STD) NMR experiments the S-isomers were shown to bind with a higher affinity and a conformation similar to that preferred in solution, in contrast to the R-isomer. The fact that the S-form of the propranolol enantiomer is pre-arranged for binding to the protein is also observed for a crystal structure of dihydroxy-(S)-propranolol and Cel7A presented herein. Whereas the binding of propranolol is entropy driven, the complexation with the dihydroxy analogue is anticipated to be favored also by an enthalpic term, such as for its enantiomer, that is, dihydroxy-(R)-propranolol, because hydrogen-bond donation replaces the corresponding bonding from hydroxyl groups in glucosyl residues of the natural substrate. In addition to a favorable entropy component, albeit lesser in magnitude, this represents an effect of enthalpy-to-entropy compensation in ligand-protein interactions.

  • 50.
    Hellwig, Raphael
    et al.
    Tech Univ Munich, Germany.
    Uphoff, Martin
    Tech Univ Munich, Germany.
    Paintner, Tobias
    Tech Univ Munich, Germany.
    Björk, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Ruben, Mario
    KIT, Sweden; Univ Strasbourg, France.
    Klappenberger, Florian
    Tech Univ Munich, Germany.
    Barth, Johannes V.
    Tech Univ Munich, Germany.
    Ho-Mediated Alkyne Reactions at Low Temperatures on Ag(111)2018In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 60, p. 16126-16135Article in journal (Refereed)
    Abstract [en]

    Low-temperature approaches to catalytic conversions promise efficiency, selectivity, and sustainable processes. Control over certain coupling reactions can be obtained via the pre-positioning of reactive moieties by self-assembly. However, in the striving field of on-surface synthesis atomistic precision and control remains largely elusive, because the employed coupling reactions proceed at temperatures beyond the thermal stability of the supramolecular templates. Here, utilizing scanning tunneling microscopy, we demonstrate terminal alkyne on-surface reactions mediated by Ho atoms at a weakly reactive Ag(111) substrate at lowtemperatures. Density functional theory calculations confirm the catalytic activity of the involved adatoms. Pre-deposited Ho induces alkyne dehydrogenation starting at substrate temperatures as low as 100 K. Ho arriving at molecularly pre-covered surfaces held at 130 and 200 K produces covalent enyne-linked dimers and initiates cyclotrimerization, respectively. Statistical product analysis indicates a two-step pathway for the latter, whereby the enyne intermediates influence the distribution of the products. High chemoselectivity results from the absence of cyclotetramerization and diyne-forming homocoupling. Our analysis indicates that mainly the arriving Ho adatoms enable the coupling. These findings support the concept of dynamic heterogeneity by single-atom catalysts and pave the way for alternative means to control on-surface reactions.

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